Vitamin B12 and folate fail to protect heart in new study

Background: For the last few years, cardiologists have been following a blood test called homocysteine, as a risk indicator for heart and stroke. Previous studies have showed an association between lower homocysteine levels and lower coronary heart disease. However, no studies have yet been able to prove a benefit (i.e. less heart disease) from interventions which lower homocysteine.

This week, in JAMA, the latest study on this topic was published. It was a double-blinded, randomized, placebo-controlled trial (the best kind) of 12,000+ people who had previously survived a heart attack. They were given vitamin b12 and folate supplements, which are known reduce homocysteine levels by about 30%. During the 6.7 years of follow up, it was found that even though the blood levels of homocysteine were lowered by about 28%, there were no apparent beneficial effects on major coronary events or other non-coronary vascular events. The vitamin supplements didn't cause any harm, though, with no changes in mortality or the appearance of other cancers.

Sadly, the vitamins didn't help. The homocysteine molecule itself doesn't seem to have a direct effect on the heart.

What does this mean? We have to focus on what actually has been proven to work when it comes to risk reduction for heart disease: lifestyle changes (like avoiding excessive weight gain and quitting smoking), controlling blood pressure and cholesterol, and so on. Vitamin B12 and folate supplements, unfortunately, are not the magic bullets.

DHEA: super supplement or snake oil?

DHEA supplements are widely claimed in the lay press to help with a huge number of diverse conditions: anti-aging, cardiovascular disease, chronic fatigue & fibromyalgia, body building, obesity, osteoporosis, sexual dysfunction, and lupus - just to name a few. Most of this excitement was based on positive results seen in early scientific studies done in mice, and from some anecdotal reports from enthusiastic users...and things took off from there.

These days, many people now take the widely available DHEA tablets, hoping to get a health benefit - are they wasting their money and effort? Or is DHEA a "fountain of youth" hormone in a bottle?

What is DHEA?
DHEA (dehydroepiandrosterone) is a hormone that is made by the adrenal glands, out of cholesterol. It is an intermediate product in the chain of biochemical events that convert cholesterol into active hormones like testosterone and estrogen. Production of DHEA seems to peak in the mid-20's, and starts to decline after the mid-30's. (Unlike testosterone and estrogen, we don't have any evidence that DHEA is particularly active by itself.)

So, the theory goes, that if we can boost the falling levels of this hormone back to the levels seen in healthy young adults, then various "good things" will happen, and we should feel young again. Sounds promising, but does it work in this case?

The evidence:

We can divide DHEA uses into 2 main groups: 1) deficiency states due to a specific disease, and 2) supplementation for otherwise normal, healthy people.

Scientific evidence supporting the use of DHEA is mostly positive when it is used as part of the treatment of specific problems, such as:
- adrenal insufficiency ("Addison's disease")
- systemic lupus erythematosus ("lupus")
- depression

So far, most of the other proposed indications for DHEA use in disease states (like cancer or heart disease prevention) have not been proven yet, based on the studies that have been completed to date.

In terms of using DHEA as an "anti-aging" supplement for normal, healthy people who just want to feel younger, the recent scientific trials that have been carefully conducted in people, rather than mice, are pretty disheartening:

- A double-blinded, placebo controlled study from France in 2003, looked at the effect of DHEA on muscle mass over a 12 month period in healthy 60-80 year olds. Although the DHEA supplements caused the blood levels of DHEA to go up to the range found in young adults, there was no significant difference in muscle strength, or muscle volume compared to the placebo group.

- A 2005 study from University of Pennsylvania looked at muscle mass, strength, endurance and quality of life measurements (feelings of well-being, sleep & sexual function) in postmenopausal women. Once again, while the levels of DHEA in the blood went up, there was no significant difference in the treated group on any of the parameters, compared to the people that had no hormone therapy at all.

- A 2001 study from Germany looked at DHEA supplementation in healthy men, aged 50-69, using a double-blinded cross-over study design with placebo controls. While the blood levels of the hormones again went up to youthful levels, there was no effect seen on serum lipids, bone markers, body composition & muscle mass or exercise capacity.

- In a study done in healthy men aged 35-65, the effect of 12 weeks of DHEA supplementation was examined in conjunction with a high-intensity fitness program. They found no enhancement above the results obtained by physical training alone, and worse, a 6.5% increase in cardiac risk, due to unfavorable changes in the cholesterol profile.

DHEA also has a number of common side effects: acne, unwanted hair growth, unfavorable changes in lipid (cholesterol) profiles.

The bottom line: DHEA supplementation remains controversial as a supplement for normal, healthy people.

Based on my own interpretation of these and other studies, I don't currently recommend DHEA to my patients as a general anti-aging supplement. It does not seem to have conclusively-proven effects on either the physical or mental aspects of aging. While there might be some sub-groups of people where DHEA therapy may have some benefit, these groups are still being defined, and more research is needed.

People that have known hormonally-sensitive cancers (breast, prostate, etc.) should especially avoid DHEA.

Another tough day for vitamin makers & takers

Another blow to the idea that taking vitamins helps to keep us healthy was published in the latest issue of the "Archives of Internal Medicine". The study, called "Multivitamin Use and Risk of Cancer and Cardiovascular Disease in the Women's Health Initiative Cohorts", looked at 161,000 post-menopausal women over an 8 year time period, to see whether vitamin supplements reduced cancer rates, cardiovascular disease, or improved overall mortality rates.

The investigators compared the rates for cancers of the breast, colon & rectum, endometrium, kidney, bladder, stomach, ovary, and lung, as well as the rates of heart attack, stroke, DVT (blood clot) and total mortality in the vitamin supplement group, versus the same rates in the group without supplements. Unfortunately, there was no statistical improvement in the vitamin group for any of these parameters. Not one.

So, this is a convincing piece of evidence that vitamins do not prevent common cancers or cardiovascular disease, nor do they extend one's life expectancy, at least in the postmenopausal women of the study group.

What remains unanswered though, is whether there were any improvements in the "quality of life" parameters in the vitamin group. That's where believers in supplements, not to mention the multi-billion dollar supplement industry, are putting their hopes...

Does taking Vitamin E supplements prevent prostate cancer?

In the mid-1990's, two medical studies that were looking at the effects of vitamin and mineral supplements on cancer rates came on a finding, quite by happenstance during the post-study data analysis. It seemed that men who took Vitamin E supplements had a lower rate of prostate cancer. While neither study was particularly designed to investigate prostate cancer issues, the finding generated a great deal of excitment, as prostate cancer is very common in middle-aged and older men. Suddenly, men everywhere were taking Vitamin E and selenium, for prostate health

In the latest issue of the Journal of the American Medical Association (JAMA)are two major studies, which were designed to look specifically at this issue. The first study, known as "SELECT", looked at 35,000 men in the U.S., Canada and Puerto Rico, and compared the effects of 400 units per day of Vitamin E and/or Selenium supplements versus placebo. The second study, "PHS-II", looked at 14,600 American physicians over a 10 year period, and was also a randomized, double-blinded, placebo controlled study.

Bad news: unfortunately, neither of these two new, powerful studies found any significant reduction in prostate cancer rates due to Vitamin E, Vitamin C or Selenium supplements in the dosages given.

It seems that the positive results of the earlier studies were a chance occurrence - a fluke, if you will. Sometimes that happens - which is why scientists always double-check their initial findings with further studies. Given the large size of these two new studies, and their careful design, it is unlikely that an effect of the supplements, good or bad, would be missed.

So, it's back to the drawing board...guys, you can stop taking the selenium and Vitamin E now.