© April 2004

Whole Foods Magazine

Coenzyme Q-10 and Heart Health

An interview with Dr. Stephen Sinatra: Part 3

Coenzyme Q-10 and L-carnitine are the twin pillars of heart health.

By Richard A. Passwater, Ph.D.

In the February issue, we chatted with cardiologist Stephen Sinatra about the real risk factors in cardiovascular disease and how Dr. Sinatra became involved with coenzyme Q-10 in his cardiology practice. We also discussed the actions of coenzyme Q-10 that especially benefit heart and vascular health, and how Dr. Sinatra uses coenzyme Q-10 in his cardiology practice. In the March issue, we looked into why coenzyme Q-10, the nutrient Dr. Sinatra calls "the fertilizer for the heart," is becoming used as an adjunct treatment by more and more cardiologists, and we discussed the studies behind this acceptance. We also covered congestive heart failure (CHF) and mitral valve prolapse and talked about a couple of dramatic cases.

In this session, Dr. Sinatra discusses the "The Twin Pillars of Heart Health," and we learn that his clinical experience now suggests that even better heart health can be obtained with a third nutrient to form what Dr. Sinatra sees now as the "Triad" that may become the new frontier for metabolic cardiology.

Stephen T. Sinatra, M.D., F.A.C.C., F.A.C.N., C.N.S., is a board-certified cardiologist and a certified bioenergetic psychotherapist. He has more than 25 years of experience in helping patients prevent and reverse heart disease. He also is certified in anti-aging medicine. He is a fellow of the American College of Cardiology and former chief of cardiology at Manchester Memorial Hospital where he was director of medical education for 18 years. Dr. Sinatra is also assistant clinical professor of medicine at the University of Connecticut School of Medicine.

At his New England Heart & Longevity Center in Manchester, CT, Dr. Sinatra integrates conventional medical treatments for heart disease with complementary nutritional, anti-aging and psychological therapies that help heal the heart. He is uniquely qualified to give advice on nutritional supplements and the heart. Dr. Sinatra is one of the few medical doctors who formulates his own vitamins. He knows how to pick quality ingredients and is expert in dosage, absorption and the effects of combining supplements with cardiac medications.

Dr. Sinatra has authored and/or co-authored several books on heart disease and is the editor of the monthly newsletter on heart health, The Sinatra Health Report. His most recent book, co-authored with his wife, Jan Sinatra A.P.R.N., is Lower Your Blood Pressure in Eight Weeks (Ballantine Books, 2003). Additional information can be found on his website at www.drsinatra.com.

Passwater: I noticed that you presented a paper at the 2002 International Coenzyme Q-10 Symposium in London that was a study conducted by your son, Drew Sinatra. What did he find out about coenzyme Q-10? Is he also going to be a cardiologist?

Sinatra: My son Drew was at Franklin & Marshall University and needed to do an experiment as part of his education. He intends to become a naturopathic physician. I knew he was interested in coenzyme Q-10 because I used to treat his asthma for years with it, so I suggested he do something with coenzyme Q-10. One of the things I mentioned was the research of Dr. Stephen Coles in the 90s.

Passwater: Oh, yes, I remember Dr. Colesí research. I helped obtain funding for part of it. He was in Dr. Ray Walfordís laboratory at UCLA at about the time of the Biosphere experiments.

Sinatra: The experiment Dr. Coles did with laboratory rats showed that coenzyme Q-10 didnít significantly increase their lifespan; but at the end of their lifespan, the rats had shinier coats and were literally jumping out of their cages.

Passwater: Dr. Coles would send me videotapes taken at various stages of the experiment. You could really see the differences in activity and appearance in the mice given coenzyme Q-10 compared to those receiving the placebo. The coenzyme Q-10-treated rats looked and acted much younger. I thought that it was an impressive experiment.

Sinatra: I said to my son, "Letís do an experiment similar to that but use some young rats as well as old rats, and weíll see if there is a difference." Well, my son liked the idea and obtained approval from his professor to conduct the study.

In my sonís study, he took groups of young and old laboratory mice and gave some of each group coenzyme Q-10, while the others were given a placebo to serve as controls. The "young" mice were three months old and the "old" mice were two years old. The amount of coenzyme Q-10 given to the "treated" group was five milliliters. This is approximately equivalent of giving people something near the 1,200 mg of coenzyme Q-10 daily that produced encouraging results in the Parkinsonís disease clinical trial. The experiment was conducted for four months.

Since coenzyme Q-10 levels fall with age, I suspected that there would be a difference in the older mice, but there wasnít. What the study did show, and this really excited me, was that both young mice and older mice had more exploratory behavior when given coenzyme Q-10 compared to those not given coenzyme Q-10. They were daring, had less anxiety, and explored more. Nobody has ever reported this in the scientific literature before. Dr. Gian Littarru, who was at the meeting, was also excited about the findings. He said he never realized coenzyme Q-10 could have a central effect.

Weíre going to publish that paper showing that mice both young and old mice treated with coenzyme Q-10 were livelier. We donít know whether itís due to psychomotor stimulation, reduced anxiety, a combination, or maybe a central effect. This has a direct application to cardiology as well as to geriatric patients. Many of my patients are olderóin their 80s and 90s. They are afraid they will take a bad step. They walk slowly; they are afraid of hip fractures. Then I put them on coenzyme Q-10 for their heart disease, and the majority of them tell me they have more energy and that they are walking more. They also tell me that they are taking more chances, are doing more things and participating more in life. Itís similar to our laboratory animal study, although we didnít do a formal study with my patients. However, when the anecdotal evidence is so strong, when you keep hearing the same remarks hundreds of times, you have to consider that evidence.

Passwater: Indeed! And the same can be said of your findings with what you call "The Twin Pillars of Heart Health." You found that about 15% of people to whom you gave coenzyme Q-10 were refractory to it, and when you added the L-carnitine you got greater response. Please take our readers through the relationship here.

Sinatra: After the Ancona, Italy coenzyme Q-10 meeting in 1996, I started to use high-dose Q. It was at that meeting in 1996 when I presented some refractory cases of heart failure patients who improved on 300 or more mg of coenzyme Q-10. We started to use higher dose coenzyme Q-10 after I presented those three cases. I would be using 500, 600, 700 mg in some patients and I would draw blood levels, but they still werenít absorbing it. Occasionally I would get blood levels of 3.5 mcg of coenzyme Q-10 per milliliter of blood and the patient wasnít getting better. I asked myself if there was anything else I could do for mitochondria support and sure enough there wasóL-carnitine. I call coenzyme Q-10 and L-carnitine the Batman and Robin of cardiology. As you know, coenzyme Q-10 ignites the spark that generates ATP, but L-carnitine is like the freight train shuttling in the fatty acids that are burned as fuel. What a lot of people donít understand, including researchers and cardiologists, is that more than 60% of the energy of the heart is generated from the burning of fat, not carbohydrates. The brain requires carbohydrates.

Passwater: Earlier in this series on coenzyme Q-10, I discussed the biochemistry of this nutrient with Dr. Fred Crane. Would you mind covering the basics on L-carnitine for our readers?

Sinatra: Well, L-carnitine is often classified as an amino acid, but it isnít. L-carnitine can be thought of as a close cousin of amino acids, but technically it is a nitrogen-containing, short-chain carboxylic acid. It can also be described as a quaternary amine. Its chemical structure resembles choline. L-carnitine is not used as a building block by the body to form proteins. L-carnitine is a vital compound, but it is not classified as a vitamin as the body can usually make enough, starting with the amino acid lysine as its precursor. However, the synthesis is complex, involving five different steps and with the first step having to be repeated three times. As we age, we are less efficient in producing L-carnitine just as we are less efficient in producing Coenzyme Q-10. As many people shun red meats and especially lamb (which may be the best food-source for L-carnitine), their blood levels can become too low in L-carnitine.

A major role of L-carnitine is too transport long-chain fats into the inner membrane of mitochondria. Remember, the heart needs a lot of energy and the best source of energy-producing fuel in the body is fat. A gram of fat supplies nine calories whereas a gram of carbohydrate supplies only four calories. The heart uses free fatty acids as its main energy source, and the only way for long-chain fatty acids to get to the inner membrane of the mitochondria where energy is produced in the respiratory chain is for L-carnitine to carry them there.

Inside the mitochondria, fatty acids are oxidized by oxygen. It is a "slow burn" that releases electrons that pass along complexes in what is called the respiratory chain to eventually produce adenosine triphosphate (ATP). The ATP is eventually transported to various parts of the cell to supply energy when needed. It is the generation of this energy that supplies the vital force so necessary for life. Enzymes use ATP as the chemical energy to make reactions go. Enzymes can make chemical reactions go at rates more than a billion times faster, but they need energy to do this. This whole process of energy formation and transfer is called respiration. The final products that are generated by fatty acid oxidation are water and carbon dioxide.

Passwater: You made it clear why L-carnitine and coenzyme Q-10 are "twin pillars" of health. Letís pick up where you were telling us that more than 60% of the energy to power the heart comes from fats.

Sinatra: It dawned on me, like a light bulb that went off in my head, if we could burn fat more effectively in the heart cellsóagain we are going back to those 5,000 mitochondria for heart cells compared to only 250 in most other muscle cellsócould we get more efficiency out of the heart, less angina, less heart failure, less arrhythmia, better blood pressure, etc.?

Thatís been my clinical experience. First I was using L-carnitine in my failures on coenzyme Q-10. Where they werenít improving, I would add L-carnitine and, sure enough, the people were feeling better. But I had to add very high doses, like 1, 2, 3 even 4 grams of L-carnitine. This is one of the advantages of being a clinician where you can really try these out in your practice. Some of these patients would improve and it would blow me away.

Now, Iím starting to use D-ribose, another mitochondrial support nutrient, in my patients. This Triad of coenzyme Q-10, L-carnitine and D-ribose will be a new frontier for metabolic cardiology.

Passwater: We havenít talked about D-ribose yet. D-ribose is a five-carbon sugar that is a regulator in the production of ATP. Itís the carbohydrate backbone of genetic material such as RNA and is also core to the production of many essential metabolic compounds. In sufficient levels, D-ribose increases the levels of 5-phosphoribosyl 1-pyrophosphate (PRPP), which then facilitates the biosynthesis of purine nucleotides, including ATP.

Sinatra: When the blood flow to the heart is reduced by arterial plaque or clots, the oxygen needed for producing energy is also reduced. This is a condition called ischemia. Under these conditions, ATP production is also reduced and may remain reduced for quite some time even after blood flow and available oxygen is improved. Supplemental D-ribose restores ATP production in heart cells to almost normal within 24 hours. Supplemental D-ribose helps the heart rebuild and maintain energy,

Passwater: So, in your program you suggest the long-chain omega-3 fats, L-carnitine to transport them to the inner membrane of mitochondria, coenzyme Q-10 to spark the production of ATP and D-ribose to help produce ATP.

When arterial plaque reduces the blood flow to the heart, the heart doesnít receive enough oxygen to produce the energy it needs. Or when the heart canít pump strongly enough to deliver enough oxygen-rich blood to its own cells, then the heart canít produce enough energy. Deficiencies of L-carnitine and/or coenzyme Q-10 have the same effect as not enough oxygen, and the heart canít produce the energy it needs to function.

Sinatra: I remember one patient, a grandmother who was riding a motorcycle after I put her on L-carnitine. It was incredible. She came into the office and she felt so good. The L-carnitine was needed in spite of the fact that I had her on 400 mg of coenzyme Q-10. After I added 2 grams of L-carnitine she was like a new woman. An anecdotal case again, but Italian researchers have done research on the synergy of coenzyme Q-10 and L-carnitine. They are synergistic, and both of these nutraceuticals can reach the inner mitochondrial membrane. Alpha-lipoic acid also can reach the inner mitochondrial membrane, as can vitamins C and E. If you give these nutraceuticals and build up the inner mitochondria membrane, it is my belief that you increase the efficiency of the heart cell. When you do that you will improve the efficiency of the tissue as well as the organ, so I have been very interested in using L-carnitine in combination with coenzyme Q-10.

Passwater: I believe you use L-carnitine fumarate; why do you prefer that to L-carnitine tartrate?

Sinatra: L-carnitine fumarate is best, especially for the heart, because fumarate is a Krebs cycle component.


Passwater: The Krebs cycle is also called the citric acid cycle or tricarboxylic acid cycle (TCA). This is the cycle in which pyruvic acid from glycolysis is completely oxidized to carbon dioxide via interconversions of the carboxylic acids (oxaloacetate, citrate, ketoglutarate, succinate, fumarate and oxalate).

Sinatra: Studies at George Washington University show that L-carnitine fumarate has a sparing effect in ischemia in the mitochondrion. In other words, you can probably get more mileage out of the fumarate over the tartrate because fumarate is a Krebs cycle component and is more easily assimilated or metabolized in cells that are struggling for oxygen.

L-carnitine fumarate appears to be better absorbed than L-carnitine tartrate. L-Carnitine fumarate has an available L-carnitine content of 60% and a fumaric acid content of 40%. L-carnitine in the free base form is very hygroscopic, that is, it draws moisture and is unstable. The increased bioavailability of L-carnitine fumarate may be due to the very fine particle size that can be produced since it is less hygroscopic. These are the reasons why I use L-carnitine fumarate.


Passwater: Would you use acetyl L-carnitine for heart patients?

Sinatra: L-carnitine fumarate is better for the heart, and acetyl L-carnitine may be better for the brain, as it crosses the blood brain barrier.


Passwater: How about dosage?

Sinatra: Well, dosage varies with the patient and the ailment. I generally recommend doses of 250 to 500 mg of L-carnitine fumarate three to four times a day.


Passwater: You were talking about the heart with all the mitochondria and the fact that the heart goes on fatty acid metabolism for energy over glycolysis. How about muscle cells? Would there be any increase in energy? When people tell you they have more energy, is that coming just from their improvement in the production of energy within the heart, or is that increased energy coming from other areas?

Sinatra: It could be a peripheral effect as well. One of the best indications of L-carnitine deficiency is claudication. L-carnitine is like a freight train in that it shuttles fatty acids into cells to be burned. It also shuttles out the metabolites of these fatty acidsóthe acetyl groups. Lactic acid is very toxic to these cells. L-carnitine is one of the best indications for peripheral claudication because the fatty acids are burned more effectively and the toxic metabolites are shuttled out as well. When you remove all these toxic metabolites of fat you also improve the efficiency of the cells. That is why L-carnitine works in anginaóbecause the heart is a muscle. Also, skeletal muscles such as leg muscles work through the same mechanism.

So you get an essential effect in the heart and you get a peripheral effect as well. That is really good stuff, but if you werenít a clinician, if you werenít taking care of patients on a day-to-day basis, you wouldnít know this information. That is the great thing about being a doctor. That is the joy of medicine where you can really see these benefits and results.

Passwater: How does this coenzyme Q-10/L-carnitine combination increase the burning of stored body fat?

Sinatra: The combination increases metabolism and makes the cells more efficient in burning fat. Now I thought that if we use high doses of L-carnitine and coenzyme Q-10 we could accomplish weight loss. I tried this combination with some patients with the goal of weight loss, but it didnít work that well. It wasnít until I also added chromium and a lot of exercise that most patients achieved substantial weight loss. I believe the coenzyme Q-10 and L-carnitine combination aloneówithout high-dose chromium or exercise wonít produce significant weight loss. For people who take L-carnitine and coenzyme Q-10 for weight loss by itself it wonít work. You really need to make that energy-producing machinery more efficient, and this is where exercise comes in.

Exercise is one way of enhancing the metabolic rate, getting the insulin into the cells and making the cells work more effectively. When that happens, you get better burning of fat because active muscles need to be efficient metabolically and this is just what the body makes the cells becomeómore efficient energy producers. When you combine exercise and chromium along with the coenzyme Q-10 and L-carnitine you can get greater weight loss.

Passwater: You have published quite a bit on coenzyme Q-10. Have you published anything on the coenzyme Q-10 and L-carnitine combination?

Sinatra: Yes, I have written papers on L-carnitine and coenzyme Q-10 where I describe the synergy of the combination. I have published findings indicating that L-carnitine and coenzyme Q-10 have an effect on apoptosis as well. This is an interest of mine right now because as people age, they lose heart cells. Perhaps you can delay the death of heart cells by keeping these cells more alive by using these supportive nutraceuticals. L-carnitine and coenzyme Q-10 nurture the inner mitochondria membrane. Can you prolong the life of the heart cells? I donít think there are data on that but there are a lot of data on coenzyme Q-10 delaying apoptosis. I think in the future you are going to see more and more research on the combination of coenzyme Q-10 and L-carnitine in trying to extend the life of heart cells. I have not done any individual research on that, but it is an interest of mine. Perhaps as the amount of research on coenzyme Q-10 and L-carnitine grows, we will hopefully explain this mystery of apoptosis and the heart.

Passwater: Thank you Dr. Sinatra. I am sure that this information will help many people, but I know you have more to teach us. Letís take a break and then chat about what you have found to be effective to help people with high blood pressure in a future article. WF

© 2004 Whole Foods Magazine and Richard A. Passwater, Ph.D.

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