Weitz Sports Chiropractic and Nutrition
Weitz Sports Chiropractic and Nutrition
Methylation with Dr. Jess Armine: Rational Wellness Podcast 129
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Dr. Jess Armine discusses The Truth About Methylation with Dr. Ben Weitz.

[If you enjoy this podcast, please give us a rating and review on Itunes, so more people will find The Rational Wellness Podcast. Also check out the video version on YouTube at https://www.youtube.com/user/weitzchiro/]

 

Podcast Highlights

4:31  What the hell is methylation and why should we care about it?  Methylation, which refers to placing a methyl group on a protein, is an important process in all points of DNA replication and in the actual turning on and turning off different genetic pathways.  Methylation affects whether certain genes get expressed or not. This is the way our physiology gets regulated.

7:00  Dr. Armine says that sometimes he will get a call from a patient who is fearful because they found out that they have MTHFR, which is one of the genes that regulates the methylation pathway. The first two variants that were studied were the C677T and the 1298C, but there are actually 50 different variants.  If you have one copy of one of these variants, you are said to be heterozygous and if you have two copies of one of these variants, you are said to be homozygous.  If you are heterozygous for one of these variants–if the genetic report shows yellow–it means that the enzyme that that gene creates is working at about 60% of the way that it should. If you are homozygous for one of these variants–if the genetic report shows red–it is working at about 20% of the way it should be doing.

 

10:59  When you look at the folate pathway, which starts with FOLR1 and FOLR2 and then goes to DHFR, which goes to MTHFD1, until you get MTHFS, until you get to MTHFR.  That pathway requires those genes and their enzymes to function, which requires NAD, vitamin B3. For MTHFR to work it needs at least B2 and B3 and if you don’t have enough B2 and B3 and you already have a 40% reduction due to a heterozygous SNP, then that is really significant. Other factors that can slow down the folate pathway are dairy antibodies, methotrexate, synthetic folic acid, large amounts of green tea, and grapefruit seed extract, among others. Synthetic folic acid is a problem because if there is a SNP, then it may not get conjugated and create the end product, 5,10-Methylenetetrahydrofolate. Therefore, synthetic folic acid if it is not properly metabolized can lead to an increase in homocysteine and a hypercoagulable state that increases the risk of blood clots, accelerated atherosclerosis, and miscarriage.  Also consider that in contrast to the natural folate found in green, leafy vegetables like kale, spinach, arugula, and swiss chard, synthetic folic acid is added to many flours, breads, and to other processed foods, as well as in many multivitamins, including prenatals.  Unmetabolized synthetic folic acid can also lead to an immune dysfunction through the dysregulation of natural killer cells, and potentially increasing the risk colorectal and other forms of cancer. [Here is one article on this topic: The hazards of excessive folic acid intake in MTHFR gene mutation carriers: An obstetric and gynecological perspective.]  Dr. Armine explained that when managing a patient who may have genetic variants of the MTHFR gene, it is important to start with foundational lifestyle factors like drinking better water, breathing better air, managing stress, earthing, etc.

20:52  Dr. Armine may run a methylation panel, such as the panels from Doctor’s Data (Methylation Profile) and Genova (Methylation Panel), that measures some of the methyl donors like methionine, S-adnosylmethionine, and choline and plasma metabolites like homocysteine.  He mentioned that it is now preferable to get the raw genetic data from Ancestry.com, since the 23 and Me panel now measures far fewer genes than they used to. 

24:05  When you see Dr. Armine, he will take your raw genetic data and put it through a software analysis, such as Dr. Ben Lynch’s StrateGene and MTHFRsupport.com to be able to pull out the data that allows him to make specific recommendations for diet and supplements to improve your health.  Dr. Armine also said that he likes to run an organic acids profile, which shows the results of the pathways.  You can see indicators of mold, of candida, of SIBO, of clostridia.  You can see the oxylate status, since high oxylates is a major reason for illness. High oxylates is secondary to candida.  In the organic acids profile you can see the function of the Kreb’s cycle and you can see the neurotransmitter metabolites.

29:42  Dr. Armine talked about the importance of cell wall integrity and if you have inflammation, you have leaky cells, which is a lack of cell wall integrity or function. Dr. Armine wrote a book with Elizma Lambert, an Australian Naturopath, called Leaky Gut, Leaky Cells, Leaky Brain. Often we don’t look at the function of the cell wall and one way to assess that is with the Omega Quant test for omega 3 status.

31:32  The idea of methylation essentially is to create SAM-e. Some practitioners concentrate solely on giving methylated vitamins: methylfolate, methyl B12, dimethylglycine, trimethylglycine, or SAM-e.  But there are some patients that respond negatively with methylated B vitamins, esp. those with anxiety.  If patients do react poorly to methylated B vitamins, there are now multivitamins and B-complex products that use folinic acid or natural folate instead of 5-methylfolate and they have hydroxocobalamin and/or adenosylcobalamin, instead of methylcobalamin or the synthetic cyanocobalamin, which is very poorly absorbed, and patients usually don’t have a negative reaction to these.

39:35  If you have a patient with elevated homocysteine and you place them on a formula of methyl B vitamins to reduce their risk of heart disease and if they don’t feel well, then you have to look at the methylation pathways and see where the blockage is.  This is when running a methylation panel and doing organic acids testing can be especially helpful.  The transsulfuration pathway could be blocked up by CBS going backwards.  Homocysteine goes down the transsulfuration pathway past something called cystathione B synthase to become cystathione, and then cysteine to eventually become glutathione, and then glutathione, when it gets used up and gets oxidized, gets recycled. So that whole big, long pathway can get blocked up, if you will, and if you think about it like a highway, it’s going to block up, and where it’s going to block may be one of the reasons for higher homocysteine.  We have to look for reasons why you have inflammation in your body, which from a Functional Medicine perspective could be mold, heavy metals, other toxins, food sensitivities, nutritional deficiencies, leaky gut and other gut problems.

43:31  Overmethylation is not a good thing and could even increase risk of breast cancer.  If you are taking methylated B vitamins or a multi with methyl B vitamins and you feel anxious or other symptoms of being overmethylated, the first thing you should do is stop taking the supplement and switch to a multi with hydroxycobalmin and Naturefolate.  A first aid solution is to take plain niacin, the flushing kind, about 25 mg per hour and it will chew up the methyl groups.  Keep in mind that if you are taking a large dosage of niacin, it can result in undermethylation and elevated homocysteine.  But ultimately you need to discover and treat the underlying causes of inflammation using the Functional Medicine model.

 

 



Dr. Jess Armine is a Doctor of Chiropractic and a Registered Nurse and has been in healthcare for over 37 years. His focus is using a Functional Medicine approach to treating various neurological and immunological conditions in patients with a focus on taking a careful history, lab work, and also looking at genetics. You can contact Dr. Armine at his website DrJessArmine.com  Dr. Armine offers new clients a free 15 minute consultation to see if he can help them and he does consultations via phone or Skype.

Dr. Ben Weitz is available for 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, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111 or go to www.drweitz.com.



 

Podcast Transcript

Dr. Weitz:            This is Dr. Ben Weitz with The Rational Wellness Podcast, bringing you the cutting edge information on health and nutrition from the latest scientific research and by interviewing the top experts in the field.  Please subscribe to The Rational Wellness Podcast on iTunes and YouTube, and sign up for my free e-book on my website by going to DrWeitz.com. Let’s get started on your road to better health.  Hello, Ration Wellness Podcasters. Thank you so much for joining me again, today. Please go to Apple Podcasts and give us a ratings and write a review. That would really help us. More people will find us when they do a search for alternative health podcasts. Also, if you’d like to see the video version, go to my YouTube page. If you go to my DrWeitz.com website, you can find detailed shownotes and a complete transcript.

                                Our topic for today is the truth about methylation with Dr. Jess Armine. Methylation refers to a chemical process involving the attachment of a methyl group, I know that sounds very scientific, which is a carbon and three hydrogen atoms joined together to our DNA, and this has received quite a lot of attention over the past several years, especially in the functional medicine world.  DNA methylation is essential for normal development and for many functions in the body including DNA production, liver detoxification, controlling inflammation, hystamine metabolism, estrogen metabolism, immune function, energy production, mood balancing, among others. Methylation deficits have been associated with many disease states including various autoimmune diseases, autism, cardiovascular disease, depression, inflammatory bowel disorder, insomnia, fertility problems, among others.

                                On the other hand, over-methylation can also cause a number of health problems including increased risk of breast cancer, etc. It has now become common practice in the functional medicine community to … That’s Dr. Armine. He’s flying in from the East Coast. It’s now become common practice in the functional medicine community to assess methylation status by measuring a few genetic polymorphisms including the SNPs for MTHFR and COMT, and some practitioners will also measure homocysteine levels.  There’s a tendency for those of us who think about methylation to concentrate solely on the gene aspect, but today we’ll discuss the significance of methylation, what it is, what it isn’t, how you can help the methylation process, and what pitfalls to be aware of.

Our interview today with Dr. Jess Armine, he is a doctor of chiropractic, a registered nurse, and he’s been a healthcare professional for over 37 years. He’s trained in chiropractic, methylation, genetic research, neuroendoimmunology, say that three times fast, functional medicine, applied kinesiology, and cranial manipulation.  He’s one of the few specialists in the United States who’s an expert at correlating the genetic SNPs with the neuroendoimmunology. He also correlates this with acquired mitochondrial dysfunction and cell wall integrity, if you have any idea what that means, to identify hidden imbalances and hidden stressors in the body. Then he develops individualized treatment plans for patients. Dr. Armine, thank you so much for joining me today.

Dr. Armine:         Thanks so much, Ben. I appreciate it. It’s a very good introduction.

Dr. Weitz:            So I tell you what-

Dr. Armine:         Whatever this is.

Dr. Weitz:            What the hell is methylation, and why should we care about it?

Dr. Armine:         Well I’ll tell you, methylation is a term that’s been bandied about very, very significantly for the past couple of decades now. Methylation is an important process in all points of DNA replication and in the actual turning on and turning off different genetic pathways.

Dr. Weitz:            Okay, so let me just stop you real quick there. So what you’re saying is we all have these genes, we’re born with the genes. Essentially, they don’t change.  However, some genes get expressed and some genes don’t get expressed.  You could also refer to this as the gene is turned on or the gene is turned off.

Dr. Armine:         That is correct.

Dr. Weitz:            And what you’re saying is that when genes get methylated, they either get turned off or turned on. Is that correct?

Dr. Armine:         Essentially, that’s correct because … If you really want to learn about methylation, honestly, you can go to YouTube and look for the simple … there’s a couple methylation raps, and some people do about a two or three minute video, and it gives you a general idea of what’s happening. One of my favorite sayings lately is that we can understand the body right down to the quantum level, but we can only intervene globally.  The understanding of methylation should be as follows: number one, we’re not talking about the genome, we’re talking about the epigenome. You’ll hear the word epigenetics, and that means that set of genes that creates or encodes the enzymes that run our bodily processes. They are static as is our genome, but the environment and other factors can interfere, can alter, those enzymatic pathways.  Without getting super, super technical, because super technical doesn’t help us.  What helps us is understanding that methylating proteins, putting a methyl group on different proteins, in certain areas will turn things off, in certain areas will turn things on. Let’s think of it as balancing and regulating physiology because that’s what it does. The reason that we should look at it like that is to decrease the amount of angst and fear that I constantly hear from people.  As you said, I’m an epigenetic expert.  I’m one of the recognized in the world.  I take that as a sacred trust.  So when I get a call from somebody who says, “I just found out.  I have MTHFR, compound heterozygous.”  You can hear them sweating over the phone.  My first question is-

Dr. Weitz:            By the way, compound heterozygous?

Dr. Armine:         I’ll explain it in a second.

Dr. Weitz:            Okay.

Dr. Armine:         I’ll simply say to them, “Look, were you sick yesterday?”  “No, I feel fine.”   “Then you’re not sick today.” MTHFR, that was my segue into MTHFR, okay?  MTHFR is one of the quintessential genes that represents the methylation pathway.  MTHFR, the big word is methylene tetrahydrofolate reductase. I always tell my patients, “When I say something fast, ignore it.  Because I’m going to explain it.”   What MTHFR does, really, is take the result of what we do with folates and turn it into the active five level folate.  Which contributes to the creation of SAM-e, and SAM-e is what takes your methyl donors and puts them all around to different places. So the creation of SAM-e becomes a primary thing to do. But we think of the active methylfolate as being the thing that helps DNA repair, and it would be correct.  Does the mechanism really make a difference?  Not unless you’re a practitioner and you have to intervene, in which case then you should know the basics because you want to know how to intervene to the patient’s best benefit.  

                                MTHFR, when they first studied it, they studied two variants. You have to understand something about genes. It’s not just a gene. You have a gene with a whole ton of variance. For instance, MTHFR has got 50, count them five zero, variants. Generally speaking, the C677T and the 1298C are the ones that were studied at first. When they talk about heterozygous and homozygous in a gene, we’re talking about the estimate of its innate ability to function.  You look at a genetic report, you see green next to something which is usually -/-. It means that the enzyme that that gene creates is going to work the way it’s supposed to, given nothing else going on. If it’s yellow, or heterozygous which is a +/- means that it’s working at about 60% of the way it should given nothing else. If it’s red, or homozygous, working about 20% of the way it should be doing, given nothing else going on.  So when somebody has compound heterozygous, they are +/- or heterozygous for the 1298C and the C677T.

Dr. Weitz:            So let me just stop you real quick. I often hear practitioners say, “Well, you’re heterozygous for that so it’s really no significance.”

Dr. Armine:         That’s true. Here’s the-

Dr. Weitz:            And the reports usually say that, too.

Dr. Armine:         True.

Dr. Weitz:            You only have one copy so it doesn’t mean anything, but you’re saying you can still have a 40% reduction of your ability to create that enzyme or for that process in the body to happen. So that could still be significant.

Dr. Armine:         It can be. Let me ask you a question.

Dr. Weitz:            I mean, if I told you you had a 40% reduced heart function, you’d want to know about that.

Dr. Armine:         Well yes you would, but let me frame it in the way that it’s working. First of all, remember that you’re born like this.  If you’re as a baby functioning well means that it doesn’t matter where the polymorphisms are. Now remember… 

Dr. Weitz:            There’s probably different genes that-

Dr. Armine:         There are, but here’s the reality of the situation. Let’s take the folate pathway which starts from FOLR1, don’t worry about these letters, FOLR1 and FOLR 2, DHFR, and DHFD1, until you get MTHFS until you get to MTHFR.  Don’t worry about all of that big stuff.  That pathway requires those genes, those enzymes, most of them require NAD to work, B3.  For MTHFR to work, it needs at least B2 and B3 to work.  So for instance, if you don’t have enough B3 in your cells and B2, those enzymes are going to slow down significantly, and if there’s already a 40% reduction, wow.  Now, there are factors that will slow down the enzymatic reactions. For instance, in the folate pathway, dairy antibodies, methotrexate, folic acid, large amounts of green tea, grapefruit seed extract, are some of the things that will slow those enzymatic reactions down.  Now, I want you to think of the yellow or heterozygous variants…

Dr. Weitz:            Now, you said folic acid. So you’re talking about something different than what is often recommended by a doctor like you-

Dr. Armine:         Right.

Dr. Weitz:            … which would be a form of folate versus folic acid-

Dr. Armine:         Exactly.

Dr. Weitz:            … which is the synthetic form, which is-

Dr. Armine:         There’s significant problems with the synthetic form, and thanks for bringing it up because it’s true. It’s been used many, many years, but there are problems with the way that it’s conjugated. It doesn’t create the end product, which is 5,10-Methylenetetrahydrofolate that MTHFR, methylene tetrahydrofolate reductase turns into 5,10-methylenetetrahydrofolate or 5-methylfolate.  Here’s the thing that I want people to understand, that let’s say that yellow is a four lane highway, red’s a two lane highway, and green’s an eight lane highway. If I had a bunch of yellows and everything’s running the way it should be because nothing wrong with me, but then I start blocking those areas by putting all of those factors in that slow it down, like the dairy antibodies and so forth, and then I don’t give my body enough B2 and B3, that’s like taking a four lane highway and putting a construction crew in there so that maybe one or two lanes are going by. That’s when you start getting symptoms.  It’s the polymorphisms or the SNPs will give you an indicator of what a pathway may not work so well under an oxidated stress load or when other things are going on that would slow it down innately. By itself, it means nothing. Rather it gives you a heads up.  Now if you’ve got a compound heterozygous, you start looking around on the internet, this is where I get the panicked calls. You have to realize-

Dr. Weitz:            This is where you have … When you have a genetic variant, you can have one copy which is a heterozygous.  So let’s say the normal is AA, and then you have an AG, which is one copy of a variant gene, or a homozygous whereas you have a GG instead of an AA, so you have two copies. So you’re saying if you have one copy of one gene, and then you have one copy of another gene involved in the same process that that’s what you’re calling a compound heterozygous.

Dr. Armine:         Yeah, that’s a fairly commonly used term for heterozygous of the gene variants that are usually studied, the 1298C and the C677T. So you go to a LabCorp or you go to Quest, and they test MTHFR. Those are the two variants they’re testing, okay? They’re not testing the other 48 variants, and it’s hard to get a study where you can see a lot of those variants.  Nevertheless, the thing that everybody needs to know, practitioner and lay person, is that when you go to those websites that say, “MTHFR, or SNPs of MTHFR, cause this,” and they’ll say, “cause blood clots, cause infertility, cause stillbirths,” and then if you’ve got compound heterozygous, oh my god you should jump off a bridge because this is a list of symptoms, list of things, you’re going to get it. Those are incorrect, and I’m going to tell you why.

                            When MTHFR was first studied, it was studied in relation to homocysteine.  So they thought that if they looked at the SNPs of MTHFR, we could predict high homocysteine or homocysteinemia and that would be a predictor of cardiac disease.  That didn’t work out so well.  So anybody who had anything wrong with them started testing for these genes, and the erroneous conclusion, because a lot of people have polymorphisms, a lot of people have SNPs. They just do. It’s just the way our genome is, epigenome.

Dr. Weitz:            It’s like 60% of the population has at least a heterozygous SNP for MTHFR.

Dr. Armine:         Right.

Dr. Weitz:            But homocysteine is still a recognized risk factor for heart disease.

Dr. Armine:         Oh it is, absolutely.  Absolutely, it was the relationship between MTHFR and homocysteine.  So everybody started testing for it, and anybody who had anything wrong with them … So the erroneous conclusion was that they came up with these lists of things that MTHFR would cause.  A gene doesn’t cause anything.  So everybody got scared and said, “Look, if I have this problem, I’m going to concentrate on this.”  Well, that’s wrong.  You have to concentrate on the bigger picture.  So yeah, it does have a relationship to homocysteine.  High homocysteine is one of the ways you can test if you have problems with MTHFR and high homocysteine, now you know it’s expressing.  Now you know what to do, okay?

Dr. Weitz:            So any gene is just going to increase or decrease your tendency for something to possibly happen?

Dr. Armine:         Exactly. Okay, and that is more basic … This is where we came up with foundational treatment, otherwise known as the framework…

Dr. Weitz:            Right, it’s your environment, your lifestyle, your diet, your exercise, all of those things that will determine whether or not that genetic tendency get expressed and you actually have some issue in your body.

Dr. Armine:         Hence, hence when you go to look at your MTHFR status and your practitioner does some testing to make sure that you’re not in any kind of danger, the beginning fix is to do exactly that, changing your lifestyle, drinking better water, breathing better air, managing stress.  There’s a lot of talking about earthing these days, grounding, and so forth.  I love on beautiful Cape Cod, except for the sharks. So I do a lot of walking on the beach. I don’t do a lot of swimming. They’re passing by. I know they’re only waving at me, but in the water let’s face it, I look like a seal. I don’t want to look like a seal in front of those guys.

Dr. Weitz:            “Dr. Armine, come in the water.”

Dr. Armine:         No. I’m like this, “Unless you’re a land shark, I’m staying here.”

Dr. Weitz:            A little nibble won’t hurt you.

Dr. Armine:         Yeah. On my phone, we have this thing called Sharktivity, so every time they see a shark, I kid you not, it goes off, and you see it’s plotted where all the sharks are. They close the beaches. Well, now it’s September. The sharks are still around, and there’s a lot of them around. I’m not going in the water, and they’re everywhere. I see some of them, they’re getting a little tired so they’re like on the highways going like this with their thumbs out, if they had thumbs, they’re like,… You know? Get back in the water. No, no, no, no, no. 

Dr. Weitz:            We need some better food. These fish are all loaded with plastic. We can’t eat them anymore.

Dr. Armine:         The reason they’re here is because we have the national seashore, and it’s got thousands of seals. Thousands.  And the seals protect themselves by swimming close to shore. So you see the great whites, we have videos of them, 10 feet off the shore, 15 feet off the shore. That’s not even waist deep, guys. You know? I’m not arguing with a great white shark. I went whale watching. There were whales all over the place. We saw dolphins, and then a great white came by saying, “How are you doing?”  Okay. You know? We’re just waiting for one of those whales to bite.  There was this big whale that was dead, and they were just all feeding off, they were having a good time.  They’re not really aggressive. It’s just you don’t want to look like a seal.

Dr. Weitz:            Right.

Dr. Armine:         You know, like he looks like a seal.

Dr. Weitz:            So let’s get back to methylation.

Dr. Armine:         Well the sharks methylate too, I mean really.

Dr. Weitz:            Of course.

Dr. Armine:         Hey, we all need to methylate. You know, they’re like, “You know about methylation?” You know, like whoa. Okay, guys, just you know.

Dr. Weitz:            That’s how you get over-methylated.

Dr. Armine:         That’s right. You want to know about …, my other background it says the new thing you know, “Keep calm and swim fast.” You know? I’m sorry, I’m in trouble. Go ahead.

Dr. Weitz:            Or use the buddy system. If you see a shark, give them your buddy.

Dr. Armine:         Just remember, it’s like seeing a bear. I don’t have to outrun the bear, I have to outrun you. That’s true, you know. The same thing with the shark. I’m just going to lay there. You’re going to be flapping around. It’s going to go after you, not me. 

Dr. Weitz:            Okay, so if these genes that code for methylation tendencies …

Dr. Armine:         Yes.

Dr. Weitz:            So if we measure some of these genes, do we also want to measure serum levels of the substances that result from the expression of methylation?  Like you mentioned, homocysteine.  There’s some labs like Doctor’s Data that have-

Dr. Armine:         A methylation panel.

Dr. Weitz:            … a methylation panel and measure methionine and SAM-e, and some of these others.

Dr. Armine:         Exactly.

Dr. Weitz:            Is that what you want to do because that tells us whether the genes are getting expressed?

Dr. Armine:         Exactly, and I’ll tell you why.  First of all, if you have a genetic test, whether you get your data from 23andMe or from Ancestry.com.  By the way, I wouldn’t suggest 23andMe anymore.  Okay, Ancestry.com 

Dr. Weitz:            You don’t?  How come?  What’s wrong with 23andMe?

Dr. Armine:         23andMe has changed their … when you do a test, it’s run through a computer, and there’s a chip that reads the genes. It used to be the V2 chip, and it read 500,000 genes.

Dr. Weitz:            Right.

Dr. Armine:         And then they came out with the V4 which is 250,000. Now, they changed their chip, 23andMe, to read only the genes that they were utilizing for their purposes only. The reason 23andMe got so big was because people like myself were able to take the raw data and put it into different programs so that we could pull out what we wanted. Okay, for what we needed to see.

Dr. Weitz:            That’s what we do in the office as well.

Dr. Armine:         Yeah, but they’ve changed it. So what I’ve recommended to my patients, for whatever it’s worth, is to use Ancestry.com’s, their cheapest offering, and they still use a V4 chip.  So wherever I put that data, I’m getting more data, and-

Dr. Weitz:            What about the outside labs that do genetic testing? I know Diagnostic Solutions has … I think they just recently released a new genetic panel.

Dr. Armine:         They have. I haven’t had the chance. I read what everybody sends me, but I have a … You and I have been in practice a long time. I’ve been in practice actually more than 43 years now. Okay, so we’ve seen a few things come down the pike, haven’t we?

Dr. Weitz:            Yes, we have.

Dr. Armine:         Chromium picolinate, ahh. Then all of a sudden, “It’s just chromium,” you know? I remember when GHB was a weightlifting drug, and now it’s a date rape drug. I wait, okay. So when I see … No, seriously. Come on, how many things have you seen come down the pike? CoQ10, the greatest thing since sliced bread, right? No, it only helped a few people here, but in Japan it was helping a lot of people because their diet was deficient in it.

Dr. Weitz:            Right, well DHEA was going to be the almighty …

Dr. Armine:         Right, exactly.

Dr. Weitz:            DHEA was going to reverse everything.

Dr. Armine:         Right, and that’s the way it always comes down. So when something new comes out, I read it, I wait, and usually some patients will bring the test to me, I’ll read it, and after I read several of them, if I see that what I’m looking at correlates with their symptoms then I’m going to start believing the validity of the test. It’s just too early with that one.

Dr. Weitz:            Okay, so you don’t have a favorite panel right now.

Dr. Armine:         The two panels I tend to use are StrateGene, which a new version is supposed to be coming out this month, which is going to be more robust, and I use MTHFRsupport.com, although that’s gotten top heavy lately because there’s too much information in there, and unless you’re a practitioner it’s hard to pull out what’s important. Although, if you wanted to see every pathway like nobody’s business, it’s all going to be there.

Dr. Weitz:            Is that analysis software, or that’s testing?

Dr. Armine:         That’s analysis software. The testing, you would use either the Ancestry or the 23andMe 

Dr. Weitz:            Oh, those are the only two panels you use? You haven’t used any of the other panels?

Dr. Armine:         I haven’t used any of the other panels. I’ve read them. I haven’t recommended them, but people come to me with all different panels from all different places, and I can read them. That’s not a problem, but when I’m looking at … Somebody says, “What do I do with this data?” I give them the options of one of the two, and it works because what you have to do is correlate what you’re reading with their particular symptom complex, and with a good history you’re going to figure out what.  You have your genetic tests in front of you, and then you have a suspicion based on their symptom complex of what might not be working, and if you want to confirm that, things like the methylation panel. They are really strong on the methylation issue. The methylation panel is great. Things like the organic acid tests are great. There’s another test-

Dr. Weitz:            So what can you get out of an organic acids panel?  What will that confirm for you?

Dr. Armine:         The organic acid panel is measuring organic acids, which are the result of the pathways.  So in the typical organic acid test from let’s say Great Plains, you’re going to see indicators of mold, of candida, of SIBO, of clostridia. You’re going to see the oxalate status which is really important because high oxylates is one of the major reasons for illness. It’s secondary to candida, but you’ll see it there.  You’ll see the function of the entire Kreb cycle, how you create your energy. You’ll see the neurotransmitter metabolites. You’ll see the functioning of glutathione and many other things, and you’ll see the levels of the various B vitamins and some minerals. So you can have a really good idea of what’s going on physiologically because you’re not measuring serum levels, you’re measuring the organic acid that is a result of the intracellular functions. So what they’re dumping out of the cell is what you’re measuring. So you can extrapolate the cellular function.

Dr. Weitz:            It’s gone through metabolism, it’s being processed, and that’s what the body’s getting rid of.

Dr. Armine:         Right. So you can really extrapolate easily if you just think of it like that.

Dr. Weitz:            Okay.

Dr. Armine:         Everything’s got a couple of glitches, but once you know how to read it, it’s not a big deal.

Dr. Weitz:            So organic acids panel. Any other tests you like to use?

Dr. Armine:         I don’t use the methylation panel too often because I treat methylation on a more basic level.

Dr. Weitz:            Do you measure homocysteine levels?

Dr. Armine:         I do. It depends on the individual. If they’re in the States, they usually have insurance that will cover LabCorp requests, and I can write them a script for that, and then I can get those, like vitamin D 25, 125, yadda, yadda, yadda. I can get those tests that way. There’s another-

Dr. Weitz:            You ever do a full nutritional status panel like the SpectraCell Micronutrient Test or the Genova NutrEval test?

Dr. Armine:         Concerning NutrEval, NutrEval and the GPL OAT, when I weigh the both of them I lean towards the GPL OAT. The SpectraCell Micronutrient analysis is really wonderful because you can see the status of what’s going on inside the cell, and you’re looking at a six month status. You know how a hemoglobin A1c measures your sugar for the past three months? 

Dr. Weitz:            Supposedly, yeah.

Dr. Armine:         Well, roughly. It’s never an exactitude, but you can see generally speaking what’s been going on.

Dr. Weitz:            Right.

Dr. Armine:         Okay, because of the glycosylation of the proteins, but since the SpectraCell test measures what’s going on inside the white blood cells and they generally last around six month, you can get a bigger view. So instead of seeing what happened over the past couple of days, you’re seeing what’s happening over the past couple of months. Plus, they measure and they test the function of the immune system and the function of the antioxidants, okay? So that’s really valuable.  There’s another type of testing, functional diagnostic testing, and on the status quo, the ODX which is a massive panel that you can do that covers … it’s a blood test, and it covers, oh my god, so many different areas.

Dr. Weitz:            If you do the SpectraCell micronutrient test, if you throw in the cardiometabolic panel, you’ll get blood sugar, lipids, hemoglobin A1c, it’ll include homocysteine as well.

Dr. Armine:         Oh, cool.

Dr. Weitz:            It’s pretty reasonably priced.

Dr. Armine:         That’s good.

Dr. Weitz:            When you order the micronutrient test, you can throw that one in.

Dr. Armine:         Okay, thank you. I didn’t know 

Dr. Weitz:            And oh, it also includes omega-3s.

Dr. Armine:         Wonderful.

Dr. Weitz:            Yeah.

Dr. Armine:         Yeah, I measure omega-3s through something called OmegaQuant, but if there’s a single test. I like 

Dr. Weitz:            Yeah, they include it in their cardiometabolic panel, the 6:3 ratio and all of that.

Dr. Armine:         Yeah, because that’s how you tell what’s going on. You also need the AA:EPA ratio.

Dr. Weitz:            Yeah.

Dr. Armine:         You talked a little bit about cell wall integrity, what does that mean? You have to remember that the cell wall is not just a wall. The cell membrane is what determines what goes out of the cell, what’s being allowed into the cell, and it’s being called, recently but it’s gaining speed, it’s being called the master of the cell more than the nucleus.  When you have chronic inflammation, you have a lot of problems, people talk about leaky cells. What that means is a lack of cell wall integrity or cell wall function, which can come from a lack of phospholipids or a whole lot of other things, and when that happens your cells aren’t going to work.  And if your cells don’t work, nothing-

Dr. Weitz:            Because the cell wall essentially is a phospholipid membrane.

Dr. Armine:         It is a phospholipid bilayer, exactly.

Dr. Weitz:            Right.

Dr. Armine:         Okay. I wrote a book with Elizma Lambert called Leaky Gut, Leaky Cells, Leaky Brain which went through it really, really well. It’s a simple book, it’s an e-book, and I made a very, very large point very easily … because when I write…

Dr. Weitz:            Send me an email with a link so I can put it in the show notes, please.

Dr. Armine:         Oh, absolutely I will. Absolutely. We spent two years on it, and I think it’s kind of a masterpiece because it’s so easy to understand.

Dr. Weitz:            Great.

Dr. Armine:         Nevertheless, when we talk about cell wall integrity as being part of considering how to look at somebody’s condition, you consider the epigenetics, you consider the relationship between neurology, endocrinology, and immunology which is known as the NEI supersystem, you consider the function of the mitochondria, and what many people don’t do is look at the function of the cell wall, and that particular omega test is one of the ways you look at it.

Dr. Weitz:            Okay, cool.

Dr. Armine:         So when you’re talking about methylation, what the idea of methylation is is to create SAM-e, which goes around putting the methyl groups where it belongs. When everything is properly methylated, physiology works the way it was intended.  It gets a little crazy about how the DNA wrapped around histones and it gets a little nuts.  And it’s true, it gets nuts, but the reality is if you get methylation to work correctly, it’s going to be a big contributor to you recreating and maintaining your homeostasis.  Now, how hell the do you do that?  How the heck do you do that?  A lot of people concentrate solely on giving methylated vitamins: methylfolate, methyl B12, dimethylglycine, trimethylglycine, or SAM-e itself. That’s okay. There are plenty of products out there.

Dr. Weitz:            Yeah, for example what if somebody was out there either a patient or a practitioner who was thinking, “You know what? Instead of doing all of this testing, why don’t I do the following?  I’ll avoid any foods or supplements with folic acid, and I’ll just take methyl B vitamins, and aren’t I covered?

Dr. Armine:         Usually, yes.  Here’s the thing that people should know.  First of all, my particular practice is made up of people who have been here, there, and everywhere that aren’t getting success out of their treatments. So obviously I have a very focused population. There are a certain percentage of people that respond very negatively to the methyl vitamins. So, well let’s just talk methylfolate for a second.

Dr. Weitz:            Okay.

Dr. Armine:         There’s loads of reasons for this

Dr. Weitz:            So we have methylfolate which is B9, we have methyl B12 which is methylcobalamin, and then we also have the … I don’t think they’re methyl forms, right? Of B2 and B6, they’re activated forms, right?

Dr. Armine:         No, they’re activated. They’re B2 and B6 would be P5P, B2 would be Riboflavin 5′-Phosphate. Like you said, there are loads of products out there that will put together, and they usually will make a big advertising point about it, and they usually put all the active/methylated vitamins together. This is my advice to everyone who takes this kind of stuff.  Do an experiment with yourself.  Do yourself a favor, especially if you’ve had some really nasty chronic illness for a long time, especially if it’s associated with any kind of anxiety or what I liked to call neuroexcitation.  Only because the reaction to the methyls, they’re going to up-regulate that which is very uncomfortable.  Either take the product you’re going to use or use one methylated product like methylfolate which you can like anywhere, start with a quarter of a dose or a half dose, and over a period of two weeks work your way up to a full dose.

                            Here are the four reactions you’re going to see:   One, if you start taking it and you feel bad, do me a favor: stop. I can’t tell you the people who will say, “I can only take a little crumb of methyl B12.” 

                            I said, “Why are you taking it?”

                            “I need the methyl group.”

                            “No, you don’t. If you’re not taking a therapeutic dose, what’s the sense?” 

Dr. Weitz:            I would like to give a caveat since I’ve been doing the functional medicine stuff like you for a long time, and a lot of times when people feel really crappy and whatever it is they ate or what they took, they automatically assume that that means, “I can never eat that food again,” and… Probably try it a few times in a row before you decide for sure the fact that you’re feeling crappy right now has directly to do with that.

Dr. Armine:         It’s a tough one sometimes to figure out where it is, but often the second scenario is where people get confused because the reality is is some people will start taking the, I’m just going to say the methyl vitamins, the methyl vitamins, and they feel, okay they don’t feel, you know whatever. Then within about two weeks they start feeling bad, and it’s very hard to realize that they’ve blocked up all the pathways, if you want to look at it like that, and they need to stop the methyl vitamins. That’s the second scenario, and if you have an ear for it you’ll say, “Okay, just simply stop what you’re doing and see in a few days if you don’t feel better because if that is, then you know what caused it.” Three-

Dr. Weitz:            You know, a lot of multis now have the methyl B vitamins in it.

Dr. Armine:         Yeah, it’s a big deal. It’s a big deal. Methylation, you really need to understand, is big business. This is why before, when we first started-

Dr. Weitz:            Well, everybody’s doing it because we don’t want to give people unmetabolized folic acid, so.

Dr. Armine:         That’s true. That’s true, but when we first started everybody’s like, “Methylation, no big deal.” Soon as the companies grabbed onto the fact that methylation was important, everybody was testing for everything in their trimethyl groups, and it became hard to find a vitamin that didn’t have it. So in the third scenario-

Dr. Weitz:            Are you saying the average person should take a multivitamin that doesn’t have methyl forms of B vitamins?

Dr. Armine:         No, what I’m saying is that when you take your vitamins, be cognizant of the fact whether they have the methyl B’s in there, and if you start taking that vitamin and you feel bad, it’s most probably that, and simply stop taking it.

Dr. Weitz:            Okay.

Dr. Armine:         If you start taking the vitamins and within two weeks you feel bad, then stop. Okay?

Dr. Weitz:            Okay, sounds good.

Dr. Armine:         If you start taking the vitamins and it’s like you start feeling better, and better, and better, you hit the nail on the head. If you start taking the vitamins and you don’t feel better or you don’t feel worse, it means your body is accepting it, but it’s not the answer to your symptom complex.

Dr. Weitz:            Now, is the amount in a multivitamin typically enough to create negative reactions in more than a small number of people?

Dr. Armine:         Yeah, it is, and a lot of times the amount of folate is limited because of the FDA restrictions. You’ll usually see B12 at reasonable amounts. You’ll always know that you’re getting a bad form of B12 when it says that you’re being given 1,667% of the percent daily value. It usually means you’re getting cyanocobalamin, which is very poorly absorbed.  These days, that doesn’t exist, but if you do have a problem with the methyl Bs, there’s a ton of vitamins out there that have things like folinic acid or natural folate, and they have hydroxocobalamin and/or adenosylcobalamin.  People usually don’t respond … we don’t negatively react to those. The reason I’m- The reason I’m making the point is because if you do have a reaction to it, it’s usually in the excitation, anxiety, or if it’s a child increase in hyperactivity, and you’re looking at it, and the mindset is, “I need this for his methylation, yet I’m going to just fork my way through it, and this …” Remember that if you give somebody substrate and you give them what they need to metabolize it, they’ll create the methylfolate.  Maybe a little slower than the next person, but they’ll create it. There’s usually loads of reasons why you’re not creating it, and that includes lack of B2, lack of B3, lack of substrate, lack of folate like the person doesn’t eat green vegetables at all. Those are the reasons that you don’t produce it.  Now, you can give somebody the problem, give somebody the vitamin, but you also remember what we have to do is find out how they got there in the first place. Because they can take vitamins for the rest of their lives, but that’s not fixing anybody. Yeah, we all need a good multivitamin and multimineral, but we’re talking the bigger picture of having to actually fix things and reestablish normal homeostasis which starts at that basic stuff that you were talking about before: good food, good water, good stress relief.

Dr. Weitz:            Well let’s say you have a patient that has elevated homocysteine levels and you want to reduce their risk of heart disease, and you give them a methyl B formula, a homocysteine oriented, product.  Something designed to help lower homocysteine levels, and they don’t feel well on it.  What other choices do you have?

Dr. Armine:         Well remember, the presumption is their high homocysteine is causing symptoms.

Dr. Weitz:            No, no. Let’s say they’re not having symptoms, but they want to reduce their risk of having a heart attack.

Dr. Armine:         Okay…

Dr. Weitz:            And their homocysteine is 15.

Dr. Armine:         If their homocysteine doesn’t come down, then you definitely want to do the methylation panels, you definitely want to do the organic acid test, and you want to find out where the pathway this is being backed up, if you will, and it could be down the transsulfuration pathway. It could be blocked up by CBS going backwards.  There’s loads of reasons, but this is where a good history and reasonable testing comes in. I agree with you, most doctors that I know-

Dr. Weitz:            But what is CBS going backwards mean?

Dr. Armine:         It just means that if CBS is … I said that…

Dr. Weitz:            If NBC goes backwards, is that the same thing?

Dr. Armine:         Homocysteine goes down the transsulfuration pathway past something called cystathione B synthase to become cystathione, and then cysteine to eventually become glutathione, and then glutathione, when it gets used up and gets oxidized, gets recycled. So that whole big, long pathway can get blocked up, if you will, and if you think about it like a highway, it’s going to block up, and where it’s going to block may be one of the reasons for higher homocysteine.  Nevertheless, what happens is if your homocysteine’s not coming down, it’s telling you you’ve got chronic inflammation somewhere, and your practitioner needs to start investigating that, but when you investigate that, you’re going to find out the reason. It’s like looking at TSH, thyroid stimulating hormone. A lot of times I’ll see that up, I’ll see poorer thyroid function, but the thyroid antibodies are not there.  That’s generalized chronic inflammation.  I better start looking for reasons for that whole person to have inflammation and that’s usually under chronic inflammatory response syndrome, and maybe…

Dr. Weitz:            And from a Functional Medicine perspective, typically we start looking for possibilities like mold, heavy metals, other toxins, food sensitivities, leaky gut and other gut problems, etc, right?

Dr. Armine:         Exactly. This is why…

Dr. Weitz:            Other nutritional deficiencies.

Dr. Armine:         This is why functional medicine and allopathic medicine should actually work in concert with one another. Because the allopaths are really, really good at finding out the gross pathologies. You don’t want to miss those. Okay, you don’t want to miss those. But once they don’t find a gross pathology, the typical joke, “All your tests are negative. You’re fine.” Nope. Okay, if you’re still hurting the functional medicine doctor simply goes back, looks at it from a wider point of view, takes care of the basis of the body, the cell wall function, the absorption of nutrients, the absorption of vitamins and minerals, all that stuff, and then starts looking at it from the point of view of, “What could possibly be contributing to this?” And the functional medicine doc never sits there and says, “That can’t happen.” What they say is, “Well, it’s happening. Why may it be happening?”

Dr. Weitz:            Right.

Dr. Armine:         That’s why we find things that other types of practitioners don’t, so we know what to do. If the normal stuff doesn’t work, that’s where we shine. Okay?

Dr. Weitz:            Right, so I just want to pull out, you mention I think is a really good clinical pearl. If you have a patient and they’re taking a modern multivitamin, say from a practitioner or some of these professional brands, pretty much the majority of them have switched over to methyl B vitamins, and they’re not feeling well or they’re feeling anxious, some of the symptoms that might happen from being over-methylated. Then you should try to find a multivitamin that instead of having methylcobalamin has hydroxocobalamin because you don’t want to take cyanocobalamin because that’s small levels of cyanide, right? You want something called NatureFolate as opposed to 5-methylfolate, and they won’t typically have the same reaction.

Dr. Armine:         True. True.

Dr. Weitz:            Okay, good. So what else-

Dr. Armine:         The way you would know that is simply by stopping the vitamin that you’re taking.

Dr. Weitz:            Right, so what else can happen with over-methylation? What are some of the other dangers? Isn’t there a danger of increased risk of cancer?

Dr. Armine:         In the long-term, in the long-term. Over-methylation as well as under-methylation, remember too much and too little in the body is just as bad. It’s easier to understand if something is too low, if you have DNA hypomethylation, if you will, there’s no sense in even using the terms. When you have too little methylation, you know it makes sense that things won’t work. If you have too much methylation, often if you have an acute over-methylation, you’re going to be … And by the way, if that should happen because you’ve taken too many methylated vitamins, you get regular niacin, you know the cheap stuff, nicotinic acid, the one that causes the flush, and you take about 25 mg an hour, and within a few hours that will calm down because it chews up the methyl groups. Okay?

Dr. Weitz:            Oh, interesting.

Dr. Armine:         It’s the first aid for over-methylation. The other thing is you have to realize that if you are taking B3 and you’re taking a large amount, you may be causing the under-methylation. You might be causing the hypomethylation because you’re chewing up the groups. Nevertheless, hypermethylation, over-methylation, just like hypomethylation can cause different things. Sometimes it’s contributing to breast cancer or any of the estrogen loving cancers.  I really would advise people to look for normal methylation function rather than concentrating horribly on over or under methylation, just trying to normalize it. The over-

Dr. Weitz:            How do we know if we’re over-methylating, assuming you don’t have symptoms?

Dr. Armine:         It’s really tough because some people have related it to the histamine levels and so forth. I haven’t seen the correlation with that. If you’re not having symptoms and you are feeling well, for the most part you’re not over-methylating or under-methylating. If you have a high homocysteine and you add methyl groups … Remember, if you’re really having problems with the methylation system, you’re going to have multisystem symptoms. That’s why methylation is important, to treat or at least consider it. It’s not going to be a thing because the DNA production, protein production, is going to be off which is what’s going to cause problems with histamine and metabolism, neurotransmitters, detoxification. You’re not going to have one problem.

                                If you just have a high homocysteine, usually it’s the simple things that will fix it. Yes, you can use the methylated vitamins, but remember, think about why it got there. If you really are under-methylated, if your methylation’s not working, you’re usually going to be sick. You’re usually going to have chronic fatigue. You’re going to have a whole mess of different things going on, and the effect of the root cause, or the effect of what caused that, causes problems in the methylation system. So yeah, you want to treat it. You want to get that person’s homeostasis as stable as you can, but you want to look for the root causes also. Otherwise, it’s just going to come back.

Dr. Weitz:            Okay. You’ve provided us with …

Dr. Armine:         Been very confusing.

Dr. Weitz:            We could go on for hours, but …;

Dr. Armine:         Yes, we could.

Dr. Weitz:            I do have a patient coming up, and-

Dr. Armine:         I know,

Dr. Weitz:            … we’ve talked about a lot of things. We’ve talked about the connection between great white sharks and methylation, and we’ve talked about the problems-

Dr. Armine:         It’s an important point. Let’s face it, it’s an important point.

Dr. Weitz:            I think…

Dr. Armine:         Especially to the shark.

Dr. Weitz:            This is probably the only podcast that has covered the connection between MTHFR and great white sharks.

Dr. Armine:         If you think about it, it could be shark defense also. You get the methylated vitamins, they’re coming at you, you throw them this way, they’re like, “Ahh,” and they go after them. Like, “All right, thanks. That’s what I was looking for.”   I’m like, “I know. I’m out of here.”

Dr. Weitz:            Oh, no. I got methylated before Dr. Armine jumped in.  So we’ve talked about some of the ways to test our genes, and to look at some of the methylation pathways, and some of the things to look at, and then some of the dangers of over-methylation. How can our listeners, patient and practitioners, get a hold of you and find out about some of your programs?

Dr. Armine:         You can go to my website which is DrJessArmine.com.  You can contact my office of Dr. Jess Armine, or call that number, and I’d be happy … I offer a 15 minute get acquainted session. So you can schedule that, and we can have a chat to see if I can help your particular condition. Practitioners, I also run mentoring groups. I do personal mentoring, but I do group mentoring which seems to work out very, very well. I run those on Tuesdays and Thursdays, and they are 12 week courses where we get together every week as practitioners, go over tough cases, and then take the learning points from those cases and talk about those subjects. So, we find out what the group’s issues are, what they want to learn about, and I guide them through that. So I usually can take a practitioner who is not as familiar with functional medicine, and within 12 weeks have them really, really very functional within it without taking an overt amount of formalized courses.

Dr. Weitz:            When is your next group starting? Maybe you could send me a link for that that I could put in the show notes.

Dr. Armine:         I sure will. I’m going to England starting Sunday until October 3rd, so probably the middle of October, but I’ll send you a link for it because yeah, I appreciate that. I’d like to get out most of my groups are in England, and I would like to have some American groups because I know those are a necessity here. Especially for the younger practitioners who are watching who have got all of this knowledge and simply can’t put the puzzle pieces together, which is what I do. If you want to be the master healer and you want to learn how to put the puzzle pieces together, I’d be very happy to be your guide. Plus, it’s cost effective because what I charge for person to person type stuff borders on the silly. Group is much better.

Dr. Weitz:            Right. Sounds good, doc. Thank you so much.

Dr. Armine:         Thanks, brother. Thank you for having me. I really appreciate it. Take care.

 

Weitz Sports Chiropractic and Nutrition
Weitz Sports Chiropractic and Nutrition
Mitochondrial Testing with Dr. Sri Ganeshan: Rational Wellness Podcast 128
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Dr. Sri Ganeshan discusses Mitochondrial Testing with Dr. Ben Weitz.

[If you enjoy this podcast, please give us a rating and review on Itunes, so more people will find The Rational Wellness Podcast. Also check out the video version on YouTube at https://www.youtube.com/user/weitzchiro/]

 

Podcast Highlights

4:24  Dr. Ganeshan was on vacation and there was a conference on autism there and he attended some of the lectures and learned that a significant percentage of patients with autism have mitochondrial dysfunction. He found a scientist, who was working on a test and they collaborated and developed the Mitoswab test that uses a buccal swab to measure mitochondrial status. It has been shown to correlate with muscle biopsy, which is the gold standard for measuring mitochondrial disease. Non-invasive evaluation of buccal respiratory chain enzyme dysfunction in mitochondrial disease: Comparison with studies in muscle biopsy 

7:04  The mitochondria are the the organelles that are the main generators of energy for the cells of the body. All cells, except red blood cells, have mitochondria. Red blood cells carry oxygen and mitochondria use oxygen to produce energy, so if red blood cells had mitochondria, they would use up the oxygen.  After age 60, mitochondria tend to decline and that’s when you tend to see chronic diseases, like cardiovascular and neurodegenerative diseases develop. There are tools to optimize mitochondria function, like exercise.

9:55  The food we eat gets into the mitochondria through complex one and the mitochondria convert it into energy.  In complex 3 and 4 the oxygen we inhale gets converted into water. 95% gets converted into water and 5% forms oxygen free radicals, which can be useful signaling molecules in small quantities. If too much oxygen is converted into oxygenated free radicals, it damages proteins and DNA in our cells, which is a problem.  With oxygen, 5% can be useful as a signaling agent, but 20% would cause cell damage.  This can be measured with the Mitoswab test.  Complex 4 is where the energy (ATP) is produced.

12:51  The mitochondria has these five complexes that are part of this chain of processes that leads to ATP energy production and each can be associated with different diseases. Complex one is associated with diabetes, neurodevelopmental and neurodegenerative diseases. Complex 3 is very important for T-regulatory function and endothelial function. Complex 4 is associated with neuromuscular diseases and seizures. 

18:00  For patients with diabetes, we now know that part of the diabetes process involves mitochondrial dysfunction.  And by improving mitchondrial function, the diabetes will also improve.  As part of your workup for patients with diabetes, in addition to measuring blood sugar, Hemoglobin AIC, insulin, advanced lipids, inflammatory markers, etc. you might include the Mitoswab test to assess mitochondrial function.

20:03  In Functional Medicine we want to optimize the patient and optimizing mitchondrial function could help to prevent some neurodegenerative diseases, like Parkinson’s and Alzheimer’s diseases. By 2040 we expect that there will be 14.2 million people with Parkinson’s and 14 million with Alzheimer’s disease.  In particular, Parkinson’s is linked to mitochondrial function and if we see improvements in the Mitoswab test, this is linked with better outcomes for patients and Dr. Ganeshan is in the process of publishing some of this data.

24:39  Mitochondrial function is very important for cardiovascular health. One of the hallmarks of heart failure is reduced mitochondrial function and by improving mitochondrial function, by making the heart muscle pump and function better, we can slow the progress and reverse heart failure.  Nutritional supplements like Coenzyme Q10, L-Carnitine, D-ribose, alpha-lipoic acid can help with this.  They can also play a role in atherosclerosis, since the function of HDL, the reverse cholesterol transport involves the HDL picking up cholesterol and taking it to the liver for degradation requires a lot of ATP, it’s a very energy dependent process.  Here is a related paper: Mitochondrial Oxidative Phosphorylation defect in the Heart of Subjects with Coronary Artery DiseaseDr. Ganeshan said it is important to use the proper cofactors, including NADH for Complex 1, CoQ10 for Complex 1 and 4, and riboflavin for Complex 2.

 



Dr. Sri Ganeshan is the Chief Medical Officer of ReligenDx, a company focused on Mitochondrial disease research, including the development of the MitoSwab test, a non-invasive way to analyse mitochondrial dysfunction.

Dr. Ben Weitz is available for 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, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111 or go to www.drweitz.com.



 

Podcast Transcript

Dr. Weitz:                            This is Dr. Ben Weitz with the Rational Wellness podcast, bringing you the cutting edge information on health and nutrition, from the latest scientific research, and by interviewing the top experts in the field.  Please subscribe to Rational Wellness podcast on iTunes and YouTube, and sign up for my free eBook on my website by going to drweitz.com. Let’s get started on your road to better health.  Hello, Rational Wellness podcasters. Thank you so much for joining me again today. For those of you who enjoy listening to our Rational Wellness podcast, please go to Apple Podcast, or wherever you get your podcast, and give us a review and a rating. We would really appreciate that. That’ll help move us up in the rankings there, and more people can find out about the Rational Wellness podcast. Also, go to my YouTube page, and you can find a video version. And if you go to my website, drweitz.com, you can find detailed show notes and a complete transcript.

Our topic for today is mitochondrial testing with Dr. Sri Ganeshan. A mitochondrion, mitochondria is plural, is an organelle found in every human cell, except for red blood cells. In fact, most cells have numerous mitochondria. ATP is the main source of energy, chemical energy, used by cells to fuel their functions. And this ATP is generated by the mitochondria, which is why the mitochondria are often referred to as the energy powerhouse of the cell.  Mitochondria have many other roles besides energy production, including heat production, storage of calcium ions, cell signaling through reactive oxygen species, program cell death, regulation of cellular metabolism, and steroid synthesis. There are primary genetic mitochondrial diseases, which are relatively rare, such as Barth syndrome, Aminoaciduria, iron overload, Kearns-Sayre syndrome, and Mitochondrial encephalomyopathy.

But much more common is mitochondrial dysfunction, which is a characteristic of aging and a component of nearly every chronic disease, including neurodegenerative diseases like Alzheimer’s and Parkinson’s, congestive heart failure, autoimmune diseases such as MS and lupus, neurobehavioral diseases including autism, schizophrenia, bipolar disorder, chronic fatigue, fibromyalgia, and even cancer have a mitochondrial component.  Mitochondria can become dysfunctional when we lack the necessary mitochondrial support nutrients. When the energy created by the mitochondria is less than the free radicals they produce, or when mitochondria are damaged by environmental toxins, medications, or the dirty electromagnetic fields that surround us in modern life.  Environmental estrogens like bisphenol A and pesticides, glyphosate from Roundup, and heavy metals like lead and mercury all damage our mitochondria. Also, common medications like acetaminophen or Tylenol, as well as most nonsteroidal anti-inflammatory pain medications, many psychotropic medications like Prozac, cholesterol-lowering statin drugs and even metformin are all known to be toxic to our mitochondria.

Dr. Sri Ganeshan is the chief medical officer of ReligenDX, a company focused on mitochondrial disease research, including the development of the Mitoswab test, a non-invasive way to analyze mitochondrial dysfunction. Dr. Ganeshan, thank you so much for joining me today.

Dr. Ganeshan:                   Thank you, Ben. Thank you for inviting me. Thanks a lot. I thank you so much, it’s very well.

Dr. Weitz:                          So tell us about your personal journey and how you came to become involved with research on mitochondria.

Dr. Ganeshan:                   Yeah. I accidentally… I was on a vacation, and I happened to be at… The same hotel happened to have an autism conference. That’s how I found my way into the autism world. And then by learning about autism, I also found out that a significant percentage of patients with autism have mitochondrial dysfunction, up to 80%.  Now, autism, as you know, thousands of disease, hundreds of disease put into one diagnosis, and there would be different phenotypes.  Some may be because of the folate issue.  Some may be because of the mitochondrial issues.  Another may be because of a gut issue.  So, I think one treatment doesn’t fit all.  We found this scientist, and we collaborated with him and came out with this test, which he has been working on it for a long time.  That’s how the Mitoswab came into picture.  It’s a buccal swab test, very easy to do, non-invasive.  It mimics the muscle biopsy, and it has been compared to the muscle biopsy with a 84% correlation, which is published in a peer-reviewed journal.

Dr. Weitz:                          So, the muscle biopsy is, prior to this test, has been the only real test of a mitochondrial status, right? Where you actually biopsy part of the muscle?

Dr. Ganeshan:                   Yes. The muscle biopsy is being considered the gold standard. But for primary mitochondrial disease, now the genetics is taking over from the muscle biopsy because of the easy nature of doing genetics. But, overall, muscle biopsy is considered the gold standard.

Dr. Weitz:                          Right. But, of course, the average patient who maybe is coming to see a functional medicine practitioner for some mitochondrial or some condition that’s related to mitochondrial dysfunction, they’re not going to be good candidates to get a muscle biopsy?

Dr. Ganeshan:                   Absolutely, and we don’t have the kind of expertise or the knowledge house to even man it. There’re only a few people in the country who can read a muscle biopsy today. It’s going out of favor. So we need new tools and hopefully, this is a good start.

Dr. Weitz:                          I gave a little intro about the mitochondrion, but maybe you can explain a little more about exactly what a mitochondrion is and why is it so important for health?

Dr. Ganeshan:                   Ben, you did a fantastic job. There’s only very, very less I can add to that. The mitochondria, as Ben mentioned, is the primary energy source, the energy currency producers in the cell. He went in depth by telling that only the red blood cells don’t have mitochondrion, and why is that? It’s because red cells carry oxygen and so mitochondria uses this oxygen to produce energy. If that the case, red blood cells can’t carry oxygen. So, that’s God’s gift to humanity, I believe.  But, on a serious note mitochondria, the function from two to 60 years is kind of very standard and then after 60 it starts declining. That’s why when it starts declining you see a series of disease coming into our life, like cardiovascular disease, neurodegenerative disease. These are diseases of the old age. So we see them coming back.  For a healthy aging, you want your mitochondria optimum. You want it optimized. So that’s very important and that’s… The doctors are now realizing that.  The practitioners are treating that very well and there are a lot of tools to do that.  Exercise, for example, is one of them.  It’s shown consistently that it improve mitochondrial function.

Dr. Weitz:                          By the way, are you familiar with particular forms of exercise and which is the most effective form of exercise to improve mitochondria?

Dr. Ganeshan:                   Yeah. There are different studies to show that. What they call as a regular exercise, which is consistent and which is applicable to all humans, everybody, is what is making a difference.

Dr. Weitz:                            So, for example, aerobic or cardiovascular exercise versus resistance or strength training, is one of those better? Or is short bursts of aerobic exercise versus lower intensity, longer duration?

Dr. Ganeshan:                   Low intensity has shown benefit. Resistance exercise has definitely shown… These are studies I am quoting. They have shown that they are better. More intense exercise, I think, we can avoid. It’s not applicable to common… But a sports’ person, yeah, that’s very much applicable. But for a common man, I think, consistent resistance training is definitely important for muscle mitochondrial functions. So resistor, it’s very important. Yeah.

Dr. Weitz:                            Okay. And I’ve heard people discuss strategies for improving mitochondrial density?

Dr. Ganeshan:                   Yes, yes. So, to go back to the basics. The food we eat enters into the mitochondria through complex one. There are five complexes. Enters into the mitochondria through complex one and two as electrons. Now they are transported through the complex three into complex four where the oxygen we inhale is converted into water. So the mitochondria plays two important roles. One is breaking down the food we eat. The other one is converting the oxygen into water, the oxygen we inhale. 95% of the oxygen we inhale is converted into water. 5% escapes and forms oxygen free-radicals. And 5% is okay. They are known to act as signaling molecules like you pointed out.  And beyond that 5%, maybe if it’s 20% of oxygen escapes and forms oxygenated free-radicals, that’s when your body starts getting affected [negatively]. They damage the proteins, DNA in your cells, so that becomes a problem and that might-

Dr. Weitz:                          Let me just stop you for a second, so too much free oxygen is a free-radical and that can cause damage to the cells.  A certain amount is important for signaling, but too much, like you said… For example, 5% might be good as a signaling agent but 20% would be too much and cause cell damage?

Dr. Ganeshan:                   Absolutely right. That’s right. So, we can measure that in the Mitoswab. We can approximately tell you that what’s happening there. Mitoswab is very specific and it just helps you understand better.  But then, the complex four is where the energy is produced, ATP is produced. Because of this energy production, electrons escaping out, hydrogen molecules escaping into the… Creating an electro-chemical gradient in the outer membrane. What happens is the ATP is produced because of that. Because if there is a high electro-chemical gradient outside, it wants to come inside. It’s like putting more pressure, water, it’s like a dam. You save water, it wants to come out and you open up, the turbine moves and it produces electricity. It’s the same mechanism ATP is produced from ADP. Now, ATP is very important for many functions. You pointed out quite a few of them and that’s what the mitochondria does.  So, if there is a problem in the first four complexes, then there is definitely a problem with energy functions. There is leakage. We don’t want to go into complexities but it definitely affects the mitochondria, hence the body, and clinical symptoms manifest.

Dr. Weitz:                          Okay, so these different complexes you’re talking about, there is this complicated chain of processes that leads to ATP energy production, right?  And these are different pathways in that process is by… When you talk about complex one, two, three, four and five?

Dr. Ganeshan:                   Absolutely, absolutely. And certain diseases are associated with certain complexes. For example, the complex one is associated with many diseases including diabetes is one of them, neurodegenerative disease et cetera, neurodevelopmental disease. But complex four is affected with neuromuscular disease, seizures and things like that. So, there’s a lot of evidence, there’s a growing body of evidence as well. The complex three, for example, is very, very important in T-cell regulatory function, endothelial function. So every… They play a very critical role. Your defense against infection, and your defense against inflammation and things like that.  So, mitochondria is not only energy producers but also many other functions, very important, critical to the human survival.

Dr. Weitz:                          You mentioned complex one is related to the cause of diabetes. So diabetes is also considered a disease where mitochondrial dysfunction is important?

Dr. Ganeshan:                   Absolutely and there is a lot of research, ongoing research, and published research as well.  And if you look at drugs, metformin acts on the mitochondria.  It actually boils down to that critical level at that point.  So definitely, yes, diabetes is considered part of a mitochondrial dysfunction.

Dr. Weitz:                          So what does that say, practically, for those of us who are managing patients with diabetes? And by the way, I found in some of the articles that metformin can actually be a negative for mitochondria.

Dr. Ganeshan:                   Yes. So metformin, definitely works through the mitochondrial pathways.  So that’s why when you give every drug, you have to check where the effect is, like for example, statins affect, reduce CoQ10, that’s ubiquinol. And that’s very important for the electron transport from complex one and two to four. So, they’re electron carriers, that’s very important.  Now statins decrease CoQ10.  In the United States it’s not every practitioner prescribes CoQ10 along with statins.  But it’s good when your body is good, let’s say up to 50, 60 years. Then your production, internal production of CoQ10 comes down and then you give statins over that.  Then the long-term effects of that is… We don’t know but definitely we can predict something that if your CoQ10 is low, your mitochondria is not functioning well.  That’s why in countries like Japan, it’s mandatory to give CoQ10 along with statins. So, if you put a statin prescription in Japan, you have to prescribe CoQ10 as well.

Dr. Weitz:                            Yeah, I interviewed Dr. Barrie Tan recently, and he was talking about the importance of having patients who take statins, also take tocotrienols which also helps to protect their CoQ10.

Dr. Ganeshan:                   Absolutely. So there are other compounds have been… Ubiquinol is the most important one. There are other compounds as well. Avidin, is one of them. Definitely it’s easily available and there are a lot of developments which have happened in that space.



This episode of the Rational Wellness podcast is brought to you by Mitoswab which is the only non-invasive test for the mitochondria. We know that the mitochondria are the energy powerhouses of our cells. And that a breakdown of our mitochondria can play a role in many chronic health conditions, including chronic fatigue, congestive heart failure, and even cancer.

But until now, the only way to measure mitochondria has been to do a painful, invasive biopsy of our muscles. But now, by swabbing your cheek, the Mitoswab test can help us to analyze mitochondrial function by measuring the activity of the electron transport chain. And it has an 84% correlation with muscle biopsy. If you are a doctor, go to mitoswab.com to sign up and order a test kit. Or call 484-534-9311.

 If you are a patient and you have interest, you need to see a functional medicine practitioner, like myself, who could order the Mitoswab as part of the testing protocols for an analysis of your overall health to help set you up on a program to improve your health and prevent chronic diseases.

 



 

Dr. Weitz:                            So coming back to diabetes, what can we do for managing patients with diabetes, if we now know that part of the diabetes process involves mitochondrial dysfunction?

Dr. Ganeshan:                   Excellent question. You want to think about… When you have a patient with diabetes, your multi-system is affected. It’s not just one system is being affected. Your multi-system is affected. And you want to… Earlier on the cycle I think there are pioneers in this field who are looking at mitochondrial function in diabetes. For this to come to mainstream it’s going to take another 10, 15 years. Because we don’t have the tools to do that, optimized tools and it’s not part of any guidelines.  So right now, treat them as you treat, but also look at the mitochondrial function. By improving the mitochondrial function, you may be able to optimize the drugs, reduce the number of drugs, get the patient better, or reduce the side effects of diabetes, like vascular dysfunction, improve cardiovascular dysfunction, or things like that. You may be too long term, diabetes is not a short-term disease.  It’s effect is long term.  It’s years and years.  So you want to minimize by improving the mitochondrial dysfunction. Your requirement of medications may decrease. It’s not shown in any studies. I am sure somebody is working on that. But definitely that’s something, the pathway to go to improve mitochondrial function. So you optimize the patient overall.

Dr. Weitz:                            Right. So, you’re saying that when we have a patient with diabetes, in addition to looking at a lot of the typical things we might look at like, blood sugar and hemoglobin A1C and advanced lipid analysis and inflammatory markers, we might look at mitochondrial function by say, giving the patient the Mitoswab test as part of better managing their condition?

Dr. Ganeshan:                   Absolutely, this could be one of the tools available, easy tool to see what the mitochondrial… See, in functional medicine you want to optimize the patient, you want to reduce the patient’s disease burden.  You want to be preventing. I think, when you talk of preventing, less medicine, mitochondrial function becomes critical. Like, if you take neurodegenerative disease.  Now, we are expecting to have 14.2 million people with Parkinson’s in 2040 and 14 million people with Alzheimer’s. That’s a huge burden on the society.  If you look at Parkinson’s disease, that’s clearly linked to mitochondrial function.  There is a lot of evidence. You can search the publicly available peer-reviewed evidence.  There is a lot of evidence on Parkinson’s and mitochondria.  In fact, some of the mitochondrial genes have been implicated in Parkinson’s disease.  Now by identifying earlier on, you may… This may be too early to the cycle, but if you may be identifying a vulnerable patient, by taking action and correctly following up, for example, at least this stage, somebody with a family history of neurodegenerative disease or Parkinson’s disease. You may want to identify if there is a mitochondrial dysfunction. And you want to kind of take, at least, that one equation out of your cycle. There may be other factors, environmental and unknown factors, but at least you are taking… By improving mitochondrial function, you are able to clean up your body better. You are able to chelate chemicals better. You are able to remove unwanted substance better.  I think the mitochondrial function plays a critical role in kind of modifying that. I think the future research, if you see the number of publications in mitochondria, they’re tremendously improved. There is a significant improvement of publications on neurodegenerative disease and mitochondrial function.  I think the next 10, 15 years you will see a significant improvement in mitochondrial diagnostics and management of mitochondrial-

Dr. Weitz:                            Interesting. Is there data to show that if we… Let’s say, we work up a patient for Parkinson’s from a functional medicine approach and we’re trying to look at various markers of disease progression. And we add mitochondrial analysis, say through the Mitoswab. If we can improve that, does that correlate with better outcomes for Parkinson’s?

Dr. Ganeshan:                   Yeah, these are long-term studies. We don’t have data at this point of time. We have some animal data showing that improving mitochondrial function, may improve our outcomes. And we have also some human data as well. But we need more work on that. We need to understand more advances there. And I am pretty sure that 10 years ago, 15 years ago, if somebody talked about the microbiome, you were an alien. So, today, mitochondria is kind of the next generation thing.  I think you can definitely decrease the disease burden, improve outcomes. We don’t have evidence because these studies will take 10, 20 years to do, to prove that and so we have to look at large databases. And with the tools like artificial intelligence and data analysis, I’m sure we can come out with some solid data.

Dr. Weitz:                            Right. But do we have data now showing that patients with more advanced Parkinson’s, Alzheimer’s tend to have worse scores, on say the Mitoswab test?

Dr. Ganeshan:                   We are collecting data. We don’t have that published data as of today. But definitely that’s a goal that… We are definitely collecting data that retrospectively ask, talking to physicians consistently doing that. But I am pretty sure that it will be available in, maybe two years’ time.

Dr. Weitz:                          Interesting. Have you talked to Dr. Dale Bredesen, who has his program for prevention and reversal of Alzheimer’s?

Dr. Ganeshan:                   Very briefly, yes. Very brief.

Dr. Weitz:                          I would think he’d probably be interested in this as another marker for being able to gauge progress in making some progress against some patients with some of these very serious neurological diseases.

Dr. Ganeshan:                   Yeah. He had expressed interest. But the contracting and the process takes a long time for clinical studies.

Dr. Weitz:                          Okay. You mentioned cardiovascular disease. What part does mitochondria play in cardiovascular health and disease?

Dr. Ganeshan:                   Many. I mean, if you look at all the heart-failure patients. Mitochondria are significant. So muscle function. Let’s go to the basics again. You mentioned that different parts of the cells have different type, different number of mitochondria per cell. Like if you look at the skin. Skin may have 10 mitochondria per cell. There is only one nucleus per cell. But if you look at the muscle, which has more energy needs, you need thousands of mitochondria per cell. And if you look at the brain cells, it’s similar, it’s more energy needs. So based on the energy needs, the number of mitochondria per cell also differs. Heart cells naturally need more energy and they have more mitochondria.

One of the hallmarks of heart failure and if you look at… There is one actually published paper every month or two or three published papers in heart failure and mitochondrial function. So definitely mitochondrial function plays a critical role in heart failure. So one of the things we are trying to do is validate this test with the heart muscles as well. And also look at whether, by treating these patients, by producing the energy production, by making the heart muscle function better, pump better, making more energy, are we able to have better outcomes? Are we able to delay the process of heart failure? So, we are thinking in that direction.

There is also a recent paper looking at coronary vascular disease and mitochondrial function. Especially the electron transport chain, was published within the last two months. A very nice paper looking at electron transport chain function and cardiovascular disease, heart failure. I am talking of coronary vascular disease.  So, by measuring it, are you predicting that, “Hey, a low mitochondrial function patients may be vulnerable to cardiovascular disease-

Dr. Weitz:                          So, how does the mitochondria play a role in this process that we normally think of as involving an inflammatory, oxidized LDL particles, creating plaque in the arteries?

Dr. Ganeshan:                   Fantastic question. So the LDL deposits the cholesterol in the heart vessel walls and the HDL picks up those cholesterol and takes it to the liver for degradation. And that process involves a process called reverse cholesterol transport. And that process involves ATP.  ATP plays a very significant role there.  And that’s energy dependent process.  So mitochondria definitely plays a role there, in cholesterol transport, and also in the health of those patients.

Dr. Weitz:                          Interesting. So, what you’re saying is some of the nutritional things we do to support the mitochondria, say like nutritional supplements like Coenzyme Q10, L-Carnitine, D-ribose, alpha-lipoic acid. Things like that, that tend to support the health of the mitochondria, it’s now part of functional medicine protocol to use those for patients with congestive heart failure. But you’re saying that those will be beneficial for patients with atherosclerosis as well.

Dr. Ganeshan:                   Yeah, so atherosclerosis is a chronic disease, I would say. It goes for a long period of time. And you only don’t know when it develops and when it kind of ends, right? So you don’t know when it starts. There are very less tools to identify that right now, and there are some tools now, but definitely I am looking at mitochondrial function plays a critical role in that cycle. That’s what that paper also kind of suggested.  Definitely, all the supplements you mentioned, they have critical roles. For example, carnitine helps in the transport of long-chain fatty acids, that is fatty acids with more than 14 carbon atoms, into the mitochondria. Now, the small-chain fatty acids, they enter the mitochondria without any help. But carnitine is used to transport long-chain fatty acids. CoQ10 is an antioxidant and helps in the transport of electrons. It’s an electron transporter. It helps in the transport.

Dr. Weitz:                          By the way, what are some examples of short-chain fatty acids and what are some examples of long-chain fatty acids?

Dr. Ganeshan:                   Yeah. The short-chain fatty acids, you are talking of butyric acid, propionic acid and things like that which is less than six carbon atoms-

Dr. Weitz:                          And those are typically produced by gut bacteria?

Dr. Ganeshan:                   Absolutely right. I mean, there is a lot of evidence on butyric acid especially, very important for the colon function. And butyric acid also improves mitochondrial function, especially. We have papers in the autism kids showing that butyric acid helps the complex four function. And overall modifying the mitochondria. So, very important-

Dr. Weitz:                          And we could probably add medium-chain triglycerides such as from coconut oil as well, right?

Dr. Ganeshan:                   Yes, they have a different role to play. But short-chain fatty, especially the butyric acid is very critical to mitochondrial health and everything and also the mitochondrial function. The large, long-chain fatty acids, palmitic acid and things like that, normally available in your food. So they don’t have-

Dr. Weitz:                          So, these are found in things like saturated fats and polyunsaturated fats, like omega-6’s and omega-3’s.

Dr. Ganeshan:                   Yes. So, carnitine is needed. If you do a carnitine profile and carnitine is low, that means your long-chain fatty acid is not entering the mitochondria. Now if you take fat, they produce more energy per molecule that’s compared to carbohydrates. That’s also very critical technically speaking. So-

Dr. Weitz:                          Nine calories per gram for a fat versus four calories per gram for a carbohydrate and that’s a measure of energy.

Dr. Ganeshan:                   Good, yeah. That’s something like that. Certain diseases for example, you are talking of keto diet and that sort of thing, so you want to be very careful as well. You don’t want to give a supplement just for the sake of giving it.  For example, if you’re looking for carnitine, you want to give carnitine. You want to know if this patient really needs carnitine.  You don’t want to throw in carnitine just like that. You what to know whether the… what is the rule, what supplement you… You don’t want to over-supplement. You don’t want to under-supplement. You want optimal supplementation. And you want to know only what cofactors are needed.  For example, the cofactors for complex one and four are CoQ10 and people have been using NADH. NADH is good for complex one. So it’s supplement riboflavin for complex two. The supplement cofactors differ. You want to be careful on what supplement you give. What is the amount you give. Things like that. To add to that point, we don’t have a FDA approved drug for mitochondrial dysfunction.

There are several companies investigating and focusing that in the next few years. There are several drugs, focusing on mitochondrial functioning into that market. So that will really give a boost to this whole world and education, physician education. In addition to people like you who are trying to get the word out, there is also going to be these companies putting their resources behind, to develop the education tools for physicians to understand.

Dr. Weitz:                          But there are certainly studies say, for example, with congestive heart failure that CoQ10, L-carnitine and D-ribose have all been shown to be beneficial?

Dr. Ganeshan:                   Absolutely. Absolutely. Yeah, absolutely. So-

Dr. Weitz:                          This is something that’s been pointed out a lot of times by Dr. Stephen Sinatra who has written a lot about this.

Dr. Ganeshan:                   … No, absolutely. Definitely, the nutritional supplements which help mitochondria have shown benefit in double-blind placebo-controlled studies. CoQ10 is one of them, which is used. For example just imagine this, this is just… I don’t have the evidence to talk, but look at it, if somebody’s having statins for 30 years or 25 years. And consistently, one point of time, the body is able to keep up producing CoQ10. At one point of time you become a little older and the body’s ability to produce CoQ10 decreases. What happens in that case scenario? There is no studies to prove that, but just we need to be proactive in thinking in that direction. So we are able to… And so research studies have to be designed on that too.

Dr. Weitz:                            Interesting. In addition to your Mitoswab test, since we’ve been talking about cardiovascular disease, you also have been instrumental in bringing to the market a cholesterol efflux capacity test. Can you tell us what that is and…

Dr. Ganeshan:                   Yeah, fantastic. This is a very new test we launched last week. The cholesterol efflux is the first step in the reverse cholesterol transport. As I mentioned earlier, the LDL deposits cholesterol in the blood vessels and HDL picks it up, brings it to the liver for degradation. Now-

Dr. Weitz:                            By the way, for people who are not familiar, for the laypersons who are listening to this, LDL is the so-called bad cholesterol because it tends to be involved in the process of leading to clogging of the arteries. Whereas HDL is the so-called good cholesterol because it takes some of that cholesterol from the arteries and remove it from the body.

Dr. Ganeshan:                   Absolutely. Thank you for pointing this out. So this is a very good way of explaining. LDL is considered the bad cholesterol and HDL is considered the good cholesterol. But, we have traditionally reduced LDL by taking statins. Statins are very successful in reducing LDL. But they don’t have an effect on the HDL. There are several drugs which have been tried-

Dr. Weitz:                            They also don’t do anything about increasing LDL particle size, or…

Dr. Ganeshan:                   … Yeah, so when you go back to the HDL, HDL is very important. You want HDL, that’s the good cholesterol within a particular range. You don’t want to have it too low. You don’t want to have it too high, that means more than 100. I mean, very few people have that kind of level. What you want to do-

Dr. Weitz:                            Usually if the HDL is too high, that’s because it’s not functional, right?

Dr. Ganeshan:                   … Yes, too high is also not functional. Too low is also not getting loose. So you want it somewhere in a good range, somewhere above 40, somewhere less than 90, 80.

Dr. Weitz:                            Now, prior to this test, basically the best measure we have is if the HDL particles are larger, then that’s an indication that they are more likely to be functional?

Dr. Ganeshan:                   Yes, you’re right. And HDL particles has also been examined in double-blind placebo-controlled studies. The cholesterol efflux is studied and published more than 4,800 times in peer-reviewed journals including 14 papers in the New England Journal of Medicine. That’s very well described, but converting that into a commercially available test has been very difficult. The reason being, it’s a cell-culture assay. It’s a very cumbersome process. So we’ve been able to do that. It’s a proprietary test. We’ve been able to do that. Our lab is one of the best, our partner lab, which we kind of collaborate is one of the best labs in the vascular medicine. They mostly work with research groups and pharmaceutical companies. We thought there is a critical need for this test for patients and so we are trying to get it to patients.

So coming back to the HDL transport, in the reverse cholesterol transport the first step is, getting the cholesterol outside the blood vessel walls, the macrophages there. That process is called cholesterol efflux and that process is also energy dependent. There is a mitochondrial component there. But also if that process is not working properly, there’s a problem. You may have a good HDL level. You may have a good HDL level. You may not have a good cholesterol efflux. So that means your HDL level is not going to matter. So there are studies showing that independent of the HDL, LDL and cholesterol particle size, cholesterol efflux is an independent risk factor for patients who do not have diagnosed heart disease and people who have diagnosed heart disease, or coronary vascular disease.

So, it’s considered an independent risk factor. If you look at the drugs which were developed to increase HDL, they all increased HDL. They did that function, but that increase in HDL is not translated into improved cardiovascular outcomes. That’s what many of these drugs fail. Now, one of the reasons for that is that they didn’t translate it into a cholesterol efflux function. They didn’t account for that. So that becomes very important and I hope this marker is going to help a lot of people.  Also recently, this cholesterol efflux has been compared to coronary CT. Now coronary CT is becoming very popular because of it’s cost-effective and it’s producing something called-

Dr. Weitz:                          You’re talking about the coronary calcium scan, right?

Dr. Ganeshan:                   Yes, absolutely. So that’s becoming popular but there was a correlation study recently published within the last five days, looking at whether it’s compared to the… This is the only one which was compared, cholesterol efflux, the only one, which was compared to coronary calcium score. So I think combining, people have come up with scoring systems and things like that and no drug currently available improves cholesterol efflux. The only thing which will improve is exercise, which is showed in a study and also behavioral modification.

So it’s very important to understand your risk score. So somebody comes to you, for example, tomorrow to understand, “Hey I have a family history of heart attacks and what do I do?” So, one of the things you may want to consider for this particular patient is the cholesterol efflux test.  I am hoping that in the next few years, maybe three to five years, this becomes part of the guidelines recommendation by the American Heart Association. That’s the expectation, hopefully. That’s something-

Dr. Weitz:                          So, other than exercise, are there any nutraceuticals or dietary changes that can be beneficial for improving cholesterol efflux?

Dr. Ganeshan:                   Good question. So, we have seen exercise in a very notable study shown to improve cholesterol efflux. That’s the only one which has shown. Nutritionally, there are studies which are shown to improve but I think we need more studies. There are definitely studies that by improving mitochondrial function they have shown to improve cholesterol efflux but definitely we need more robust studies, well-designed studies.

Dr. Weitz:                          What about niacin? Can that improve cholesterol efflux?

Dr. Ganeshan:                   Niacin has been studied but it’s not shown to improve cholesterol efflux.

Dr. Weitz:                          Okay. So right now, we don’t have anything?

Dr. Ganeshan:                   No, nothing. One of the things we may consider, there are studies in corporate and other things, that may be something to consider but we still need that much more well defined double-blind-

Dr. Weitz:                          I see, interesting. The studies that were done with CoQ10, do you know any idea what the dosages used were?

Dr. Ganeshan:                   I don’t know off the top of my head but CoQ10, is a number of factors… CoQ10, the dosage matters, the formulation matters. It’s very sensitive to light, it gets oxidized. So, there are a lot of factors in CoQ10. And I’ve been… Even though we don’t have the evidence to support, selecting a good CoQ10 is also an art, I say. We need standardized protocols for a good CoQ10.

Dr. Weitz:                          What do you mean a good CoQ10?

Dr. Ganeshan:                   How they are transported, how they are protected against light and things like that. What is the formulation? Because we need to… There is also an attempt to make CoQ10 a drug. But I think the supplement companies need to come together and find lot of absorption studies and things like that.

Dr. Weitz:                          So, as far as I know, all I’ve heard is that we have ubiquinone and ubiquinol and then there’s one company that has a product called MitoQ. What are you referring to in terms of formulation?

Dr. Ganeshan:                   For example, MitoQ, they’ve done a fantastic job, do a lot of research studies. They are published as well. So I would give them the benefit, but it’s also… But there also other more CoQ10s which work. There are two main manufacturers of CoQ10, one of them is a company called Kaneka and there’s another one in New York. The New York one is a bacterial fermentation process. Kaneka is a different process. The finer details, we need to understand. And also who is repacking them and things like that? Is the process much more cumbersome? So I am not telling anything bad or anything but definitely some CoQ10s definitely did not see any effect but some when you change the brand, it’s effective. So we need to kind of work on that. For example, the CoQ10 available in Costco works brilliantly.

Dr. Weitz:                          Say that again?

Dr. Ganeshan:                   The CoQ10 available in Costco works very well. Metagenics has a good brand and there are several companies which have good brands. Qunol is good.

Dr. Weitz:                          Okay. And we can monitor this by using the Mitoswab test for its effect, right? Or no, we’re talking about the cholesterol efflux test.

Dr. Ganeshan:                   Cholesterol efflux test is a good test. Cholesterol efflux test is a good test. What we can do-

Dr. Weitz:                          It’s a serum blood test?

Dr. Ganeshan:                   Yes, it’s a serum blood test. It can be used to kind of identify the issue and also monitor the effect of the issue long term.

Dr. Weitz:                          So, practitioners who want to utilize these tests, they can do the tests through your lab, is that right?

Dr. Ganeshan:                   Yes. So currently we are the only lab which are offering commercially these two tests. Cholesterol efflux is offered by some research labs at this point of time. But we think our methodology is kind of superior to the existing methodologies and so we think we offer a very unique methodology and very validated methodology.

Dr. Weitz:                          So, practitioners could call your company and get a test kit and then-

Dr. Ganeshan:                   Yes, absolutely. Absolutely. We launched it last week.

Dr. Weitz:                          Last week? Well, no wonder, I talked to a cardiologist. He said he wasn’t familiar with it. So-

Dr. Ganeshan:                   Yeah, so we are getting a lot of calls. We didn’t even advertise but we are getting a lot of calls because I do believe that this test is going to be used uniformly by everybody.

Dr. Weitz:                          What is the approximate cost?

Dr. Ganeshan:                   We work with insurance mostly. The out-of-pocket maximum should be around $300.

Dr. Weitz:                          Okay. Are you finding that some insurances are picking it up?

Dr. Ganeshan:                   Possibly, yes. For cholesterol efflux we are just awaiting approval. But for Mitoswab, Medicare pays for Mitoswab.

Dr. Weitz:                          Oh, interesting. How about commercial insurance? Are they-

Dr. Ganeshan:                   No, we work in network, but some of them pay. Some states, Medicaid also pays for Mitoswab. We’re waiting to become in-network provider for those insurances. But yeah, our goal is to get it approved by insurance.

Dr. Weitz:                            Great. Great. So how do practitioners get ahold of your lab? Where would they go to? Should they go to the website?

Dr. Ganeshan:                   Yes, we have a website www.religendx.com. Also we have another website-

Dr. Weitz:                            What was that again? www-

Dr. Ganeshan:                   … Religen, R-E-L-I-G-E-N-D-X.com

Dr. Weitz:                            Okay.

Dr. Ganeshan:                   Or they can also visit Mitoswab. We have a separate website for Mitoswab since we started with that. So they can go there, and leave an email.

Dr. Weitz:                            So they can go to Mitoswab, M-I-T-O-S-W-A-B.com?

Dr. Ganeshan:                   Absolutely right. And they can call us. They can email us.

Dr. Weitz:                            What’s your phone number?

Dr. Ganeshan:                   Our phone number is 484-534-9311.

Dr. Weitz:                            Okay. And what’s the approximate cost? What’s the cost of the Mitoswab, if the insurance doesn’t cover it?

Dr. Ganeshan:                   The maximum out-of-pocket for insurance is $400 for the patient.

Dr. Weitz:                            400? Okay.

Dr. Ganeshan:                   That is the maximum out-of-pocket for the patient.

Dr. Weitz:                            Okay. So they supply their insurance, you try to bill the insurance and if the insurance doesn’t cover it, then the max would be 400.

Dr. Ganeshan:                   Yeah. So, some of the patients don’t want to deal with the insurance and so for them the maximum out-of-pocket will be $400.

Dr. Weitz:                            Is there a discount if they just pay cash upfront?

Dr. Ganeshan:                   No.

Dr. Weitz:                            Okay.

Dr. Ganeshan:                   Upfront or later is the same thing. So, no.

Dr. Weitz:                            Okay, sounds good.  So, I appreciate the information you brought us Dr. Ganeshan. This is really interesting, another tool in our arsenal to help manage our chronic disease patients. Now we finally have a non-invasive way to monitor their mitochondrial function. So, I think this is very exciting.

Dr. Ganeshan:                   Thank you. No, no, it’s a very important tool, I think. Last 10, 15 years we heard about microbiome. We learnt a lot and we are still learning. And the next 10 years we continue to learn about microbiome and we’ll also start learning about mitochondria. The good thing is that mitochondrial medicine, there is lot of activity in the recent years. There are companies which are developing drugs, like companies which are developing diagnostics like us. We need a good, healthy competition. We need to get the best for the patient and good tools for the practitioners to identify and take effective action.

So, I think it’s a very exciting time for the mitochondrial medicine world and the experts are coming together. There’s in fact a conference, I’m thinking of attending, the George Washington University of Integrated Medicine is organizing in Dallas next… in October. So, things like that. I think you’ll hear a lot about mitochondrial medicine in the next, coming years.

Dr. Weitz:                            Actually, we’re announcing right here on this podcast that the next decade is the decade of the mitochondria.

Dr. Ganeshan:                   Yeah. Thanks to people like you, yeah. So hopefully that is… Because I think we can solve a lot of problems, unidentified problems. We don’t know why we get this… Why there is an increase in cardiovascular disease. We don’t know why there is an increase in neurodegenerative diseases. We may have an answer. Part of the answer may be lying here, what we know. I think we need more research and we need more evidence to take action. So, I think that we are going in that direction.

Dr. Weitz:                            Awesome. Thank you, Dr. Ganeshan.

Dr. Ganeshan:                   Thank you, Dr. Weitz. Thanks a lot. I appreciate your time and having us in the call.

 

Weitz Sports Chiropractic and Nutrition
Weitz Sports Chiropractic and Nutrition
Tocotrienols with Dr. Barrie Tan: Rational Wellness Podcast 127
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Dr. Barrie Tan discusses Tocotrienols with Dr. Ben Weitz.

[If you enjoy this podcast, please give us a rating and review on Itunes, so more people will find The Rational Wellness Podcast. Also check out the video version on YouTube at https://www.youtube.com/user/weitzchiro/]

 

Podcast Highlights

2:52  Dr. Tan was interested in studying carotenoids and in 1982 he got a grant from the Malaysian government to study palm oil and he was trying to figure out what kept palm oil so stable and he discovered tocotrienol.

4:00  Vitamin E is a family of molecules that includes alpha, beta, gamma, and delta tocopherol and alpha, beta, gamma, and delta tocotrienols. Alpha tocopherol was first discovered and was first called vitamin E in 1922. It was called tocopherol from Greek words meaning birth and to bear or carry because it was found to be essential for fertilized eggs to result in live births in rats.  Even today, alpha tocopherol is considered to be vitamin E and most of the research has been done with alpha tocopherol and it is most well known as an antioxidant. If you go the Linus Pauling Institute Micronutrient Information Center at Oregan State University in a long article on Vitamin E only a few sentences are devoted to tocotrienols.  Both tocopherols and tocotrienols look similar but the tail of a tocopherol is long and it is saturated, while the the tail of a tocotrienol is shorter and is unsaturated.  This tail allows tocotrienols to function differently than tocopherols.  Dr. Tan believes that the data that has shown the benefits of vitamin E was really attributable to tocotrienols rather than to tocopherol, which are both found in some of the same foods, which is why so many of the studies of vitamin E done with alpha tocopherol failed to prevent heart disease or cancer or cognitive decline or to decrease mortality.  Researchers Asaf Qureshi and Charles Elson at the University of Wisconsin first discovered in the 1980s that tocotrienol rather than tocopherol caused the reduction of cholesterol, esp. LDL, through the post-transcriptional suppression of HMGR (3-hydroxy-3-methyl-glutaryl-CoA reductase), which is the enzyme responsible for cholesterol synthesis.  Unlike statins, which also block CoQ10 synthesis, tocotrienols do not block CoQ10 synthesis, and tocotrienols can also be added to Red Yeast Rice or to statins and it enhances the effects.  When tocopherol was added to tocotrienols, it blunted the effect to lower cholesterol.  So to achieve the therapeutic benefits of tocotrienols, they must be taken apart from tocopherols.

7:22  Alpha tocopherol may actually have a negative effect on lipids. In studies where tocotrienols are shown to lower cholesterol, when tocopherols were combined, the ability of tocotrienols to lower cholesterol were blocked.  This likely explains why some of the studies on vitamin E showed little or no benefit.  Dr. Tan mentioned that tocotrienols also lower triglycerides and that they can also work synergistically with EPA/DHA fish oil for this purpose.  Here is a study showing that tocotrienols can protect against the lipid oxidation of fish oil more effectively than tocopherols:  Antioxidant activities of annatto and palm tocotrienol-rich fractions in fish oil and structured lipid-based infant formula emulsion.

14:40  Tocotrienols have been shown to have an anti-cancer effect in cellular and animal studies against bladder, brain, breast, cervical, colon, gastric, leukemia, lung, ovarian, pancreatic, prostate and skin cancer.  There are currently a number of clinical trials using tocotrienols in humans with cancer, including a phase 2 trial that was recently published on ovarian cancer. They looked at patients with metastatic ovarian cancer and gave one group Avastin and the other group Avastin plus tocotrienols–300 mg three times per day and their survival doubled at 12 months and was 25% increased at 24 months.  Dr. Tan did not think that taking tocotrienols is a problem for patients taking traditional chemo or radiation because the effect of both is not simply as a pro-oxidant but have a number of mechanisms by which they fight cancer and taking tocotrienols has not been shown to reduce their effects. In fact, so far, the opposite has been shown to be true.

21:00   Tocotrienols have been shown to improve bone health in post-menopausal women. Dr Tan talked about a study done at Texas Tech University with women with osteopenia that showed that tocotrienols improved bone formation by 100% and reduced bone breakdown by 15% and reduced oxidative stress by 48% [Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial.]  Calcium is a constituent in bone. Vitamin D is a chaperone to escort the calcium into the bone. Vitamin K2 helps to form osteocalcin which helps to trap the calcium in the bone.  Tocotrienol both increases osteoblastic activity and reduces osteoclastic activity, which improves bone density and strength over time.  The bisphosphonate drugs like Fosamax and Actonel reduce osteoclastic activity, so while you get an increase in bone, there is a tendency to get an accumulation of weaker, junky bone and it can cause osteonecrosis of the jaw.  But Dr. Tan has also developed another nutritional product called geranylgeraniol (GG), that will be available from Designs for Health, that can block this breakdown of the osteonecrosis of the jaw caused by bisphosphonate drugs.

25:57  Dr. Tan explained that they have studied delta tocotrienols for osteoarthritis and it improves joint health and cartilage repair and reduces inflammation.  In fact, tocotrienols reduced cartilage erosion by 200%.

27:17  Most plants that are good sources of vitamin E have both tocopherol and tocotrienol, like rice and palm.  Dr. Tan discovered that the annatto plant contains purely tocotrienols. When Dr. Qureshi, the researcher from the University of Wisconsin, found out about this, he told Dr. Tan that he was going to test it to see if it lowered cholesterol levels. Dr. Tan suggested that he also test to see if it also lowered inflammation, since this is a big factor in the pathogenesis of atherosclerosis. The study showed that tocotrienols lowered inflammation by 30% as well as lowering cholesterol by 20% and also lowering triglycerides.  Tocotrienols will also lower oxidized LDL, which is important since oxidized LDL is more atherogenic than LDL.  Here is a good review article on the benefits of tocotrienols for cardiovascular disease:  Tocotrienol is a cardioprotective agent against ageing-associated cardiovascular disease and its associated morbidities

30:55  Tocotrienols can also be beneficial for helping to reverse Non-Alcoholic Fatty Liver Disease (NAFLD).  A study showed that patients taking 600 mg tocotrienols per day and it lowered liver enzymes 15-20% and reduced C-reactive protein, a measure of inflammation.  NAFLD is common in patients who are overweight and tocotrienols also helped with weight loss. After taking tocotrienols for 3 months, patients lost 10 lbs and they lost 20 lbs after only 6 months.

36:05  Recommended dosages for tocotrienols: 600 mg for fatty liver; for cancer 400-500 for stage one but 900 for metastatic disease; for patients with lipidemia or heart disease, 250-300 mg.

43:28  Dr. Tan explained that tocotrienols also kill cancer stem cells and this has been shown with prostate, breast, pancreatic, and skin cancers. Cancer stem cells are rogue cells that can continue even after you get rid of cancer.  Dr. Tan has also edited a text book on tocotrienols called Tocotrienol, Vitamin E beyond Tocopherol.

 



Dr. Barrie Tan is a PhD in chemistry, who is dedicating to researching Vitamin E.  Dr. Tan discovered tocotrienols 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 Tocotrienol product through his American River Nutrition Company.  Dr. Tan is offering a free book, The Truth About Vitamin E .

Dr. Ben Weitz is available for 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, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111 or go to www.drweitz.com.



 

Podcast Transcript

Dr. Weitz:            This is Dr. Ben Weitz, with the Rational Wellness podcast, bringing you the cutting edge information on health and nutrition from the latest scientific research and by interviewing the top experts in the field.  Please subscribe to the Rational Wellness podcast on iTunes and YouTube, and sign up for my free ebook on my website by going to drweitz.com. Let’s get started on your road to better health.  Hello Rational Wellness podcasters. Thank you so much for joining me again today. Please, if you like the Rational Wellness podcast, go to Apple podcasts and write us a review. That’ll help us come up in the searches for alternative health in Apple podcasts. Also, if you want to see the video version, go to my YouTube page, and if you go to my website, drweitz.com, there will be detailed show notes and a complete transcript.

Our topic for today is tocotrienols with Dr. Barrie Tan.  Some of us may not know what tocotrienols are. They are part of the vitamin E family, which consists of eight fat soluble iso forms. Alpha, beta, gamma and Delta tocopherol, and alpha, beta, gamma and Delta tocotrienols.  Most multivitamins only contain alpha tocopherol, which is generally what is considered to be vitamin E. One of the better sources for research on vitamins, The Linus Pauling institutes 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.

                                Dr. Barrie Tan is a PhD in chemistry, who’s dedicated to researching vitamin E, and is 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. And there’s an annatto plant right in the background behind Dr. Tan. And since palm and rice also contain substantial amounts of tocopherols, an alpha tocopherol inhibits tocotrienols. He produces annatto Tocotrienols product through his American River Nutrition company. Dr. Tan, thank you so much for joining me today.

Dr. Tan:               Thank you for the nice welcome. I look forward to the program and to your listeners who’s participating with us.

Dr. Weitz:            Absolutely. So Dr. Tan, what got you so interested in vitamin E, and particularly in Tocotrienols

Dr. Tan:               The year was 1982, ’83. I started as an assistant professor at the university of Massachusetts. I was there for about 12 years. And during that time I got a grant from the Malaysian government trying to study what kept the Palm oil so stable. So when I extracted all… at the time I was really interested in carotenoids because Palm oil is very bright orangy color. So when I remove all the fat, remove all the carotene, which is what I was interested in, there’s a few drops of something at the bottom.  And then I found out what it was; it was largely Tocotrienol.  When I reported back to the Malaysian government they say, “Oh, that’s just vitamin E. Is it?” “No, this is a little different than normal vitamin E alpha tocopherol. It does contain some, but it contain other peaks. And then I later found out to be Tocotrienols. So that was my simple start, probably 1984 or 1985 when I did it. This was long time ago.

Dr. Weitz:            Okay. And so vitamin E, as I mentioned, is not a single molecule. Can you give us a little more detail into what vitamin E is and how it was first discovered?

Dr. Tan:                It almost looked like if it weren’t me and a few others pushing for Tocotrienol, Tocotrienol probably never would have existed today. As you mentioned, Oregon State University only gave a tiny little sentence or two about Tocotrienol.  Tocopherol was found almost 50 years before Tocotrienol. And when it was found, it was known famously as vitamin E alpha tocopherol from UC Berkeley research. And it was to help the fetus to bring into full term. Most people don’t even know that, but probably know that it’s an antioxidant. But that was the reason.

                                Now if you fast forward 40 years, Tocotrienol was found. So very simplistically, structurally, a tocopherol has a head and a tail, like that. And the tail is saturated. A Tocotrienol, same kind of head and a tail. The tail is shorter slightly. And then they have double bonds, so it is unsaturated. So chemically, a tail of a Tocotrienol is unsaturated, otherwise look pretty similar, both as antioxidant. And now if you fast forward almost 100 years later, just about every thing that show vitamin E to work belongs to Tocotrienol. Just about everything that had been shown for tocopherol study fail, with the exception that it is a fat antioxidant.

Dr. Weitz:            It’s interesting, for years I’d seen these studies where they’ve used vitamin E and you try to test it to see if it prevents heart disease or cancer, and every time I’ve looked at the studies, I always thought, “Wow, I wonder why it’s not working. Ah, I don’t think they’re giving enough vitamin E. They only gave 200 micrograms or international units or they only conducted to study for two years and that’s not long enough to prevent cancer.”

Dr. Tan:                Yeah. And actually that concern that you have, I have too. I have no intention here to demonize tocopherol. I struggle as you did. The large, large clinical study, some of them done over eight, 10 years, simply did not pan out, Alpha tocopherol did not work. At best, it didn’t work. At worse, it may even raise the possibility of cancer and cardiovascular disease. That brought a lot of concerns to me. And then they thought that maybe it’s a synthetic vitamin E, so then they moved to using natural vitamin E, till alpha tocopherol, and is still continue not to work at high doses, 400 IUs, 600 IU.  So then I knew that if vitamin E were to work, and if Tocotrienol were to have a shot, let me stay with Tocotrienol. And that all came because of the fundamental seminal work in the 1980s. Much later when they found out that Tocotrienol, without exception not tocopherol caused the reduction of lipid. That came off from University of Wisconsin.

Dr. Weitz:            Interesting. I’ve heard you say that alpha tocopherol can actually have a negative effect on lipids.

Dr. Tan:                Yes. That came about because after the Wisconsin group came up that Tocotrienol could lower cholesterol, they did several clinical trials. About 60% work and 40% not. So it’s almost 50, 50. So it bothered the researcher. So the way they did it was, wait a minute, before we do any more clinical trials, it’s too expensive and take too long, we got to stop. So they went back to the bench work to find out in animal study, and this is what they did.  They were suspicious there’s something with the Tocotrienol, maybe a matter. At first, they thought that the Tocotrienol presence will be innocuous, so they put this amount of Tocotrienol with no tocopherol, then the next study, same amount, they add in a little bit more tocopherol, and then the next one, same Tocotrienol, more tocopherol.  And then when they did this, remember, a same amount of Tocotrienol. As they increased the amount of tocopherol, then they found out that the ability to lower cholesterol simply stopped. Now that was in… They published that in 1997. Since then, 2007. And 2007, 20 years after that, people have done it for cancer, for cardiovascular disease, and for metabolic syndrome systematically.  Every time tocopherol is present with Tocotrienol, tocopherol put brakes on the function of Tocotrienol.

Dr. Weitz:            Right. So there’s quite a number of articles now looking at the benefits of tocotrienols for cardiovascular disease.  And it was interesting looking at the mechanism by which it lowers LDL cholesterol, which is different than the way statins work, right?

Dr. Tan:               That is correct. And that came about… that study was discovered probably at the very end of the 1980s.  Statins work directly. If this is the LDL receptor that the statin locks it up, and then the drop is very dramatic. But we’ve Tocotrienol, we see a lot of cholesterol coming. So the scientific lingo is post-transcriptional, after it makes it, they down regulate the HMG reductase so it lower.  So if you translate them into application, a statin would lower say 40, 50% cholesterol; very dramatic.  And a Tocotrienol will probably lower it to about 20%. But hey, for a nutritional supplement to lower 20%, I’m fine with that.

Dr. Weitz:            And by the way, we’re specifically talking about LDL, right?

Dr. Tan:               Yes. The LDL cholesterol. And we have also found, in addition, in the earliest study, the Tocotrienol also lower triglyceride.  Now triglyceride is also cardiovascular, but when you have people with high triglycerides, it’s of particular import with people who have metabolic syndrome, for example, many of your listeners would be interested to lower triglycerides, so they take fish oil.  So fish oil lowers triglycerides.  So Tocotrienol also lowers triglycerides particularly for the interests of metabolic syndrome.

Dr. Weitz:            Cool. And Tocotrienols can be used synergistically way with statins or red yeast rice. Is that correct?

Dr. Tan:                Yes. Some people even add Tocotrienol with red yeast rice to do the cholesterol lowering.  And others put Tocotrienol with fish oil to lower triglycerides. And I even tell people, a little bit of a new one.  It was just published in the American heart association that anybody who wants to lower their triglycerides to take about three grams, at least two grams, perhaps three grams of DHA and EPA.  Particularly EPA because they say that the combination of EPA and DHA will lower the triglyceride, but there’s a possibility that the LDL may increase, which is a no-no to people who are diabetic like that. So if people add fish oil to Tocotrienol, not only they lower their triglycerides, they will resist the LDL from increasing for one, but possibly even lower the LDL.  So it’s a great combo to have fish oil and Tocotrienol for lowering the triglyceride as well as the LDL.

Dr. Weitz:            Brilliant. Plus, isn’t there a synergistic benefit because when you take a lot of unsaturated fatty acids like Omega-3s, they can become oxidized and the tocotrienols taken at the same time can prevent that oxidation?

Dr. Tan:                Yes. I have been trying to support this.  I’m a member of GO-ED, the global organization, EPA and DHA. Trying to convince people, convince company to make fish oil.  Everybody knows that taking fish oil is a good thing. Everybody also knows that oxidized fish oil is a bad thing.  So they would consider the possibility of putting Tocotrienol to protect the oxidation of these very unsaturated fat that’s unstable. And we have that study. That study was done for us at University of Georgia in Athens.

Dr. Weitz:            Interesting. So let’s say I was going to take two grams of EPA, DHA, how much Tocotrienols do you think I would need to protect that?

Dr. Tan:                Okay. If it is just for the protection of the omega-3, probably anywhere from one to two milligram. In one capsule of one gram fish oil will be enough to protect the extended shelf life. But if it is to add in so that it will support your LDL to drop and not increase, then probably more like 100 milligram. So depending on the intention of this. So one or two milligram or 100 milligram.

Dr. Weitz:            Okay. So particularly it’s delta tocotrienol that’s the most potent

Dr. Tan:                Yes. If you do a PubMed search, say people out there, say, “Oh, Dr. Tan is biased.” Which is fine. I understand that because I made this compound. If you go online, if you type Tocotrienol, right up sticking up like a sore thumb would be things of Delta Tocotrienol and gamma Tocotrienol. And then a beta Tocotrienol just about doesn’t exist in any effect at all. And then Alpha Tocotrienol trail. It’s a distant third; if anytime. So therefore on Tocotrienol studies, more than 90% of it would be on the function of Delta and gamma Tocotrienol.

Dr. Weitz:            Cool. I read several papers about the anticancer effects of Tocotrienols, including this review paper written this year that, “Tocotrienols modulate a life or death decision in cancer.” Talking about Tocotrienols having anticancer effects against bladder, brain, breast, cervical, colon, gastric, leukemia, lung, ovarian, pancreatic, prostate and skin cancer.  It’s amazing.

Dr. Tan:                I know.  When people first read something like that, the first blush is it just sound like snake oil. Now, when you read all of those things there, there were actually studies done on it.  If you were to type Tocotrienol on animal and cell lines study on those, I’m going to guess they’re probably 300 to 400 papers; lots of them. So we were among the first to decide if it worked in cell line and animal study, we should be all in to do clinical trials.  Currently, we have six clinical trials on cancer study.  One of them is published on it.  And the cancers we study on human trials are ovarian, breast, lung, and colon cancer.  And my colleagues are doing it on pancreatic cancer.

                            And so if you like I can tell you the ovarian cancer that was published. So we have two groups. One group is stage four cancer, which means that the cancer have gone everywhere, and within six months or so, most of the patient did not survive, and they’re taking the very expensive drug called Avastin. What Avastin does is anti-angiogenic; it prevents the artery from the tumor, it chop off like that. But even so, most of it did not live much more than six months. And then the other group is on Avastin plus Tocotrienol. Then their survival doubled to 12 months. And even at 24 months, 25% of the patients were still living. We consider that remarkable for a simple nutritional supplement.

Dr. Weitz:            Yeah. No, it’s amazing. Now what about if patients are taking traditional chemo?  It’s generally thought that taking high dosages of antioxidants can prevent the effectiveness of chemo and radiation since… maybe not targeted drugs like Avastin, but the traditional chemo drugs work by using free radical reactions to kill cancer cells.

Dr. Tan:                Yeah. This is a particular fixation about cancer doctors in the US. I asked professor Jacobson in Denmark, where all our trials were done. He said that they don’t have that as a problem.  When a chemo drug works to stifle the ability of the cancer to cell signaling or killing the cell directly, it may or may not work to end any antioxidant capability.  At the place where Tocotrienol will work to kill the cancer is largely not as an anticancer, is anti-angiogenic, not necessarily antioxidant.  It actually turn the signal of the cancer to multiply itself, turn the cancer on to make it die itself. You see it work on other operative besides antioxidant. So to the best of my knowledge, when Tocotrienol has been used in adjunct with chemo drug or without, sometime they compare neck to neck but not in adjunct. And oftentimes, the Tocotrienol work same as the chemo or better. In the pancreatic cancer is one. In the Tamoxifen, it did not antagonize the Tamoxifen in breast cancer. But if you use alpha tocopherol, the tocopherol would antagonize a function of Tamoxifen.

Dr. Weitz:            Interesting. Interesting. Yeah. I know one prominent integrative oncologist talks about the fact that people are sometimes worried about taking 500 milligrams of vitamin C, which has a very modest antioxidant properties, and then encourage everybody to eat fruits and vegetables, and a cup of blueberries has like five, 10,000 times the antioxidant properties of a vitamin C tablet.  So how can it be that eating fruits and vegetables enhances your ability to fight cancer potentially whereas a vitamin C tablet is going to prevent it?

Dr. Tan:                Yeah. I don’t know who started this idea that if you take antioxidant it will counter the effect of cancer.  I actually have read the opposite. If you go to the study of professor Drisko, Jeanne Drisko from University of Missouri, Kansas City. She came up with a cocktail of antioxidant for women cancer survival, and then they’re able to have better quality of life.  So I’ve seen that more than that it hurts.  If a cancer drug work as a pro-oxidant to kill the cancer just like that, I believe that that will be too simplistic. If it is like that. If you look at most cancer drugs, they are very toxic to the patient. So if it really worked, it worked to kill the cancer and probably also slowly kill the patient themselves. This antioxidant and oxidant thing is too simplistic. It works on other direct mechanism to go after the tumor. But with Tocotrienol in animal study and in humans study, we have done it now over two years, we systematically do not find negative effects of Tocotrienol on the patient, whether they are cancer study or non cancer study.

Dr. Weitz:            Interesting. I also saw several papers on tocotrienols improving bone health in postmenopausal women. Can you talk about that?

Dr. Tan:                Yes. Bone health. We started a trial after we had many animal studies in Texas Tech University at Lubbock. So at the Lubbock Texas study, we did the osteopenia trial. We gave the women one year, but not more than 10 years after menopause. So we don’t want them to be in the period where they’re osteoporotic.  Only in the osteopenic stage. So we noticed that after three months, the bone turn over, which means the building of the bone, increased by 100% or more.  And the bone resorption, the indicators show drop by 15% or more. That’s resorption, the breakdown of the bone.  And then during this stage where oxidative stress is also increased, and the oxidative stress is reduced by 48%, almost 50%. So we considered that those three combo is fantastic. Now this is unique of Tocotrienol. Why? Because people who know about bone health usually think about calcium, they take above vitamin D and more recently they think about vitamin K2. But we’ve shown that in Tocotrienol, this unique vitamin E is able to do what I just told. And that was published last year. So that’s the bone study. [Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial.]

Dr. Weitz:            Interesting. Can you explain what the mechanism by which it improves bone health?

Dr. Tan:                Okay. I’ll do it based on this. Calcium is a constituent inside the bone.  So that’s why we take calcium.  Vitamin D is a chaperone that helps the calcium to get into the bone.  And hence vitamin D.  Vitamin K2 is to form the osteocalcin, the protein inside the bone.  It’s like a protein lattice to trap the calcium in its place.  So I told you all the other one.  But with Tocotrienol, Tocotrienol actually increases the bone building, the osteoblast, and decreases the bone breakdown osteoclasts. So it’s actually work on the bone cells itself. So in that way, the workings of Tocotrienol differentiate from the other three things that I mentioned to you.

Dr. Weitz:            Interesting.  Do you have any idea in humans of what percentage change it would be in bone?

Dr. Tan:                The study that we currently had done is only for three months. It’s too early to tell a dexa test to work. So we only see the biomarkers. The increase of the bone building and a decrease of the bone breakdown. So all together it would resist bone loss over time during the osteopenic stage before they get to osteoporosis.

Dr. Weitz:            Wait, but that’s amazing if it increases the osteoblastic activity because currently the drugs that are typically used for osteoporosis are drugs that block the osteoclastic activity.  And so there’s a tendency to have some problems down the line because you get more bone but you tend to get more junky bone.  We need those osteoclastic cells to clear out the old junky bone.  And so the key is really to prevent that stronger bone to prevent fractures, not simply a more bone.

Dr. Tan:                Yeah. That comment you make is very interesting Dr. Weitz because when the people use this bisphosphonate drug to make this junkie bones like that on the bone-

Dr. Weitz:            These are drugs like Fosamax, for example, and Actonel.

Dr. Tan:                Yeah. Now when they use this way, they have a very unusual side effect, the junkie bone, it cause the osteonecrosis of the jaw. It’s got B-R-O-N-J like that. We are actually working with a compound, another time you can interview me on this, it’s called geranylgeraniol, Designs for Health sells this. Just started the launches. I acronyze it to GG. And GG will stop the breakdown of the osteonecrosis of the jaw caused by bisphosphonate drugs. Isn’t that amazing?

Dr. Weitz:            Really?

Dr. Tan:                Yeah. And after the interview is over, I’ll be happy to send you some study and also if the audience are interested, I will be able to do that. But for this osteopenia, for bone health, we have so far been able to study on a clinical trial on osteopenia like I described. And then we also did an animal study and I thought that your audience will be interested because you are a chiropractor by background. We also studied this osteoarthritis, and we found out that in animals study, in two study where we gave them Delta Tocotrienol, it improved the synovial fluid, and then the cartilage repair, which is a very specific part of the bone as opposed to the solid bone here, but is the bone at the joint. And also reduce the inflammation. So I know that you didn’t ask me, so while I add it, it’s only an animal study. It reduces C-reactive protein. It’s making junky bone.  It reduces that.  It reduces the inflammation of the cell at the joint, and finally it reduces the cartilage erosion, approximately 200% or so.

Dr. Weitz:            200%. Wow.

Dr. Tan:               Yes. We’ll be happy. One of them is published last month. The other one is published about 10 years ago.

Dr. Weitz:            Wow. Amazing. You just mentioned that tocotrienols have an anti-inflammatory effect, and we think of them, we think of vitamin E or tocotrienols as an antioxidant, but it also has an anti-inflammatory effect?

Dr. Tan:               Yes. And the way we tested that was when this doctor from Wisconsin found out that we figured out how to extract this from annatto.  Annatto is a unique plant because when you think of the plant kingdom, most of them have tocopherol.

Dr. Weitz:            And that’s the plant in the picture behind you?

Dr. Tan:               Yes. That’s the plant in the picture. And this is not a weird plant. We use the annatto here for coloring cheese. If you look at cheese, they say, Annatto color. So we remove the color from the cheese here and then you have the tocotrienol. The Tocotrienol is made by the plant to protect the color that is put in the cheese like that.  So basically that is what the plant use it for. So when he found out-

Dr. Weitz:            So the plant is using the tocotrienols to protect the carotenoids that are in the plant.

Dr. Tan:               That is correct. And it was intuitively, I found out, because if you touch the plant, it stains your hand.  So usually carotenoids are bound to something, like the beta-carotene in carrot, lycopene in tomato, otherwise they’re terribly unstable like the foliage color; two weeks of fantastic splendor and then it turns brown.  It’s not stable at all.  But this color here-

Dr. Weitz:            It turns brown because it gets oxidized.

Dr. Tan:               Yes, rapidly oxidized. So in this plant here, the color does not go away fast.  So this is about 22 years ago when I stumbled on this plant. I surmised that it’s got to be a powerful antioxidant that protects it.  And fortunately, thank goodness, thank God that I discovered, they are 50 million chemicals on earth, how would I have guessed?  And when I did this, I thought it was a polyphenol.  I wasn’t thinking it was a Tocotrienol, vitamin E, much less Tocotrienol.  And then when I found out and analyzed it’s pure Tocotrienol, no tocopherol, remember most plants have tocopherol.  Some plants like rice and palm have a mixture of tocopherol and Tocotrienol.  The annatto plant consists purely of Tocotrienol.  So therefore Dr. Qureshi, who did this study, he said, “Barrie, I’m going to test this and see if it reduces cholesterol.” He did.  So I told him that the Harvard Medical school study found out that half the problem with arteriosclerosis is high cholesterol, the other half is inflammation.  Can you please do inflammation study for us, which is the question you ask.  So when the study completed, a lower triglyceride, lower cholesterol, about 15 to 20% like I indicated to you.  And then he also measured the inflammation.  So surprisingly, the C reactive protein dropped approximately 30%. I say yes. So it addresses the lipid as well as the inflammation. So yes. To answer your question, Tocotrienol clearly quenched the fire in our body.

Dr. Weitz:            Wow. So we can measure oxidized LDL on advanced lipid profile, and so we can use Tocotrienols to lower that oxidized LDL.

Dr. Tan:                Yes, we can. And other people have shown that if you use Tocotrienol, it will reduce the oxidized LDL because people said that LDL is potentially atherogenic, oxidized LDL is definitely atherogenic. So if there’s any way that you can protect, if you happen to have high LDL, if you have a compound that can protect this oxidation, is a good thing.

Dr. Weitz:            Awesome. And I understand it can also be beneficial. There’s a liver condition that is much more prevalent than people realize. It’s generally ignored, but doctors and researchers who are experts on liver disease believe that this condition is going to result in as tsunami of people needing liver transplants in the next decade or two. And it’s nonalcoholic fatty liver disease.

Dr. Tan:                Yes.

Dr. Weitz:            This is very common now in our population, maybe as many as 100 million people in the United States may have this, and it’s part of the obesity epidemic. I understand tocotrienols can have some benefit with nonalcoholic fatty liver disease (NAFLD).

Dr. Tan:                Thank you Dr. Weitz for asking this question. Currently, the reason I got into this was other people who have been studying animal study, and even the clinical trials surmising that this would work. And we already know that Tocotrienol work on metabolic syndrome, diabetes and obesity, and this kind of thing overlap each other. And then the silent group is fatty liver because you don’t feel anything. The liver is the largest solid organ. It performs 600 different function. It’s got so many function.  So if the liver failed to function properly, is a bad news. 20 more years ago, this kind of liver condition is caused by excess amount of alcohol drinking. Mayo clinic discovered it. So they had a patient coming in the doctor surmised that the patient is probably drinking too much alcohol because the liver was fatty. The patient said no. So when they found out that… So because it was not alcohol-related, that’s why they called the disease non-alcohol fatty liver disease, and it’s a dietary thing because the fat back flush into the liver and can go out anywhere.

                                So we knew this. So we did a study and is this fantastic. The study, we gave people 600 milligram per day of annatto Tocotrienol. We found that the liver enzyme dropped about 15, 20%, the fatty liver index dropped, the C-reactive protein dropped, which is a very good… By the way, C-reactive protein is manufactured in the liver.  So it’s a stress protein from the liver, usually is a marker for all inflammation, but for me, is a particular marker for the inflammation of the liver and also drop.  So we did a study, 600 milligram for three months.  We now just completed a study still at 600 milligram for six months, and a dramatic effect on these people is that at the three months, they dropped 10 pounds. Normally I do not subscribe that Tocotrienol help people to lose weight. It’s not lose weight. But after three months, it dropped 10 pounds, and after six months, it dropped almost 20 pound, like 18 pounds. Dr. Weitz, this is very important because if their weight drop, that means that their liver is recalibrating their body. Their enzymes in the liver drop, the weight drop, the C-reactive protein drop, and the fatty liver index drop. I don’t know what’s there not to like. This is fantastic.  Right now there’s no cure for this.

Dr. Weitz:            Do you know how amazing it is to have a product that would cause 18 pounds of weight loss? We have debates in the nutrition world about which diet to use for weight loss, and one diet ends up producing two and a half pounds of weight loss and that’s considered a success over a period of months. But to create 18 pounds of weight loss, that’s like unbelievable.

Dr. Tan:               Yeah. I think that probably in the next three months or so, the six months study will be published for the almost-

Dr. Weitz:            What is this? Kill their appetite or something?

Dr. Tan:               The control group and the normal group were asked to do exercise, eat a normal diet like that, but they’re not on a regiment diet, just have a healthy diet. So we know that it is compared correctly. I would say that this is really quite something. If the audience want to address fatty liver, this would be a good way to reduce the inflammation. Silence the enzyme that is highly inflamed. And in fact, we also check the glucose level, is it called HOMA-IR, it’s a homeostatic something of the glucose function. It’s an American Diabetes Association measurement. Even the HOMA-IR drop.  I am really thrilled about this, and looking much forward to the published study enable to recommend people who have fatty liver to do this, at least to control and contain further the damage to the liver, which is otherwise not good, and enable to help to reverse it possibly.

Dr. Weitz:            So let’s talk about dosages. You mentioned 600 milligrams for fatty liver. What about for reducing cholesterol and triglycerides? What kind of dosage should we use optimally?

Dr. Tan:                Probably about half that amount. Depending on a person’s weight, two to 300 milligram would suffice. And then fatty liver because a person is already gone that direction on fatty liver, 600 milligram. Many of our clinical study on cancer, they use 900 milligram. But now in the newest study it looked like if they are not end stage cancer, if they’re stage two or three, probably half the dosage will be enough. Four to 500 milligrams. So the extreme thing, 900 milligram, but the one, the frank disease, then probably about midway about 500 or five, 600 milligram. And of people who just have normal lipidemia or have a family history of this but don’t have the disease themselves, probably half that again, from two to 300 milligrams.  And remember, when you take it, it’s a lipid soluble thing. You don’t need to make it any liposomal or other thing, just take it with a meal. There’s enough emulsification in the stomach, bowel sock in the gut, and that should be able to emulsify to absorb the Tocotrienol.

Dr. Weitz:            Okay. I was reading one of the papers on cancer and they did say that there’s an issue with bioavailability.

Dr. Tan:               Yeah, the bioavailability on-

Dr. Weitz:            That 2019 Tocotrienols Modulate a Life or Death Decision in Cancer. That author talked about the bioavailability.

Dr. Tan:               Yes. They raised that as a question because in the cancer study, you may need highest dose, like it’s 900 milligram like that. Where it is not advisable, would be to take all the 900 milligram at one shot. So it should be taken 300 milligram with breakfast, lunch and dinner. So it’s T-I-D. So if you take a 600 milligram, take it 300 milligram, they call it B-I-D, which means take two doses with lunch and dinner or breakfast and lunch.  In other words, at one single dose, it should be up to 300 milligram but not more. So if you wanted to take 250 milligram, is fine. And precisely because of that, Designed for Health, for example, sells it 115 milligram and a 300 milligram. So you can go online, they have it. And you can also buy it from Amazon as well.

Dr. Weitz:            What about for cardiovascular disease?

Dr. Tan:                Cardiovascular disease. The study that we did was at 250 milligram, between 200 and 300. So at the time we make the soft gel 125 milligram. We gave to patient 125, they take two soft gel, 250, three for 375, and four for 500. So when we dose escalate, we find out that 250 hit the number. And if you want to reduce inflammation, maybe 500 milligram, otherwise if to just to reduce lipid, 250 milligram would be fine.

Dr. Weitz:            So if you’re going to take it for cardiovascular, you would do the 250, and you would do that once a day and preferably when you take your fish oil or if you’re using red yeast rice or a statin, take it with that?

Dr. Tan:                Yeah. You take it with that and take them with a meal. The statin drug, you can take it with or without a meal. The fish oil oftentimes is taken because fish oil is a lipid. So if you take it with fish oil, with a meal… When I say with a meal, and sometime people are religion, I just mean that one hour before a meal, up to two hours after a meal. Why do I say that? If you take it one hour before a meal, when you eat the meal an hour later, you masticate with the meal will be fine.  And why you can take it two hours?  Because as you eat food, the food is not going to get out of your stomach for at least two hours. So when I say with a meal, I mean one hour before, up to two hours after, not religiously must be, I eat the food, now I got to take it now. People ask me like that’s so..

Dr. Weitz:            No, no. It’s good to clarify that because some patients are trying really hard to follow the directions exactly, and they’ll agonize if they’re told to take it with the meal and they take it right after the meal or… So what you’re saying is it takes a long time for the fruit to get digested, as long as it’s somewhere around the time of the meal. That’s fine.

Dr. Tan:                That’s fine. Yeah.

Dr. Weitz:            I know you have a small book for consumers, The Truth About Vitamin E, and you also have a textbook, right? That’s available as well.

Dr. Tan:                Yeah.

Dr. Weitz:            Can you ask about those?

Dr. Tan:                I’m going to show you. This is a picture of the book here, like that. The Truth About Vitamin E. And it’s a short book. It’s only about 70, 80 pages long. So if you wanted to have a copy of this book here, you can go on barrietan.com, and my name is spelled B-A-R-R-I-E.com. And then if you put the code word, wellness, because we are on your program here, wellness, and then you can download an electronic copy.  So if you wish to have a hard copy, you can email me through that. Otherwise, if you want it faster, you get download and it’s free, and then you can see a lot more study and a lot more things that we discussed here; dosage, this and then what is useful for what area. It should be in there. So I did that as a public service, as a love for this, that I spent almost my whole life studying this, to let people know today of that special vitamin E. That’s why I say the truth about vitamin E is actually Tocotrienol, not tocopherol.  There are just too many problems with tocopherol to find that is any use.  That even if you use it, you have to tiptoe around all the benefit because of the potential negative benefit.  So I decided that I’m done with tocopherol.

Dr. Weitz:            And what about you have a textbook also?

Dr. Tan:                Oh yeah. A textbook. Yes.

Dr. Weitz:            And this is something more for clinicians who might be interested in delving deep into some of the detailed scientific information about Tocotrienols

Dr. Tan:                Yes. How about while Kim is getting me the textbook for me to show, I know that as a remark that I want to make just in case we didn’t cover it. Currently, we are continuing our study more overweight and obese people, they’re 60, 70 years old, because carrying a lot of heavy fat is not good. They’re healthy. So keep watch, in another year we’ll know that study like that. And another note that you may or may not ask, we also noticed that when you add Tocotrienol, it help… When you address cancer, 1% of cancer is called cancer STEM cell. These are rogue cancer cell that circulate in our body. We now have scientific proof that Tocotrienol actually even nail the cancer STEM cell. We have shown it on prostate cancer, breast cancer, pancreatic cancer, and skin cancer. Can you imagine that? Even if you nail the cancer, the rogue cell will go on. So we even nail after that. I am so thrilled about that.  So for no other reason, for prevention reason, we should be taking… because in our body, even if we don’t have frank cancer, we have cancer, rogue cancer cell floating around to do this. So to answer your question, for the scientists, this is a book that I added here and I’m the main editor here. So this is called Tocotrienol, Vitamin E beyond Tocopherol. And a picture of annatto here. This a summary of all the different professors and scientists on the research work.

                                So this clearly is not something I say. I’m just a mouth piece to tell other people, yes, we helped to conduct some studies ourselves, but there are other independent researchers, they have published the whatever they find is important, and if it didn’t work, they will say so, if it works, they will say so. So it’s not so much that I’m controlling, and there’s no such thing. The only thing that I have is I’ll say this, I have faith in knowing that this particular vitamin E is unique. Very few vitamin have such credential to actually intervene disease, but Tocotrienol does.

Dr. Weitz:            Yeah. I’m completely amazed and definitely immediately going to add it to my anti-aging regimen. And those are my patients who want to be on an anti-aging regimen as well.

Dr. Tan:                Well, thank you, Dr. Weitz. I’m thrilled about days that you asked me for this interview. Hopefully within a year, we… This by the way, this one here was the second symposium. It was a summary of the… When we have a conference like that, hopefully next year or the year after, we’re going to have the third international symposium, and then we’ll invite all the scientists and researchers and medical doctors of the world to come in. And then would disclose what new findings are on this.  So watch for new things to come. And then as I wrap up, I’m very passionate about this, related to Tocotrienol is a compound, which I mentioned in the program earlier called geranylgeraniol. Now I know it’s a mouthful of a word. And you simply can acronyze it to GG. GG is an endogenous nutrient in a human body, which means our human body makes it. To get your attention, you can Google geranylgeraniol, GG is required for the synthesis of CoQ10. And everybody knows CoQ10.  GG is required for the synthesis of vitamin K2.

                                You talk about vitamin K2 fermentation, is required for the synthesis of vitamin K2. And also required for the synthesis of heme in our body, because it’s endogenous. Can you imagine what it means if you don’t have GG. And the most important thing I consider, GG is required in the synthesis of protein. That is why the reason when we take statin drug to lower cholesterol, it inhibit GG. Most people don’t know that. Most people do know it inhibited CoQ10. And do you know why it inhibit CoQ10? Because it inhibit GG. And GG is required in the synthesis of CoQ10.  But if you take CoQ10, it cannot help you to solve that myopathy problem of statin. But if you take GG, GG will mitigate the problem of statin in myopathy. Get me to talk about GG another day. That is so exciting. And by the way 

Dr. Weitz:            It is available, you said.

Dr. Tan:                Yeah. GIG is. The only company is available now is for design for health, and they have a white page. Dr. Weitz, please go on the white page like that or you can even interview Dr. David Brady. He’s the chief medical officer there, or if not, if you bring me on again, I would love to do this, and be among the very first to do that. I will love to talk to you about that. It was so exciting. You know and then when you do this like… let me tell you this, the entire molecule of GG is on Tocotrienol.  Now the human mammal don’t know how to do that. The plant can do that. Next time when you get me a talk, I’ll show a picture about the picture of Tocotrienol. The entire molecule of GG is on the Tocotrienol. So this is my fate. I’m meant for this. I noticed this fun thing, but I wanted to tell you, the audience, I did not make this up. I’m just fortunate to stumble on this Amazonian plant. And if there’s sheer, pure joy to pass to the consumer is to let them know that this is good for their health.

                                So Tocotrienol is good for all the reasons for the past hour we talk about, and GG is an endogenous nutrient. Without GG, we cannot describe life as we know it, and GG, as we grow older, GG drop. Actually the lowering of CoQ10 as we age is actually a biomarker of lowering of GG because GG is required for the synthesis of Q. Forget the statin thing, the statin thing only make the CoQ10 drop even more. But even if you don’t take statin, the lower CoQ10 with age is a maker for lowering endogenous GG.  I know I got carried away, but that is the very exciting thing. So I hope it’s useful to you all. Thank you so much for inviting me to talk.

Dr. Weitz:            And thank you so much Dr. Tan. I’m going to definitely hold you to that, getting you back on to talk about GG.

Dr. Tan:               Thank you so much, and you have a wonderful day. And thanks for the audience who listen to this talk. Have a great day.

Dr. Weitz:            Thank you for all you’ve given to the world for your discoveries on Tocotrienols and now GG.

Dr. Tan:               Thank you. Much obliged.

 

 

Weitz Sports Chiropractic and Nutrition
Weitz Sports Chiropractic and Nutrition
Inflammatory Bowel Disease with Dr. Ilana Gurevich: Rational Wellness Podcast 126
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Dr. Ilana Gurevich discusses Inflammatory Bowel Disease with Dr. Ben Weitz.

[If you enjoy this podcast, please give us a rating and review on Itunes, so more people will find The Rational Wellness Podcast. Also check out the video version on YouTube at https://www.youtube.com/user/weitzchiro/]

 

Podcast Highlights

3:25  When Dr. Gurevich sees a patient with extensive GI pain and there is no frank blood, then she starts to consider the possibility of Inflammatory Bowel Ddisease.  Other symptoms include anemia, nutritional deficiencies, thin, cachexic frame, and having many bowel movements with diarrhea and often containing blood, would all indicate inflammatory bowel disease like Crohn’s disease.  Dr. Gurevich pointed out that patients with Crohn’s disease are at risk for obstructions, which is basically an acute abdomen that can present suddenly with a 14 out of 10 pain and often requiring hospitalization and surgery.  She explained that 80% of all Crohn’s disease patients have some kind of terminal ileum involvement.  With Crohn’s disease you can get a shrinking or narrowing of the lumen and eventually that narrowing can become so small that it becomes completely obstructed.  Some Crohn’s patients are living with a partial obstruction where if they eat too much they can get into an acute flare of abdominal pain.  Such patients can also develop strictures, which are little pieces of narrowing or thinning of the intestinal lumen and that can also lead to an obstruction.  Such patients often require surgery eventually.

6:10  When Dr. Gurevich has a patient she suspects of having inflammatory bowel disease she will get a stool fecal calprotectin, which is a measure of white blood cells or neutrophils that are localized within the intestine. It is very predictive for ulcerative colitis–almost 98% predictive for ulcerative colitis, and it is somewhere between 30 and 90% predictive for Crohn’s disease.  Dr. Gurevich said that with fecal calprotectin, under 50 is negative. Between 50 and 120 is borderline and over 120 is positive.  Lactoferrin is another inflammatory marker that can be run as part of a stool test.  For Crohn’s disease, you can look at inflammatory markers in serum, like SED rate and HsCRP

9:39  Dr. Gurevich said that her other favorite test for monitoring patients with Crohn’s Disease is the Prometheus Labs Monitr Crohn’s Disease test that measure 13 biomarkers for mucosal healing status.  It is considered 92% specific and 98% sensitive for Crohn’s Disease.  Prometheus also offers the IBD sgi Diagnostic which differentiates Crohn’s from Ulcerative Colitis.  Dr. Gurevich also likes to run a GI Map stool test to look for protozoans, pathogenic bacteria, fungus, and parasites.  It also looks at inflammatory markers. Sometimes she will also look at food intolerances.

11:29  From a Functional Medicine perspective, we want to review their history in detail to find some of the underlying triggers, such as hormones, dysbiosis, stress, etc. 

12:41  A scarred or open iliocecal valve can increase the risk of SIBO in patients with IBD.  Dr. Gurevich will sometimes see patients having a flare and she will do a  SIBO breath test and discover that they have IBS/SIBO and after she treats the SIBO, their IBD improves.  She finds that a lot of her IBD patients end up with SIBO as well.  80% of Crohn’s patients have a some involvement of the terminal ileum and tend to get scarring or sclerosis of the terminal ileum and this often affects the ileocecal valve. This will lead to regurgitation of bacteria from the large intestine up into the small intestine leading to bacterial overgrowth leading to more inflammation.

17:17  Dr. Gurevich will sometimes use naturopathic manual techniques to close the ileocecal valve, though it doesn’t work well if there is scarring. For patients with strictures she often uses N-acetyl glucosamine because there was on study showing that it benefited such patients. She tends to use ozone for her inflammatory bowel disease patients.  The goal is treat these patients aggressively so they never develop the strictures, but sometimes once they do, surgery is often the only option.

21:02  Besides SIBO, other common co-infections in patients with Inflammatory Bowel Disease are parasites and protozoa. Protozoa are often labelled on stool panels as commensals [meaning good], but Dr. Gurevich does not believe that protozoa are commensal.  Helminth therapy could be effective in IBD, but it usually takes 6 months for it to be effective, according to Dr. Gurevich, so they will not help if the patient is having an acute flare.

22:38  When Inflammatory Bowel Disease patients are having an acute flare of their pain, Dr. Gurevich usually starts with diet. She likes to use the Specific Carbohydrate Diet, which is the most studied for IBD and it really meat heavy and excludes all grains and legumes, similar to paleo.  There is also a semi-vegetarian Crohn’s diet, which has no meat and is heavy on grains.  She will usually start with one of these two diets.  Dr. Gurevich finds that her most effective treatment modality is rectal ozone, which can get some amazing results.  When they are having an acute flare, they have so much reactive oxygen species, or O1s, and ozone is O3, which combines with all the O1s and renders them all into stable O2.  Rectal ozone is very uncomfortable because you are shoving a bunch of gas up them and they will likely feel bloated and crampy for the rest of the day and they may have really intense bowel movements.  But Dr. Gurevich said that she is able to get 70% of her IBD patients out of an acute flare up.  She does find Elemental diet can also be very helpful, though by day 7, it gets tough to stomach it.  L-Glutamine can also be very effective, but an effective dosage for an average 130 woman is about 27 gms per day–9 gms 3 times per day.  Saccharomyces boulardii probiotics have also been shown to be helpful.  For ulcerative colitis and especially for ulcerative proctitis, Dr. Gureviuch will use high dose vitamin E rectally.

29:38  Biologics are immunosuppressant drugs like Humira, Remicade, and Cimzia that block part of the immune system to reduce the immunological attack on the intestinal lining in Inflammatory Bowel Disease, like Crohn’s and Ulcerative Colitis.  These drugs are TNF alpha blockers. There are two new drugs, Intyvio and Stelara, that also block part of the immune system, but work via different mechanisms. Stelara blocks Interleukin 12 and Interluekin 23.  Dr. Gurevich said that while biologic drugs are not perfect drugs and can have serious side effects, if a patient is well controlled with their IBD while taking a biologic and does not have significant side effects, you should most likely not take the patient off the medication. If they have been taking a biologic and then stop it, the immune is more likely to form a reaction to the medication and if they go into another flare, then then they will no longer be able to take that drug or other drugs in that category.  Considering how severe Inflammatory Bowel Disease is, we should be very cautious to remove a medication that is working well. 

36:25   Dr. Gurevich may look for food sensitivites with the Carol Food Intolerance Test, which is an energetic based diet created by Dr. Carol in the 1920s and taught in some west coast Naturopathic schools. Dr. Gurevich has found this method of determining food sensitivities very helpful, though she admits there is little scientific validation of it. She finds standard IgG food sensitivity panels futile since virtually all of her patients have increased intestinal permeability.

 



Dr. Ilana Gurevich  is a board-certified naturopathic physician and acupuncturist and is currently co-owner of two large integrative medical clinics, one in northwest Portland and one in northeast Portland.  She runs a very busy private practice specializing in treating inflammatory bowel disease as well as IBS/SIBO and functional GI disorders.   She lectures extensively and teaches about both conventional and natural treatments for inflammatory bowel disease as well as SIBO.  She is one of the foremost experts on the intersection of IBD and IBS and how treating one resolves the other. She can be contacted through her website, naturopathicgastro.com

Dr. Ben Weitz is available for 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, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111 or go to www.drweitz.com.



 

Podcast Transcript

Dr. Weitz:                            This is Dr. Ben Weitz with The Rational Wellness Podcast, bringing you the cutting edge information on health and nutrition, from the latest scientific research and by interviewing the top experts in the field. Pre-subscribe to Rational Wellness Podcast on iTunes and YouTube and sign up for my free e-book on my website by going to drweitz.com. Let’s get started on your road to better health.

Hello, Rational Wellness Podcasters. Thank you so much for joining me again today. For those of you who enjoy listening to The Rational Wellness Podcast, please go to Apple Podcasts and give us a ratings and review. That way, more people can find out about The Rational Wellness Podcast. Also, you can go to the YouTube page and there’s a video version there, and if you go to my website, drweitz.com, you can get complete show notes and full transcript.

Our topic for today is inflammatory bowel disorders, of which Crohn’s Disease and ulcerative colitis are the most common conditions. There are also a few less common inflammatory bowel conditions, including microscopic colitis, which can only be identified upon biopsy of the intestinal wall. Inflammatory bowel disease is characterized by chronic inflammation of the gastrointestinal tract that leads to damage to the mucosal lining of this digestive tract. Crohn’s disease can affect any part of the GI tract, including the mouth, esophagus, stomach and the anus, but it most often affects the portion of the small intestine closest to the large intestine and there tends to be patchy areas of damage and the damage may reach through multiple layers of the intestinal wall. Ulcerative colitis occurs only in the large intestine and the rectum. Damaged areas tend to be continuous and usually start in the rectum and spread into the colon and is usually present only in the innermost lining of the colon.

Symptoms of inflammatory bowel disorders include persistent diarrhea, abdominal pain and cramping, bloody stools, weight loss, fatigue, among others. Anemia and other nutritional deficiencies are common. The main stays of conventional medical treatment include immuno suppressive drugs like prednisone and biologics like Humira and Remicade and surgical resection in severe cases. Dr. Ilana Gurevich is a board certified naturopathic physician and acupuncturist and is currently co-owner of two large integrative medical clinics, one in northwest Portland and one in northeast Portland.  She runs a very busy private practice, specializing in treating inflammatory bowel disease as well as IBS, SIBO and functional GI disorders.  She lectures extensively and teaches about both conventional and natural treatments for inflammatory bowel disease as well as SIBO.  Dr. Gurevich, thank you so much for joining me.

Dr. Gurevich:                     Thank you so much for having me.

Dr. Weitz:                          Excellent. When you get a patient in your office, what makes you suspect them as having inflammatory bowel disorder?

Dr. Gurevich:                     At this point, my practice is really, really specialized so I’m only seeing GI based disorders and there’s a certain subset of symptoms and when you rule out if they’re having frank blood, if they’re having extensive pain, if they’re having nutritional deficiencies, anemia is one of the most common things I see, if they’re cachexic, well below a normal healthy weight, then you’re always thinking inflammatory bowel disease. It can sometimes present with constipation but that’s much more rare and then the other things you’re generally looking at, with ulcerative colitis, you’re looking for bleeding. Ulcerative colitis patients have, depending on their severity, some are between five and 30 bowel movements a day, a lot of those bowel movements are just blood or blood and mucus. Crohn’s disease presents significantly more with pain, really intense acute abdominal pain, and Crohn’s disease patients are at risk for obstructions, which is basically an acute abdomen that can present really out of nowhere and all of a sudden they have 14 out of 10 pain and they have to be hospitalized and then they have to go in for emergency surgery to resect.

Dr. Weitz:                          What happens when they get that obstruction?

Dr. Gurevich:                     Generally speaking, the only way to get through out of a complete obstruction is to surgically remove that part of the obstruction. If it’s a harsh-

Dr. Weitz:                          What exactly’s happening anatomically in that case?

Dr. Gurevich:                     80% of all Crohn’s disease patients have some kind of terminal ileum involvement. The terminal ileum is the bottom of the intestine and the ileocecal valve is right there. That part can … Crohn’s disease, what happens with it, is you get this shrinking or narrowing of the lumen and eventually that narrowing gets so small that it’s completely obstructed. That then is the surgical emergency. There are lots of Crohn’s patients that are living with a partial obstruction, where all of a sudden they eat just a little bit too much or they eat something they’re not supposed to and they get into this acute abdominal pain, they start vomiting because you can’t push it through the intestinal tract so it comes back up and then it kind of passes and they slow down their eating and then they can kind of live this not very full life, where food is really well controlled or has to be really specifically controlled not to flare.

They can also develop strictures. Strictures are these little pieces of narrowing or thinning of the intestinal lumen and that also leads to an obstruction and a stricture … Where partial obstructions can sometimes be inflammatory tissue, it can also sometimes be scar tissue, and strictures are much more commonly to be scar tissue so biologic agents or steroids don’t always work to respond to these strictures to decrease the narrowing and so, for a lot of these patients, surgery is really … They’re just on a surgery track.

Dr. Weitz:                          Wow. How do you work these patients up?

Dr. Gurevich:                     The thing about inflammatory bowel disease is the GI’s a really, really complicated organ and it controls … We know that the majority of your neuro transmitters in your brain are actually made in your intestinal lumen, so hormones play a part. We know that if you have food poisoning, that actually upregulates your likelihood of developing inflammatory bowel disease. We know that if you take antibiotics, within six months you have a significantly higher likelihood of developing Crohn’s disease. We know that parasites and protozoa can trigger these kind of inflammatory responses. They can also sometimes be treatment for these inflammatory responses but sometimes they can trigger these diseases. Anything that you put into your GI track so pesticides, food coloring, preservatives, processed food that your body doesn’t react to, can cause this subacute or acute inflammatory reaction, which then puts them on a track for inflammatory bowel disease.  And the likelihood of developing inflammatory bowel disease is actually on the up.  We see an increase in Western cultures, we see a huge increase in cultures that never had inflammatory bowel disease that are taking up a Western diet and lifestyle, and then we see increasing amounts in just heavily medicated populations.

Dr. Weitz:                          Another aspect of the benefits of spreading American culture around the world.

Dr. Gurevich:                     Lucky us. Yep.

Dr. Weitz:                          What kind of testing do you do for these patients? Colonoscopy and endoscopy, of course, right?

Dr. Gurevich:                     That’s the gold standard. When a patient comes in to see me and if they haven’t been diagnosed, one of the first things I’ll do is a stool fecal calprotectin.  This is a stool collection that’s looking for the amount of white blood cells or neutrophils that are localized within the intestine. It is very, very, very predictive for ulcerative colitis, almost 98% predictive for ulcerative colitis. It is somewhere between 30 and 90% predictive for Crohn’s disease. I think that is partially because a lot of Crohn’s patients don’t have any disease in their large intestine, they’re really just localized to their small bowel or upper GI. Those patients are not going to be great testing subjects for calprotectin.  Lactoferrin is another test that we can do. For Crohn’s disease, you can look at inflammatory markers like a SED rate or a HsCRP, High Specific CRP, or also a regular CRP. The literature is a little bit mixed about which one is a better test for IBD. And then once you have a diagnosis, then-

Dr. Weitz:                          By the way, on a fecal calprotectin, what’s the cut off value?

Dr. Gurevich:                     50 or under is negative. If you’re between 50 and 120, you’re considered borderline, and then you’re supposed to retest in six weeks. If you’re over that, then you’re considered positive and depending on how high over that you are, that’s how significant the inflammation is, with the exception of ulcerative proctitis. Ulcerative proctitis is an ulcerative colitis that is only at the bottom part of the intestinal tract and those patients just have really, really high calprotectins because all of the white blood cells are right there. We’re collecting the stool that’s right there so you’ll often see the calprotectins for these patients in the thousands and that doesn’t necessarily talk about severity of their disease. It just talks about location and the fact that we can find them really easily.

Dr. Weitz:                          Okay.

Dr. Gurevich:                     And then my other favorite test right now, actually for monitoring, for Crohn’s disease patients, is Prometheus Labs has recently come out with something called a Crohn’s monitor score, which is a blood test, which anybody who treats IBD … Patients complain about the fact that they have to collect their poop, which is gross, and then carry their poop in their purse, which is gross, to drop it off at the lab. This is a blood test, they don’t need fasting, it takes 13 separate bio markers and it’s actually considered … I think it’s 92% specific, 98% sensitive, for Crohn’s disease, which is … That’s better than a calprotectin.

Dr. Weitz:                          Yeah, cool.

Dr. Gurevich:                     Yeah and so that’s what I’ve been using now for monitoring.

Dr. Weitz:                          Prometheus Labs.

Dr. Gurevich:                     Mm-hmm. And they’re the ones … All IBD patients know them because they’re the ones who have the Crohn’s blood test to differentiate Crohn’s and ulcerative colitis. They’re also the ones that have the blood test that looks at biologic levels to see if you’re within ranges, if the drug is working effectively, and so they’re a standard lab and so that is generally my standard workup. My Functional Medicine or naturopathic workup includes stool testing for Protozoa and parasites. I’m using DNA stool testing now.  It’s stool testing for inflammatory markers in the small bowel.  Zonulin is one that I use a lot, even though I think literature’s a little bit mixed on it.  I’m also sometimes looking at food allergies and food intolerances, not always, but sometimes, and then … What else is my workup?

Dr. Weitz:                          For the stool test, I think I heard you say that you’re using GI Map now?

Dr. Gurevich:                     Mm-hmm, that’s my favorite right now. I think that the DNA PCR is like a game changer, actually.

Dr. Weitz:                          Right. Cool. How do you apply a functional medicine approach to these patients?

Dr. Gurevich:                     I think it all comes down to the history. These people, they were not born with inflammatory bowel disease, something happened to have them develop it, and so you’re kind of figuring out when they started feeling bad, how long they felt bad, how many workups did they go through, and then based on that, you’re coming up with, ‘Okay, I think that this is a really hormonally mediated inflammatory bowel disease.  We’re going to really focus on the hormones.’ Or, ‘Oh, this is a clear cut, you were over medicated, you took too many antibiotics.  This is clearly a microbiome disorder and so we have to focus on that.’  Or, a lot of patients, stress is one of the things that could definitely trigger one of these acute attacks and so how are they mitigating their stress? I have patients time and again who are so well controlled.  I’m running calprotectins on them every three months, I’m running Crohn’s monitor on them every three months, they’re so well controlled, and then all of a sudden a stressful event occurs and we lose control. Those people, we’re all talking about the lifestyle, are they getting counseling? How are they dealing with their stress triggers? And so, every patient’s kind of their own individual and you have to figure out why this person has inflammatory bowel disease.

Dr. Weitz:                          Right. I heard you speak with Dr. Narala Jacobi on her podcast last year and you mentioned that you will often see a scarred and/or open ileocecal valve and that this can play a role in increasing their symptoms by increasing the risk of SIBO in these patients. And I spoke to Dr. Pimentel a few months ago and he did not feel like the ileocecal valve plays much of a role in IBS patients. He really focuses on motility as the key cause of SIBO and when I was talking to him, he said that even patients who have had their ileocecal valve resected, removed, do not necessarily have SIBO as long as they have good intestinal motility.

Dr. Gurevich:                     I’ve spoken to Dr. Pimentel. I really respect the work that he did. I feel like if his theory on bacterial overgrowth holds true, it’s like a game changer. However, I feel like a lot of his research is really structured in the fact that he is trying to differentiate IBS from IBD. If you look at all of his stats and all of his slides, he’s basically like, ‘We see this in IBD people, we don’t see this in IBS people, but we see this in IBS people and we don’t see this in IBD people.’ And I have to tell you, from what I’ve read in the literature, I just don’t think that holds up.  I think that what I’m seeing now, … There was this one study in 2009 that really, really old study, before I think even Pimentel started teaching, I think he was publishing a little bit then, talks about how IBS is often one of these misunderlying causes of IBD and I see this all of the time, where you see these people and you’re like, “Okay, you’re clearly in a flare, you’re in a lot of pain, you’re having diarrhea. Let’s double your biologic. Let’s triple. Okay, let’s switch your biologics. Okay, let’s add a steroid. Let’s add Budesonide.” And they’re not getting any relief and then you figure out exactly … You work them up for IBS, you find the IBS, you treat the IBS-

Dr. Weitz:                          You do a breath test.

Dr. Gurevich:                     Exactly, you do a breath test. And you treat it and they completely go into remission. I have this one patient who completely changed my … I lecture about her all the time. She changed my entire trajectory of understanding Crohn’s disease. She came in, she saw me, she was 42 years old and she had a BMI of 16, she was completely ammenorrheic for over seven years because she was so cachexic. She had such terrible inflammation in the leg, she would wear stockings, compression stockings, to keep it in, and I just happened to sit through one of Allison Siebecker, the first lecture Allison ever gave, I just attended a conference, and I was like, “Okay, let’s work you up for this.” She had been in a constant flare for, I think, 13 years. She refused any medication. She was like health guru so refused any medications but could not get rid of her flare. She was getting transfusions, she was so anemic. She was getting transfusions every three to four months because she was bleeding so heavily with the Crohn’s disease. We treated her SIBO. She has been in remission for over six years. She had no ileocecal valve. I continue to treat her SIBO, she’s on rotating herbs on a regular basis. That is the main reason why she’s in remission. There is no way that you can pretend that IBS and IBD have nothing in common.

Dr. Weitz:                          Well, if you think about it, Dr. Pimentel’s idea that IBS is really an autoimmune disease actually fits nicely with this and makes it even more likely that IBS is related to IBD.

Dr. Gurevich:                     Totally, a thousand percent. Crohn’s patients, 80% of them have some kind of involvement in their terminal ileum, right? Which basically means, if you have scarring or sclerosis of that part of your intestine, motility is going to be affected. There is no way … Functionally, that ileocecal valve is supposed to be a one way, everything dumps, and back pressure has a close up. These people who have a scarred or inflamed terminal ileum and ileocecal valve, you’re getting a ton of regurge. That is a large bowel. Pimentel himself cites 10 to the third, bacteria in the small bowel tend to the twelfth bacteria in the large bowel. It is regurging right up into the small intestine and then it’s like the wise world west. There’s all of this room, everybody’s bringing their family, everybody’s reproducing. Of course, you get bacterial overgrowth and then that bacterial overgrowth, of course, causes inflammation within the lumen. Of course.

Dr. Weitz:                            Right. And I also heard you say that sometimes you use naturopathic manual therapy techniques.

Dr. Gurevich:                     That sometimes can be really, really helpful. I’d say less for inflammatory bowel disease patients because of the scarring. In the studies, there’s only one study, I feel like, and it is was a teeny tiny type study, that said that it can turn over strictures, which is using N-acetyl glucosamine. I don’t know if that’s played out for me in my clinical practice but I have that one study so I try it on all my stricture patients. I use a lot of ozone for my inflammatory bowel disease patients, which I think it’s the best treatment that I have. It’s very uncomfortable but it’s a really effective treatment but even that sometimes [inaudible 00:18:07] the strictures. But you know, I think the goal is treat them aggressively so they never develop the strictures but sometimes once they do, surgery’s the only option.

Dr. Weitz:                            What about those techniques for using manual massage type techniques for breaking up scars in intestines?

Dr. Gurevich:                     The clear passage stuff, is that what you’re thinking about?

Dr. Weitz:                            Yeah.

Dr. Gurevich:                     They work on … And I center them a lot. They are incredible at adhesions. Scar tissue that forms from the outside. They do not have … I think, they themselves, will not say, and I personally have not seen them do great with strictures and I think it’s just different mechanism of action. A stricture, it’s inside the lumen, and so you have more localized … There’s more of an inflammatory cascade there and so, because of that, using manual therapy to break up adhesions is not going to work because that’s not the underlying cause.

Dr. Weitz:                            Right.

Dr. Gurevich:                     But I will say, one of the things that I do have my patients do all of the time, post surgery, is go to Clear Passage to get the adhesion worked on because the adhesions predisposed to a second surgery for a different underlying cause. And so, inflammatory bowel disease patients will constantly go … I think they have, on average, somewhere between two and five years before they’re expected to have a follow up surgery and so if you use the Clear Passage, Clear Passage does have the studies to show that their manual work decreases the likelihood of repeat surgeries because they’re cleaning up the adhesions.

 



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Dr. Weitz:                        Besides SIBO, what are the most common co-infections that you’ll see with your IBD patients?  I saw an article by Jill Carnahan, where she talked about parasites, Candida, and also Epstein Bar virus.

Dr. Gurevich:                   I definitely see parasites and protozoa but parasites are definitive as bad, protozoa is often labeled as commensal. I really can’t believe that. As a rule, I think that protozoa should not be within the system and there was a really interesting IBS study in 2014 that looked at protozoa being the underlying cause for a lot of IBS like symptoms.

Dr. Weitz:                         Well, there are some people claiming that parasites should be part of our system too and even using worm therapy.

Dr. Gurevich:                    I actually, and I mentioned that earlier, helminths are really interesting. The problem with helminths in IBD is it takes six months for them to become effective.

Dr. Weitz:                          Okay.

Dr. Gurevich:                     And so, if they’re in the middle of a flare, you’ve got six months and the likelihood that you can make it through six months without a, obstructing, and b, ending up on some kind of immunosuppressive modality, you would have to have a willpower of like a bull to be able to make it through. But helminths are really, really interesting and protozoa, I don’t think I would use parasites as. I think there are good worms, I think there are bad worms. I think good worms don’t reproduce within us, we can help them shift the microbiome and the environment, bad worms reproduce very aggressively and invitably will cause obstructions.

Dr. Weitz:                            Right, okay. What are your favorite options for when patients have acute flares?

Dr. Gurevich:                     Diet is always key for what I do. If they’re willing to do a specific carbohydrate diet, I think that’s the best studied. There’s also this other diet called semi-vegetarian Crohn’s diet, which is basically exactly the opposite of SCD. SCD is really meat heavy, very paleo, no grains. The semi-vegetarian Crohn’s diet is like a macrobiotic, really grain heavy, no meat like diets. That one’s been studied, I think, mainly in Korea. If they are willing to give me a diet, I want them to give me a diet. At this point, in my practice, ozone is my go to. ozone, rectally, is amazing. It’s super uncomfortable. The theory of ozone, the reason why I find it so effective … Or what I do in my practice is I’ll start by either running a Crohn’s monitor or a calprotectin before we start any kind of treatment because I want a baseline and then as soon as we get that result, we’ll start treatment.

When I start with ozone, you take oxygen through an oxygen tank and you put it through an ozone generator and it uses electricity to break up those very stable bonds and so what happens with those bonds is, we know about 20% of them reform in the ozone or O3, which is super, super, super unstable. In fact, if you leave that ozone in a bag, at the end of 30 minutes, it’s going to be all oxygen because all of those third electrons are going to find each other. If you administer it rectally, what happens is because they’re in an acute flare, they’re having all this chronic inflammatory cascade and so what’s happening is they have all these reactive oxygen species, or O1s, that are just looking to unbreak their bonds and that’s causing the inflammation. If you insulffate rectally ozone, that O3 finds those reactive oxygen species and, just like that, immediately it’s an anti-inflammatory. It works really, really quickly, it is very, very safe. However, it is so uncomfortable. It’s really a borderline torture. Maybe that’s extreme.

The large intestine, it’s supposed to squeeze and push things out and I am having them put in 750 ccs of gas up and so what they get is bloating, obviously, cramping. Oftentimes, they’ll have intense bowel movements because the large intestine is getting the receptor, the information, to stretch, which is making it purge. It will, at 750 ccs, which is what I use for Crohn’s patients, they are burping up ozone. It is literally going up their entire GI system, which means for the rest of that day, they are feeling gassy, bloated, distended, crampy. It’s not comfortable. I don’t use this treatment for my IBS people but IBD, if I can give them this ozone, which we know, rectally, is 100% safe, and we know that because they recently did an animal study, not a human study, but an animal study. If I can give them that instead of a steroid or a biologic, for me it’s a no brainer. And it doesn’t work across the board but I’m going to say 70% of my population, I can get into a remission with it.

Dr. Weitz:                          What about elemental diet?

Dr. Gurevich:                     Elemental diet, it’s always a trick for me, what is more torturous? Putting a bunch of gas up your butt and getting bloated and distended or drinking … This drink tastes great, day one, minute one. Day seven, minute God knows what, it’s borderline torture. But if they’re not willing to do the gas, I’ll totally go elemental diet. Glutamine has the potential to be really, really effective. The dosage for glutamine is about 27 grams. That’s nine grams, three times a day, for somebody who’s my build. That’s a really high dose. Glutamine does not dissolve really well in water, it doesn’t taste bad, but some people consider that torture, some people get really good efficacy from it.  Saccharomyces boulardii has really good potential to get people into remission.  For ulcerative colitis, there’s lots of good studies on the mixed probiotics. They used to study VSL3.  Now that product is re marketed as vis biome, but that is another really … For UC, that’s something that I always try. Vitamin E. Vitamin E, rectally.

Dr. Weitz:                          Really? Interesting.

Dr. Gurevich:                     And they have studies on it actually. For ulcerative proctitis, vitamin E is generally … Also, for ulcerative proctitis patients, I’ll start there. Basically, you use Now brand has this 54,600 IU per dose of vitamin E. It’s got no fillers, no carrier oils, it’s a-

Dr. Weitz:                          Are you talking about D Alpha or mixed tocopherols?

Dr. Gurevich:                     I think it’s DL, I think.

Dr. Weitz:                          D Alpha? Okay.

Dr. Gurevich:                     Yeah. It’s definitely rectally at that time, like a retention enema, about csc.

Dr. Weitz:                          Oh, so it comes in an enema or it-

Dr. Gurevich:                     No, it comes in … It’s like $15 a bottle. It just comes as-

Dr. Weitz:                          So, liquid, okay.

Dr. Gurevich:                     Yeah, and you give patients syringes and if they want rectal catheters, I can give them that too. But that’s where I’ll usually start with ulcerative proctitis patients, if I work them up and it looks like they have a microbiome inflammatory based ulcerative proctitis.

Dr. Weitz:                          What about curcumin, which is the original TNF alpha blocker?

Dr. Gurevich:                     I’m using turmeric instead of curcumin, mainly because I … Did you read that study? It was actually done with the … It was this Indian PhD, who was the guy who originally did all the curcumin research. He turned around and he repeated his research like 20 years later, using curcumin-free turmeric because in India, the turmeric market got so large.  So India was sitting with all of this curcumin-free turmeric.

Dr. Weitz:                          What to do with it?

Dr. Gurevich:                     Totally and he was like, “Let me study it.” And it was as efficacious and it’s cheaper. Yes, I totally use turmeric. I use turmeric more. Ill use it sometimes acutely. I’d never seen it, alone, get somebody out of a flare but I’ll use it as my, “This is what you’re on indefinitely until you don’t flare again”, protocol.

Dr. Weitz:                          Right. I’m seeing mastic gum and then there’s this herb that I’ve seen mentioned called Thunder God Vine.

Dr. Gurevich:                     I’ve never heard of that. There is a really interesting study on wormwood, artemesia on about keeping IBD … I have a couple of bad track records with using artemisia and getting really high LFTs, which once you discontinue, the liver function has to resolve. I’m a little bit wary.

Dr. Weitz:                          Okay. Can you talk about the use of biologics and some of the risks associated with taking them and coming off them?

Dr. Gurevich:                     Yes. Actually, I feel like this is a little bit of my soap box. Biologics are really serious medications. They are immuno suppressants so they really dull the immune system, dulling the immune system then theoretically dulls the response of the neutrophils and lymphocytes that are attacking the lumen of the patients and actually, the way that helminths work, is by giving the immune system something else to attack so that it’s not attacking itself.

Dr. Weitz:                          Right.

Dr. Gurevich:                     Biologics, especially with peds, but even with adults, I’m very slow to start somebody on a biologic. I’m fortunate enough to live and work in Portland, Oregon, where I have a good gastro group that I refer to, that refers to me, and so they feel a little bit sometimes more comfortable holding off on the biologics. Some patients find because maybe they don’t want to be on biologics. They have a lot of serious side effects, about one in a thousand people will end up with some kind of lymphoma or cancer, higher likelihood of infections and sometimes they don’t work. However, and this is where my soapbox kicks in-

Dr. Weitz:                          And as we can see, biologics basically are blocking part of the immune system.

Dr. Gurevich:                     And in the past, with Crohn’s disease patients,-

Dr. Weitz:                          And we’re talking about drugs like Humira and Remicade and there was a whole series of-

Dr. Gurevich:                     Humira, Remicade and Cimzia are all TNF alpha inhibitors, so that’s where curcumin works on that. There’s two new ones that are out, which is Intyvio and Stelara. Intyvio is large bowel only and Stelara just came out, it’s a new one for Crohn’s. They are all monoleukocyte inhibitors, I think, which is exciting because in the past, we had one mechanism of action. If you didn’t respond, you’re done. They would try you on those three drugs in that order and then you’re done. Now, we have these two other drugs. I think Intivio, 40% efficacy of bringing you into remission so not great stats but if it works, it works. But the most important things is these drugs are biologic mimickers, right?  They mimic the biology of the system, which means that, one, your immune system might form a reaction to them, and two, if you take them out of the system and the person goes into a flare, there is a significantly higher likelihood that when you put it back into the system, they’re going to form a reaction to that drug and then this really, really great tool that was working to keep the people out of a flare and keep them in a remission is no longer an option and a lot of the other drugs in the same class that are slightly different might also not be an option.

Dr. Gurevich:                     If a patient comes in, and is well controlled and doesn’t have side effects on a biologic, it’s not going to be my advice to get off the biologic.

Dr. Weitz:                          Yeah, I’ve had patients come in and every time they take their biologic, they got such a severe skin breakout and had to take prednisolone just to take the biologic.

Dr. Gurevich:                     Yeah, absolutely. By no means is a biologic a perfect treatment for inflammatory bowel disease but if it is a perfect treatment and you’re in a total remission, I’m hard pressed to say, “You need to come off this biologic.” I am going to give you everything we can to decrease likelihood of developing a lot of these lymphomas, other ways to mitigate the immune system, get them on a clean diet, try to clean up their exposures and do everything else in my field of ability but I am going to be hard pressed to say, “God, you have been controlled, why would I stop that?” Because this disease is terrible.

Dr. Weitz:                          So, why is it that they’re more likely to react to the biologic if they stop it and bring it back?

Dr. Gurevich:                     Because now the immune system, which was suppressed, is unsuppressed and so revving and as the biologic is fading out of their system, the immune system can tack onto that protein and then up regulate the immune response so when they see it again, they’re much more likely to form a reaction.

Dr. Weitz:                          I see. Interesting.

Dr. Gurevich:                     One of the ways that we use biologics, or the standard medical community uses biologics, is they’ll match it with immuno suppressants. Back when I was diagnosed 25 years ago, we had three drugs that I could choose from. We had Prednisolone, we had Mesalamine, and then we had 6MP, which is also called Imuran or Azathioprine.  They’re all the same drug class. The studies have proven out of the last 20 years that those drugs are actually not very effective for treating inflammatory bowel disease but what they will do is they will use combination therapy. They’ll start somebody on a biologic and then also start them on immunosuppressants to decrease the immune system even more from forming a reaction against the biologics.  Biologics are not good. Immuno suppressants are awful. Liver inflammation, liver swelling, infections, cancers, they’re awful, and so these patients will get started on double treatments and then nobody takes them off. And so, when I was putting together my very long presentation for Nirala Jacobi’s masterclass on IBD and I was just looking through the literature on what studies have they looked at on how long somebody should be on these immune suppressants and how effective they are.

And, of course, nobody’s done big studies on them. They’re a little bit smaller studies but what the literature has panned out is it is only effective if you do Remicade. If you do Humira, because Remicade is 75% human mimicker, 25% mouse genes. Humira’s 100% human mimicker and so if you give Remicade, because of those mouse genes, you’re much more likely to form a reaction obviously because the body’s much more likely to react to a mouse protein. And after six months, it has no efficacy and the studies that they did outside of-

Dr. Weitz:                          You have to restrict cheese intake, in that case. I’m just kidding.

Dr. Gurevich:                     Sometimes you do for other reasons.

Dr. Weitz:                          The mouse, the cheese. Yeah, okay. Sorry.

Dr. Gurevich:                     The side effect profiles, the way they did the study is, is they did biologic followed by immuno suppressant, or biologic and immuno suppressant together, and they did it over two years and so the side effect profiles appeared almost identical because everybody got the immuno suppressants. And so, generally, if I’m going to counsel, I’m going to counsel. If they can, they’re okay with injections, Humira’s a better option and I don’t counsel to do immuno suppressants usually.

Dr. Weitz:                            Okay. Now, you mentioned, with respect to diet, food sensitivities. How do you sort through that and are there certain … You mentioned two completely different types of diets, paleo type of diet, which restricts grains and legumes and things like that, and then you also mentioned more of a vegetarian type of diet.

Dr. Gurevich:                     What I use in my practice is called the Carol Food Intolerance Test, which nobody has heard about unless they’re a naturopath who graduated from one of the west coast schools. It is this really, really kooky energetic based diet that Dr. Carol created it in the 1920’s. We do it in basically the same ways. For me, I think there’s no studies on it, there’s no science on it, but for me, clinically, it’s one of the ways that I’ve been able to keep my disease in remission and I feel like it’s kind of often the most accurate. I don’t use any of the IGG … I don’t use any of those tests. I find that those, in my clinical practice, are futile. My entire population has intestinal permeability. They have intestinal permeability because they’re seeking out my treatment and waiting to get in with me for appointments, right? So, that test is just going to do a good job really telling me what they’re eating. I don’t use that test at all. I think elimination is probably the gold standard and so what I’ll do is I’ll start them on SCD if they’re okay with meat and I think it’s better studied. If I can get them into remission, great. If I can’t or if they hate me, I’ll start them with the other one. I’ll flip.

Dr. Weitz:                          Have you used Low FODMAP?

Dr. Gurevich:                     Yes, definitely, and I feel like what I’ll do is I’ll put them on any diet. I’ll put them on a restricted diet, either SCD, whatever they want to start with, until they’re able to get into control and then once they’ve been in control for a little while, … It’s not sustainable to do that diet for the rest of your life. I call that diet a skeleton and then we want to build … We want to put the meat in the muscle and skeleton. Introduce, challenge, did you do okay? Great. Introduce, challenge, did you do okay? No? Okay, stop. Go back to where you just ended, let’s give it a couple of days. Okay, now you’re ready. Introduce, challenge. I want them to figure out what they can eat and what they can’t eat.

Dr. Weitz:                          If you do an elimination diet, how many foods do you eliminate?

Dr. Gurevich:                     All of the main intolerances. Dairy, gluten, eggs that are not organic, soy, corn, nightshades, sugar. The standard anti-inflammatory diet.

Dr. Weitz:                          How often do you find that gluten and dairy need to be kept out?

Dr. Gurevich:                     Not as much as I would have expected.

Dr. Weitz:                          Okay.

Dr. Gurevich:                     I feel like people who react know right away. Not as much as I would expect.

Dr. Weitz:                          Okay. How often do you find heavy metals or mold as co-factors?

Dr. Gurevich:                     I think I am probably under treating and under testing because there is this entire theory about fungus being one of the big underlying causes of Crohn’s disease and I think that I’m not paying enough attention to it, if I’m honest.

Dr. Weitz:                          Right. Well, it’s a lot of stuff to pay attention to.

Dr. Gurevich:                     Yeah, that’s true.

Dr. Weitz:                          Okay. I think those are the main question I had. I thought that was a good interview.

Dr. Gurevich:                     Thank you. You are also extraordinarily researched. I’ve been listening to a lot of your podcasts.

Dr. Weitz:                          Oh, you have?

Dr. Gurevich:                     Yeah, you are extraordinarily researched. I don’t know how you find time to do it.

Dr. Weitz:                          I just don’t sleep.

Dr. Gurevich:                     Great, that’s healthy. Totally no side effects to that.

Dr. Weitz:                          Exactly. How can our viewers find and get hold of you and find out about your programs? I know you have this IBD course, right? That’s available through Nirala.

Dr. Gurevich:                     Yep it’s SIBO Doctor Master Course through Nirala Jacobi. I think you Google that. That is going to be … I do my final interview with her tomorrow. It’s going to be five and a half hours just on inflammatory bowel disease. I do a lot of teaching and a lot of lecturing around. You can find me at my website, is naturopathicgastro.com and I still see patients and I also have some residents who work under me where if people don’t want to wait, they can absolutely … The residents run all of their cases through me and so we work on the cases together but it’s a lot cheaper and it’s a lot easier to get in with them.

Dr. Weitz:                          Awesome.

Dr. Gurevich:                     Thank you.

Dr. Weitz:                          So much.

Dr. Gurevich:                     That was so fun. Thank you.