Mitochondrial Testing with Dr. Sri Ganeshan: Rational Wellness Podcast 128

Dr. Sri Ganeshan discusses Mitochondrial Testing with Dr. Ben Weitz.

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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.


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