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Research Newsletter-Fall/Winter 2010


Balz Frei, Ph.D.
LPI Director and Endowed Chair
Distinguished Professor of Biochemistry and Biophysics

In my last director's column (LPI Research Newsletter Spring/Summer 2010), I described my daily dietary supplement regimen, which consists of:

I also pointed out that I make sure to get 1,000 mg of calcium daily from my supplements and diet combined and that I currently don't take a vitamin E supplement because of concerns of an increased tendency to bleed when I take vitamin E together with a fish oil supplement.

I was pleased to see that my column inspired several articles in the popular media, including an upcoming article in Vogue magazine. My column also elicited feedback from my faculty colleagues and several LPI supporters around the country. One loyal donor from New York wrote me, "I do everything you do. So maybe that's why I just passed my 95th birthday." He continued, "Two things that I do that you left out, [but] I'm sure that you will add along the way: 1. Resveratrol 2. Coenzyme Q10." He was not the only LPI donor who asked about those two supplements.

In addition, Dr. Maret Traber, LPI Principal Investigator and one of the world's foremost authorities on vitamin E, wasn't quite happy that I preferred fish oil over her favorite vitamin. On the other hand, Dr. Donald Jump, an LPI Principal Investigator who is doing cutting-edge research on the biology and health effects of omega-3 fatty acids, including fish oils, didn’t object. So, in this column, let me further comment on those three supplements—vitamin E, resveratrol, and coenzyme Q.

As you may know, vitamin E has taken a beating lately in both the scientific literature and popular press. Numerous large, randomized, placebo-controlled trials (RCT) of vitamin E supplementation for the prevention or treatment of heart disease or cancer have shown mixed and overall disappointing results. Some "meta-analyses" even suggested that vitamin E supplements may increase the risk of dying! Hence, the medical community, with a few exceptions, has all but dismissed any health benefit of supplemental vitamin E. However, these RCT, which are considered "the gold standard" for showing efficacy and safety of a medical drug, are far from being the ideal approach to test the efficacy and safety of micronutrient supplements like vitamins and essential minerals.

For example, while drugs are being recognized by the body as foreign substances ("xenobiotics") that are rapidly metabolized, detoxified, and excreted, vitamins are essential for life ("vita" meaning life in Latin). Humans have evolved specific mechanisms to absorb and transport these essential nutrients to target cells and tissues for use in enzyme reactions and other biological functions. This also means that every person has been "exposed" to these micronutrients through their diet over their lifetime, which is not true for synthetic drugs that are only taken as part of the study. Therefore, RCT of micronutrients are not controlled: while the investigators give a placebo pill to the "control" group, all subjects in this control group have substantial levels of the vitamin to be tested in their bodies from the outset and throughout the course of the study! This severely limits the statistical power of the trial. For these and other reasons, the deck is stacked heavily against showing an effect of vitamin supplements in RCT.

A much better approach to evaluate the possible health benefits of vitamins is to look at the totality of evidence—test tube, cell culture, and animal studies, as well as epidemiological studies (human population studies) other than RCT. This totality of evidence shows that vitamin E acts as an important, fat-soluble antioxidant in our bodies and is very likely to have benefits in reducing the risk of diseases that have oxidative stress as a contributing factor, such as heart disease, ischemic stroke, Alzheimer's disease, and, possibly, certain cancers and Lou Gehrig's disease. Therefore, I firmly stand behind LPI's recommendation to take a daily supplement of 200 IU (133 mg) of natural source alpha-tocopherol (d-alpha-tocopherol) with a meal.

Coenzyme Q is often taken for two purposes: 1) to strengthen mitochondria, the "power plants" in our cells, and enhance energy metabolism; and 2) as an antioxidant to protect cell membranes and lipoproteins against oxidative damage. In fact, I co-authored two papers 20 years ago in Proceedings of the National Academy of Sciences USA showing that coenzyme Q is an effective fatsoluble antioxidant and protects low density lipoprotein—the "bad cholesterol" contributing to heart disease and stroke—more efficiently against oxidative damage than vitamin E. Coenzyme Q, unlike vitamins, is not an essential nutrient because it is synthesized in our bodies. A major problem with coenzyme Q supplements is that they are poorly absorbed, although some formulations are available that have increased bioavailability. It is also unclear whether supplemental coenzyme Q reaches its target tissues in the body, such as muscles, heart, and brain, especially in healthy individuals.

There is some evidence that coenzyme Q supplementation is useful as an adjunct to conventional drug therapy for congestive heart failure and may help in the treatment of other cardiovascular diseases and certain neurodegenerative diseases, such as Parkinson's or Huntington's disease. It's also possible, but not proven, that heart disease patients taking cholesterol-lowering statins may benefit from coenzyme Q supplementation. Statins are known to inhibit coenzyme Q synthesis in the body because they target the same pathway as cholesterol synthesis. Because of the limited overall evidence for benefit in healthy individuals, its low bioavailability, and the relatively high cost, LPI does not recommend regular coenzyme Q supplementation for healthy individuals. Certain subpopulations with specific diseases, older people, and individuals taking statin drugs may derive some benefit from coenzyme Q supplements.

Finally, resveratrol has been one of the hottest topics among the health-conscious public, as attested by the fact that the resveratrol article on LPI's Micronutrient Information Center is visited over 50,000 times each month. As we explain on that Web site, there is intriguing evidence that resveratrol "can inhibit the growth of cancer cells in culture and in some animal models" and may mimic caloric restriction and extend "the lifespan of yeast, worms, fruit flies, fish, and mice fed a high-calorie diet." However, there is very little evidence for any health benefits of resveratrol supplements in humans, let alone evidence that it extends lifespan. The LPI research focus has been more on healthspan than lifespan, as we believe it is more important for people to attain a healthy old age than just a long life.

Commercially available resveratrol supplements contain doses that are hundreds or thousands of times higher than the amount naturally present in red wine or grapes. We don't know if taking such large doses of resveratrol over long periods of time is safe. Hence, at our current state of knowledge, the risk/benefit ratio seems unfavorable. LPI does not recommend resveratrol supplements, nor do I take them personally. I prefer to get my resveratrol the natural way. So, here's to your health!

Last updated November 2010