Dr. Michael Gruttadauria discusses a Functional Medicine Approach to Depression and Anxiety with Dr. Ben Weitz.

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Podcast Highlights

2:24  Dr. Gruttadauria first saw a patient with severe depression six years ago. He was 23 years old and he seemed to have a lot going for him but he was severely depressed. He had been to see a number of doctors, was going to talk therapy, and had been on multiple medications and nothing was helping him.  He had a good job, had a girlfriend, and was in a band that had just signed a record deal. He was also working out five days per week and was eating a healthy diet. And he did not have any childhood trauma and had a great childhood. Dr. Gruttadauria concluded that this patient’s depression must be physiological rather than psychological.  He ran a series of labs and looked at stool testing and epigenetics. This patient had MTHFR, gut dysbiosis, food sensitivities, and issues with nutritional deficiencies. After correcting these things with a diet, lifestyle, and nutritional supplement approach, his depression was gone in six weeks.

6:34  The Neurotransmitter theory of depression.  Patients with anxiety and depression are often prescribed medications that typically increase serotonin levels in the brain, such as the SSRIs, since the hypothesis is that depression is caused by a deficiency in serotonin in the brain. This hypothesis that mood disorders are caused by deficiencies or imbalances in the neurotransmitters not only is not true, but even if it were, it doesn’t get to the root cause, which is why do they have a neurotransmitter imbalance?  There is a concert of neurotransmitters that function in the brain. Glutamate gets the brain excited and GABA calms the brain and then there are all these dimmer switches, which are serotonin, dopamine, acetylcholine, glycine, and all these other neurotransmitters.  All of these neurotransmitters are made from amino acids contained in protein foods. Tyrosine makes dopamine and tryptophan makes serotonin. But you have to go through a series of biochemical steps to make that happen. So, if our epigenetics are skewed, which we all have these epigenetic weaknesses called SNPs, you may have a genetic predisposition to make a little less serotonin or dopamine than somebody else might. Or if your diet’s deficient in protein, or you have a gastrointestinal issue and you’re not digesting and absorbing protein, you’re not going to have the building blocks for these kinds of transmits, or you have nutrient deficiencies that affect your ability to methylate, this will keep you from producing these neurotransmitters.  And if you don’t produce enough serotonin, then an SSRI medication will not have much effect.

17:06  When we look at the underlying physiological triggers for mood disorders, first we need to understand that inflammation is an underlying factor in all chronic illness, including mood disorders. Depression is essentially an inflammatory disorder, essentially chronic neuroinflammation. Over time, neuroinflammation will become neurodegeneration and we end up with Alzheimer’s and other neurodegenerative diseases.  We need to look for the some of the underlying triggers for inflammation, which includes diet, toxins, and gut function. If we don’t assess the gastrointestinal system, we are missing the boat.  There is such a connection between the gut and brain that if the gut is on fire, the brain is on fire.  One of the things that happens is a change in our nervous system from parasympathetic dominance to sympathetic dominance, which slows down the motility of the gut, which adversely affects the microbiome.  Dr. Gruttadauria prefers using the GI Map stool test to assess the microbiome and gut health.  By treating the gut, we are not treating depression but restoring health, which results in less depression.

23:37  Diet.  If the patient is starting with the Standard American diet and they are eating junk food and drinking 3 cokes a day and they live on Ring Dings, then just taking away all that processed food will be a massive shift.  And getting people to drink water is a big shift for a lot of people. Many people only drink soda, coffee, and juice. Reducing chronically elevated blood sugar is an important thing. We also need to remove food sensitivities.  The dietary approach that Dr. Gruttadauria feels is best is a paleo style diet with lots of plants and significant amounts of protein. If we can get people to eat vegetables and lean proteins and we can get them to drink water and go out in the sun and exercise 20 to 30 minutes a day, probably we’d knock out 50% of the depression and anxiety.

25:15  The importance of Sleep and Circadian Rhythm.  The brain has two pacemakers. One is driven by movement and the other is driven by light. We have receptors in the back of the eye called melanopsin receptors that pick up light, transcribe it, and drive the hypothalamus. And it drives an area of the brain called a super charismatic nucleus, which generates this day night cycle.  Most of us have overexposure to blue light due to indoor lights, due to looking at our phones and computer screens, and due to staying up and watching TV till late.  This can dysregulate our cortisol melatonin rhythm, and that changes everything about our brain.

30:23  Nutritional Supplements.  Nutritional supplements are recommended that testing shows they are low in, such as vitamin D, omega 3, vitamin B12 or magnesium. Dr. Gruttadauria likes to use herbals to reduce bacterial overgrowth in the gut, followed by gut healing protocols.  If patients have a lot of inflammation, he will use fish or krill oil. He will also use anti-inflammatory nutritional products like Boswellia or Inflammatone by Designs For Health.  He likes protein shakes like MediClear by Thorne, which is a pea based protein with a lot of vitamins and minerals. Dr. Gruttadauria also often recommends free form amino acids. He often recommends magnesium threonate, which does a good job crossing the blood brain barrier.  He also likes the product NeuroCalm by Designs For Health, which helps with anxiety.  Of course, chiropractic adjustments are also very helpful in normalizing the nervous system.  He will sometimes recommend low dose lithium orotate at a dosage of 5 mg per day, which can be very helpful and is quite safe at this low dosage.

 



Dr. Michael Gruttadauria is a Doctor of Chiropractic with a Board Certification in Chiropractic Neurology and he is on the Advisory Board of Functional Medicine University.  He is the CEO and Director of The Optimum U, which is his private practice in New York.  Dr. Gruttadauria is also the Founder of the SameHere Global Functional Doctor’s Alliance, which is an international mental health non profit dedicated to spreading the word about mental health and not just mental illness. Practitioners interested in joining this alliance can send him an email to dr.mike.gruttadauria@gmail.com.

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.

 



 

Podcast Transcript

Dr. Weitz:                            Hey. This is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website, drweitz.com. Thanks for joining me, and let’s jump into the podcast.

                                                Hello, Rational Wellness podcasters. Today, we have an exciting discussion on a functional medicine approach to anxiety and depression with Dr. Michael Gruttadauria. Dr. Michael Gruttadauria is a doctor of chiropractic with a board certification in chiropractic neurology. He’s on the advisory board of Functional Medicine University, and a CEO and director of the Optimum U. Rates of depression and anxiety in the United States were already quite high, but then the pandemic hit that we’ve just lived through since 2020, and we’ve seen an increase in the rates of these disorders by approximately 28 and 26%.             Depression is a mood disorder involving feeling sad, that is distinct from normal mood swings and short term emotional responses to the daily challenges of life. Depression can be dangerous to your health, especially if it’s severe. It can result in the depressed person suffering and being unable to perform well in school, work, and social life. Severe depression can even lead to suicide. And every year, over 700,000 people die by suicide in the United States. Anxiety involves fear or uneasiness of future situations and problems and can lead to behavior that avoid situations that might trigger this anxiety. This can also affect job, academic, and personal relationships. And 62% of Americans report feeling anxious at some point in their lives. Dr. Gruttadauria, thank you so much for joining us. I hope I pronounced your name correctly.

Dr. Gruttadauria:            Yes. You did a really, really good job. I’m very, very happy to be here, and I really appreciate you having me on.

Dr. Weitz:                        So, how did you get interested in treating patients with mood disorders?

Dr. Gruttadauria:            Oh my goodness. About probably six years ago, I was in my office and I had a patient call me up and say, “One of my friend’s sons is really in trouble. Can you see him?” And I said, “Sure, I’ll be happy to see him.” And she goes, “No, can you see him tonight?” And I said, “Yeah, what’s up?” And she said, “He’s tremendously depressed. He’s at the end of his rope. He’s been to every doctor. He’s been on every medication, and he needs to meet with you.” So, I said, “Sure.” So after hours, in walks this young man and his mom, and just this handsome, vibrant, young 23 year old man. And I sit down and we start talking and he’s telling me about his life. And he says, “I graduated from college and I have a great job. I moved back in with my parents. I work with my dad on the weekends. I work out five days a week. I eat a healthy diet. I have a girlfriend. I’m in a band, a rock band, and we just got signed to a record label.”

Dr. Weitz:                        Wow. Sounds like he’s got everything going for him.

Dr. Gruttadauria:            I said, “It sounds to me like you have the perfect life. What am I missing?” And he said, “Every morning I wake up with this overwhelming feeling of dread and loss of energy and lack of motivation, and I just have a hard time going on, and I’ve had some really dark thoughts. And I’ve been on multiple medications and nothing has helped me. I’ve been in therapy.” And I said, “Tell me about your history. Have you ever been traumatized, emotional, physical, any kind of trauma?” He said, “No, I had a great childhood. I’ve never experienced any real trauma.” And that’s when the light bulb went on. And I said, this is physiological. Something is wrong with this young man. This isn’t… And I’m going to challenge the idea that depression and anxiety are diseases, because they’re looked at as… These labels are given to people, and it’s almost as if it’s a disease, but we can’t send somebody for an MRI or a blood test to look for depression or anxiety.  They don’t exist, because really, depression and anxiety are the culmination of a series of dysfunctions that happen in the nervous system as a result of what’s going on emotionally, what’s going on in our environment, what’s going on epigenetically, what’s going on with our diet. All these factors all play in, and the perfect storm comes together to form what we label as anxiety and depression. So, I went on to do a whole series of labs and we looked at his stool testing and we looked at his epigenetics. And of course, he has MTHFR and he has gut dysbiosis and he has food sensitivities, and he has multiple issues with nutrient density and so on. And literally within six weeks, this young man’s depression was gone. And I said, “It’s amazing that you’ve been feeling this way for three years.” He goes, “No, I told you it was three years, but I never told anybody. It’s been eight years that I’ve been suffering with this. I just never wanted to tell anybody.”

                                                So, we have an epidemic of these issues, these anxiety and depression. But again, we really need to start looking at mental health and not just looking at the disorders. Because what that does is it creates a barrier. It says Americans constantly promote the fact that one in five people has a mental health disorder, anxiety, depression, bipolar, whatever it might be. But what that infers is that 20% of people have this problem, and the rest of us 80 percenters are fine. And that’s just not true because we’re all impacted by stress. We’re all impacted by lifestyle challenges. And the fact that we’re sitting down and lying down 90 plus percent of the day, and we don’t get enough sunlight exposure, we eat food that’s toxic, and all of the different challenges that we have in American living, and it’s no wonder that we have such a high rate of mental health challenges. And we just need to start talking about it because we hold it in. And as a result, it only gets worse.

Dr. Weitz:                        So, his depression wasn’t caused by a deficiency of Prozac?

Dr. Gruttadauria:            Exactly, exactly. And it’s funny. It’s great that you say that because I use that term all the time. You certainly do not have a Prozac deficiency. And it’s incredible because they’ve actually just recently come out and said, “Well, that whole serotonin hypothesis where we have a serotonin deficiency really isn’t true.” So, for the last 30 years we’ve been giving people SSRI medications, literally hundreds of thousands of them every year, and they give people some relief, some-

Dr. Weitz:                        But that’s a predominant theory of depression and anxiety, is that they’re caused by neurotransmitter imbalances or deficiencies.

Dr. Gruttadauria:            So, then the question from our perspective, from a functional medicine perspective is, why does somebody have a neurotransmitter deficiency?

Dr. Weitz:                        Right.

Dr. Gruttadauria:            I mean-

Dr. Weitz:                        What’s the root cause? Yeah.

Dr. Gruttadauria:            What’s the root cause? Why? I mean, we know that serotonin and dopamine, modulatory neurotransmitters. We have… The brain gets turned on by glutamate and it gets turned off by GABA. Those are the on and off switches. And then we have all these modulating, if you think about it as almost like dimmer switches, serotonin and dopamine, acetylcholine, glycine, all these other neurotransmitters, and they’re made from protein. They’re made directly from amino acids. Tyrosine makes dopamine and tryptophan makes serotonin. But you have to go through a series of biochemical steps to make that happen. So, if our epigenetics are skewed, which we all have these epigenetic weaknesses called SNPs, you may have a genetic predisposition to make a little less serotonin or dopamine than somebody else might. Or if your diet’s deficient in protein, or you have a gastrointestinal issue and you’re not digesting and absorbing protein, you’re not going to have the building blocks for these kinds of transmits, or you have nutrient deficiencies because we know that methylation, this process called methylation is involved.  So many different pieces of the puzzle that are just not being looked at. You walk into a psychiatrist’s office and you tell them that you have depression, and within 15 minutes, you’re pretty much walking out with a prescription.

Dr. Weitz:                        Right. Now, interestingly, they’re often walking out with a prescription for SSRI, which is designed to increase serotonin, but there’s actually one medication on the market that decreases serotonin and seems to have equal efficacy as the medications that increase serotonin.

Dr. Gruttadauria:            It’s crazy because actually, what they’re doing is… An SSRI medication is actually designed to make the serotonin that your body has in the synapse between the nerve cells stay in there longer.

Dr. Weitz:                        Right.

Dr. Gruttadauria:            The uptake inhibitor, and it stops it from being taken up into the following cell. But what if your body’s not producing as much as it should to begin with?

Dr. Weitz:                        Right.

Dr. Gruttadauria:            You get the label of treatment resistant depression.

Dr. Weitz:                        Right.

Dr. Gruttadauria:            Because you’re resistant to the treatment we’re trying to give you, which is the standard of care, well, now you have treatment resistant depression, and we don’t really know what to do with you. Maybe TMS, maybe we’ll try ketamine next, maybe we’ll try electroconvulsive therapy. And you have all these other things that are trying to kill the depression, which is, again, the symptom that happens as a result of all these others.

Dr. Weitz:                        Yeah, it’s interesting that ketamine and low dose hallucinogens are the new treatment for depression.

Dr. Gruttadauria:            Right. And that’s the whole thing. If we step back and we think about the word treatment, what are we actually treating if we can’t see it? We’re treating the symptom and we’re never really looking for the root cause.

Dr. Weitz:                        Right.

Dr. Gruttadauria:            That is the biggest challenge that we face in a functional health environment, is working with people that have these mental health challenges and helping them to understand and make changes to their lifestyle when they feel at they’re worst. So, it’s not that easy.

Dr. Weitz:                        Right. So, when you have a new patient who’s coming to you, say, with depression, how do you assess them? How do you decide what testing to do?

Dr. Gruttadauria:            So, I’m very lucky to be working in an environment where I work very closely with psychologists and psychiatrists. So, a lot of times, they’re in counseling, because as a functional medicine practitioner, I want to make sure that they have the emotional support that they need. And we look for integrative psychologists, people who are looking to do breath work and who are really open to the ideas of functional medicine, as well as yoga and all these other techniques, because we need to rearrange the way the brain is working. It’s not just about talk therapy. It’s a great modality, but it’s one of many. What I do then, because I have this background in neurology, I always want to assess the brain because these are really neurological issues. And what we see is, and there was actually just an article recently in Psychology Today, can concussion cause depression? And the answer is yes. And actually, this happened to me, Ben. When I was in graduate school, I was in a car accident, and I went through a windshield, believe it or not.

Dr. Weitz:                        Oh wow.

Dr. Gruttadauria:            And after having head injury, neck injury, and about three months of rehabilitation, I was back and everything was fine. And one day I’m driving in my car and I have this massive tunnel vision, my heart starts to pump, and I’m having what I thought was a stroke at 22 years old. And meanwhile, I was in the best shape of my life, I was competing in body building, I had the great… Everything was fine. And I get to the hospital and they tell me I have a panic attack. And I said, well, I just went through a windshield. And they said, no one thing has nothing to do with the other. And for about five years, I had emotional dysregulation, up and down, up and down, and everybody just wanted to throw drugs at me. And I said, I know that this is due to my head injury. I smashed my head.  And they didn’t want to know about it. So, from a functional neurological perspective, we look at brain stem issues and we look at eye movements and we contract them and videotape them. We look at computerized balance assessments. So, we really need to get an idea of what’s going on in the brain. Then we need to look at blood, urine stool, food sensitivities, toxicology, all these different things. And everybody’s different, so we don’t have to run every test on everybody, but it really starts with the questions. Tell me about your life. What’s happened to you? Tell me your story. And that brings me to really this amazing organization that I work with, which is called Same Here Global.  A few years ago, I was posting all about depression on my Facebook page and I get on one of the posts from a gentleman that I really never met before.  His name’s Andrew Pleener.   And he reaches out to me and says, “Listen, I’m an integrative psychiatrist in Florida and I work with a gentleman named Eric Cuson who started an organization called Same Here Global. Can you tell us why you are working with people with depression when you’re not a psychiatrist or a psychologist?”  And I gave them the whole overview of the functional medicine, functional neurological approach, and then I put together a presentation.  And they said, “We want you to build a network of like-minded doctors.  We want you to find functional medicine, functional neurology, integrative medicine, anybody who is interested in helping us to get this message out.”  And really, the story behind Same Here was that this gentleman, Eric Cuson, was a big time executive in the sports world.  He was on his way to becoming the the CFO of a major basketball franchise, one of the NBA franchises.  And at 38 years old, wakes up and basically has a nervous breakdown. Had no idea why. Everything was great in his life. And he started the merry go round of going to the best doctors. And literally 52 medication combinations later and two and a half years, had to move back in with his parents because he was unable to function.  And he was told by the doctors at Cornell in Manhattan, “Your last resort is electroconvulsive therapy.”  Nobody ever did any blood tests on him.  Nobody looked at his stool, nobody did epigenetic testing.  Nobody did anything but prescribe medication for this guy.

Dr. Weitz:                        Of course.

Dr. Gruttadauria:            And afterward, he ends up in an integrative psychologist office because nothing worked. He was just as bad as he was. He was worse. And they said, “Tell me about your story. Tell me about your life.” And it was really interesting to him that they didn’t just say, “Tell me about your depression,” because he realized that it wasn’t just about the label. And he tells the story… He’s much better at telling it than I am, but essentially when he was a little boy, he had an older brother. His older brother ended up getting cancer, and his family was in this tumultuous, crazy situation for years, multiple years. Eventually pulls out of it. Then, so it was like his life was upside down for years, tremendous amounts of stress as a young kid. Then the same brother was in the back of a Jeep when he was in high school. And the Jeep gets into an accident, he has a head injury, he goes into a coma.

                                                Again, the whole family is in total, total upset. And then in college, the brother ended up having a relapse of his cancer. So, it was literally like a decade of massive amounts of stress. And the way the psychologist explained it was, imagine you were at a mud wrestling event and you’re in the front row. You’re not wrestling, but every time somebody throws somebody down, it splashes onto you. So, time the event is over, you are just as covered in mud as the person in the wrestling match. And that hit me so hard. I thought that was the greatest analogy. And that stress causes changes in us. It causes changes in our brain, in our nervous system function. We end up in a constant fight or flight mode. We end up with changes in our adrenal glands, neurochemistry. Everything changes as a result of stress. And unless we get to the bottom line and help people to not only understand what’s going on in their bodies, we can actually reverse these things. And that’s what we do.   And it’s like magic when you get to help somebody that nobody else has been able to help, because we’re really just looking at a common sense approach to restoring health versus treating illness.

Dr. Weitz:                        So, let’s go through some of the underlying physiological triggers and things that you might see coming back from testing that’s going to help you treat patients for these mood disorders like depression and anxiety. List off some of the most important factors. One thing I want to touch on is blood sugar balance.

Dr. Gruttadauria:            Yes. So, inflammation is… And I know you’ve talked about this hundreds of times on your podcast. Inflammation seems to be an underlying factor in all chronic illness, including mood disorders. Depression is actually an inflammatory problem. So, when we have chronic inflammation… Inflammation is essentially a chemical and cellular response to injury, and it’s normal. It’s a very healthy response. It’s part of the immune system. But when it becomes a chronic problem, then it changes our biochemistry overall. And when chronic body inflammation gets to the brain, it causes something called neuroinflammation. Now, the brain has its own immune system, and we have these things called microglia, which are these supportive cells that react in such a way that it creates this ongoing chronic neuroinflammation. Eventually, that newer inflammation causes changes in brain function, so people show up with brain fog, chronic fatigue, anxiety, depression, headaches. All those things are all as a result of changes neurologically. Eventually, that neuroinflammation will become neurodegeneration and we end up with other things like Alzheimer’s disease and other neurodegenerative diseases.

                                                So, we need to understand what is somebody’s inflammatory load? Where do people get inflamed? They get inflamed through their diet and toxins, through many different factors. But one of the biggest things really is gut function. And that that’s really almost the foundation for everything. If we don’t assess the gastrointestinal system, we are missing the boat. There is such a direct link between the gut and the brain that actually, in functional medicine, and I’m sure you’ve said this a million times, the gut’s on fire, the brain’s on fire. They work together. There are more neurons, more nerve cells in the gut than there are in the entire spinal cord.

Dr. Weitz:                        So, how do you assess the gastrointestinal function?

Dr. Gruttadauria:            Yeah. So, one of the things that we know happens is when we have these issues, we usually have a shift in nervous system function toward sympathetic dominance. So we have a sympathetic and parasympathetic nervous system and they work opposite each other. When sympathetic systems high, parasympathetic is low, and vice versa. We’re only supposed to be in sympathetic mode one 10th of 1% of the time. It’s really like an emergency mode. And we’re supposed to live in a parasympathetic dominance, meaning rest and digest. Our body’s supposed to be at rest and we’re supposed to have this normal digestion. But when we’re in this hyper stress mode where we’re in the sympathetic dominance, we can test for that. We can look at heart rate variability, we can look at pupil diameter. We can look for all these other things that tell us about sympathetic nervous system function.

                                        But what ends up happening is we have a shutdown of the gut. So, if we slow down secretions in motility of the gut, now we have changes in what we call the microbiome. And the microbiome is this bacterial colony that we found in the late two thousands that we didn’t even know existed. We used to think that all bacteria was bad, so we got crazy about antibacterial soap and Purell and taking antibiotics every time we had a sniffle. Now, what we realize is for decades, we’ve been damaging this amazing organ that we have called the microbiome, which is a collection of bacteria and other microbes that actually have a relationship with us and live inside of us.

Dr. Weitz:                        Just think about all the damage to the collective microbiome from the use of 20 zillion tons of hand sanitizer over the last couple of years.

Dr. Gruttadauria:            Just think about it, right? And again, we are so vigilant about this-

Dr. Weitz:                        And Lysol and all these other chemicals.

Dr. Gruttadauria:            I mean, it’s crazy because we’ve been brainwashed into thinking that all bacteria was bad and we need to sanitize everything. I remember as a kid, mom used to spray my whole room with Lysol. “Sleep on that pillow.” I’d be like, “This pillow smells like Lysol.” [inaudible 00:21:41] that in every day. Sorry, mom. But as it turns out, we are exposed to so many chemicals, so many.

Dr. Weitz:                        How do we assess the microbiome? How do we assess the gut? Is it a stool test? Is it other testing? What do you [inaudible 00:21:56]?

Dr. Gruttadauria:            Stool testing is number one.

Dr. Weitz:                        What’s your favorite stool test?

Dr. Gruttadauria:            I’m a big fan of the GI Map.

Dr. Weitz:                        Okay, yeah, that’s what I use too.

Dr. Gruttadauria:            Yeah, so the GI Map is really… It gives us a really good appreciation for what’s going on in the gut. So, we have this whole healthy bacterial colony. We know that we have other bacteria that can live inside of us, just at low levels. It’s okay. Our body can handle it. But sometimes we have an overgrowth of bacteria and we have an undergrowth of healthy bacteria. We can end up with parasites and yeast and just functional disconnection in how the gut is supposed to function. And then next thing you know, you have reflex back to the brain because the communication between the microbiome, the immune system and the nervous system is so powerful that everything changes as a result of the gut. So, it’s an amazing test. I mean, I tell all my patients, five years from now, this is going to be standard of care. Right now, we’re the only ones doing it.

Dr. Weitz:                        I think maybe 15 years from now, because how long it takes for conventional medicine to change.

Dr. Gruttadauria:            Yeah, it’s really a shame, but I think people are amazed when we have this initial conversation about how we’re going to approach this. And again, I’m not treating depression. I’m restoring health to people.

Dr. Weitz:                        Right.

Dr. Gruttadauria:            And it’s a huge distinction between those two things. And they really understand that that’s what I want. I want to feel good, I want to feel healthy. And what we need to do is figure out where the imbalances are. And at a very basic level, what you and I do is we take away what’s hurting people and we give them what we’re missing.

Dr. Weitz:                        Yeah.

Dr. Gruttadauria:            The body does the magic. We’re just facilitating it.

Dr. Weitz:                        So, let’s talk about diet. What’s the best dietary approach for depression and anxiety? And I’m sure it depends on each person.

Dr. Gruttadauria:            Well, of course, but it really depends on what’s going on with that person’s diet when they start. So, if you have somebody come in and they have the standard American diet and they’re eating fast food and drinking three cokes a day and five coffees and they live on Ring Dings, I mean, just taking away that stuff is a massive shift.

Dr. Weitz:                        Right.

Dr. Gruttadauria:            Blood sugar, elevated blood sugar, chronically elevated blood sugar causes chronic inflammation. So immediately, their whole body shifts. Getting people to drink water, which is a shocking thing. We take that for granted, but it’s… You’d be surprised… I’m sure you’re not, but many people would be surprised that people do not drink any water.

Dr. Weitz:                        Absolutely.

Dr. Gruttadauria:            Soda, coffee and juice, and that’s it. No water. So with somebody like that, it’s real easy. We just got to do a cleanup. But sometimes people have challenges to foods that they think are really good for them, but their body’s reacting negatively, so long term gut dysfunction creates changes in actually the intestinal lining and we end up what’s commonly called is leaky gut, which is an intestinal permeability problem. Now, people can react to foods that are usually good for people, but it might be terrible for them. They have a sensitivity to eggs or dairy or common foods, and that’s creating this chronic immune system dysregulation. And again, the immune system and brain are one in same. They worked so hand in hand.

Dr. Weitz:                        How important is sleep and circadian rhythm?

Dr. Gruttadauria:            Oh my goodness, I’m so glad you brought that up. The brain has two pacemakers. One is driven by movement. So every time we move, signals is sent to the brain and it powers it up, and the other one’s driven by light. And we have receptors in the back of the eye called melanopsin receptors that pick up light, transcribe it, and actually drive the hypothalamus. And it drives an area of the brain called a super charismatic nucleus, which generates this day night cycle. And we know that this rhythm that we were born to have on a regular basis is so imperative to normal brain function. But if you think about the overexposure to blue light that we have due to technology, due to indoor lights, due to staying up and watching TV till two o’clock in the morning, it disregulates our cortisol melatonin rhythm, and that changes everything about our brain. We have so many challenges to live in a technological-

Dr. Weitz:                        What do you about restoring circadian rhythm for your patients?

Dr. Gruttadauria:            The number one thing is, again, depending on what their lifestyle is like… I mean, you have people that work the night shift. And we know, I mean, studies are very, very clear that people who work the night shift disrupt the circadian biology and they have poor health outcomes over the long term. So, one of the things that I do is I have people wake up when the sun comes up and sit outside for 15 minutes and watch the sun come up. I know if people are like, “Oh my god, that’s so early.” Listen, do you want to get your brain back? These are the things you need to do. And then after dark, we have them wear blue blocking glasses. So, you could get inexpensive pair of 100% blue blocking glasses on Amazon for 20 bucks. But it’s really, really important that they wear it to reduce the amount of blue light.

                                                So, in any room, in any room that we’re in right now, we have this white light, but white light really is made up of all the colors of the rainbow. But in order to make a computer screen or an iPhone stand out against the rest of the room, it has to be very powerfully driven with blue frequencies. And those blue frequencies are very damaging when overexposed. It’s like eating… They’re fine when it’s combined with everything else in white light, but if you just have blue, it totally messes us up. And I’m sure these studies are never going to come out because there’s so much money being made in technology that nobody’s ever going to admit that we’ve been really messing up by having this massive overexposure to technology.

Dr. Weitz:                        And what about the importance of sleep?

Dr. Gruttadauria:            Well, I mean, we need to restore sleep. That’s when the brain regenerates itself. So, I think when we help people to get their circadian rhythms back, then their sleep becomes restored. But again, how many people come in when they have these chronic mental health challenges and they’re on six to 10 different medications? They’re on medications for pain, they’re on medications for sleep, they’re on medications for stomach problems, they’re on medications for the anxiety or the depression. So, I mean, at what point do we realize these medications and this particular combination of drugs has never been studied in this particular person’s chemistry and their epigenetics. So, how much of that is contributing to their problems? Another study that came out that said they tested a thousand different medications and realized that 25% of all of the common these thousand common medications have antibiotic like effects on the gut microbiome. So, even though they’re not antibiotics, 25% of all drugs damage the microbiome.

Dr. Weitz:                        Wow.

Dr. Gruttadauria:            Crazy.

Dr. Weitz:                        There’s a clinical pearl for you. So, I asked about diet, but is there kind of a dietary approach that you think this is… Forgetting about the person who’s just following a standard American diet and you’re going to clean it up, let’s say you got somebody who comes into your office and they’re suffering from some level of depression and they want to optimize their health. What kind of dietary approach do you think might be best?

Dr. Gruttadauria:            After years and years and years of doing this, what I feel is the best approach is a paleo style diet. People have a plant based diet with a significant amount of protein. And I’m big fan of eggs and meat, and so on. And so I really feel like people need to be getting at least one to one and a half grams of protein a day per pound so that they’re able to maintain it. Because it’s not how much protein you take in, it’s how much you digest and absorb that really matters.

Dr. Weitz:                        Right.

Dr. Gruttadauria:            So, we have to make sure people are digesting appropriately, so sometimes we’ll use digestive enzymes. We have to heal the gut. That’s a big, big piece. So, we have that dysbiosis and that inflammatory issue. But I mean, if we can get people to eat vegetables and we can get eat lean proteins and we can get them to drink water and go out the sun and exercise 20 to 30 minutes a day, probably we’d knock out 50% of the depression and anxiety.

Dr. Weitz:                        Right. There you go. I recommend a similar approach. I would call it a low glycemic Mediterranean diet. You’re calling it a paleo diet, but sounds very similar.

Dr. Gruttadauria:            Yeah, very, very similar. Exactly.

Dr. Weitz:                        So apart from diet, we have nutritional supplements, and some can be of real benefit for depression and anxiety. Maybe you can talk about some of the benefits of specific nutritional supplements.

Dr. Gruttadauria:            Okay.

Dr. Weitz:                        Obviously, it depends on the person.

Dr. Gruttadauria:            Depends on the person, and a lot of times based on their labs. One of the things that we want to make sure is that they have a proper zinc copper balance, because that plays a big role in what’s going on neurologically.

Dr. Weitz:                        Now, do you measure serum zinc and copper or do you measure plasma?

Dr. Gruttadauria:            Yeah, pretty much in every patient?

Dr. Weitz:                        Okay. Serum versus plasma? Okay.

Dr. Gruttadauria:            And then the other piece is, a lot of times, especially if they come back and their high sensitivity CRP or ESR elevated or we find dysbiosis, we want them to be on an anti-inflammatory hype supplement program. So, we’ll use fish oil, krill oil. We’ll use Boswellia or Inflammatone, or other kinds of herbal supplements that we know can help with inflammation.

Dr. Weitz:                        Right.

Dr. Gruttadauria:            Really good. And then I’m a big fan of the herbals to try to restore the gut. And then remove whatever we need to remove, and then eventually work on healing the gut. So, from a very straight point of view, I think… I don’t want to over supplement people because I feel like don’t want to use supplements in exchange for pills and medication.

Dr. Weitz:                        Right. Of course.

Dr. Gruttadauria:            Our goal is to restore health.

Dr. Weitz:                        Yeah, we’re talking about once you’ve established more healthy diet, you’ve got them exercising, you’ve got them sleeping.

Dr. Gruttadauria:            And I’m a big fan of protein shakes. So, I think that they’re a great meal replacement. I really am a big believer in intermittent fasting because we need to kick in this process of autophagy. Autophagy is like self-cleaning.

Dr. Weitz:                        What’s your favorite protein shake?

Dr. Gruttadauria:            I’m a big fan of MediClear by Thorne.

Dr. Weitz:                        Okay.

Dr. Gruttadauria:            Yeah, it’s a pea based protein and it has a lot of different supplements in it. So, when people are taking that, they get so much supplementation just from having to shake that they don’t really need a lot of extra, especially vitamins and minerals. I’m a big fan of amino acids, because again, we have to make sure that we’re getting a sufficient amount and that they’re in their free form. So, everybody’s different. Of course, we have this biochemical individuality, which is the premise of everything about functional medicine. But I mean, when we can approach a patient that has these kinds of challenges and we just apply some common sense and we break it down and restore the things that we know are out of balance, they all improve. And when they’re working with a good therapist and they start working on their lifestyle, it’s incredible what happens to people.

Dr. Weitz:                        What about magnesium for patients with anxiety in particular?

Dr. Gruttadauria:            Yeah, that’s a great one. Magnesium threanate, which is seen shown to be crossing the blood brain barrier, I’m a fan of that. And you can take one during the day, two at night. There are other things that you can take. There’s something called NeuroCalm by Designs for Health, which is an herbal supplement that has a lot of different herbs to ease anxiety. So, yeah, we can definitely use those to try to handle symptoms, especially in the beginning. And then again, eventually, we kind of wean people off of that. We don’t want them to be dependent on supplements. We really want them to be able to have their body working efficiently so they can get what they need from food. I’m a big fan, obviously, of chiropractic. If somebody wakes up and their elbows stuck, they run right to the doctor. We have 20, 24 vertebrae in the spine and we don’t know if they’re moving or not appropriately, and the only way we do know is if we get an evaluation by a chiropractor.  And what ends up happening is each time we move our body, we powerfully the brain and the receptors in the spine have… We have more receptors in the spine than in any other part of the body. So, that’s really responsible for a lot of brain function. So, evaluating somebody’s spine is also central to overall brain health.

Dr. Weitz:                        Great. I’m glad you mentioned that. That’s super important, and most people are not aware of that.

Dr. Gruttadauria:            Yeah. So, we have non-constant receptors in the body. Our eyes, ears, nose and tongue are non-constant, meaning we can close our eyes and our eyes don’t work. But because gravity’s always working on us, our balanced system, our vestibular system and our musculoskeletal system are always active because we always need to resist gravity. So as a result, those are the two most powerful drivers of brain function. In fact, those are the two systems that allow for brain development in children. And we can see as children develop, they go from that lying on their back, and then we flip them over and they get some tummy time and they start lifting up their head. As they stand up and they resist gravity, the amount of receptive potentiation they get from having to resist gravity is what drives brain expansion. And then it’s not by accident that when they stand and walk, they also talk. So, it’s pretty incredible when we think about brain development and the musculoskeletal system.

Dr. Weitz:                        What about supplements like 5-HTP, Mucuna that help the body to naturally produce neurotransmitters?

Dr. Gruttadauria:            So, I think that they all have their place. If somebody… We’ll run an amino acid panel and if they have really, really low levels of triptophan to fan tyrosine, I might use those particular things in addition to their shake to give them extra just those two. But as long as they’re taking it with… I never really want to put people on individual aminos because it creates imbalances. But if you add that in with an already established protein meal or shake, it gives them an extra boost because those are directly linked to the creation of these things. But methylation is a big deal, using something called 5-MPHF, like methyl folate, because you need methyl folate to drive conversion of these amino acids into neurotransmitters. That can be really helpful. So, there’s so much that we can do. Our toolbox is gigantic. And I think that when we step back and we look at the totality of the situation, we are able to apply individualized approaches to each patient.

Dr. Weitz:                            Are there any specialized products that sometimes you use to put things over the top? I’m thinking about maybe things like low dose lithium, saffron. There’s a number of supplements.

Dr. Gruttadauria:            You are the best, you are the best, Dr. [inaudible 00:36:59]. Yes. Yes. Those things are outstanding. Lithium orotate, five milligrams of lithium orotate is… People hear the word lithium and they flip out because lithium carbonate at 300 milligrams is a drug, a very powerful drug.

Dr. Weitz:                        Right.

Dr. Gruttadauria:            Lithium orotate is a mineral.

Dr. Weitz:                        Right.

Dr. Gruttadauria:            There have been studies that show that people who live in areas that have low levels of lithium in the drinking water have much higher levels of depression, whereas people who live in areas that have higher levels of lithium in the drinking water have lower levels of depression. So, that’s definitely a good one. These are all really very interesting things that, again, go back to where we live. Where do we live on the planet too is-

Dr. Weitz:                        And then of course, some people have high levels of arsenic in their drinking water and that that’s a big negative for health. And maybe you could talk about heavy metals and some of the toxins that can be problems.

Dr. Gruttadauria:            Yeah. I mean, it’s incredible just the fact that we continue to have amalgam fillings in people. And amalgam fillings are 50% mercury.

Dr. Weitz:                       Those are silver fillings for people.

Dr. Gruttadauria:            Silver fillings. So, people who are probably over maybe 35.

Dr. Weitz:                       Most dentists will tell you that silver fillings are not a problem.

Dr. Gruttadauria:            I know, and that interesting. Well, they’re not a problem because they’re actually really good at keeping the teeth healthy, keeping the teeth together from not breaking, but the fact that every time you drink something hot or eat something hot, it liberates mercury gas and then you inhale it is probably not that good.

Dr. Weitz:                        Right.

Dr. Gruttadauria:            Mercury toxicity is a real deal. And usually, the only way we get to see it is by doing challenge testing on people where we give them like DMSA or EDTA and we look at a urinary challenge test.

Dr. Weitz:                       But DMSA is prescription only, right?

Dr. Gruttadauria:            Right. Right. So, you’re working with integrative docs who can get these things done. But what’s interesting is sometimes you see a patient who has a mouthful of these amalgam fillings and I’ll run a mercury level and I’ll be astounded that it comes back literally two and three times the upper limit, which really tells you about how toxic they really are, because the body just can’t stand toxic metals in the bloodstream. It pulls it out of the blood and stores it in bone and fat. So, if it’s high in the blood, unless it’s a really acute exposure, that means that that patient is so burdened with metals that it just literally suppresses all function. It’s neurotoxic.

Dr. Weitz:                       So, what do you do about high levels of metals?

Dr. Gruttadauria:            So, again, I’m a big, big fan of using binders.

Dr. Weitz:                        Right.

Dr. Gruttadauria:            Binders are really, really important to help carry out things out of our system.

Dr. Weitz:                        Ultra Binder or something like that.

Dr. Gruttadauria:            So, apple pectin and activated charcoal and the different types of clay.

Dr. Weitz:                        Right.

Dr. Gruttadauria:            All these things, they’re all really great binders. And as long as a patient is moving their bowels regularly, because you can never ever want to detox a constipated patient. So, [inaudible 00:40:00] is getting everything moving, and then eventually using binders to help pull this stuff out.

Dr. Weitz:                        Use liposomal glutathione or something like that as well?

Dr. Gruttadauria:            I work in an integrative practice, so a lot of times we’ll use IV glutathione, which is really neat. But liposomal… Yeah, I think all these things are all very, very beneficial. I’m a little on the fence about the glutathione only because I would love to see studies showing the amount that actually makes it into the bloodstream because it’s a small protein that a lot of times will just get digested by stomach acid.

Dr. Weitz:                            Well, originally years ago, we were told that glutathione could not be taken orally, was all going to get broken down, but supposedly that data has changed, and if you get the right liposomal formula, supposedly, it does get absorbed.

Dr. Gruttadauria:            Yeah. Yeah. I mean, I’ve taken it myself, but again, I’d like to see that literature, because people are really smart these days. They want to know why they’re taking something and I want be able to tell them, “Here’s some literature.”

Dr. Weitz:                        We often measure glutathione levels as well.

Dr. Gruttadauria:            That’s great.

Dr. Weitz:                        It’s included in a neutra eval or we’ll do it as part of micronutrient test.

Dr. Gruttadauria:            Right. Right. Yeah, I mean, it’s a powerful antioxidant and absolutely essential for overall health and wellbeing.

Dr. Weitz:                        So, how important are hormones for mood disorders?

Dr. Gruttadauria:            Well, we have two regulatory systems in the body, the brain and the endocrine system. So, when the hormonal system is not working well, obviously you can have changes in mood. We can see that with people who have… When women go from having a regular menstrual cycle to having abnormal menstrual cycles, their mood can change. And we’ve had patients like that. And a lot of times what we see is disregulation in the menstrual cycle and something like PCOS, polycystical ovarian syndrome, can radically change mood. So, yeah, I mean, it’s important to see that, and then, again, figure out why is this person having this dysregulation in their system? And I always go back to light because the master gland and the hypothalamus that that’s kind of running the whole endocrine system is driven by light, and an abnormal light environment is going to cause hormonal dysregulation,

Dr. Weitz:                        Thyroid, how important is that for mood disorders?

Dr. Gruttadauria:            Very. And we always have to be cognizant of the autoimmune thyroid because when people have these chronic health issues and their immune system becomes dysregulated, and now all of a sudden they have thyroid problems, there’s a direct relationship between mood and thyroid hormone. And unfortunately, the standard of care in most doctors’ offices is to really just check TSH or TSH, and free T4. A lot of times you’re missing the [inaudible 00:42:58] because you’re not really seeing the whole picture. Somebody could have a normal TSH and free T4 and have very low conversion, and the T3 can be extremely low and nobody’s really even picking that up.

Dr. Weitz:                        Right. And to assess whether or not they have a autoimmune thyroids, you got to look at the antibodies as well, the TPL and the TGB.

Dr. Gruttadauria:            Yeah. Yeah. And when people have chronic inflammation, a lot of times they end up with an elevated reverse T3. So, you have this inactivated thyroid hormone secondary to chronic inflammation. The other thing about chronic inflammation is it can actually cause tryptophan to go down a different pathway and not converted to serotonin. So, again, there’s so many interconnections between what’s going on with the overall health of the patient and what’s actually going on in their brain and their mood.

Dr. Weitz:                        Cool. I think those are most of the questions that I had prepared. Any other things you want to talk about?

Dr. Gruttadauria:            No. The message that I really want to convey is that we’re all affected by stress. Every single one of us has different levels of stress. And not only do we have different levels of stress, we handle it differently. And we all have experienced trauma. There’s all different levels of trauma, and those traumas stay with us. We know that the body keeps the score. And so when we have trauma that builds up and we don’t know how to mitigate it, to release it, we don’t work on exercise and we don’t have a therapist or a coach that we can talk to, or we’re not really doing things to actively reduce that stress, it builds up and it shifts the nervous system. And then that nervous system controls and coordinates the rest of the body, and then it shifts your biochemistry. And you combine that with a lifestyle that’s really not conducive to health or an indoor over exposure to lighting or a lack of exercise or not drinking enough water.

                                                I mean, these are all such common, common issues, and we really need to be able to talk about it. And I think that’s really the main message, is that we really want to get out and educate people as to we need to have this conversation about mental health. And you see… I mean, all of a sudden, you see out of the blue, all these stories about all these professional and collegiate and Olympic athletes having to take time away from their sport to handle their mental health, singers and all these different performers having to take time away because now they’re actually feeling emboldened by the fact that they want to tell people that this is going on because it’s the same thing going on with all of us. We are not immune. We’re all potentially affected by stress, and it’s important that we get that message out. And that’s why the Same Here Global organization is growing so rapidly.  And I know that you reach out to a lot of doctors. And if there are functional doctors out there that would like to be involved in the Same Here Global Doctors Alliance, I would love to have a conversation with them.

Dr. Weitz:                        How did he find out about that?

Dr. Gruttadauria:            You can go to samehereglobal.org and maybe you can put my email in the comments section and [inaudible 00:46:15]

Dr. Weitz:                        You got it. Actually, I have one more question. You were talking about drinking water. What about drinking coffee and alcohol? Are those negative or positive, or what do you thin their effect might be for patients with either depression or anxiety?

Dr. Gruttadauria:            So, as a stimulant, coffee can actually create anxiety. But if people are okay with it and it’s part of their routine and they use it in moderation, I usually don’t have an issue with it. Alcohol is a depressant, and a lot of times people self medicate with alcohol. So, it’s incredible how we search for things to help us feel good. So when somebody has anxiety and they find alcohol, all of a sudden they realize, “Wow, this makes me feel normal,” which is really a shame because their body’s out of balance and they need to have alcohol to bring them down to a point where they actually feel like they can communicate, they can be out in public, and things like that. So, it becomes very addictive. The same thing when somebody has depression and they drink, they withdraw even more a lot of times. And so these things become really, really bad for us, obviously. It’s never a good thing.

Dr. Weitz:                        So, how can viewers, listeners get ahold of you, find out more about what you have to offer?

Dr. Gruttadauria:            So, I mean, people can reach out to me on… They could see me on Instagram or on they my website, which is theoptimumu, the letter you, .com. And that’s probably always the best way to find me. And I would love to be able to continue this conversation at some point because there’s so many new things going on all the time in the mental health field. And I think that we as functional medicine docs are really at the forefront of the charge because we’re seeing it from a totally different perspective. And people are more aware these days. They don’t want to just take more and more medications. They don’t want to be on three different drugs at a time. They don’t want to be on that merry go round of, “This didn’t work, I feel like a Guinea pig. It’s just trial and error. Let me try to find the root cause of why I feel the way I feel.” So, I really am… I feel very fortunate that you asked me to be on your podcast and I want to really thank you so much.

Dr. Weitz:                        Absolutely. And one of the great things about the functional medicine approach, not only is there mood disorders likely to improve, but their overall health as well.

Dr. Gruttadauria:            100%.

Dr. Weitz:                        Okay. Thank you, Michael.

Dr. Gruttadauria:            Thank you very much. I appreciate it, Ben.

 


 

Dr. Weitz:                        Thank you for making it all the way through this episode of the Rational Wellness Podcast. And if you enjoyed this podcast, please go to Apple Podcast and give us a five star rating and review. That way, more people will be able to find this Rational Wellness podcast when they’re searching for health podcasts. And I want it to let everybody know that I do now have a few openings for new nutritional consultations for patients at my Santa Monica White Sports Chiropractic and Nutrition Clinic. So, if you’re interested, please call my office (310) 395-3111 and sign up for one of the few remaining slots for a comprehensive nutritional consultation with Dr. Ben Weitz. Thank you, and see you next week.

 

Dr. Barrie Tan discusses Tocotrienols and Their Many Benefits with Dr. Ben Weitz.

[If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.] 

 

Podcast Highlights

2:53  Annatto Tocotrienols.  In 1994, a professor, Johanna Seddon at Harvard Medical School was an opthamologist who discovered that in the back of the retina of the eye there are certain polyphenols, zeaxanthin and lutein, that filter the blue light to protect the retina from macular degeneration.  Dr. Tan went down to South America to the Amazon to harvest some giant marigolds to extract the polyphenols and he noticed the annatto plant, which has this beautiful red color and he figured that it must have some polyphenols producing that color.  But he discovered that it contained little to no polyphenols but it contained tocotrienols that were protecting the color from degradation and tocotrienols with no tocopherol.  The other sources of tocotrienols that Dr. Tan had discovered–palm and rice–also contain 25 to 50% tocopherols, so annatto is a unique source of tocotrienols.  And since tocopherols can inhibit tocotrienols, then the annatto is very important.

8:05  When the first form of vitamin E was discovered in 1922, two scientists at UC Berkley discovered that alpha tocopherol was necessary to help a rat fetus go to full term and for this reason it was given the status of a vitamin.  It was discovered that vitamin E is a powerful antioxidant that protects the fetus from oxidative damage. They also discovered that this alpha tocopherol is found in vegetable oil and that it protects the vegetable oil from oxidation.  We got locked into alpha tocopherol as vitamin E and ignored the other isotopes of vitamin E.  There are actually 8 different isotopes of vitamin E: Alpha, Beta, Gamma, and Delta tocopherol and Alpha, Beta, Gamma, and Delta tocotrienol.  In the 1960s tocotrienols were discovered in rubber that they protect the rubber from oxidation.

11:26  There is a case to be made for gamma tocopherol, which is the most common form of vitamin E found in plants and its purpose, as for the other forms of vitamin E, is to prevent the oxidation of fats.  Our cell membranes are made of fatty acids, so preventing fat oxidation is crucial for the proper working of our cells.

16:12  Tocotrienols are more effective than gamma tocopherol because the tocotrienol molecular tail is shorter and can travel around the cell much faster to be able to capture oxygen radicals.

18:15  Alpha tocopherol inhibits tocotrienols, esp. if the amount of tocopherol is above 100 mg or higher.  If you take a multivitamin that has only 15-20 mg, then it would not inhibit tocotrienols. But Dr. Tan recommends not taking multivitamins that contain tocopherol at all, with the exception being for pregnant women and the US RDA for alpha tocopherol is 15 mg per day.  Designs For Health offers several multivitamins that contain only tocotrienols and no tocopherols, such as their Primal Multi. 

21:15  The health benefits of tocotrienols.  Let’s start with the potential to help prevent cancer. Most of the research on tocotrienols is on their benefits for chronic conditions, but about 10% of the research is on cancer.  There are several mechanisms by which tocotrienols may kill cancer cells and one is to short circuit the ability of cancer cells to multiply faster than normal cells. This appears to be by interfering with the PI3K-AKT, the MAP kinase and WNT signaling pathways. Tocotrienols may also interfere with angiogenesis, which is the ability of cancer tumors to grow new blood vessels to allow them to continue to grow. The third mechanism is by inhibiting cholesterol synthesis that cancer cells need to be able to form new cell walls and be able to multiply.

28:17  Most oncologists and radiation oncologists tell their patients not to take antioxidants for fear that this would block the cancer killing effects of chemotherapy and radiation that work through oxidation.  Tocotrienols have been studied with patients with stage three and four cancer who were taking the standard of care and they were given a very high dose of tocotrienols–300 mg three times per day with meals that contain enough fat to be able to emulsify and absorb it. After six months only one patient given standard of care was alive, while the patients taking tocotrienols, 60% were still alive.  After 24 months, 24% were still alive in the tocotrienol group.

38:20  Tocotrienols for preventing and reversing Cardiovascular Disease.  Tocotrienols have been shown to lower triglycerides and elevated triglycerides precedes hyperglycemia, which results in diabetes.  High triglycerides often leads to Non-alcoholic Fatty Liver Disease (NAFLD) and such fatty liver can eventually lead to liver failure.  Recent studies show that taking tocotrienols reduces fatty liver and it resulted in both reduce inflammation and reduced fat deposition in the liver.  Fatty liver can eventually lead to fibrosis and scarring as NAFLD becomes Non-alcoholic Steatohepatitits (NASH).  The studies even showed either the containment of the fibrosis or the reversal of the fibrosis.

 

 



Dr. Barrie Tan is a PhD in chemistry and he is world’s foremost expert on vitamin E.  He is credited with discovering tocotrienols, a form of vitamin E, in palm, rice, and annatto, with annatto being the most efficient source, since palm and rice also contain substantial amounts of tocopherols and alpha tocopherol inhibits tocotrienols. He produces an Annatto Tocotrienols product through his American River Nutrition company. He is also the Chief Science Officer for Designs For Health. Designs For Health supplements are professional supplements sold through licensed doctors and practitioners like myself.

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.

 



 

Podcast Transcript

Dr. Weitz:            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates, and to learn more, check out my website, drweitz.com. Thanks for joining me, and let’s jump into the podcast.

                                Hello, Rational Wellness podcasters. I’m very excited today to be speaking with Dr. Barry Tan, and we’ll be talking about tocotrienols and also about GG. Tocotrienols, many of us may not know what they are, but they are part of the Vitamin E family, which consists of eight fat-soluble isoforms, alpha, beta, gamma, and delta tocopherol, and alpha, beta, gamma and delta tocotrienols. Most multivitamins and other nutritional supplements that contain vitamin E only contain alpha tocopherol, which is generally what is considered to be vitamin E in popular nomenclature.  One of the better sources for research on vitamins, the Linus Pauling Institute’s Micronutrient Information Center, in its detailed article on vitamin E, is almost exclusively about alpha tocopherol, and there’s only one small paragraph about tocotrienols. So, the word has not really gotten out, and that’s one of the things we want to do today, is get the word out about tocotrienols.

                                Dr. Barry Tan will be joining us today, and he has a PhD in chemistry. He’s dedicated to researching vitamin E and related compounds, and he is or was previously an assistant professor at the University of Massachusetts. He’s credited with discovering tocotrienols in palm rice and annatto, with annatto being the most efficient source, since palm and rice also contain substantial amounts of tocopherols. Alpha tocopherol, as we’ll talk about, acts to inhibit tocotrienols. Dr. Tan produces annatto tocotrienols through his American River and Nutrition Company. Dr. Tan, thank you so much for joining us today.

Dr. Tan:                Thank you. Thank you, Ben. I look forward to being on your show and to your followers that listen to you. So I’m hoping that this will be a good time to disseminate information about vitamin E, which 20 years ago was at high point, and then it dipped down. Then, vitamin D, we talk about, and then now we talk about vitamin K. I’m hoping to bring back something of vitamin E that is long forgotten or not known, so hopefully-

Dr. Weitz:            A long forgotten fat-soluble vitamin.

Dr. Tan:                Yes, yes, yes, yes.

Dr. Weitz:            So I thought, since everybody likes a love story, perhaps you can tell us how you went down to South America and met one of the true loves of your life.

Dr. Tan:                Yes, thank you. That’s a wonderful thing. The year was 1994, and at the time, there was a professor, Johanna Seddon, at Harvard Medical School. She was a ophthalmologist. She found out that, in the back of the retina of the eye, where the fovea, the main point, have a lot of zeaxanthin, as you flank out the retina, have lutein, and of course, if you… And it filters the blue light to protect the retina. And today, of course, everybody know, “Oh, Dr. Tan is talking about macular degeneration. I know about that.” But remember, this is 1994. It was a while back like that, and then I knew there were giant marigold. So I went to South America and this is a younger me with a little bit more hair, but you can see the giant marigold in my hair, it was just like that. And this is, by way, this is in “The Truth about Vitamin E” book that you can, later, I can give you the link, you can download this free of charge. I did this as a labor of love to tell the story.  But anyway, I did that. So when I went down to South America, I had already studied vitamin E now for 20 years, I was taking a break because of this unusual lutein and zeaxanthin thing. And truth has it, literally 20 feet away from me, I found this annatto plant, and the annatto plant is a beautiful plant to look like this. Look at how beautiful it is. If you touch this as it were, I’m doing it like that, it will sting your hand. Now, the color is keratin and I know, and this is truly an Amazonian plant. Here, I took this in the botanical garden in Tampa, this is a very zoom in, the frog is about the size of a dime. So the seed is about the size of a grape seed, so this is a very tiny, it’s called the Amazonian tree frog, so here, to keep themselves away from the elements.

                                All this to say, I discovered from this Amazonian plant. I thought that to protect the keratin, it would be some antioxidant like polyphenol. There are many polyphenols like that. To my surprise, it contained little to no polyphenol, so that’s not the one that protect the color from degradation. And then I thought, “Oh.” Then I found out that it only contained vitamin E, surprisingly. And most surprisingly, it contained only tocotrienols, free of tocopherol, and I said, “Oh my goodness.” I previously discovered tocotrienol from palm and rice that you mentioned, and palm and rice typically contain 25% to 50% tocopherol. So this plant containing free of tocopherol and only to tocotrienol is unique in nature.  I believe the plant makes the tocotrienol, the two most potent vitamin E, to protect the degradation of the color keratin, so that it deceive the birds of the air and the animal thinking that the wonderful looking seed is actually a fruit. You see, it’s actually a seed. Then they swallow the seed and therefore able to procreate. But if the color disappear, then you look brownish, it doesn’t look like a fruit, neither does it have the nice floral smell. That was it. It was an accidental find, like much of my life. I am no smarter than any other scientist, I just happened to be in the right place at right time. And for the audience to suggest that why this is so…

                                As a chemist, there are more than 50 million chemicals documented by the American Chemical Society, and most people would tell story because they’re medicine men, they go to this, that and other places. Yes, I was in Amazonia, but it was an accidental thing. I did not go and nearly bitten to death by snake or mosquito like that. I just was looking for something for macular degeneration protection, which is lutein and zeaxanthin, I show you the picture. But this was literally 20 feet away I saw this plant, my curiosity was aroused and therefore I look. And that was 1999, thereabouts. And so for the last 20 or 25 or so years, my time had been arrested. I returned back to tocotrienol, which I already previously have 20 years of experiencing it. All told, I’ve been on to tocotrienol now for almost 40 years, if not that. Thank you so much for allowing me to tell that story.

Dr. Weitz:            So how did we make this mistake and think that alpha tocopherol was really the most important vitamin E compound?

Dr. Tan:                Okay. The mistake, if I can so call it, is because when we lock onto something, we tend hard to change. It’s just kind of human nature, and if it’s true of human being, it’s probably also true of scientists. In the vitamin E, there are four tocopherols and four tocotrienols, and with the four Greek letter, alpha, beta, delta, gamma, alpha, beta, delta, gamma, like that. So when in 1922, exactly 100 years ago, and is a very American affair. Two scientists, medical doctor at UC Berkeley, they discovered that vitamin E helped the fetus to go to full term. That was a discovery. Because it helped the fetus to full term, for that alone, it was therefore given the status of a vitamin. And they followed each of the letter and the next letter was E, so vitamin E helped to bring the fetus to full term.  However, in the process of knowing that, they found out that it protects the fetus from oxidative damage. And very quickly, they found out that this is found in plant. And they found in plant, they’re rich in vegetable oil, it protect the vegetable oil from oxidation. So to this day, most people know vitamin E as an antioxidant, powerful antioxidant. And that antioxidant and that additional vitamin E was alpha tocopherol, so we kind of lock in on that and then we move on.

                                If I have time to tell you other story about vitamin K, about vitamin D, it’s the same thing. We got locked into one and did not move on. Vitamin K would be classic. It was discovered as anti-clotting, and today, much of the vitamin K activity is in menaquinone MK-4, but let’s say…

                                So the tocotrienol piece was discovered about 40 years after alpha tocopherol, so it is almost a distant brother of vitamin E tocopherol, that almost missed the chance of discovery. It was discovered by USDA and scientists at University of Liverpool, England. Together, they found that in rubber, to protect the rubber from oxidation. And then another 40 years later, I show up as a young assistant professor at University of Massachusetts stumbling on this. At that time, everybody was studying alpha tocopherol, but I was doing the path less travel on tocotrienol. And then, as you know, towards the end of 1990s and 2000, and all the published study of alpha tocopherol came out nada, and came out even a negative for people. So I just thought, “Oh, will I be thrown away? The baby thrown away with the bath water?” He said, “I hope not.” But I persisted in tocotrienol, and now, 30 years later, thank God. My discovery of this from annatto is yielding solid fruit about tocotrienol. Properties of tocotrienol aren’t shared by tocopherol, so I love to share this with your audience.

Dr. Weitz:            It’s interesting, when I first saw those vitamin E studies, my first reaction was, “Well, they didn’t give enough vitamin E.” Then, I realize that gamma-tocopherol was really the form of tocopherol that was much more common in food and was actually more beneficial. So, my next conclusion was, the problem was that they were just giving alpha, and if they had given gamma or mixed tocopherols, then that would’ve been better. And now, this story has evolved to learn that, really, it’s tocotrienols that are much more beneficial for us.

Dr. Tan:                Yes. Now, on the gamma tocopherols in the plant, there is a case for gamma tocopherol. If you look into the plants, where else, the discovery of alpha tocopherol is the vitamin. And where else, alpha tocopherol help the fetus to go to full term, all correct. However, in the plant, the most dominant vitamin E it produces is gamma tocopherol. It produces gamma tocopherol to protect the fat and the oil in the plant not to go bad, like in corn, because you have corn oil. Like in soy, because you have soy oil like that. And then canola, many other things. So they are mostly gamma tocopherol, a few exception, but mostly gamma tocopherol.

                                So now, for tocotrienol in a plant is even rarer. But when we first did the study, people can synthesize the tocotrienol, so something about tocotrienol that is different. So while, at this, I may explain. If you think of a cell, the cell looked like a bean shape like that, and all the constituent in the cell that we know of, like mitochondria, the nucleus and all these other thing, it had to have the cell wall to contain the content we call organelles in the cell for the cell to function.

                                Now, for the audience simplistically, the major composition of the cell membrane is fatty acid. They need protection like mad. And you probably have interviewed people to take omega-3, very good fat, and omega-3 is very unstable. When you take the omega-3, first you go into blood, eventually, it doesn’t stay in the blood. Eventually, it stay in the cell membrane. And why is a cell membrane so important? The nucleus is the holy of holy. The mitochondria produce energy and the other golgi apparatus, endoplasmic reticulum, I know those, this is kind of like… They make things your body need when you make protein, they’re required. So therefore, inside the cell, it’s very well protected and the cell membrane is a gated community. You want nutrients to go in, you want ways to go out. If the cell membrane is compromised, then life as we know it will age. That is, I’ve called, aging process.  Now, come back to the original thing again. The cell membrane is mostly fat and the fat need antioxidant. Vitamin E is the kind of molecule that best can protect the integrity of the gated community. They have done study on this, there are many… I know the audience is bewildered with many words of antioxidant, I will cut it to the chase. If you learn this, I am grateful and hope you are grateful.

                                With everything people talk about is antioxidant, but I want to champion to you, what is the critical antioxidant you care about?  It’s not like protecting ding ding or ding ding or whatever, other ding ding, like that. If you put a stick of butter in the summertime, that’s off smell. If you drive past a road kill, that off smell. That first oxidation thing is fat. So as the same thing, the lowest lying food of oxidation is fat. Yes, protein oxidation is no good, carbohydrate oxidation is no good, nucleic acid, which DNA, oxidation is no good, but none of them get oxidized so fast. The fastest thing to get oxidized is fat. So therefore, to protect the fat, if people remember the story of Massachusetts, they will be the minute man. The minute man will be the first to go off and the minute man is tocotrienol, you want it to protect the fat because it’ll be the first to go. So if you care about that-

Dr. Weitz:            Now, are tocotrienols better than gamma tocopherol as-

Dr. Tan:                Yes.

Dr. Weitz:            …. As a antioxidant for fat?

Dr. Tan:                Yeah, it’s better in this way. The tocopherol tail, this is a vitamin E molecule, this one here like that. And this, if I block it, this O, H, that’s an antioxidant. And if I block it the other way, the tail, this is the tail here. If you look carefully on the tail, you see at three, four places the double bond, it look like an O ring, like my finger pointing here. That is double bond and hence, we are trying three double bond. In tocopherol, the three double bond disappear, therefore, a tocopherol tail is longer. All that to say, a tocopherol tail is longer, anchored deeper into the cell membrane. A tocotrienol tail is shorter and less deeper.   So I am sure you hear this for the first time. A tocopherol would go around the cell membrane like this, let’s say one mile per hour. And the tocotrienol will go around the cell 50 times faster, like that. So to capture oxygen radical, to protect the fat from going bad. So therefore, a tocotrienol and tocopherol does the same job, like a police to capture the bad guys. A tocopherol will be like a police person that stay in the confine of the town. A tocotrienol would be like a state trooper that will cross the entire state, so it cover a larger surface area faster. So if you got that, I have given you the simplistic understanding why tocotrienol is 50 time more potent than tocopherol, simply because the tail is slightly shorter. Thank you for asking, that is, often time I miss that if people don’t ask me the question. Thank you, Ben.

Dr. Weitz:            Now, I’ve heard you say multiple times in interviews that taking tocopherols inhibits tocotrienols. Now, a lot of multivitamins and other supplements contain some tocopherol. Is it okay to take a multi that maybe has a modest amount of tocopherol and also take a tocotrienol? Or is it okay, say for example, to take your multi at one time and take your tocotrienols at another time? Or is it better to just get rid of any supplements that have tocopherols?

Dr. Tan:                So, your question is three layer. Personally, I have stopped taking tocopherol for the last 20, 30 years, and I’m still alive. Nothing is happening to me, I would say the only-

Dr. Weitz:            But have you brought a rat fetus to term?

Dr. Tan:                I have not done that. I use it sometimes as a joke. Also, if you think about that, if it is a vitamin, is to bring a fetus to full term, men shouldn’t have necessarily… I would say the only exception would be in a prenatal, then a person should have 100% IU of the vitamin E as alpha tocopherol, but the 100% RDA for vitamin E is about 15 milligram. Now, keep that in mind. 15 milligram 100%, but most people take 400 IU and 800 IU. That’s insanely high amount like that, and 100% is merely 15, 20 IU like that. Now, if it is in a multi, if the multi has about 15 to 20 IU and then one would take tocotrienol 100 to 200 milligram or higher, then the amount of tocotrienol would not be interfered by tocopherol. Personally, I would take a multi that only contain tocotrienol, and Designs For Health have such, they call it, “Primal multi” like that.   And we are trying to convince more company to… It is pennies for them to replace it because the multivitamin is a long list of many other things, this is only one line something. So when does the tocopherol interfere? When you take supplement of anywhere 100 IU and above, and most vitamin E is about 400 to 800 IU. Then at 400 to 800 IU, the tocotrienol would not have a [inaudible 00:20:55] to be absorbed, that the alpha tocopherol would block the absorption. But not typically in a multi, and certainly are not discouraging a pregnant woman to not take a prenatal that the doctor would accept, because that was the reason why alpha tocopherol was first discovered.

Dr. Weitz:            Okay, let’s get into the health benefits of tocotrienols. So I’d like to start with the big C because, as we know, that’s a major killer for today and cancer rates are increasing. Can you explain how tocotrienols may help to prevent, and may even be helpful as part of a treatment approach for cancer?

Dr. Tan:                Yes. Before I said that right, I started my career on tocotrienol on chronic conditions, and then in the 1990, if you find all the published work, about 90% of the published work will be in chronic condition, not cancer. And about 10% will be on cancer and chronic conditions like prediabetes, diabetes, Metabolic Syndrome, fatty liver disease, lipidemia, and all this other thing like that. And then, as I went 20 years into it, I noticed that this will be in the 2000. 50% will be on chronic condition, 50% will be on cancer. It changed like that.

Dr. Weitz:            And, of course, a lot of us now recognize cancer as a chronic condition as well.

Dr. Tan:                Yes, it is. And there is so much study on this, and then I said, “Wow, there are nobody doing clinical study on cancer.” And then the compelling reason on cancer, so we embarked about 10 years ago, to engage in the clinical trial. Now, when I do this, for the audience purposes, to let you know that I’m not a pusher of sales like that. I am truly interested in science. If it bears out, you can go and read it. But how is the nutritional supplement allowed by the FDA for cancer prevention or cancer treatment is not going to be allowed.  But if I believe the scientific enterprise and then, as it happened, in the kingdom of Denmark, they decided to conduct five clinical trial and now they’ve expanded it to six or seven like that, I’m losing count. In the US, there’s one on pancreatic cancer. And the four cancers that we study, some of them are repeat on different angles like that, altogether five, if you include the other one in Florida, then it’ll be six. But the four in Denmark will be breast cancer, ovarian cancer, lung and colon cancer. So those are the four cancer. And you ask for the mechanism how it killed-

Dr. Weitz:            If you want to increase research in the United States, you need to have the drug companies patent some new form of tocotrienol that they can make billions off of.

Dr. Tan:                I know.

Dr. Weitz:            Then the research will happen.

Dr. Tan:                I know. And because this is a natural extract, they’re not going to pump in any money on this.

Dr. Weitz:            No.

Dr. Tan:                So I’m doing this for what it can do and the audience can read-

Dr. Weitz:            Don’t worry, some drug company will come up with some way to bind it with some other compound and patent it.

Dr. Tan:                And they probably very well might. I have companies sometime, from time to time, contacting us for this and another thing, but nothing materialized. So my goal is to push forward in it. So right now-

Dr. Weitz:            Okay.

Dr. Tan:                … I see two mechanism that I believe, two or three, I believe the strongest. There are many mechanism how they think that this will kill cancer. One would be, because the cancer cell multiply say about a hundred time faster than normal cell, they have certain connection. So it’s like circuitry. They have certain… We call it cell signaling, so it’s a circuitry that short chain it to get there faster. And so the tocotrienol is able to file off the short chain, they cut it off so they cannot do this, so that’s certain mechanism that do that.

Dr. Weitz:            Yeah. I was looking at an article and he mentioned the PI3K-AKT, the MAP kinase and WNT signaling pathways

Dr. Tan:                Yeah. And all these kind of signaling pathway allow certain application of the cell to multiply and increase ferociously much faster. So therefore, if you can file this thing off, you cut off the circuitry that make them grow better. That’s it. Another one would be, this is already past that stage where the cell has become a tumor. So it’s not a cancer cell, it’s now it’s a cluster of cancer cell-

Dr. Weitz:            Which means you now have billions of cancer cells.

Dr. Tan:                Yes, the billion of cancer cells, so it’s a solid mass. Now, not all cancer are solid mass, most cancer are. The cancer that are not solid mass would be like leukemia, but most other cancer is a solid mass. They stay put in the place, they can also metastasize, of course. So when you have a solid mass somewhere like that, they still have to grow. So when, in order to feel its massive grow, it grow artery out of the tumor, into the nearby artery, to suck nutrient to feed it. So in this case, it’s an aberrant, unusual plumbing job. That’s it. So this artery is called angiogenesis, a growth of new artery. So a way to kill this it with anti-angiogenic drug, if you go to Amgen, and you can see they have anti-angiogenic drug. Angiogenesis is a growth of new artery, anti-angiogenesis is to cut off. And tocotrienol function to cut off the artery and angiogenesis, to block the feeding tube to feed the tumor, so essentially starving the tumor to death. So if the tumor is already in place, you want to starve the tumor to death. So that is a second mechanism.

                                And the third one is, when the cell is multiplying so fast, they need a lot of cholesterol on the cell wall. It’s well known, cholesterol is on the cell wall and tocotrienol inhibits cell wall cholesterol synthesis, and therefore it cannot furnish the cell wall, and therefore the multiplication of the cell is… It cannot grow fast. So those are the three mechanism I buy the most. But mostly, when we saw in animal study, we saw the death of the cancer cell, we saw the shrinking of the tumor, and we also saw the reduction of metastasis of the tumor from the origin to other places. So those are just fantastic model mechanism for which we believe the tocotrienol work against cancer.

Dr. Weitz:            Now, obviously there would not be any problems in a preventative approach, but in a treatment setting where a patient is undergoing chemo or radiation, it’s well known that most oncologists and almost all radiation experts are going to tell their patients, “Under no circumstances should you ever take any antioxidants because they will uncouple the therapy.”

Dr. Tan:                Yes. That concept is in the US and a few drugs are in that kind of a regime like that. We did not have problem, this was raised as a question, we did not have problem in arriving at the IRB. IRB means institutional review board. You have to pass that stage to ethically approve the use of a certain medicine or supplement to mitigate a certain condition. And those five clinical studies done in Denmark are giving a patient with very high dose tocotrienol, 900 milligram, three capsule of 300 milligram for breakfast, for lunch and dinner. They should be taken with a meal, have enough fat or oil so that they can emulsify and absorb properly. And now, in none of those clinical study did we ever see any contraindication or negative impact of the tocotrienol on those cancer patients.

                                Now, before you move on, just for the audience purposes, every study has a contact. When we did this study in Denmark, they were not studying a stage one and two cancer patient. We were studying stage three and four cancer patient, which means that the cancer have already metastasized. In stage four, it even gone the last stage, which means that there are no available options given, so that the patient is under palliative care. So therefore, they are taking standard of care with the anti-angiogenic drugs, and in the other study, standard of care and with tocotrienol. That’s the only study, if they’re interested, I’ll tell you briefly what the study is, so be like this. So in other word, they are not based on people with stage one and two with many options available, operative, radiation and chemo. On the stage four, only chemo is allowed because you barely, they are so ill you cannot operate anymore, so there are no options available except for chemo.

Dr. Weitz:            And that study’s already been published?

Dr. Tan:                That study is published and the shorthand is this. Because they’re stage four on ovarian cancer on standard of care, after six months, there are no more patients. They’re one. And then in the standard of care with tocotrienol, after six months, 60% still survive.

Dr. Weitz:            Wow.

Dr. Tan:                Would this to be a medicine? So wow, they didn’t save all, correct. We’re talking about patient with stage four. If this were to be a medicine, this will hit the Wall Street already, but it isn’t.

Dr. Weitz:            It would be a multi-billion dollar drug. Absolutely.

Dr. Tan:                And then, even after 24 months, 24% still survive. So we consider this to be a significant place the tocotrienol is making an impact to a situation that is not good, at the very end stage of a person’s life.

Dr. Weitz:            A cancer drug is considered successful in a clinical trial if it extends life by three months.

Dr. Tan:                I know, you are right. Thank you for providing that knowledge. So right now, we are trying to do other upgraded study, but as the audience know, and I know sometime when people have conditions like this, we are impatient, and I fully understand. But we are a small company and not a pharmaceutical company. The fact that we can even do study like this is intended, I do this… We don’t want to be a snake oil company, we just simply want to do this and then the audience will know this. We will never be able to say on any bottle. So if you want to have… “Well, so if I have, blah, blah, blah, this and that, should I be taking?” I cannot advise you on this.

Dr. Weitz:            Right.

Dr. Tan:                But if you go on a website, we will tell you all the different studies have been done. They are literally about, more than 500, possibly close to 1000 published study in animal study, on about 300 to 400 cancer, how tocotrienol worked to kill the cancer. Oh, by the way, and all the tocotrienol kill the cancer, alpha tocopherol just about didn’t work. And the top two vitamin E that do work are delta and gamma tocotrienol, and the one that worked the best is delta tocotrienol.  Now, having said that, we have a machine that when we study from this annatto plant that we extract from this annatto plant here, typically, when you run a machine, they will have four or five peaks. They’ll have a mixture of tocopherol and a mixture of tocotrienol. And most of the time, it will have more tocopherol than tocotrienol, like in palm and annatto. You see 25% to 50% tocopherol, and then the other 50% to 75% tocotrienol. When you do this spectrum to read tocopherol, it will look like this. It would have… No, this one here, of the color in the background. This will be delta tocotrienol. Then, it would have this amount of gamma tocotrienol, and then where the tocopherol is, nothing, just like that. So it’s 90% delta, 10% gamma. So therefore, annatto contain almost the most active vitamin E that have been ever studied like this. So to us, it’s not a surprise, which is why Denmark decided to study this. And the pancreatic cancer done in University of Southern Florida in Tampa, also was using pure delta tocotrienol on cancer.

Dr. Weitz:            Right. Okay. Just in case, if anybody’s partisan to words, I think when you were explaining that, you meant to say, “If you look at palm or rice, you’ll see that there’s a combination of tocopherol and tocotrienol, but only in annatto is it almost exclusively tocotrienols.

Dr. Tan:               Yes.

Dr. Weitz:            Okay.

Dr. Tan:               Thank you. Yeah.

Dr. Weitz:            I saw somewhere where you said that, or there was an article or something that, tocotrienols help to counter some of the side effects of radiation.

Dr. Tan:               Yes. Those studies were done by the US armed forces, very interesting. If the audience want to read about that and you go to AFRRI, it’s just acronym for Armed Forces Radiobiology and Radiation Institute. So this is inside the Uniform Services University in Maryland. This is a place that the US government are not training soldiers. This is a place the US government are training our armed forces to get Masters and PhD degrees.  So why did I mention that? It was during the Iraq war, I’m not making a political statement, I’m just trying to give you the fact. During the Iraq war, President Bush said that it was axis of mass destruction in Iraq, like that, and as it turned out, it wasn’t. Our armed forces are doing research. If our army were to go to a hotspot, most of the time they’ll never come back out alive, because you’ll be radiated to death like that. Just like in Fukushima, except that was a tsunami type situation. So the armed forces is wanting to do research study, what would be supplement of medicine they can take to protect, like a shield for them. And they study hundreds and hundreds of different compound, and I kid you not, and of the hundreds of different compounds, in the short list of six, is delta and gamma tocotrienol. If you type AFRRI or Uniform Services University, and you type tocotrienol and radiation protection, you’ll be able to find on the site. We did nothing, we only provided the pure gamma tocotrienol and pure delta tocotrienol.

Dr. Weitz:            It’d be interesting to see if it has some benefits for patients getting targeted radiation for cancer, because that has a lot of devastating side effects.

Dr. Tan:                Yes. My gut feeling it has. They do not study that, they clearly told me that, we are doing… He said that’s an important concern is that we do not study civilian who have cancer.

Dr. Weitz:            Right, okay.

Dr. Tan:                We study armed forces, but because they study in so severe situation, as opposed to what you, that is total body radiation, and this is a targeted radiation. And I’m still trying to find a radiation oncologist that can help me to do this study. To date, we are not a successful in finding. If I could, then I would go down that road.

Dr. Weitz:            So let’s talk about the role of tocotrienols for preventing and reversing cardiovascular disease.

Dr. Tan:                Okay.

Dr. Weitz:            This is obviously the number one killer in the United States and around the world.

Dr. Tan:                Yeah. The first study in this, Ben, was a lower cholesterol. It was done in the mid 80s, and then I follow through, and as we were studying, it did lower cholesterol and then we got stumble on 10 years delay, because we didn’t know that alpha tocopherol will interfere and it did. So we had to figure out that, and we figured out, we pick up from where we left, and continue on that. And when we continue, we notice the cholesterol lower, but even more dramatically, the triglyceride lower more. Now, is still cardiovascular disease, but the triglyceride lowering is peculiar to people with Metabolic Syndrome. Meaning that the triglyceride lower has to do with people with diabetes, Metabolic Syndrome and fatty liver.  How do we come up to that? Before it was called Metabolic Syndrome, Ben, it was called Syndrome X. If you were around in 1990, it was called Syndrome X.

Dr. Weitz:            Yep, yep.

Dr. Tan:                Because it was a sexy phrase, because we-

Dr. Weitz:            [Inaudible 00:39:41].

Dr. Tan:                Yep. And then the X Files, this and that, so the Syndrome X. So in the Syndrome X, they just notice that the sugar is moderately high, but not high enough to be diabetes. The triglyceride is high, but not high enough to make people really sick, but it bothers people on this condition. I met the professor who came up with Metabolic Syndrome. His name is Gerald Reaven, R, E, A, V, E, N. You can Google him from Stanford, he did all this clinical study. He shorthand answer is that I met him one time, he was catching a plane, he didn’t want to be disturbed. I was really an impediment to him going to the airport, but he just gave me the shorthand, and even though he gave me the shorthand I never forgot what he said. I’ll say it exactly what he said, and then I shorten it for you.

                                He said, “Hypertriglyceridemia precedes hyperglycemia. That means high triglyceride precedes high sugar. So you do not have type two diabetes until you have high triglyceride and you cannot contain the high triglycerides, the floodgates open and the sugar shoots up and then you have diabetes.” So hypertriglyceridemia, then, is a hallmark of Metabolic Syndrome. And remember, I accidentally got introduced, because I noticed that the triglyceride in people with high cholesterol, the triglyceride dropped. Then I said, “Wait a minute. Why does the high triglyceride drop?” Then I know it, “Oh my goodness, this high triglyceride drop addresses Metabolic Syndrome.”

                                So I went after it hardcore. So I use tocotrienol to study pre-diabetes, worked. I use it to study diabetes, worked. And that was when I finally, in the last eight years, I went hard after people with fatty liver disease, for fatty liver is a silent disease. No pain, no nothing, until the doctor find out that you have high triglyceride, jaundice or whatever in the liver. About 25 to 30 million American have fatty liver, NAFLD D, non-alcohol fatty liver disease. And it’s such an awkward phrase. All that to say, the liver, when you study them, you have a biopsies, they look like people with alcohol cirrhosis. Who would have guessed, 30, 40 years today, our liver can be damaged by a bad diet exactly as alcohol would destroy the liver.

Dr. Weitz:            Absolutely. No, this has been talked about, this as a major pandemic that nobody’s really thinking about. But this is, in large part, related to our consumption of refined carbohydrates and sugar. And we’re going to end up with the tsunami of patients needing liver transplants and we got to do something about this.

Dr. Tan:                And the tsunami of liver transplant, Ben, is not sustainable because you have 90 million people, if they all need liver transplant, you simply will not have 90 million livers available live. We had it managed when we were alcohol cirrhosis for liver transplant. But who would have guessed? I had thought this numerous time. When people abuse the liver with excess of alcohol, now we are saying you can do this to the liver by carbohydrate, refined carb and high fat diet, exactly as alcohol can do. It’s a stunning… And this is only discovered in Mayo Clinic. I was in Minneapolis this past weekend, discovered in Minneapolis in the 1980. It was not long ago when the doctor said that, “Mr. Jones, do you drink alcohol?” Because they read the thing, and Mr. Jones said, “No.” And then he went back to look at the data, come back, “Are you sure you do not drink alcohol?” And now, Mr. Jones feel accused. He said, “No, I do not drink alcohol.” That was when the phrase non-alcohol fatty liver disease was discovered.

                                So in the last eight years, I want to really tell you the study. In the last eight years, it took me eight years, ladies and gentlemen, to do it. We did fatty liver, and because we went for the big one like that. First we did a three month study, then we did a six month study and finally, we did a 12 month study. We get the same dose. So this is a time dependent, they are different patient. So the three month study, we were studying if did the liver enzyme drop, the liver enzyme drop. So we were happy. So in a six month study, we continue to study, whenever we study. We published the three months study and then six months study, the liver enzyme drop. Now we study, did the inflammation drop? The inflammation drop. And then, did the fat remove from the liver? We used ultrasound, the fat removed from the liver. Then we also study, did the sugar in the blood drop a little bit and then the triglyceride drop a little bit. So definitely is back out of [inaudible 00:45:16] back into balance again.

                                Something else also dropped, but I wasn’t… Then I decided that, because it’s the largest organ in the body, I need to know if it’s sustainable after 12 months. So we did the 12 month study, which is really long. And the 12 month study is finished and we just published live. So the three month study published, the six month study, the 12 months study, so this is actual. In a 12 month study, all the other things I said before, also drug, this time, we use a CAT scan to understand if the fibrosis. If the fat is stored in the liver too much, they become fibrotic, which means they have scarring tissue. And generally, hepatologists, people who see scarring tissue, is not reversible, which means NAFLD will go to NASH, N, A, S, H. It just acronyzed for non alcohol steatohepatitis. So they begin fibrotic like that, not good.

                                So we saw either the containment of the fibrosis or the reversal of the fibrosis. We saw that also, my chief assigned director told me, he said, “Barry, did you notice that in the three month and the six month something else?” I didn’t want to pay attention to it, but it was reverse, reduce, sustain and statistically relevant, then that is weight loss. I did not want to mention weight loss because if you tell the public weight loss, they’re going to expect something is going to happen in two weeks and four weeks. We never had a study two to four weeks. It would be insane to see the liver have something happen in weight. It’d be total waste of a study. But we had a study at three months, six months and 12 months. So now, I have to report, and truth be told, statistically significant in three, six and 12 months, the patient with fatty liver disease have weight loss and sustain about 10 to 15 pound, approximately 5% of the body weight. I am floored. So I have to report this, I did not set up the study for weight loss you can see-

Dr. Weitz:            Dr. Tan, this is incredible news about tocotrienols, but unfortunately, some of those patients were probably taking their tocotrienols after they had their Big Mac and fries. Can we repeat this study and put people on a healthy diet and exercise as well? And this shows why it’s absolutely crucial, if we’re going to do something about the chronic disease burden in this country, that we focus on prevention.

Dr. Tan:                Yes, please. Please do. Because as you know, I’m so skittish about talking about weight loss. In normal healthy people this did not happen, neither did we find this in the cancer patient. But in people with fatty liver, they are most certainly to be overweight. Not sure if they’re obese, but they’re overweight. And losing weight for people who are overweight is nothing to sneeze at, regardless. And by the way, on this subject, we are now doing a study in Texas. They are not fatty liver patient but they’re obese patient men and women, it’s ongoing, we will know that by the end of next year, I’ll report to you for people who have no NAFLD, but they are obese. What would happen to them? I don’t know yet. But for now, I am good enough to say at three, six and 12 month with fatty liver people, they lose approximately 5% or less of their body weight. But mostly, I believe-

Dr. Weitz:            Well, let’s keep going on the-

Dr. Tan:                Okay.

Dr. Weitz:            … On the cardiovascular disease a little more. The tocotrienols also inhibit the LDL cholesterol synthesis in the liver, and I saw that it can even potentially be beneficial for reducing lipoprotein A, which is a particularly atherogenic particle and quite challenging to try to reduce.

Dr. Tan:                Yes. We haven’t done too much with LP little A, sometime people call them.

Dr. Weitz:            Yes.

Dr. Tan:                Because they’re an atherogenic particle like that. I have personally, I have genetic hypercholesterolemia. I am a five feet four Asian men, typical, not tall by any measure, and 125 pounds. So I am not otherwise… So you would think that my cholesterol would be normal, but I have genetic hypercholesterolemia, so I take tocotrienol like that and it moderately reduce my cholesterol. I’m still on statin drugs and I’ll come back to see about all the GGPs. But I notice that my LP little A certainly is low and in check, so I’m very pleased. And also, they have another measurement, buoyant LDL and dense LDL.

Dr. Weitz:            Yes.

Dr. Tan:                Dense LDL is more atherogenic which have a lot more LP little A, and the buoyant LDL is less atherogenic, and most of my LDL is in the buoyant LDL. So those specific nuance-

Dr. Weitz:            Yeah, people sometimes refer to it as small, dense LDL or large, fluffy LDL.

Dr. Tan:                Yeah. And mine is mostly the fluffy LDL.

Dr. Weitz:            Right.

Dr. Tan:                Which have very little LP little A, so therefore, the nuance part is also supported, besides the LDL being dropped. So that would help me in the atherogenic thing, keeping my fingers crossed.

Dr. Weitz:            That’s great. Excellent. And is there a synergistic effect of using, say, tocotrienols with, say, natural agents to help manage cholesterol? I’ve often been using tocotrienols along with red yeast rice and, or niacin, as part of a natural LDL managing program.

Dr. Tan:                Yeah. Yes. If it is red yeast rice, if small amount of monacolin, that mimic that of a statin. And if you don’t have muscle problem, taking red yeast rice is fine. Some people have genetic disposition to them and that would also work on it. Niacin love to drop triglyceride, and so it also good if you don’t have a red lobster flush, I call it, then it’ll be fine like that. So now, I found that tocotrienol also lower triglycerides dramatically, very good. So therefore, you should include in your dossier of using niacin, if it does not give you the red flush, and red yeast rice, if it doesn’t give you muscle problem, to include tocotrienol. They have no known site effect. The tocotrienol particularly is good to reduce inflammation. It’s just really a fantastic thing to take. So if you would be normal person without any of this condition, an antioxidant use of Tocotrienol would be called for.

Dr. Weitz:            So dosage for a patient with cardiovascular risk factors like elevated small dense LDL and lipoprotein A, et cetera, would it be 300 milligrams? Would it be 600 milligrams?

Dr. Tan:                I would put it this way, Ben. Good, good question. This is a protocol thing. If a person is squeaky clean with no this and that other condition, just using as an antioxidant. Remember at the beginning of the talk I said you have to protect the cell wall from oxidation, then 100 to 200 milligram would be just fine like that.

Dr. Weitz:            Okay.

Dr. Tan:                So for normal antioxidative protection. If a person had mild chronic condition, like pre-diabetes, this and that, some of the studies that we have done, would be probably from 200 to 300 milligram like that, they’ll be good. And 400 milligram, depending on the weight of the person, otherwise 200 to 300 milligram would be good.  If a person have a severe chronic condition, and I show you some of the clinical trial fatty liver that we use, they use 600 milligram. And the cancer trial, we use 900 milligram. We don’t really encourage people to take the 900 milligram, keeping only in mind we did the 900 milligram because they was stage four cancer patient. So in any other condition that considers serious, probably 400 to 600 milligram would be fine. So that would be my dossier, indicated from clinical study that we have.

Dr. Weitz:            And I guess there’s even some animal research showing that it may reverse arterial sclerosis.

Dr. Tan:                Yes. In the animal study, it clearly reversed arterial sclerosis. We saw that in the study we done in 2000 ,that the to tocotrienol reverse carotid arterial sclerosis on a carotid artery here like that. But yes, we saw that, we did not have a study, the closest we can do a study like that would be calcification arterial sclerosis, but we don’t have a study such as that. So in animal study, yes, there are at least four to six different study showing that kind reversal of arterial sclerosis.

Dr. Weitz:            I’m pretty much out of time, but I’d like to see if we could just real quickly say something about bone health and then wrap it up.

Dr. Tan:                Okay. Bone health, we have a study with tocotrienol with bone health. It reduces the loss of bone in postmenopausal women with osteopenia, and we publish that also. They were taking 300 and 600 milligrams. So if it’s osteopenic, 300 milligram would be satisfactory. 600 milligram would be more on osteoporosis. Maybe another time when you get to interview me, after I extract the tocotrienol, we also found another compound that is endogenous in the body called GG. [Inaudible 00:55:45] Gigi and like that. If I were to go move away from my chair, that is the molecule of GG here, in the background is a long, long molecule of coQ10. This is endogenous molecule, our body makes it. If you take this, it will help our body, is required in our body to make a coQ10.  It also help in a body to make MK-4, menaquinone four that will make stronger bone and also help in the body to make muscle, skeletal muscle protein. Hopefully, you’ll interview me in another half year, a year from now. Would love to talk to you. That is very exciting. It’s an endogenous compound, it’s meant to be in our body to do that, and now we have a supplement. By the way-

Dr. Weitz:            I’m sorry, Dr. Tan, I know we talked about wanting to talk about GG of part of this discussion. Unfortunately, I’ve got to get my first patient of the day.

Dr. Tan:                Okay, no problem.

Dr. Weitz:            But I would love to do another interview with you and talk about GG.

Dr. Tan:                Yeah, come to my website and download the book, is “The Truth About Vitamin E”, is barrytan.com/book, and then you can download the book. And then hopefully we will connect again at another time, and then blessing to you all, good health, and have a wonderful-

Dr. Weitz:            Are you going to the Designs for Health seminar in Orlando?

Dr. Tan:                Yes, I will be. Will you be going?

Dr. Weitz:            I’m going, so I’ll look.

Dr. Tan:                Oh.

Dr. Weitz:            Yeah, so look for me there. I’ll say hello to you.

Dr. Tan:                Oh, Dr. Weitz, I will look for you.

Dr. Weitz:            Grab a cup of coffee or something.

Dr. Tan:                Yeah, will do. Thank you.

Dr. Weitz:            Thank you, Dr. Tan. Okay. Bye.

Dr. Tan:                All right. Bye-bye.

 


 

Dr. Weitz:            Thank you for making it all the way through this episode of the Rational Wellness Podcast. And if you enjoyed this podcast, please go to Apple Podcast and give us a five star ratings and review. That way, more people will be able to find this Rational Wellness podcast when they’re searching for health podcasts. And I wanted to let everybody know that I do now have a few openings for new nutritional consultations for patients at my Santa Monica White Sports Chiropractic and Nutrition Clinic. So if you’re interested, please call my office (310) 395-3111, and sign up for one of the few remaining slots for a comprehensive nutritional consultation with Dr. Ben Weitz. Thank you and see you next week.

 

Dr. Felice Gersh discusses Female and Male Differences in Immune Function with Dr. Ben Weitz at the Functional Medicine Discussion Group meeting on October 27, 2022.

[If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.] 

 

Podcast Highlights

9:51  The Prime Directive of Life is the creation of new life.  Everything in the female body is designed for successful reproduction and this involves fertility, a successful pregnancy, birthing the baby, having the baby nurse, and raising that child to its sexual maturity, so that it can carry on the process of new life creation.  In general, women have a more responsive and robust immune system compared to males. But during pregnancy the immune system has to have very significant moderation and modulation and alterations so that it does not kill this little foreign creature growing in her, that little fetus and this is accomplished through estradiol, which is decreased during pregnancy.  Before and after pregnancy, estradiol stimulates the immune system, which is why women have a stronger immune function and can better fight off infections than men, but also have a higher rate of autoimmune disease.

17:43  Women have a more robust and powerful immune system than men and this is why the mortality rate from COVID in New York City was 60% for males versus 38% for females.

19:03  Women are also more likely to have Long COVID because we believe that it involves an autoimmune component and 80% of those with autoimmune diseases are women.  When you have an infection, the body makes antibodies and because women have more B-cells, they tend to make more antibodies. When you make antibodies against bacteria and viruses they can cross react and attack cells and tissues in our body that have a similar amino acid structure. Having leaky gut and leaky brains and leaky vagina increase the risk of autoimmune diseases because this means that the barriers that prevent pathogens from entering these organs.  The dendrites are the immune cells that facilitate this cross reactivity.

25:48  Women are born with two X chromosomes and this extra X chromosome is instrumental in women having a stronger immune system.  It is believed that one of the X chromosomes is randomly silenced during the time of being an embryo, but what really happens is both X chromosomes are functioning for several weeks. And during that time, before the one random one is quieted down, they actually are changing how genes express themselves within the immune system. And even when that X chromosome is silenced, it turns out that 15% of the genes are not silenced and they keep functioning. And this is why it is critically important not have fetuses and babies exposed to endocrine disruptors and other toxic chemicals, since this can make them more prone to childhood cancers like acute lymphocytic leukemia.

28:41  There are a number of genes that have immunological functions on the X chromosome, including pattern recognition genes, cytokine receptor genes, transcriptional factor genes, noncoding DNA regions, and even immune cells themselves. 

29:37  When you look at where estradiol receptors are, they are everywhere and this affects the immune system in various ways.  Dr. Gersh published a paper on the estradiol and the renin-angiotensin-aldosterone system, Gersh FL, O’Keefe JH, Lavie CJ, Henry BM. The Renin-Angiotensin-Aldosterone System in Postmenopausal Women: The Promise of Hormone Therapy. Mayo Clin Proc. 2021 Dec;96(12):3130-3141. Estradiol is the switch that can turn on and turn off inflammation as needed. 

 

                   



Dr. Felice Gersh is a board certified OBGYN and she is also fellowship-trained in Integrative Medicine. Dr. Gersh is the Director of the Integrative Medical Group of Irvine and she specializes in hormonal management. Her website is IntegrativeMGI.com, and she is available to see patients at 949-753-7475.  Dr. Gersh lectures around the world, and she has just written her third book, Menopause: 50 things you need to know: What to expect during the three stages of menopause.  Her other two books are PCOS SOS: A Gynecologist’s Lifeline to Restoring Your Rhythms, Hormones, and Happiness and PCOS Fertility Fast Track and she has also published a very influential paper in the prestigious journal Heart, which is part of the British Medical Journal family of journals: Postmenopausal Hormone Therapy for Cardiovascular Health: the Evolving Data.

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.



 

Podcast Transcript

Dr. Weitz:                            Hey, this is Dr. Ben Weitz host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates and to learn more, check out my website, drwweitz.com. Thanks for joining me and let’s jump into the podcast.

                                                All right, welcome everybody to the Functional Medicine Discussion Group meeting tonight on why males and females have different immune systems and why it matters, with Dr. Felice Gersh. I’m Dr. Ben Weitz and I’ll start by making some introductory remarks. Then I’ll introduce our sponsor for this evening, Integrative Therapeutics, and then I’ll introduce our speaker, Dr. Gersh. I encourage each of you to participate and ask questions by typing your question into the chat box. And then I’ll either call on you or I’ll ask Dr. Gersh your question when it’s appropriate.  So thank you for joining our Functional Medicine Discussion Group, monthly meeting, and I hope you consider attending some of our future events. And I look forward to meeting in person again, once the Santa Monica library goes back to their normal hours. I’m not sure when that will be. And so our future events, November 17th, Julia Zaslow will be speaking about the business of functional medicine. So we’ll go into a bit about marketing and how to run your practice. There’s going be no meeting in December, and then we’ll start up again in January. And if you are not aware, we have a closed Facebook page, the Functional Medicine Discussion Group of Santa Monica that you should join so we can continue the conversation when this evening is over.  I’m recording this event and I’ll include it in my weekly Rational Wellness podcast, which you can subscribe to on Apple Podcast, Spotify, or YouTube. And if you listen to the Rational Wellness Podcast, please, please, please give me a five star ratings and review on Apple Podcast. So I’m pleased that the sponsor for this evening is Integrative therapeutics, and Steve Snyder is going to tell us a bit about some of their products. Steve?

Steve Snyder:              Hello everyone. Just tonight, just a couple little updates, one not so little update. As most of you probably know, Cortisol Manager is by far our biggest selling product. It’s a formula to help people fall asleep when they’re elevated cortisol at night. The original product was compressed tablets. In about two years ago, we released a newer version, an allergen free version that was capsules, but a lot of people stayed with the tablets. And there’s a big update that if you’re using those tablets, or your patients are using those tablets, you’re going to hear about it. We took the titanium dioxide out of the product and basically all that was, was a cosmetic to make the tablets white. It kept the tablets looking uniform, and so that they were, from batch to batch, they looked the same.  We’ve gotten to the point where we’re consistent enough in our manufacturing that that’s not an issue anymore. And a lot of people, I think just because of the name titanium dioxide mostly, didn’t like that ingredient. And so it’s no longer in the product. It’s a big difference in looks. So if you have people taking that one, they’re going to say, “Hey, this isn’t the same thing I normally get.” And you can tell them that they can be sure it’s the same formula, just a different color. So we think it’s a good thing overall. We don’t really have a position on titanium dioxide itself, but there’s a perception out there. So we reacted to market concerns.

                                                The other one is just a really quick immune update. We have a product called V Clear, used to be called Vibra Clear. It’s a pelargonium extract that has been studied in over 20 clinical studies. It’s actually, technically a homeopathic product, although it’s really just an extract. But because it’s labeled as a homeopathic product, we’re able to make claims on it. And the claims we can make are that it treats the common cold and flu. There’s about 20 studies on it over 9000- Over 9,000 subjects so far, 3000 [inaudible 00:05:01] … And the most recent one basically compared V Clear to upper bacterial infections, lung infections, and showed V Clear to be more efficacious with less side effects. So it’s the real deal. We can make it because we’re a drug manufacturing facility, even though we don’t make drugs, we have the GMP practices in place to make a product like this. And as far as we know, so far, we’re the only drug GMP manufacturer of supplements. So it adds a lot of layers to the quality control and stuff. But anyway, remember V Clear, it’s the real deal in upper respiratory infections.

Dr. Weitz:                            Thank you, Steve. Dr. Felice Gersh is a board certified OBGYN, and she’s fellowship trained in integrative medicine. Dr. Gersh is the director of the integrative medical group of Irvine, and she specializes in hormonal management and care of patients for many chronic diseases. Her website is integrativemgi.com, and she’s available to see patients. Her phone number is (949) 753-7475. Dr. Gersh lectures around the world. She’s published three great books. Her most recent book is Menopause, 50 Things You Need To Know. She also has a book on PCOS, PCOS SOS and PCOS Fertility Fast Track, her third book. She’s also published a very influential paper in this prestigious journal HEART, which is part of the British Medical Journal family of journals on postmenopausal hormone therapy for cardiovascular health. And if estradiol were a corporation and were to a hire lobbyist, it would most surely be Dr. Felice Gersh. Dr. Gersh, welcome to our meeting.

Dr. Gersh:                           Well, thank you. It’s such a pleasure. It’s been too long. And I’m so happy that, even though we’re not in person, that we have this opportunity to get together. And I get to talk about some of my favorite topics, of course, involving estradiol. And I am going to share my screen here. So my topic for tonight is all about immune regulation, the relationship to hormones and what to do about it because hormones are so important and there are such differences between males and females.  Now notice I put flowers everywhere. You know this is a girly talk, right? Because I definitely love flowers. Now, these flowers that I have pictures of here, were taken by my youngest daughter because she loves taking pictures of flowers in her yard, in her garden, she got a new house. And flowers are very symbolic to me of all kinds of things, beauty and happiness and love. And it’s the reproductive organ of a plant, right? And a beautiful, healthy plant is going to have beautiful, healthy flowers. And of course, when you have an unhealthy plant, it’s not going to create gorgeous flowers. If you’ve ever tried to grow plants with flowers, you know that, right? So everything about the female is about beautiful reproduction and flowers and health and vitality, which of course, involve a healthy set of hormones and immune function.

                                                I do work with a number of companies as an educator. Now, it’s so important to know, that in order to be healthy, you have to have what? You have to have optimal immune function, optimal metabolic function, and optimal hormonal status. Now, unfortunately, for women, this is really problematic these days because of the ubiquitous endocrine disruptors, xenoestrogens that are everywhere, that interrupt our normal hormone production, receptor function, degradation, elimination. And of course, every woman universal, unavoidable, maybe deferrable, but not for very long, has to deal with menopause, ovarian senescence and loss of ovarian hormone production. Now, this creates a huge hit on immune function, metabolic function, because it’s one body.  It sinks and swims together as a whole because the prime directive of life is what? I knew this after I delivered just a few 100 babies and I’ve delivered 1000s. It is the creation of new life.  Now, humans are the only species on this planet that actually controls, hopefully we control it, when and if we have children. And I’m all for having timed kids when we want them, or not having them if you don’t want them. But we’re the only animal that tries to say, “Oh, this isn’t a good year.” You put a bunch of animals together like a herd of deer, and they’re not going to say, “Oh, this isn’t a good year to mate.” It doesn’t work that way. So they just do what comes naturally. And so they have the creation of new life.

                                                So it turns out that once you accept that the prime directive of life is in fact, the creation of new life, then you can see how everything in the female body is designed for successful reproduction. And that involves fertility, having a successful pregnancy, then having the baby born, having the baby nurse, raising that child to its sexual maturity. So it can carry on the process of new life creation. And doing this, as a human, multiple times in order to make sure that the species can survive. And that requires a wonderfully healthy body and a hugely important and very dynamic immune system because pregnancy is an incredibly unique state of being, when the immune system has to have very significant moderation and modulation and alterations in order to be successful. And of course, not have the immune system of the woman kill its little foreign creature growing in her, that little fetus.  So in order for that to be successful, for there to be a baby that’s born, that’s healthy, and then the mom is healthy, and then this happens over and over, a female has to have an incredibly responsive and robust immune system compared to males because males don’t go through this incredible process called pregnancy. Now, whether a woman wants to have a baby or not, her body is essentially designed for that purpose. And in order for that to happen, you need to have what I call the mother hormone, the hormone of life, estradiol. Now, I often in my slides, I use estrogen to be synonymous with estradiol, just because that’s the word that people use. But we’re going to talk a little bit about estrogen because there’s so much misuse and misunderstanding about estrogen, estrogens. And the thing about women, is that because they have this amazing, more responsive and robust immune system compared to males, when things go wrong, they go wrong in a bigger way.  And we’ll talk about the issue of autoimmune disease. Now, quite epidemic, as you probably know from your own practices, how many women are dealing with autoimmune disease and autoimmunity, right?  Because we, as functional medicine practitioners don’t just care about end stage disease. In fact, our goal is to prevent end stage disease by recognizing the early incipient signs like autoimmunity, like positive ANAs before the actual autoimmune disease is evolved. So estrogen, in order to maintain the immune system working properly, has receptor systems all through it, all aspects of the immune system are involved with estrogen.

                                                Now, I mentioned men and women are different. This comes up all the time in all my talks and the gut microbiome, which is talked about in everything now, as the center of the universe, who knew 15 years ago that we have this little control center in our gut that has these trillions of microbes that’s actually could sort of like pulling the strings around our bodies? Well, men and women, as they have very different immune systems, you may say what? They have all the same cells. Well, they actually work in somewhat different ways, and we have actually, different microbiomes in our gut. And this was found out when they did some fecal transplants, for example, and they gave male transplants of fecal material into females, and then the females started making a whole bunch of testosterone. And so it’s really interesting. We are different in so many ways.

                                                And when I was back as a younger woman, I was growing up during the age of feminism, when the word even evolved, the word feminist. Did you ever hear that? So I was an early feminist and I thought men and women should be the same, that we should wear those men’s suits as a female. Well, that’s not true. We are really different and we can accomplish all the same things, but we are different. And we need to, if we’re going to take care of women, we need to understand their physiologic differences from males, so we can optimize care. Did you know that it wasn’t until 2015, that’s not that ancient, that history, that it was not required by the National Institute of Health that females be incorporated into studies?  So we have actually, kind of limited data on a lot of female topics because nobody was studying women. Why was that? Well, because we’re more complicated because we have cycles. We could get pregnant, we could be on contraceptives, which are chemicals, and we could go through menopause and all these things complicate women as study subjects. So they just left us out. That was it. So who knows about women? Well, we’re trying, but I’m telling you, we need more data. Always. When people say to me, what about this, what about that? I say, well, I’ll give you my best guess based on the science. Because guess what? We have actually no data, but we do have information. We do have science. And we do know, as I mentioned, that females and males have a lot of differences within how their immune systems work. So it’s not just about how things look from the outside, it’s how they work from the inside.

                                                So males and females, their differences are driven by their chromosomes. Now I’m sure you know this, what’s a guy, male from birth? We won’t talk about what they choose to be later just from birth. So they were, say, an XY. So they’ve got this big X and this little bitty y, but you guys out there don’t think it’s inferior. It’s just different, that little y. And we have females born with two big X’s, and we’ll talk more about that. And of course, it’s not just having chromosomes and genes, it’s how they’re expressed. And hormones are very big on that, our gut microbiomes, our circadian rhythms. And then of course, females are more limited, in that they have a very defined time when they can be reproductively successful, whereas males potentially, could create new babies at any stage of their lives. It turns out this isn’t just a human kind of a situation because when you look at other animals, in fact looking at insects and lizards and birds and other mammals, they also show immunological differences between the male and the female.

                                                Now, females, as I mentioned, have a more robust, more dynamic, we’ll say more powerful immune system, and that allows greater survival in things like pandemics. And this became actually, very evident early on in the COVID pandemic in New York where things were really in disarray back at the time of March and April 2020. And looking at the mortality rate in New York City from COVID, males made up over 60% of the deaths versus females, 38%. That is, why is that? Because males do not do as well because their immune systems are a little bit weaker in terms of their ability to fight off infections and sepsis.  In fact, going way back into 1998, ancient times for many of you perhaps, when they looked at survival of males and females who suffered with sepsis, look at the difference in the survival rate. About three quarters of women survive versus only a little over 30% of males. Women just have a higher survival rate from pathogens because of their very robust immune systems.

Dr. Weitz:                            Dr. Gersh, do we know about the likelihood of having long COVID for women versus men?

Dr. Gersh:                           It seems that women are more subjected to, more likely to have long COVID than males. And that’s because when women are challenged and they’re having metabolic problems and they develop these, we’ll say long acting viruses, they have chronic viruses, they end up having more autoimmune. A lot of the long COVID is felt to be possibly, I mean we don’t even totally know, but it may be an autoimmune driven thing. And women, which we’re going to talk about, make up 80% of all the autoimmune sufferers. And we know that women are just more prone to having reactions. And we’ll talk about it, actually, I can talk about why does an infection even cause autoimmunity?  In fact, let me just tell you why, okay. So why is it that chronic infections and the common ones are all the different herpes viruses. So there’re a lot of chronic infections with herpes. And then of course, now we think that the SARS-CoV-2 can cause a chronic infection. There’s chronic infections with various hepatitis viruses, right? Hepatitis B, hepatitis C. HIV is obviously, sort of chronic and so can HPV.  So when you have an infection, an acute infection, the body makes antibodies by the adaptive immune system. Well, I’m going to cover this, but I can jump ahead because what, who says, we have to go in any specific order here? So this is very important. Women have more B cells. Women actually make, women have more immune cells than men. Women make antibodies in greater quantity and more robustly and more readily.  So every time you have an infection, the body will create antibodies. And that of course, applies to vaccines as well. That’s why every single vaccine has the potential to have an autoimmune reaction. This is a 100%. Every single infection has the ability to create an autoimmune response. Why is that? Because you always make antibodies with every infection. And it turns out that we and viruses and bacteria, come from the same primordial pool of nucleotides. The building blocks of RNA and DNA are the same throughout every life form on planet earth. They’re just rearranged differently. Like amino acids to create different proteins.  And so these nucleotides, RNA, DNA are similars. So when you make antibodies against a virus or a bacteria, there is always what we call molecular mimicry. These antibodies will always attack our own cells, always, a 100%, but it should be in an acute situation it’s short lived. So you make antibodies against whatever tissue in the body is most similar to that particular pathogen. And in fact, they even have charts showing different pathogens that are associated with different autoimmune diseases. Because if you have a chronic infection, and remember leaky gut is like a chronic infection because you’re having influx into the body of pathogens from the gut. But you can have leaky other things too. Women can have leaky vaginas, where they have any barrier between the outside world and the inner body can be leaky. So you can have leakiness in the sinuses, in the bronchial tree, but the gut is the biggest potential source of this leakiness.

                                                And when you have an infection that is coming from, not from the gut say, with these other bacteria, people can have chronic strep infections where they have in the crypts of their tonsils, they can have the strep just kind of hiding out there. And that can create all kinds of problems. And of course, we know that strep infections, before we had antibiotics, the penicillins, they could sometimes give you things like scarlet fever, rheumatic heart disease, that’s autoimmune based. And if any of you’ve read Little Women, there was a little death in that family from a young girl who had the autoimmune response to a strep infection. And those are tragic things.  But autoimmune diseases are ongoing and we have so many disruptors to our immune system, so many more chronic infections that we’re having this autoimmune. And of course the leaky gut is a big source of these chronic pathogens entering into the body. So we have this molecular mimicry issue, where you make antibodies against the pathogen, but it cross reacts with ourselves and women because they make more antibodies than men, make them more readily and have more B cells that make and the antibodies and women have more of the dendritic cells. These are the ones that are the passers onners of the antigen. So they communicate with the other immune cells like neutrophils and mass cells, and they then have their little arms that stick out and then they connect with the B lymphocytes that make the antibodies.   So the females have a better, we’ll say, directional system of communicating the antigen being there to the cells that make the antibodies. And so this is going to apply to COVID as well. And so this is a huge problem for long COVID is more female, just like autoimmune. And so women have the advantage in survival for acute infections, but for long term chronic infections, it’s a problem because autoimmune disease can definitely ensue.  And over time there can be other things that sort of take over and almost get a life of its own, where the antibodies continue and sometimes you can never find what the original pathogen was that initiated this whole sequence of events. And if we go back here to COVID and we look, we can see that deaths and hospitalizations were also varied by gender as well.

                                                So I mentioned the X chromosome is different. This is actually not a small matter because this is huge, now you see hormones are a big part, but it’s never just one thing, right? Everything is always complex. So it turns out that extra X chromosome that females have…  So it turns out that that extra X chromosome that females have is very instrumental in creating this more robust immune system. So the estrogen sort of perpetuates it, but the X chromosomes actually initiate it. So when you are made as a female, you have two X chromosomes. Now, it’s belief that one of those X chromosomes is randomly silenced during the time of being an embryo. But what really happens is both X chromosomes are functioning for several weeks. And during that time, before the one random one is quieted down, they actually are changing how genes express themselves within the immune system.   So during those first beginning weeks of life, both X chromosomes in a female are acting, they’re functional, and it’s changing how genes are being programmed to behave and in terms of how immune cells will react. And then when that X chromosome is silenced, it’s actually not completely silenced.  It turns out that about 15% of the genes are not silenced. They keep functioning. And it turns out that most of those ongoing functioning genes of the extra X chromosome, they’re actually related to immune function.

So women are so programmed to have different immune systems from the earliest state of embryological life. And of course this is why it’s so important to not have endocrine disruptors and chemicals and things on board right from the get go because things are critically happening right from the beginning of life. And when things are not right, and we have improperly programmed receptors and these systems that are coming on board that makes women much more prone to diseases and cancers and so on.  They’ve now identified for example, that early age like little bitty kids, like two year olds and such who get acute lymphocytic leukemia in these really early childhood years that they were exposed in utero to things like high levels of pesticides. It changes how the immune system is working in utero. That’s why I’m so big on preconceptual planning and maintaining the cleanest possible environment and food intake and water intake during every stage of pregnancy including the very, very beginning.  So once you recognize that these genes that are involved in so many of the immunological functions are located on the X chromosome then you can see how the… Look at these different types of genes that are all X chromosomes, the pattern recognition genes, cytokine receptor genes, transcriptional factor genes, noncoding DNA regions, immune cells themselves. These are unbelievable. Even when you get rid of the hormones, okay? Females are going to function differently than males. And even in an environment where you take away the sex hormones, the X chromosome, the double X chromosome females, and this is in mice because sometimes remember we don’t have everything in humans, but we have a lot of data, they also had more of the mouse equivalent of lupus and MS.  So genes are not insignificant.

When we look at where estradiol receptors are, it’s everywhere and it affects the immune system in a whole host of ways. Now, you mentioned that I had a paper that was published in Heart last December. I had a paper that was on estradiol and the renin-angiotensin-aldosterone system, which is very related to survival and the immune system as well.  And basically the basic tenet of that is that estradiol, when you have the right balance of estradiol in the body, it actually operates the switch. The switch that turns on inflammation and turns off inflammation. That’s why sometimes it’s very tricky that people say, “Well, it’s proinflammatory. Well, it’s anti-inflammatory. Well, guess what? It’s all of the above because estradiol is a modulator regulator of the immune system.  So when you have an immune system that’s activated because of appropriately, it’s because a pathogen of some kind is trying to get into the body or there’s trauma. So the PAMs and the DAMs, right? so the immune cells are activated by pathogens and by damage. And so when this happens, it’s estradiol into action. It activates the immune system. It actually turns on monocytes, neutrophils, mass cells, all of that to get going to create the inflammatory response to save that woman’s life.  That’s why women have higher survival and infections and sepsis. But you don’t want unending inflammation. That’s a killer, right? Chronic inflammation is the last thing anybody wants. Estradiol also turns off the switch from pro-inflammatory into anti-inflammation and pro-healing. So this is really important that estradiol modulates every aspect of the immune system, which includes every immune cell and the platelets.

                                                So platelets are very involved in immune function and the way that’s involved with the renal angiotensin aldosterone system is that’s a system for survival. So if you’re infected or you’re traumatized, you’re bleeding, you want to activate the pro-inflammatory arm of the RAS system so that you have increased aldosterone. You have fluid retention to maintain volume in your vascular system.

                                                So you don’t go into shock. You want to actually create leakiness in arteries. You want leakiness because when you have immune cells circulating, if they can’t get out of the blood vessels, how are they going to get to the extracellular sites of infection? So you create a leakiness in the vascular system to allow platelets and to allow the immune cells to exit the conduit, the artery and the capillary so it can get out into the tissues.

                                                And then it activates the immune cells so that cells like macrophages, neutrophils, they put out all of their toxic products to destroy the invading pathogen and it activates… Estradiol, activates phagocytosis so that you can actually gobble up and then get rid of dead damage tissue, get rid of the pathogens. All of this is modulated by estradiol. And a lot of this is not as active of course in males because look at here what I put in a little, I don’t know what color that is, sort of RNG.

                                                I wrote testosterone suppresses immune cell activity. Sorry, guys. You have many other skill sets, but you are not as good at creating the pro-inflammatory state to deal with trauma, to deal with sepsis, to deal with infection. And I’ll tell you why in a minute. In case, you’re wondering, why is this? Well, why women have to have this dynamic immune system, it’s so that it can mod be modulated during pregnancy, but also because… Okay, I’m going to give it to you straight. If you had a pandemic and you had 10 men survive to every female, that’s not going to get you where you need to go as a species.

                                                But if you have 10 women survive to every male, well, you can repopulate the planet. Right? So nature wants survival of the species. So women have to raise the children. Women have to procreate and make new kids. So you need to have more women survive than men. If you have trauma, if you have infections, it’s just the way it is. Who’s better at surviving a famine? Who holds onto their fat more? Oh, it’s us. So it’s just what it is.  But you guys, you are bigger, stronger. You have more muscle mess and that’s where a lot of your energy goes. Where else does your energy go? Making all those sperm? Oh my gosh. It takes a lot of energy from the body to keep making sperm. It takes a lot of energy in the female to keep that immune system going. So it’s a division of labor and energy.   So there’s only so much energy that you can create in the body. The female puts an enormous amount of her energy into maintaining that robust immune system with all those cells, those extra cells, all that extra activity. And males put it their extra energy into maintaining a larger structure, more lean body mass, more volume, more mass. And the energy it takes to keep making all those sperm. So it’s just how nature divided up. Everything in life is about successful reproduction and survival for that purpose.

                                                And then indirectly, the hormones are going to be involved in microbiomes and circadian rhythms. There’s differences in every single part of the immune system between males and females. So women, as I mentioned have higher numbers of cells that are immune cells. Women have higher white counts. Women have more immune cells and they are more active. So you can see, I mean, we can go through everything. Women have more of this, they have more of that.

                                                By the way, anyone can have my slides. I share everything. Estradiol is so important that half of all the activated genes in the T-cell have estrogen response elements. Estrogen is involved in immune function. Now, men do have a lot of activity involving their immune system through estradiol as well. Because you know all estradiol is derived from what, a hundred percent, no exceptions, testosterone. The precursor of estradiol is testosterone, is converted by the enzyme aromatase.   And many, many tissues have the enzyme aromatase in them, many, including arteries, including the heart, including the brain, including the skin, including the gut. And that enzyme helps convert testosterone for the male into estradiol so that it can have… A lot of the benefits and functions of testosterone don’t come directly from testosterone receptors, but rather from its conversion into estradiol. So men have plenty of estradiol, but it’s not circulating.  It better not be, okay? So they shouldn’t have high circulating. It’s locally produced [inaudible 00:37:24] production and stays in those tissues. So I mean, I just put a lot of things here, but it’s really repetitious because I already told you women have more B cells. Women have more T helper cells. They have more T helper 1, they have more T helper 2. They make more antibodies. They have more immunoglobulin. we just have more of everything that has to do with immune function.   As I mentioned, it’s all about ultimate survival. Women have a bigger response to vaccines. And this drives me crazy. We don’t make sex specific vaccines. This is wrong because women have a greater reaction to them than men do. So they’re going to get more antibodies produced. So I mean they’re more effective in women, so that’s a good thing. But if they get an autoimmune response, then it’s going to be greater. So women are more likely to develop, for example, Guillain-Barré or Bell’s palsy from a vaccine than a male because we have a bigger response. But they don’t diagnose the vaccine for women because nobody cares. But we care. It’s doesn’t seem right.

                                                And so I mention, I call estrogen, I named this. There’s no book that says this is me. I said it’s the mother hormone. It’s the hormone of life itself. It’s the master of all metabolic functions, metabolic homeostasis and immune function. And what is metabolic anyway? It’s the creation, distribution, utilization, storage of energy. So estrogen, and I say estrogen, but I’m talking estradiol, the ovarian produced estrogen. It’s involved in everything that has to do with energy.

                                                Now, why does energy matter? Because energy is the driver of everything. You need to have energy, it’s life itself. And in order to have proper energy, you need to have a regulation in the brain that says eat more, eat less. That’s regulated. Actually the nutrient sensors in the brain all have estrogen receptors and that’s a problem when you have a body full of endocrine disruptors, these diabetogens or you don’t have enough hormones or if you’re on chemicals like hormonal contraceptives where it can dysregulate your appetites.

                                                So your energy needs become mismatched to your energy consumption. This is a highly regulated system through estrogen because it’s so important for humans and every animal species to have the right amount of intake of food, AKA energy to match the energy needs of the body. You don’t want under and you certainly don’t want over. But the default is when things are not right, it’s over as you well know from all of your patient population.

                                                So just what is this hormone thing? A hormone is an information delivery system. It gets to the cell. It binds to receptors. They could be in the nucleus. They could be on the cell membrane and information is delivered. It’s like having a pony express and then when finally, the messenger gets there and he says, “I forgot to bring the message,” then it’s like, “What do we do? We don’t have the message?” That’s like, “What does the cell do if it doesn’t get the message or worse yet you have endocrine disruptors, it gets the wrong message.”

                                                Well, that cell is not going to behave properly. And that’s another competing problem for why we have such dysregulation of our immune system. I know when I was back in training back in the day and residency, I didn’t learn anything useful about hormones other than they had something to do with reproduction. But it’s really about survival and life itself because we now know that many creatures have estrogen receptors that do not have reproduction that’s anything like humans.

                                                For example, animals that predated clams. They actually have estrogen receptors. In fact, it’s believed that the first steroid receptor that existed in any life form was actually estrogen receptors. So that’s why it’s the preeminent hormone of life. And here I put down that invertebrates had no sexual production we have, and yet they had ancestral estrogen receptors.  This is really amazing when you think about it that estrogen, which we think in our current medical system as all about reproduction, really had its first entry into life forms as a metabolic regulator. Of course you can’t have successful reproduction without optimal metabolism. That’s like an essential. We know that estrogen, and I talk estradiol, it does a million things in the body. I go on and on, it’s like you already know I’m the lobbyist for estrogen as was said, right?   It’s like somebody’s got to stand up for the underdog here. Estradiol regulates everything. You name it because it’s about maintaining life. And there are these receptors. We now know alpha, beta.

Dr. Weitz:                            Now in your last slide you had estrogen increases lean body mass. Isn’t that what testosterone does?

Dr. Gersh:                           Well, testosterone does that too. That’s right. In fact, one of the biggest problems in menopause is actually sarcopenia. Estradiol is very big on maintaining lean body mass and muscle mass. That’s correct. Estradiol doesn’t get its place in the sun. I have whole lectures. Maybe another tale I’ll come back about how sexual functions, sex drive and everything relies on estradiol and the relationship to peptides and vasoactive intestinal peptide and oxytocin. A lot of the male stuff, it does rely on conversion into estradiol.  So yes, absolutely. One of the big problems after menopause is loss of lean body mass and the production of really toxic inflammatory adipose tissue, especially in the belly and the visceral fat is so horrible. So, oh my goodness, I am going to write a book. I have to get to it on the wonders of estrogen, but I don’t know who’ll buy that book.   But I’ll just give out copies because I want people to know how wonderful this hormone is that has been so maligned so terribly. And this is a little piece of important information that I always want to share. The estrogen receptors, which are more predominant in different organs, like the alpha receptor, is heavily in the hypothalamus and regulates a lot of the metabolic processes like appetite regulation, reproduction, like the menstrual cycle and so on, the circadian rhythm. The master clock is in the hypothalamus, which is heavily modulated by estradiol.

                                                In the gut, the intestinal tract is predominantly beta. The cerebral cortex is predominantly beta. Arteries are predominantly alpha. That’s why you don’t want one or the other. You want the balance of both. And when you have the… And these receptors are up and down regulating each other. Nothing is as simple as you may ever think. The more you learn, the more complex things become. And these receptors interact with one another.  High beta like estriol. Estriol works on the beta receptor. Estriol on the alpha estradiol is balanced. And high stimulation of the beta receptor actually downregulates the alpha receptor. And this is very key in pregnancy when you have lots of estriol because estriol is beta and it downregulates alpha and where is alpha? It’s on the innate immune cells. The innate immune cells. But it’s also on the arteries. That’s why pregnancy is the ultimate stress test for women because you have vascular challenges. You have changes in gut microbiome, which I’ll talk about.

                                                You have instantly dysbiotic gut microbiome very shortly, not instantly, but shortly after pregnancy occurs and it progresses and that’s designed to do what? To create a small degree of insulin resistance. Inflammation causes insulin resistance. And so every woman who’s pregnant is sort of on the fringe on thin ice between having just a little bit of insulin resistance and crossing the line into gestational diabetes.

                                                If you’re going like, “Why do women who are pregnant get these diseases like gestational hypertension, gestational diabetes, preeclampsia?” It’s because they become pro-inflammatory but for a purpose to increase insulin resistance, but just enough to increase fat storage and production in the pregnant woman because women have to store a bunch of fat. That’s why women who are pregnant gain weight even if they don’t eat more because they are insulin resistant. And insulin drives fat storage in production that also creates more blood sugar, enough to cross into the placenta into the baby to help grow that baby.

                                                Remember humans evolved during times of food deficiency. We didn’t have food on every corner so we had to be very capable of putting on fat and of growing that baby. And that’s why women who are pregnant become insulin resistant and their immune systems are altered because the alpha is on the innate immune cells.

                                                And you want to down-regulate them so that they are the attack animals, so they don’t go and attack and put out their inflammatory cytokines to kill the baby. That’s why women who are pregnant will often go into remission for many autoimmune diseases because they produce fewer inflammatory cytokines.

                                                They also are less capable of fending off pathogens, COVID, the flu, chicken pox and such because their innate immune cells are not going to be as functional. This is all part of the strategy of surviving during pregnancy for the baby to survive. So the mom’s immune system doesn’t kill off the baby. But we do not want to take a post-menopausal woman and try to recreate the scenario of a pregnancy because estrogen receptor alpha down beta, the beta receptor when it’s highly bound, it will actually down regulate alpha.

                                                And you need alpha. You’re not trying to get rid of alpha. The only time you’d want to get rid of alpha is if you’re treating someone specifically with breast cancer because breast cancer positive is always when it has receptor positive for estrogen breast cancer, it’s the alpha receptor. Okay? But that doesn’t mean that you don’t need alpha, okay? So you want everything balanced. That’s why for postmenopausal women please give estradiol not estriol because we don’t want to alter the immune status of women who are postmenopausal, so their innate immune cells are less functional. We’re not trying to do that.

                                                Pregnancy is a very unique state, so don’t try to replicate it because you’re not, and it’s not going to be beneficial. Don’t try to recreate human females in a way that they never exist on this planet. So understanding this dynamic between the receptors and how the immune system is working. So we’ll show you some other things here. I already went over a lot of this stuff, the different forms of estrogen and how they react differently with different receptors. And that there are estrogen receptors throughout the entire human body, as I mentioned, and on every single immune cell.

                                                So just getting to basics, why do we even have an immune system? Well, it’s just amazing. I mean I didn’t learn enough about the immune system back in the day when I was in medical school. I can tell you I didn’t realize all the things that it does, but it’s a tremendous information system. The inflammatory cytokines, and there are antiinflammatory cytokines as well. They’re also communication systems that really tell different cells what to do.

                                                So it’s amazing what the immune system does and we need to do everything we can to maintain it. In this busy looking slide, it’s just looking at some of the different peptides and enzymes that are all modulated by estrogen, estradiol. And I highlighted in yellow a lot of the ones that are specific for the immune system. But basically everything interacts with the immune system, but it involves all the issues with lipid metabolism, coagulation.

                                                So remember, estradiol does not cause blood clotting. When you have a regulated immune system. It causes blood clotting when you need blood clotting like when? If you have hemorrhaging, okay? Or as well platelets are activated if you have an infection. Why would platelets be activated if you have an infection? Because platelets help to create the encapsulation of… If you wonder, how the heck do you make an encapsulation of an abscess? How does that happen in the body? That’s through the action of platelets.

                                                So they’re activated in infections as well. But if you have a really severe chronic infection, this has happened with COVID, right? That you can end up having uncontrolled inflammation and then you can have abnormal blood clotting that of course can kill people. So it’s a fine line. Just like pregnancy is a fine line. SO2 is navigating an infection so that you can control the proinflammation and the anti-inflammation. And in order for that to happen properly, you need to have the right amount of hormones and elderly people don’t, that’s why who tends to die the most from COVID? The elderly… That’s why, who tends to die the most from COVID? The elderly people. By the way, right at the beginning of COVID, I said we need to do a study with estrogen to see if estrogen is going, like menopausal women who are on estrogen, they’re going to have better survival. But I couldn’t get any of my friends who actually do studies, because I’m a clinician. I couldn’t get anyone to be interested in it. Well, there were some studies and there were some published data that yes, indeed, estradiol helps to prevent COVID deaths. Because duh, it modulates the immune system. And of course, pregnant women, now papers have come out that has been significant excess female maternal mortality related to COVID, because pregnant women are not as able because of their innate immune cells being down-regulated by estriol. And we don’t want to do that to our postmenopausal women. So understand that in the end, estradiol modulates all of these systems.

Dr. Weitz:                           Well, essentially you’re saying no Biest cream recommended.

Dr. Gersh:                           I am. I am saying that. I’m begging you to stop using that. And then if you are using it, then say, why? Where did you get this data? What is it based on? Somebody who said something 35 years ago who didn’t even know, not through any fault of his own.

Dr. Weitz:                           So there’s no decreased breast cancer risk.

Dr. Gersh:                           No. Where’s the data on that? If you’re treating breast cancer there, why do they give tamoxifen? Okay, Tamoxifen is a chemical version, to some degree, of estriol. So I’m not saying also, there is some published data that estriol can help modulate the immune system. Think of it as an immune modulator. So it will down-regulate the production of inflammatory cytokines just like Remicade and Humira, and all these drugs that are now so prevalent all over the place that are blocking, this one blocks tumor necrosis factor alpha. This one blocks interferon, this blocks some interleukin and so on. Well, guess what? Estriol decreases the production of all of them. So there’s some data that it can help with MS. So I’m not saying there can’t be potentially. Now of course, we have pharmaceuticals that are doing all these things. So they never used a natural product because no money in that, right?

                                                But understanding the mechanisms, yes, there may be some benefit. If you have breast cancer, there may be some benefit if you have MS. But to give it to just the typical average woman who’s in menopause, what the heck are you doing? You’re not treating breast cancer. And by the way, estradiol helps prevent breast cancer. That even came out in that stupid Women’s Health Initiative study. So how does this happen? Let me just step back a minute, because breast cancer always comes up. When you don’t have enough estradiol, who gets the most breast cancer? Postmenopausal women. Postmenopausal, not premenopausal. When you have enough estradiol, you’re modulating the immune system. So you’re preventing runaway inflammation. Okay? You’re maintaining a healthy gut microbiome, you’re controlling your immune cells, right? It’s the controller. You’re controlling all this. When you don’t have enough estradiol, you end up in this pro-inflammatory state.

                                                You have gut dysbiosis, you have leaky gut, and you end up in this default system where the anti-inflammatory pathways can’t be activated. It turns out that the anti-inflammatory pathways are probably more beta-driven and the pro-inflammatory more alpha. Well, after menopause, what do you make if you’re a female? You make estrone. Now, estrone is made through the conversion of androgens, predominantly coming from the adrenal gland, which makes huge amounts. That’s where the biggest steroid hormone is what? It’s DHEAS. So that can be converted into estrone. Now, when you have chronic inflammation and postmenopausal women like inflammation, they become low-grade chronic inflammatory people. And inflammation up-regulates the enzyme aromatase. So now you’re converting these androgens to estrone. Inflammation blocks to a significant degree the enzyme that converts estrone to estradiol, because it should be back and forth. But the enzyme to convert estrone to estradiol is now largely blocked.

                                                So you end up stuck with estrone, the alpha receptor agonist. Now when you have that, you’re ending up feeding the inflammatory state, you’re activating the innate immune cells even more. And when you have chronic inflammation, it’s everywhere in the body, including in the breast tissue. Then chronic inflammation drives DNA instability and breakage. You get cancer. Now, estradiol and estrone, they’re all growth hormones. Now they promote growth. Now growth is evil if it’s uncontrolled, but it’s essential for life, because growth isn’t about just getting bigger, like the uterine lining gets bigger. Growth is about repair, rejuvenation. That’s why everyone loves stem cells. And you know, can’t replace old dead cells, senescent cells, regenerate healed wounds or anything if you don’t have estradiol. So it’s like the growth hormone of rejuvenation, okay? That’s why you can put it on your skin. And guess what? Wrinkles go away. I’m not kidding.      There’s data on that. Okay? So the thing is, you don’t want uncontrolled growth, because uncontrolled growth can grow cancer cells that have those estrogen receptors. I told you breast cancer is alpha-receptor positive. So now you have the perfect scenario, you have chronic inflammation that’s driving DNA instability and breakage, and then you have breast cells exposed to estrone. Now, estrone is made wherever there’s adipose tissue in an inflamed person. Now, where is breast tissue? What is breast tissue composed of in postmenopausal women? Largely fat. So estrone is made in the breast. So when you talk about where’s the estrogen coming from, it’s coming from in the breast tissue itself. And so that’s driving the growth of that breast cancer, which is estrogen receptor-positive for alpha receptor. But if you had estradiol present in the first place, then you modulate the immune system to keep that inflammation, to keep the gut microbiome healthy and proper, so that you don’t become elderly in the sense that you have this inflammaging process.

                                                So by starting your women patients on bioidentical estradiol and progesterone in a physiologic way, you can help to maintain them in a premenopausal health status to a large degree. It’s not like getting 25-year-old ovaries, but it’s sure better than the opposite. And estriol is not designed for that. And remember, estriol is beta, so it’s not on the arteries, it’s not the same. Please stop trying to create some new dynamic that doesn’t exist. So just give the body what it does best on during the reproductive years, and that’s estradiol. And you will make estriol, by the way, from estradiol, when it’s needed in the right amounts. So please, please think about why are you giving Biest, and who told you to do that? I’m evidence-driven. There’s no good data on that. It’s only negative when you understand the science and when you look at what estradiol does, look, it’s helps prevent people dying from influenza and more.   These are just articles that have been published. You can read this. The content, it’s so interesting. Estrogen receptors regulate innate immune cells in signaling pathways. I mean, the takeaway from tonight is estradiol is wonderful, and you can’t have a functional immune system if you don’t have it. Okay, got it, everybody? And look at the different pathways. It’s like, so 17 beta estradiol, that’s made in the ovary upregulates, the, I call it NERF2. I don’t know what you say, but this is not optional. This is so important. Everybody wants to increase NERF2, right? Well, estradiol does it. Estradiol does everything that you think you want to do. Where do you think you get NAD to activate? Okay, that’s a co-enzyme with the sirtuins. Guess what? Estradiol promotes NAD function. What else? How about the sirtuins that you want from fasting?

                                                That’s a bidirectional effect between estradiol and the sirtuins. So all of you antiaging fanatics, you can’t have any of these whole enzymes and enzymes work properly in an absence of estradiol. Okay? And look, I look for articles everywhere. So everything is science, evidence-based. You want to control inflammation, you get estradiol on board. And look at all what estradiol is regulating through the innate adaptive immune cells. I mean, all the neutrophils, all of these cytokines, everything is regulated by estradiol, Th1, Th2, the Tregs. If you don’t have enough estradiol, guess what happens? You don’t have proper functioning of your T regulatory cells, which help to control things in the body. So definitely need that. So I think you know why we have inflammation, well, inflammation needs to be tightly regulated by the toll-like receptors, which are circadian. And of course, estradiol helps regulate the circadian block, as I mentioned.

                                                Now I have a whole bunch of slides here that just to, oh, and I mentioned that estradiol is essential for phagocytosis. And what’s a cousin of phagocytosis? Autophagy. Okay, estradiol. You always want autophagy, right? You never want continuous autophagy, but you want autophagy so that you can have cellular renewal. I call it house cleaning. You get rid of the junk and you turn it into fresh. Well, you need estradiol for that. And if you don’t believe me, go on PubMed. There’s a ton of articles on that. Now I put this here to show you this is actually a mass cell. And look what’s smack in the middle there. ER alpha, oh, estrogen receptor alpha. I told you, it’s on all the innate immune cells. And there’s the toll-like receptors, and it’s being activated in this case by the damage. This is actually endometriosis that they’re talking about here.

                                                But this could be a mass cell with any kind of injury. And then it de-granulates and releases all of its toxic products in order to deal with an invading pathogen, or damaged tissue and trauma. And then the mass cell then calls in the troops through its chemokines and activates all the other immune cells. And if you don’t have proper estrogen receptor alpha function, oh, remember, estriol doesn’t work on it and actually downregulates it. You’re not going to have proper immune response. Now this is just showing this is a mass cell, all the millions of things that mass cells do. And you see how it links to pain? Who has more pain? Men or women? Women. Women experience greater pain. Who frequents cannabis dispensaries if you went to their cannabis dispensary? It’s two groups of people in general. Young males looking for recreational cannabis, and postmenopausal women looking for something to help them to deal with pain and insomnia and menopausal symptoms and such. Because women are more sensitive, and mood problems, to all of these things.

                                                A lot of these things are actually driven through the inflammation that becomes uncontrolled after menopause. So menopausal women are frequently visiting the cannabis dispensaries. And they need you to guide them so that they don’t feel they’re on their own, nobody cares about them. And then I just go through all the different immune cells. So you can look at this later, how estrogen works through all of these different immune cells. And you need to know at some point, I think, you know what these different immune cells do. It’s really fascinating. So I just put down a lot of the things that neutrophils do and macrophages. And of course, what are specialized macrophages? The microglia in the brain are specialized macrophages, microglia in the gut are specialized macrophages, osteoclast in bone are specialized macrophages. And after menopause, they all go wild without control. They’re like weapons of mass destruction without control, damaging the brain, damaging the gut, and of course, causing more osteoporosis.

                                                That’s why the best thing for bone is what? Estradiol. I do whole lectures on bone health. And of course, everyone out there who deals with the musculoskeletal system needs to appreciate that, because women have 80% of osteoporotic fractures. This is preventable. Over 50% of women have osteoporotic fractures. And bone is amazing tissue. It not only is structural, but it also is an endocrine organ as well. So the dendritic cells I’ve mentioned, they are the messengers between the innate and adaptive immune systems. Women have more of them and are better able to transmit the information to the adaptive immune cells, the lymphocytes that make the antibodies. And all of the T cells are up-regulated and functional with estradiol, the T lymphocytes of all the B1s. And so all of these things you have to think about when you’re giving chemical endocrine disruptors like oral contraceptives.

                                                I mean, this is really important when you understand the importance of how hormones work in the female body. What the heck are we doing when we give chemicals that prevent ovarian function during the reproductive years? I don’t think this should be ignored. We know, for example, that young women, because we don’t have data on women over 20, but girls in their teens who start on birth control pills have higher lifetime risk of cardiovascular events. They never reach optimal potential for bone density and muscle growth. So these are big deals. And then think about all the endocrine disruptors. And then once again, think about what hormones do you want to give women in menopause? The lymphocytes, of course, and they’re all involved with the function of the immune system and regulated by estradiol. It’s important to know estradiol is essential for proper phagocytosis. I mean, most people don’t know that.

                                                So antibodies lock onto the antigen, but they don’t kill it. Antibodies alone do not kill. It’s the phagocytosis that actually does the killing. It’s the one-two punch. And all of that involves estradiol for optimal function. And estradiol, its effects are variable depending on levels. That’s why the whole concept that came out after the Women’s Health Initiative of give the lowest dose. That’s insane. What you want to do is give the most physiologic efficacious dose. Because women who have very low estrogen are more pro-inflammatory. What’s a pro-inflammatory state of a woman in a natural cycle? It’s when she’s having her period, that’s when estradiol is the lowest of the menstrual cycle. And why is that? Because having a period is actually a pro-inflammatory state. Because your body is contracting the uterus, getting rid of the lining, and it produces pro-inflammatory prostaglandin. And of course, when you don’t have proper regulation, you end up with what?

                                                Heavy periods and terrible cramps. That’s a red flag that this person is not properly regulated. They have too much inflammation. They may be stressed, they may have nutrient deficiencies, hormonal imbalances, endocrine disruptors. So remember, the menstrual cycle is a vital sign of female health status. So when you have a messed-up menstrual period, it means they have something wrong with the owner of that menstrual period. The solution isn’t to give her chemical endocrine disruptors. The solution, that’s smoke and mirrors. The solution is find out what’s wrong and fix it like we always do in functional medicine, right? And so also, it affects Th1, Th2. Who has more allergies? Oh, women, did you know that? And that’s Th2-driven in pregnancy. Progesterone pushes towards Th2. Okay? And down regulates Th1, because you don’t want to have so much cell-mediated immunity, you go more to humoral immunity.

                                                And I would love to give a whole course on immune system if you don’t know what I’m talking about. But these are things that you should look up if you don’t, because this is really important to understand. I think foundational to understanding how to treat anyone is understanding the basics of the immune system. And I mentioned progesterone is actually innately anti-inflammatory. Because remember, everything’s about survival. And pregnancy is about reproduction and survival of the fetus and the mother. So you don’t want to have the immune system killing that fetus. Progesterone is innately anti-inflammatory. And that’s really important, because some people don’t give progesterone to women who don’t have a uterus if they’re going in menopause. This is so important. It has all the functions of down-regulating muscle. So that’s why women in pregnancy are often more constipated. They have more laxity, I’m sure, dealing with people in their joints. That pregnant women are more likely to have more laxity in their joints because everything is a little bit looser.

                                                And so everything, when you think about it, it’s all about survival. And just to let you know how important estradiol is in modulating the immune system and inflammation, here is looking at ERR alpha. ERR stands for estrogen-related receptor. Estrogen works not only directly estradiol on its receptors, but also through other ligands that are binding to receptors. We don’t even know what those ligands are that are binding, but they don’t work properly in an absence of estradiol, and see how it helps to regulate or modulate a block, NF-kappaB. And it helps improve mitochondrial function and biogenesis. This is all through secondary actions of estradiol. And I mentioned about autoimmune disease, but now I think you already know, because women have more robust immune systems, they are going to make more antibodies more robustly. They’ve delivered the information to their immune cells more aggressively.

                                                And it’s just a big problem for women now. And we know that, I’ve already talked about sepsis is definitely works better. So here when you took out the ovaries in rats and then you didn’t give them estrogen, they died. If you gave them estrogen, they didn’t die. That’s pretty good. And in terms of the microbiome, estradiol is very key to regulating the microbiome. Women in menopause have an altered gut microbiome. It’s dysbiotic. Women in pregnancy have an altered gut microbiome, but that’s intentional to create a low-level controlled fire, low-level inflammation and low-level leaky gut. But so many women now, pregnancy-related complications are through the roof. Horrible, through the roof. So it’s important to understand that every woman going through pregnancy needs to be optimally healthy first, because this is such a stress test for women. So I know we don’t want to be here forever, but if I’m let alone, I probably will keep you here. So I’m going to-

Dr. Weitz:                            Can I just ask a question? Speaking for men, who don’t have a lot of estrogen, but-

Dr. Gersh:                           They make it. Remember, they make it.

Dr. Weitz:                           Yes. I know we have some estrogen, but are there strategies that can allow men to get some of the benefits that women get from this estrogen?

Dr. Gersh:                           Absolutely. Because once you know that men, okay, so it’s changing a bit now because of all the endocrine disruptors. But traditionally, men had much higher rates of non-reproductive cancers. Way back in the day when I was being taught in medical school, men were the ones who had most lung cancer, bladder cancer, pancreatic cancer. Like I said, it’s not the same as it used to be, because of all the endocrine disruptors that are present. But men do have more deaths from immune-related issues. So what they have to do is maintain a high intake of antioxidants and polyphenols to help to deal with that, and take targeted supplements. A new article just came out, shocker alert, that low vitamin D is associated with increased mortality. I mean, how many people got in line because we said in COVID, “Take vitamin D.” It’s like, oh no, you can’t say that.

                                                It’s like, “Oh, get out.” So make sure that if you’re a male, of course females too, that you don’t have deficiency states. And make sure you have plenty of testosterone. Males have dramatically reduced testosterone levels, even young males, because a pro-inflammatory male is not going to make adequate testosterone. It’s a huge problem. I’ve seen young males, I don’t even see very many males in my practice. They’re usually someone’s relative who gets brought in. And I’ve seen young males with testosterone levels in the low 200s, and they’re 24 years old. What do you think their immune system is going to work like? But men, for example, in their brains during the reproductive years, they’re manufacturing from their testosterone six to eight times more estradiol. Remember, all the testosterone turns into estradiol when it’s converted. But women do fine if they have functioning ovaries, because they get plenty of estradiol from their ovaries.

                                                Well, what happens if they don’t have functioning ovaries because they’re being suppressed through contraceptive methods, or through anorexia or whatever? Then their brains are not going to work right. And their brains are the control centers too. So men, you have to do all the lifestyle stuff to keep at a low level of inflammation. So that what you do have, those little tiny quantities of immune cells that you have, they’re going to work optimally, right? Nature doesn’t want you men to die. It just, if you have a pandemic, it picks women to survive more. But nobody should die. Everyone should stay healthy. Take your vitamin D, make sure you get all your antioxidants in, and don’t eat a processed food. I mean, when’s the last time you ate a bunch of processed food? I bet then you don’t eat it.

Dr. Weitz:                           I just don’t do it. Yeah.

Dr. Gersh:                           Me either. To me, it’s-

Dr. Weitz:                           Haven’t for decades. Yeah.

Dr. Gersh:                           I never eat that stuff. Why was any, I look in the grocery store and I say, “Why is anyone buying that poisonous garbage? Real food tastes so much better.”

Dr. Weitz:                           Right. But one reason why is for $5, you can get all this stuff. And I won’t call it food.

Dr. Gersh:                           I get organic dried beans, I make the best bean soup, lentil. This stuff is really inexpensive. Eat your beans, guys. Okay?

Dr. Weitz:                           Can I ask one more question right now?

Dr. Gersh:                           Yes. And in fact, if this is too many slides, we can stop anytime. I don’t want to be here forever.

Dr. Weitz:                           No, it’s okay. We can go on a little longer. But since we’re talking about breast cancer risk, and I mentioned using estriol as one of the strategies, another strategy that is utilized is to follow estrogen metabolites. And then if estrogen is going down the wrong pathway, then we can use perhaps nutrients, [inaudible 01:17:16], calcium, D-Glucarate, et cetera, et cetera. Do you follow estrogen metabolites? And if so, what testing do you like to use?

Dr. Gersh:                           So I don’t now. I used to. And the reason I don’t is that they’re pricey and I use, I can figure it out. I’m always right. Okay. I look at the person, I look at their other inflammatory markers that I can have covered, and I pretty much know who’s doing what. If you have a pro-inflammatory, inflamed, obese woman, I can guarantee you her liver is probably fatty liver. She’s not detoxifying well, she has the wrong, I have a whole bunch of slides here on the estrabolan alone that is so important that to make.  And the estrobolome that is so important to maintain to prevent reproductive diseases of women and cancer. So I just do everything to support, I give all those antioxidants, I use them, I do everything to support liver detoxification capability. I do everything to support restoration of a healthy gut microbiome. Recognizing, for example, the biggest risk factor for postmenopausal breast cancer is obesity. So we know the risk factors, so everyone should just treat them all as if they have bad metabolites. That’s the way I approach it. You can tell at a glance, all of us know you can walk down the street, and we do this in our heads, even if we don’t point at them and say, “You have diabetes,” but you look at someone, they’re going to have inflammation, insulin resistance, just by their body shape.

                                                And now I do body compositions in my office so I want to know, and can’t always judge what someone’s body composition is just by looking at them walking down the street, but you can get a pretty good idea. I bet you when you’re working with your patients and you see what their arms look like, their muscles or legs, you got a pretty good idea of what’s going on, and the skin by the way, is an excellent… I never understood how the Chinese could do it, “Stick out your tongue and then let me look at your hands,” and all that. I mean, they look at signs and things that we just ignore. But if you start actually using your amazing powers of observation, you will be able to judge a book by its cover in many cases.   Look at someone’s skin, and not just their face because maybe they had 20 peels and laser treatments, look at the other skin. When people have a lot of melasma, when people have a lot of aging spots, wrinkles, bruising, you know that the outside is the representative of the inside. So use all your powers of observation, if you feel comfortable, and assume the people who look unhealthy and have other unhealthy markers are probably unhealthy inside as far as their detoxification pathways. And save them the money so that they can save that money to buy the healthy food at the market, and not that garbage processed stuff.

Dr. Weitz:                            Do you use any-

Dr. Gersh:                           Unless all your patients are multimillionaires, then it doesn’t matter.

Dr. Weitz:                            Do you use any particular supplements when you recommend hormone replacement to make sure that they’re efficiently metabolizing their estrogen?

Dr. Gersh:                           Well, we have sort of a plan. We don’t enforce it, we don’t make people do anything, but we recommend that they do what we call the Anti-Inflammatory Gut Reset, that’s what we named it. We don’t actually use the word detox in my office, because in conventional medical circles they all roll their eyes. So we don’t want people rolling their eyes at us, because we don’t say we’re detoxing people, what we’re doing is supporting detoxification pathways and helping reduce inflammation. And if we use the word detox, you’re detoxing off of crap, processed food. It’s like people detoxing off of alcohol or heroin. You got to get rid of all that ridiculous sugar that you’re now addicted to.

                                                People go through sugar withdrawals, right? So it is kind of like a detox, but we go through, we do a lot of education about endocrine disruptors, how to live in a cleaner environment. We talk about time-restricted eating, then later on, we go into fasting possibilities. So basically, I start all my patients out doing everything I can to help them to optimize their detoxification pathways, and then we give the same stuff that I’m sure all of you give, some L-glutamine, we give some coating agents, sometimes I give butyrate and sometimes I give NAC and derivatives from milk thistle and selenium. All the usual stuff that all the nutraceuticals companies sell different packages for gut support and liver support, we use those kinds of things.

                                                And then we try to maintain all the lifestyle. We really incorporate a lot of lifestyle. We do the HeartMath for stress, which is so huge in women. Women have a dysregulated autonomic nervous system, particularly after menopause, but they’re more prone to it anyway. That’s why, who gets POTS Syndrome the most? It’s females. And so we work with that. We work with sleep, I work with body work for pains and aches and so on. That’s why I tried to recruit you here to my office. So I do, we try to cover it all. I hate, I hate, I hate with a passion hormone clinics, where they just, and this is now getting to be like a fad thing, where plastic surgery offices and cosmetic dermatologists are bringing someone in just to dispense hormones. But I don’t believe in that. I believe in looking at the total patient.

                                                Just like you were saying, I mean, we got to look at the total health, we got to look at supporting all the systems. Just giving hormones and leaving everything else on the table unattended to is not acceptable medicine in my book. So you got to look at the total person, you got to work on all these things, include all of this, and not just pass out hormones. That’s not good quality medicine. Hormones to me are like foundational, but building the foundation of the house isn’t the end. You got to do all the other stuff to make the house beautiful and inhabitable, and that’s how I feel about the human body.

Dr. Weitz:                            So, heal the gut, detox before you put hormones in, so you have a healthier body then going into it?

Dr. Gersh:                           All the way. All the way, a hundred percent. And we have a fitness specialist, happens to be my husband, but that’s convenient, so we do fitness assessments, exercise prescriptions, we have some small group classes for exercise, we do body compositions. So to me you’ve got to look at and you’ve got to deal with every lifestyle issue, as much as people will let you. Because, yes, just giving hormones in an absence of dealing with all these other things and looking at detoxification, even though I don’t get the metabolites, we cover it. I just assume, I make assumptions that everyone could do better. So that’s how I address it. But I don’t mind if anyone gets them, I’m just saying, I just assume that they could use all the stuff I’m giving them.

Dr. Weitz:                            And when you do recommend hormones, what’s your favorite combination of products that you like to use?

Dr. Gersh:                           Honestly, I’ll give whatever the patient is willing and can afford, because I actually don’t have all millionaires in my practice and we don’t price it that way. So, if something’s covered by insurance, as long as it’s bio human identical and I can measure levels and I get to physiologic levels, I’m happy. I will use all the gels, the patches that are commercial products, but I use compounded a lot too. The skin, it’s amazing. The skin was not evolved for delivery system for hormones. It’s supposed to be a barrier. It’s supposed to keep things out, and that’s why they developed the patch. It’s a special matrix dot to try to get the hormones through the skin, but sometimes it doesn’t get in.

                                                I’ve had patients where I give every dose of the highest doses of every commercial product and I can’t get levels up at all. So then I have to go to compounded, and then I have them place it around the inner labia minora, around the outer area of the vagina, because that area is very thin, the skin is thinner. It’s easier to penetrate and get it absorbed, because that’s when you say, “Okay, put it behind your knees, put it on your inner arm,” the thinnest areas of skin you can find to try to get it into the body. That’s why measuring levels is so important, unless the whole purpose is just symptom suppression.

Dr. Weitz:                            And you like to use serum levels for [inaudible 01:26:14], right?

Dr. Gersh:                           Yeah. I don’t, yeah, I don’t-

Dr. Weitz:                            But isn’t there an issue with when you use topical estrogen that maybe serum’s not the best way to measure it?

Dr. Gersh:                           No, it’s the best we’ve got, and we have the most data on that, and I’m waiting for the day that there’s some support for saliva. By the way, urinary is pretty good too. It’s just not very practical. But the saliva really has not held up. I know there are people out there who just adore-

Dr. Weitz:                            Why is urine not practical?

Dr. Gersh:                           Well, it’s expensive, it’s not covered by any insurances, so you have to send it out to specialty labs. But I do menstrual mapping with the urine when it’s appropriate. I am really, truly cost-conscious, because you can see all the things we ask our patients to do, right? Fitness and detox, what we call it reset, and buying these different supplements, and I tell them, “Please buy the best organic foods and things.” So I realize I can’t bankrupt every patient that comes through my door.

Dr. Weitz:                            Yeah, I guess as a chiropractor, I don’t ever expect any testing to be covered and we don’t even try to put it through insurance.

Dr. Gersh:                           Oh, well, since I can order tests that are covered by insurance, as much as I can, I try to get things covered by insurance. But if money is no object, then I will do other things, but you know?

Dr. Weitz:                            Yeah, you can get a-

Dr. Gersh:                           [inaudible 01:27:39] in my world.

Dr. Weitz:                            … female DUTCH panel for 150 bucks.

Dr. Gersh:                         Well, the DUTCH panel is fine, but not if you’re on hormones. I don’t actually think it’s as useful for someone who’s on hormones, but if they’re not on hormones, it’s fine. But I can get serum levels in someone who’s not on hormones and it’s usually close to zero or zero, but I’m totally fine with whatever people are willing to get or get. I just believe very strongly in monitoring. I don’t think that you should-

Dr. Weitz:                            Right.

Dr. Gersh:                           Yeah, I really believe that you got to measure and monitor and follow, unless your goal is nothing but suppressing night sweats and hot flashes. In that case, then you don’t have to measure anything. You just give the lowest dose, and when they say they feel better, you stop. But that’s not what I do. I’m going for healthy longevity. I’m not going for just suppression of the symptoms. But that’s what the conventional world is doing, though. We’re exceptions to the rule. We are, by looking at healthy longevity using hormones, because most, still even doesn’t matter what the data shows, the current mantra is use the smallest dose for the shortest time. It hasn’t changed. That’s why I’m out there trying to get it into people’s heads that if you want to have a long healthy life, you need to have hormones. It’s like foundational.  That’s why I say, you want to have metabolic health, you have to have hormones. You want to have immune function, you got to have hormones. You don’t want to be a status chronic inflammageing? Then get those hormones. But it’s necessary but not sufficient. You still need the nutrients. What’s the point, if you are deficient in half the antioxidants in your body and you have no healthy gut microbiome, just throwing hormones into someone? That’s why I don’t like hormone clinics where they just throw hormones at people. I think we’re all on the same page, because everyone who’s here, everyone who listens, we’re exceptions to the rule. We formed our own little club and we’re living in our own little cocoon because we know that this is the right thing to do. But that’s why I keep trying to break into that other gigantic cocoon, which is everybody else out there in the medical world, so that it’s not just us convincing us, but we learn from each other.

Dr. Weitz:                            So, Lindel asked a question about studies to back up what you’re talking about, but every one of your slides is supported by references that you have on the slides.

Dr. Gersh:                           I’m very evidence based, and I show evidence-based research in my office to my patients. I want them to know that you can’t be more evidence based than me. I research everything. I’m like a PubMed, Google Scholar addict. I labeled myself a synthesizer. I’m not a researcher, I’m a clinician, and I have never published a single independent research paper. I wish I had, but that’s not who I decided to become. I was offered to be an MD PhD at NYU and I walked away from it. I just wanted to be a clinician. I didn’t want to be a researcher.  And so I’m a synthesizer. I look at everyone else’s research, everyone else’s published peer-reviewed reports, and I put it together to create a clinical message. Because what I hate is science that’s never applied clinically. That is crazy. You have all these amazing researchers, they figure all this stuff out and then it just languishes and doesn’t get applied in any clinical fashion to actually help people, unless a pharmaceutical company takes it over, and that’s not what we want. So that’s why my job is to research everything and put it together in some kind of cohesive whole and then apply it clinically.

Dr. Weitz:                            Okay. Maybe-

Dr. Gersh:                           So, yes, I can support everything I say.

Dr. Weitz:                            I’m sure you can, and-

Dr. Gersh:                           But sometimes I tell you it’s a rat study, and, “Sorry, there’s no human study.” I tell my patients all the time, “This is my best guess. There’s no data.” I’m always honest. When there’s no data, there’s no data. And I thought, well, what I can do is just make these slides available to people, because at the end I have my usual, which is, “Okay, what are you going to do? Well, you already know about hormones,” but then you incorporate all the lifestyle stuff, which I’m sure you’re all as expert as I am in it. I just emphasize over and over feed your gut and nurture your gut microbiome. And that’s really important for overall health of every organ system. Now the more we learn about these microbiomes, the more we know they’re precious material, precious cargo on board. We don’t want to torture them, kill them, or starve them. That’s not useful.

                                                So basically, I talk about how these hormones protect the brain from neuroinflammation, how the gut transmits signals to maintain, like here, it shows that you have the fermentation of the fibers and then you have the short-chain fatty acids and all of this information, there’s immune cells that line the gut, the gut-associated lymphoid tissue, and it communicates between the different cells, the immune cells that line the gut. And then you have the Peyer’s patches which have the lymphocytes and how all of this interacts to maintain proper function. And hormones have a huge impact on the gut microbiome. The gut microbiome is so important with estrogen that there’s a specific group of microbes called the estrobolome that are essential for the metabolism of estrogen, and this is so important to maintain. And we’ve talked about pregnancy a lot, and so-

Dr. Weitz:                            By the way, are there certain gut bacteria that you can point to that are important for the estrobolome?

Dr. Gersh:                           No, it’s like there’s trillions of bacteria, so we’re just breaking into it. But I tell people eat fermented foods. I’m a big fan of kimchi. My middle daughter married someone who’s half Korean, so we’re big on kimchi. My little granddaughter, her favorite food is kimchi soup. So that’s great. And I grew up with sauerkraut, fortunately I actually like this stuff, but it’s really essential. So I use a variety of probiotics. I think don’t use the same one over and over. We don’t want to push towards one species. We want to have diversity. If there’s one thing we know, it’s diversity of the gut microbiome is what really brings optimal health. And in this slide, I’d really love this slide because it shows when you have gut dysbiosis, you have estrobolome dysfunction. Look at all the things. It’s all interlinked. Increase of endometriosis, PCOS, obesity, metabolic syndrome, cancer and brain health goes down the tubes.

                                                That’s why focus on the gut. Focus on the gut. All of this stuff is interrelated. That’s why all of my women patients have to have gut restoration treatments. And this is like when you don’t have the right gut microbiome, you end up with autoimmune diseases and all these problems, and the circadian rhythm is regulated. When you eat matters as much as what you eat, so you have synchronization and you have metabolic health. And circadian rhythm is modulated by estrogen. Women who work night shifts have high rates of cancer, metabolic dysfunction, increased risk of dementia and mood problems, and I showed this, SCN stands for suprachiasmatic nucleus, the master clock, and here you see in the brain, this is the hypothalamus ER, ER, that stands for estrogen receptor. And see, it shows beta and alpha. That’s why you don’t want just one. You don’t want just any one. You want them all.

                                                See how they work together too, and they have, see these peptides? Everybody loves peptides. Well, you make them naturally when you give the right stuff, and see, VIP comes from the suprachiasmatic nucleus to the area, the neurons in the hypothalamus that then put out the little triggers that go to the pituitary to make the gonadotropins. The kisspeptins are peptides that feed, that recognize nutrient status, which is all regulated by estradiol. Without estradiol, you’re going to have massive problems in appetite regulation and circadian rhythm, and that translates into reproductive problems, but also metabolic problems. It’s all interrelated. So, this is about shift work. The immune system is incredibly circadian. When you have disruption, look what you get, low-grade inflammation, you have compromised adaptive immunity, autoimmunity, allergic responses, decreased tumor surveillance. That’s why it’s so important to get to sleep, to eat at the right times, and to have hormones, because it regulates.

                                                So, this is where I just go over my recommendations. Eat lots of healthy plants, eat at the right times, make sure you get some sleep, work on stress, sometimes do fasting, get exercise. And I have this whole section, which I’m not going to do because I love talking about more stuff, but I think I talked out. But HPV is an estrogen-modulated virus, and this is not well understood. So for example, estrogen is very important for, and metabolites of estrogen, that’s why DIM is often given to women who have HPV, chronic HPV. And this is important because oral contraceptives increase cervical cancer risk dramatically, dramatically. After 10 years of use, I have patients on 30 years of birth control pills, it increases the risk of cervical cancer 400%, four times. And so we’re giving all these women the vaccine for HPV, and at the same time that we’re giving them birth control pills, which dramatically increases the risk of cervical cancer. Why is this not talked about?

                                                The World Health Organization, WHO, this is back from 2002, published in the British Medical Journal, links long-term pill use to cervical cancer. This is not debatable. I put down from, I just copied a bunch of stuff from the article, because this is huge. And women who have babies, five full-term pregnancies and took the pill for more than five years, have increased risk of cervical cancer 12 fold. Come on, guys. Why is people not… And then what do you do nutritionally? Well, a lot of them have high homocysteine, you want to deal with that. So, who know high homocysteine increases cervical neoplasia? So we want to want to do all the things that we do. All the antioxidants, folate is always so important for protecting DNA. The fruits and the vegetables.

                                                So, you have patients who have chronic HPV, this is what I’m telling you to do to help them, that they need to recognize the birth control pill is increasing the risk of cervical cancer. Get off of it and do something else for prevention of unwanted pregnancies, and get all of these polyphenols and antioxidants from plants and such into the body. And soy isoflavones, eating organic whole soy and having green tea is very good for prevention of cervical cancer, and there’s studies to show that. And when you eat the wrong diet, guess what? It changes the vaginal microbiome. They’ve linked vaginal microbiomes to the Western diet. How is that? And then you have patients that come in with vaginitis, think about what they’re eating. Who’s thinking about that, right? Think about that. So, when you have the wrong vaginal microbiome, you increase your risk dramatically of getting cervical cancer. And they’ve shown the different, like you asked me about specific types of bacteria, we actually have that for the vagina. So you can look at this.

                                                So, the takeaway message, hormones matter. Females are better than men when it comes to immune function, but men are super great. We love them, okay? Just don’t get sick, please, because you’re less likely to survive. But if you eat all the right foods and you do everything, you will survive, okay? And maintain that testosterone and don’t have a lot of inflammation that lowers your testosterone. And in fact, inflammation lowers estrogen production. I deal with that with PCOS women. They have inflamed ovaries. Inflamed ovaries will cause earlier menopause. We do not want that. We need our ovaries to last as long as possible.  So, women are powerful with their immune systems. They’re more likely to get autoimmune diseases. When things go wrong, they go wrong bigger in those women who have smaller muscles, but great immune systems and lots of immune cells. So you want to do it all. Get sunlight, get love, exercise, eat, sometimes don’t eat, eat the right foods, keep your pathways going, work on your circadian rhythm, and you will live a happy life and so will your patients.

 


 

Dr. Weitz:                            Thank you, Dr. Gersh. Awesome presentation. Thank you for making it all the way through this episode of the Rational Wellness Podcast. And if you enjoyed this podcast, please go to Apple Podcasts and give us a five star rating and review. That way, more people will be able to find this Rational Wellness Podcast when they’re searching for health podcasts. And I wanted to let everybody know that I do now have a few openings for new nutritional consultations for patients at my Santa Monica Weitz Sports Chiropractic and Nutrition Clinic. So if you’re interested, please call my office, 310-395-3111, and sign up for one of the few remaining slots for a comprehensive nutritional consultation with Dr. Ben Weitz. Thank you, and see you next week.

 

Beth Shirley discusses How to Improve Your Health with Nitric Oxide with Dr. Ben Weitz.

[If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.] 

 

Podcast Highlights

3:15  The nitric oxide pathways have a powerful impact on our health, esp. for cardiovascular health.  Nitric oxide governs circulation and micro circulation and if circulation is impaired, that means that oxygen, glucose, and nutrients aren’t being delivered to cells and tissues.  Therefore, nitric oxide is critical for keeping cells healthy.  One pathway that we make nitric oxide is the nitric oxide synthase pathway, which takes arginine and/or citrulline.  This pathway can be uncoupled by an acidic pH, which we see in diabetics.  We also have the nitrate to nitrite, to nitric oxide pathway.  We consume nitrates, which get absorbed and concentrate in our salivary glands. The salivary glands release the nitrate and anaerobic bacteria on our tongue reduce the nitrate to nitrite.  The nitrite in the stomach gets further reduced to nitric oxide and this nitric oxide is also protection against H. pylori infection.

7:45  When you discuss nitrates, many people are concerned about the nitrates in processed meats and we have all heard about them being carcinogenic.  However, we get most of our nitrates through vegetables, much more than we get from processed meats.  Whatever there is in processed meats that increases cancer risk, it’s not the nitrates.  Also, if you add antioxidants like vitamin C with nitrates, you will less likely get nitrosamines formed.  Also, there are far more nitrates in vegetables than there are in processed meats. For example, a hot dog may have 10 mg of nitrate or nitrite added, but 5 oz of spinach has 325 mg of nitrite.

 

 

 



Beth Shirley is a Registered Pharmacist and also a Certified Clinical Nutritionist.  Beth is the executive Director of the Berkeley Life Scientific Advisory Board and Berkeley Life has developed products that support nitric oxide production.  The website for Berkeley Life is BerkeleyLife.com.

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.

 



 

Podcast Transcript

Dr. Weitz:            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts, and researchers in the field, to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates, and to learn more, check out my website, drweitz.com. Thanks for joining me, and let’s jump into the podcast.

                                Hello, Rational Wellness Podcasters. Today we’re going to be speaking about how to improve your health by promoting nitric oxide production with Beth Shirley. Nitric oxide is a very important gaseous signaling molecule in the body, made up of a combination of a nitrogen, and an oxygen molecule, and nitric oxide has an incredible number of beneficial functions, especially for the cardiovascular system.  Nitric oxide promotes the dilation of blood vessels, thus improving blood flow, reversing erectile dysfunction. It helps to lower blood pressure, it reduces coronary artery disease, and it also helps to regulate cardiac muscle contractility. Nitric oxide also supports brain health, gut health, immune function, and it may help with exercise performance. Nitric oxide was awarded molecule of the year in 1992, and three scientists who discovered nitric oxide’s role in the body were awarded the Nobel Prize in Medicine in 1998. Nitric oxide will be starring in a new series debuting on Netflix in 2023.

Beth:                     Oh really?

Dr. Weitz:            Beth Shirley is a registered pharmacist, and also a certified clinical nutritionist. Beth is the executive director of the Berkeley Life Scientific Advisory Board, and Berkeley Life has developed some products that support nitric oxide production. Thank you so much for joining us today.

Beth:                     Thanks for having me.

Dr. Weitz:            So, how did you become interested in nitric oxide?

Beth:                   Well, back in 2009, I was working with the Neo40 people.

Dr. Weitz:            Okay.

Beth:                   Helping to formulate the Neo40 lozenge. So, I’ve been around the nitric oxide world for quite a while.

Dr. Weitz:            Okay.

Beth:                   But I was a pharmacist for 20 years, and I became a pharmacist because I thought I was going to be able to help people. But I saw them coming back sicker, and sicker, on more and more drugs. So, in 1997, I became a certified clinical nutritionist. So, I became the pharmacist to go to if you wanted to get off of drugs, or not go down that road. And since 1997, I’ve been helping people get healthy without drugs. So, the natural progression to the nitric oxide story just fit right in.

Dr. Weitz:            Okay. So, can you explain a little bit about the nitric oxide pathway, and why it has such a powerful impact on our health, especially our cardiovascular health?

Beth:                    Nitric oxide is a miracle molecule, truly. It governs circulation and micro circulation. When you have impaired micro circulation, that means that oxygen, glucose, and nutrients aren’t being able to be delivered to cells, and tissues. And just as importantly, debris can’t be carried away, and cells can’t be more than two cells away from a micro capillary, or they die.  So, nitric oxide is critical for keeping cells healthy, and we make nitric oxide through two different pathways. One is the NOS pathway, the nitric oxide synthase pathway, and this takes arginine, and oxidizes it into citrulline and nitric oxide. However, this pathway is real sensitive to environmental factors, and just everyday factors that we come into contact all the time. It’s pH dependent, like acidity uncouples at NOS enzyme, and in most chronic conditions like diabetes, you’re more acidic.  It’s pH dependent. So, hypoxia uncouples that NOS enzyme.  And then we’ve got the nitrate to nitrite, to nitric oxide pathway. And this pathway, we consume the nitrates, they get absorbed, they circulate around, they get concentrated in our salivary glands. The salivary glands release the nitrate. We’ve got good anaerobic bacteria on our tongue that will reduce that nitrate to nitrite. And when you use the strips to test your nitric oxide, you’re actually testing the nitrite concentration on your tongue.  We swallow the nitrite, and in the acidic environment of the stomach, some of that nitrite gets reduced further to nitric oxide. Here’s your protection against h. pylori, e. coli. But most of the nitrite gets absorbed, and acts like a nitric oxide donor molecule. And in different tissues, they can reduce that nitrite to nitric oxide on an as needed basis, like in the muscle, when you’re exercising, you need more food being delivered to your muscles, and debris to be carried away, so myoglobin can reduce nitrate to nitric oxide. The electron transport chain can reduce nitrate to nitric oxide as needed. When the electron transport chain is uncoupled, it starts cranking out super oxide, and not the water. So the nitrite can help recouple that, to decrease the oxidative stress, and decreases superoxide production.

Dr. Weitz:            So, nitric oxide’s a gas.

Beth:                   Right.

Dr. Weitz:            It’s hard for me to understand how a gas could play such a powerful role in the body?  As a gas, I’m assuming it can’t be around for all that long. Right?

Beth:                    Less than a second.

Dr. Weitz:            Okay.

Beth:                    However, a lot of the metabolites from nitric oxide, and actually even peroxynitrite, can make what’s called nitrosothiols. So, like a nitroso glutathione. So, which is storage form of both nitric oxide, and glutathione. So, it makes these other molecules that can hang around longer, and have beneficial actions even themselves.

Dr. Weitz:            I was also reading that hydrogen sulfide gas works synergistically with nitric oxide.

Beth:                   Nitric oxide.

Dr. Weitz:            Which is interesting because that’s when the gas is involved in causing SIBO.

Beth:                   An overproduction of the hydrogen sulfite. Yeah.

Dr. Weitz:            Right.

Beth:                    Yeah. But, nitrate is such a wonderful molecule for supporting healthy microbiomes everywhere. So, even by optimizing your nitrate intake, you’re going to support your good, healthy microbiome.

Dr. Weitz:            Now, whenever you talk about nitrates, so many of us have heard about processed meats that contain nitrates, and how these nitrates are carcinogenic, and every time we try to figure out exactly what sorts of foods are more likely to cause cancer, processed meats are high on that list. And it’s apparently because the nitrates convert into nitrosamines.

Beth:                    However, we get most of our nitrates through vegetables, way more than we ever do with any processed meat.

Dr. Weitz:            Okay.

Beth:                    Vegetables are not connected with unhealthy lifestyles. So, nitrosamines will only form if there’s a lot of superoxide, or oxidative stress. So, in these foods, which that whole premise has been debunked, so this was something that they found in the test tube, not in real life.

Dr. Weitz:            Okay.

Beth:                   And in those foods, you will see a vitamin C, or a vitamin E analog, like erythropoietin, that actually, when you add an antioxidant, the nitrosamines means will not be formed.

Dr. Weitz:            But, even in epidemiological data, when you’re trying to suss out what sorts of dietary factors might increase cancer, they almost always include processed meats.

Beth:                   Right. But there’s probably other things in processed meets that are not so healthy for us. But it’s not the nitrate, or the nitrites. So, like in a hot dog, if they add nitrate, or nitrite to the hot dog, they’re only adding 10 milligrams. And in five ounces of spinach, there’s like 325 milligrams of nitrite.

Dr. Weitz:            So it’s not the fact that it’s a synthetic nitrate versus a actual nitrate.

Beth:                    No.

Dr. Weitz:            Okay.

Beth:                    No.

Dr. Weitz:            Okay.

Beth:                    No. No. But when you buy things that say, “No nitrates, nitrates added,” they actually use celery seed salt, which has way more nitrates, and nitrites than if they would’ve just added the nitrate, or nitrite.

Dr. Weitz:            Right. Another interesting fact is that nitric oxide is a free radical.

Beth:                    Yes. But that’s a-

Dr. Weitz:            So, normally adding to our oxidative stress can potentially be problematic. Right?

Beth:                    There’s a different perspective. So, only a free radical can scavenge another free radical.

Dr. Weitz:            Okay.

Beth:                    So, nitric oxide can scavenge all these free radicals, like the free radicals from the Fenton reaction, your hydroxyl radical, your FE3+ free radical. Nitric oxide scavenges the super oxide free radical. So, only a free radical can scavenge another one.

Dr. Weitz:            Right. So, let’s talk about some of the various ways that our body produces nitric oxide. And I read that nose breathing is one thing that stimulates nitric oxide production.

Beth:                    Well, it sure can, as long as you’ve got coupled NOS, or good nitrate nitrite stores. So, do you want me to explain what a coupled NOS means?

Dr. Weitz:            Sure. Yeah.

Beth:                    Okay. When the NOS enzyme is a dimer-

Dr. Weitz:            So that’s nitric oxide synthase, right?

Beth:                    Right. It’s a dimer, and it’s connected. It’s held together, this dimer is held together by BH4. And so this electron is handed down from NADPH, through your flavin molecules, to the heme part of the NOS enzyme, and then then down to arginine, to nitric oxide. But when nitric oxide is uncoupled, it is not a dimer. It’s only one strand, and that electron is handed down from NADPH through your flavins, but it’s handed down then to oxygen, and makes super oxide. So, an uncoupled NOS enzyme is a super oxide generator, not a nitric oxide generator. So, that’s like giving arginine to someone with an uncoupled NOS can actually increase oxidative stress.

Dr. Weitz:            So, what factors lead to uncoupling of NOS?

Beth:                    Age. By the time we’re 40, that NOS is only functioning about 50%. By the time we’re 65, it’s only functioning about 15%.

Dr. Weitz:            Now, is that just a function of chronological age, or is that more related to biological aging?

Beth:                    Biological.

Dr. Weitz:            Okay.

Beth:                    Okay? The standard American diet, devoid of nitrate rich veggies, and essential co-factors, and nutrients. Medications like antibiotics, antifungals, especially the azole antifungals, antidepressants, birth control pills, NSAIDs, PPIs. PPIs inhibit the production of nitric oxide through both pathways. EMFs. EMFs are everywhere. EMFs increase an enzyme called NADPH oxidase, which increases super oxide, increases oxidative stress, oxidative stress uncouples at NOS.

Dr. Weitz:            When I see all these electric cars, I-

Beth:                    Oh, it’s terrible.

Dr. Weitz:            I know, I want to get an electric car, but I don’t want to be in an EMF-

Beth:                    No, no. Yields.

Dr. Weitz:            Accelerating-

Beth:                    Fry your brain. You’re frying your brain. You’re destroying your blood brain barrier.

Dr. Weitz:            Boy, that’s something.

Beth:                    You’re increasing diabetes.

Dr. Weitz:            That’s something we got to figure out, how you can have an electric car and not get exposed to all these EMFs, on top of all the EMFs we’re getting exposed to from 5G, and everything else.

Beth:                    Yeah, yep. And stress. Stress uncouples that NOS enzyme. Glyphosate, genetic snips. So, that’s why by the time we’re 40, it’s only functioning about 50%, because all the people that are sitting in front of us, they’ve got a lot of oxidative stress going on. They’ve got something going on that’s making them not so well.

Dr. Weitz:            One more in the long list of reasons why we should avoid eating gluten, is glyphosate leading to decreased nitric oxide production.

Beth:                     Precisely. Precisely.

Dr. Weitz:            So, let’s talk about the foods that are the richest sources of nitrates in our diet.

Beth:                     Arugula has got the highest nitrate concentration, and no oxalate concerns. But spinach, butter lettuce, celery, bok choy, beets, kale, all of these are high nitrate veggies.

 

Dr. Weitz:            I’ve really been enjoying this discussion, but I’d like to take a minute to tell you about a new product that I’m very excited about. I’d like to tell you about a new wearable called the Apollo. This is a device that can be worn on the wrist, or the ankle, and it uses vibrations to stimulate your parasympathetic nervous system. This device has amazing benefits in terms of getting you out of that stressed out sympathetic nervous system, and stimulating the parasympathetic nervous system.

                                It’s has a number of different functions, especially helping you to relax, to focus, to concentrate, to get into a deeper meditative state, even to help you sleep. And there’s even a mode to help you wake up. This all occurs through the scientific use of subtle vibrations. For those of you who might be interested in getting the Apollo for yourself, to help you reset your nervous system, go to apolloneuro.com, and use the affiliate code Weitz10. That’s my last name. W-E-I-T-Z 10. And now back to the discussion.

 

Dr. Weitz:  Now, what about eating foods that are high in arginine, or citrulline, like grass fed beef, or line caught wild fish, cage-free eggs? And then I guess watermelon is really high in citrulline.

Beth:                    Citrulline, yeah, that’s my favorite fruit. Well, if you’re under a lot of oxidative stress, increasing your arginine intake is not really the smartest idea.

Dr. Weitz:            Okay. And why is that?

Beth:                    Because arginine has other pathways it can go down besides just your NOS pathway. So arginine can increase this molecule called ADMA, asymmetric dimethyl arginine, which, it was connected to all cause mortality. Arginine can increase ammonia, and if you’re having trouble clearing ammonia, then you’ve got kidney problems. Can increase urea, and if you’re having kidney issues, this is not good there, either. So, just think about it. If you’ve got like a latent herpes virus, and you eat high arginine foods, like some nuts, or something, you can reactivate that, and that’s due to that oxidative stress you’re increasing.

Dr. Weitz:            But arginine is an essential amino acid, too.

Beth:                    Sure it is, but the amount of arginine it takes to feed that NOS enzyme is very, very small. In fact, there’s rarely anybody with an arginine deficiency. Rarely.

Dr. Weitz:            But, we must all be feeding our NOS enzymes, because if you’re eating a balanced diet that has the essential amino acids, we’re all getting arginine.

Beth:                    Right. But you don’t necessarily want to take arginine supplements, is what I’m talking about.

Dr. Weitz:            Right. Right. So when it comes to the discussion of supplements to simulate nitric oxide production, the two major strategies that you see on the market, and a lot of products have both strategies in it, one is to include arginine, and or citrulline. What if you just have citrulline rather than arginine? Does that avoid the arginine issues?

Beth:                    Well, citrulline is better than arginine, because actually the cell uses citrulline to make its own arginine to feed the NOS. However, you’re still trying to make an uncoupled dysfunctional NOS work, and it’s just not going to.

Dr. Weitz:            Okay.

Beth:                     Nitrate supplementation actually helps recouple that NOS.

Dr. Weitz:            Right. So, the product that you recommend the most is a product that contains beetroot. Right? Extract.

Beth:                     Well, it’s mainly a nitrate supplement.

Dr. Weitz:            Okay. I saw the potassium nitrate.

Beth:                     Yes.

Dr. Weitz:            That’s a first ingredient. So, tell us about why that’s good to consume.

Beth:                     Because that’s supporting your nitrate, to nitrite, to nitric oxide pathway.

Dr. Weitz:            And why is that better than taking beets, or beet juice, or a beet extract?

Beth:                     Well, part of the reason is you just never know exactly how much nitrate you’re getting in these beet products.

Dr. Weitz:            Oh, okay.

Beth:                     Okay? Because beets grown in different environments will have different concentrations. This is a standardized dose of nitrate, where all the studies show that it takes three to 400 milligrams of nitrate to make these physiological changes, and that’s what you’re getting with two caps of the Berkeley. So, that’s kind of equal to five ounces of spinach, or seven ounces of beets. So, you can get it through your diet, you can get enough through your diet. And in fact, the DASH diet, the dietary approaches to stop hypertension, it is used as medicine, and that has 12 to 1500 milligrams of nitrate per day.

Dr. Weitz:            Right.

Beth:                     [inaudible].

Dr. Weitz:            Most mornings I have a big omelet, and I put beet kimchi on the side.

Beth:                     Oh, good.

Dr. Weitz:            So, I get my beets, and I get some probiotics, on top of the other probiotics I take. So, let’s talk about a few more benefits of nitric oxide that people aren’t familiar with. I know most of us are familiar with the cardiovascular, but in fact, I mean the cardiovascular benefits are really pretty amazing, in terms of blood pressure, and this is largely through the vasal dilation effects. Is that right?

Beth:                     Right.

Dr. Weitz:            Now, is there more of an effect on the micro circulation, I thought I read?

Beth:                     Yes. Oh, excuse me.

Dr. Weitz:            Yeah.

Beth:                    Yeah. Because that’s where all the action happens.

Dr. Weitz:            Okay.

Beth:                    So, the micro circulation, that’s where all the action happens.

Dr. Weitz:            Yeah, and one of the things… I also organize a functional medicine meeting, and I also have a mastermind group, and one of the women who was in our mastermind group, she was in her mid to later fifties, and she just died of a heart attack with no history of heart disease. And interestingly, I’ve done some reading about this, and women have a tendency to have a type of cardiovascular disease where they get blockages in micro circulation, rather than in the major vessels.  Now of course, they do get blockages in the major vessels too, but there is this variant of heart disease that tends to become more common in women, and I think it’s really been understudied, and sounds like nitric oxide would be particularly beneficial in those types of cases.

Beth:                    Right. And especially once a woman hits menopause, because estrogen actually stimulates that NOS enzyme, the E NOS enzyme to make nitric oxide. So once our estrogen production goes way down, we’re not making nitric oxide like we need to be. So that happens quite frequently, after menopause.

Dr. Weitz:            Interesting. And there’s also some pretty amazing benefits for brain function with nitric oxide. Maybe you can talk a little bit about that mechanism.

Beth:                    Right. Brains are only about 2% of our body weight, but they use about 25% of our oxygen consumption. And brains need to be making about 20 times more nitric oxide than our whole vasculature, because that micro circulation is so critical to feed those cells in our brains. So, dementia is connected to poor blood flow.

Dr. Weitz:            Right.

Beth:                    And then nitric oxide is essential to make our neural stem cells. Nitric oxide is important for synaptic plasticity. That means to regenerate.

Dr. Weitz:            Right. That’s pretty interesting.

Beth:                    Right.

Dr. Weitz:            So, has there been any data testing nitric oxide in prevention of Alzheimer’s?

Beth:                    Well, there’s actually this one study that… Well, it wasn’t a study, it was a review of something like over six million people that had used the PDE5 inhibitors, like your Viagra, your Cialis, and the amount of dementia went down astronomically.

Dr. Weitz:            Interesting.

Beth:                    With the use of those.

Dr. Weitz:            Maybe you can talk about how those PDE5 inhibitors work, and what that tells us about nitric oxide.

Beth:                     So the PDE5 inhibitors, your Viagra, your Cialis, these allow that nitric oxide to hang around longer. However, you need enough nitric oxide in order for those to work. So, that’s why when men use them for ED, they only work in about 50% of the men, because they don’t have enough nitric oxide in order to get the erection. However, it’s the same with opening up the blood vessels in the brain, too. You need enough nitric oxide in order for them to work. So, why not just support the core? Get to the nitric oxide to begin with.

Dr. Weitz:            Right. Yeah. It’s interesting, in a similar way, a lot of people with depression, and anxiety are taking drugs that keep serotonin around, but if you’re not producing enough serotonin, they won’t work. So, sometimes you need to support that serotonin production pathway for those drugs to work.

Beth:                    However, these SSRIs uncouple that NOS.

Dr. Weitz:            Ah, interesting.

Beth:                    Okay? So now, maybe you’re got more serotonin in the synapse. However, you’re not helping your brain any, because you’re not keeping that circulation open in the brain.

Dr. Weitz:            Right.

Beth:                   Not good.

Dr. Weitz:            Now, exercise increases nitric oxide production, right?

Beth:                     Yes. Through NOS, or if you’ve got enough nitrate, nitrate stores. So by optimizing your nitric oxide prior to exercise, you will increase your exercise endurance, and decrease your recovery time.

Dr. Weitz:            Is there a particular type of exercise, or exercise strategy that will help you maximize nitric oxide production? Like in resistance training, versus aerobic, cardiovascular training, or steady state cardiovascular training, versus higher intensity training, et cetera?

Beth:                     I just want people just to do it, and I don’t really care what it is. Just do something.

Dr. Weitz:            Sure. Sure. For the average sedentary person. I’m also speaking to the biohackers, those of us who are trying to maximize our longevity.

Beth:                     Well, anything that… All exercise tries to optimize your circulation.

Dr. Weitz:            And build muscle, and stabilize your joints, and improve your balance, and burn glucose.

Beth:                     Yeah, but that’s all connected.

Dr. Weitz:            Right.

Beth:                     That micro circulation, to be able to be delivering your oxygen, glucose, and nutrients. But remember I said the myoglobin too, can reduce that nitrite to nitric oxide on an as-need basis. So, this exercise actually helps you optimize your nitric oxide even more.

Dr. Weitz:            Because… Maybe you should explain. So exercise increases myoglobin.

Beth:                     And myoglobin increases can reduce nitrite to nitric oxide, too.

Dr. Weitz:            Okay.

Beth:                     But nitric oxide also increases mitochondrial biogenesis.

Dr. Weitz:            Oh, okay.

Beth:                     [inaudible] Energy producing organelles of your cell.

Dr. Weitz:            Okay.

Beth:                     So, exercise plays a role in mitochondrial biogenesis, through that production of nitric oxide.

 

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Dr. Weitz:             Micro circulation, and impairment of micro circulation is one of the factors that seems to be related to long COVID symptoms.

Beth:                    Yeah, I’ve done webinars, and talks on this. So, that spike protein, whether it’s from the virus, or it’s from the jabs, is actually… What it does, it attacks the hemoglobin, and oxidizes the heme from your FE2+ to your FE3+.

Dr. Weitz:            Okay.

Beth:                     So it becomes-

Dr. Weitz:            What’s the FE2+?

Beth:                     2+ is your ferrous iron, and the ferrous iron can hold the oxygen.

Dr. Weitz:            Okay.

Beth:                     But your ferric iron, your FE3+ cannot do anything with the oxygen. So, that’s where the hypoxia comes in.

Dr. Weitz:            Okay.

Beth:                     However, nitric oxide is trying to help us, and it can scavenge that FE3+. And then it takes nitric oxide out of circulation from doing all these other good things, and then you’ve got these little clots, because nitric oxide is connected to platelet activation, and aggregation. So, when you’re nitric oxide deficient, you clot more. So, the spike protein is making… To get the virus to begin with, more than likely you’re nitric oxide deficient to begin with. Then once you have the virus, this makes you more nitric oxide deficient, and then all these clots, and impaired micro circulation.

Dr. Weitz:            So has there been any data on using nitric oxide strategies for helping patients clear long COVID?

Beth:                     I’ve helped a lot of people with that. But right now, Dr. Nathan Bryan has a phase three clinical trial.

Dr. Weitz:            Oh, interesting.

Beth:                     Using it for COVID, in the Black population, because it is known that the African American population actually has more of a nitric oxide issue to begin with.

Dr. Weitz:            Oh really? Why is that?

Beth:                    I don’t know exactly.

Dr. Weitz:            Okay.

Beth:                    I don’t know exactly.

Dr. Weitz:            Okay. Maybe it has to do with certain dietary factors, or?

Beth:                    And probably NOS SNPs, also.

Dr. Weitz:            Okay. Do we know a couple of common NOS SNPs that impede nitric oxide?

Beth:                    Right. Any of the NOS SNPs will.

Dr. Weitz:            Okay.

Beth:                    But also any of the SNPs that increase oxidative stress. Like if you have any SOD SNPs, or catalase SNPs.

Dr. Weitz:            Okay.

Beth:                    Or HFE SNPs, which are real common in Northern European, like the Irish.

Dr. Weitz:            Okay.

Beth:                    Anything that interferes with the production of BH4. So, BH4, which is what helps keep the NOSS coupled, like your QDPR, DHFR, if you have any MTHFR SNPs, you are by definition nitric oxide deficient. And that’s about 40% of us, right there.

Dr. Weitz:            Right.

Beth:                    Because you can’t make your BH4 correctly, or enough of it.

Dr. Weitz:            Yeah. I think it might even be a higher percentage. So, we’ve been talking about all these wonderful benefits of nitric oxide. Can you have too much nitric oxide?

Beth:                    Rare.

Dr. Weitz:            Okay.

Beth:                    Very, very rare. So, especially with the nitrate, to nitrite, to nitric oxide pathway, because our body kind of can modulate how much that we’re using.

Dr. Weitz:            Okay.

Beth:                    Remember I said by the time we’re 40, that NOS SNP is only functioning about 50%, and by the time we’re 60, it’s only about 15%.

Dr. Weitz:            Right.

Beth:                     So, it’s rare to get an overproduction of nitric oxide.

Dr. Weitz:            Okay.

Beth:                     Sometimes, when people have chronic infections, or chronic inflammatory events, you can up-regulate that iNOS, the inducible NOS. However, the beautiful thing about nitrate supplementation is nitrates actually help down-regulate that iNOS.

Dr. Weitz:            Okay.

Beth:                     Because when that iNOS is upregulated, your eNOS, your endothelial NOS, and your nNOS, your neuronal NOS, are down regulated. But if you can downregulate the iNOS, then it allows more nitric oxide to get to your blood vessels.

Dr. Weitz:            Okay. Cool. Well, I think those are the questions that I had prepared. Anything else you want to tell us about nitric oxide?

Beth:                     Right. The red blood cell, the hemoglobin actually has to have nitric oxide attached to that molecule, in order to deliver oxygen to the cells. So, you could be super saturated with oxygen, and if you don’t have enough nitric oxide, then you’re not delivering oxygen to the cells. So, for many years they thought the oxygen delivery was a two gas process, your carbon dioxide, and your oxygen. But now they know it’s a three gas process, nitric oxide, carbon dioxide, and oxygen. You’ve got to have that nitric oxide.

Dr. Weitz:            So, even though the oxygen is there, and the carbon dioxide is there, it might not be able to be utilized without the-

Beth:                     Right. Nitric oxide being attached to that hemoglobin molecule.

Dr. Weitz:            Interesting.

Beth:                     Yeah. Stem cells. Stem cells are how we heal.

Dr. Weitz:            Right.

Beth:                     They require nitric oxide in order to go where they need to go, and do what they need to do. So, if anybody is getting any kind of stem cell procedure, optimize your nitric oxide first, you’ll get much better use out of the procedure.

Dr. Weitz:            Would it be the same thing for… What’s that other injection where everybody’s getting with the…

Beth:                     PRP?

Dr. Weitz:            Yeah. PRP, platelet [inaudible] plasma.

Beth:                    Yeah. All healing comes from stem cells. All healing. And that nitric oxide plays an integral part of that.

Dr. Weitz:            Okay. Cool. Okay. Well, thank you Beth.

Beth:                    You’re welcome.

Dr. Weitz:            Are you still doing consultations with clients?

Beth:                    No, I’m doing more research now.

Dr. Weitz:            More research. Okay.

Beth:                    Yeah. I have some people that I’ve had for many years, but not taking any new ones now.

Dr. Weitz:            Right. So, for laypersons out there, should they contact a practitioner to find out about these nitric… This supplement to stimulate nitric oxide? Or can they buy it directly?

Beth:                    No, they’ve got to go through a practitioner to get it.

Dr. Weitz:            Okay, great.

Beth:                    And we’ll get you a code.

Dr. Weitz:            Okay.

Beth:                    So that people can actually order it through you, too.

Dr. Weitz:            Oh, okay.

Beth:                    Okay? Yeah, you can’t get it on Amazon.

Dr. Weitz:            Okay. Okay. And what about practitioners? How can they get in contact with you?

Beth:                    Go to info@berkeleylife.com, and the berkeleylife.com website, you can actually schedule a consult with one of the sales reps.

Dr. Weitz:            Okay.

Beth:                    I do the education.

Dr. Weitz:            Right.

Beth:                    Yeah.

Dr. Weitz:            Okay. Awesome. Thank you, Beth.

Beth:                    Thank you Ben.

Dr. Weitz:            And the website, in case people want some more information, as well?

Beth:                    Berkeleylife.com.

Dr. Weitz:            Great.

Beth:                    And then there’s a good Facebook group, a forum that I post a lot of things on, like the Berkeley Life Professional Forum.

Dr. Weitz:            Okay.

Beth:                     So you can request entry into that group, and I take recent studies, and make the nitric oxide connection.


Dr. Weitz:            Right. Awesome. Thank you for making it all the way through this episode of the Rational Wellness Podcast. And if you enjoyed this podcast, please go to Apple Podcasts, and give us a five star ratings and review. That way more people will be able to find this Rational Wellness Podcast when they’re searching for health podcasts. And I wanted to let everybody know that I do now have a few openings for new nutritional consultations for patients at my Santa Monica Weitz Sports Chiropractic and Nutrition Clinic. So if you’re interested, please call my office, (310) 395-3111, and sign up for one of the two remaining slots for a comprehensive nutritional consultation with Dr. Ben Weitz. Thank you, and see you next week.