Vitamin B and steroids: monuments to human folly

Walk into any Vitamin Shoppe or GNC and you can see them: people looking to fight a cold, reduce “stress”, sleep better, or build bigger muscles. They’re all looking for a quick fix with no downside. They’re all deluded.

Two new clinical trials testing the effects of vitamin B and steroids serve to demonstrate the folly of human hopes for quick fixes that seem harmless. But they also demonstrate the only antidote to such folly: the objective and critical assessment of those hopes.

In a study in JAMA, investigators report a placebo-controlled, double-blind, randomized trial comparing vitamin B to placebo in 238 patients with diabetic nephropathy. After 3 years, as it turned out, vitamin B appeared not only to hasten the decline in kidney function but also cause a doubling of the combined rate of MI, stroke, revascularization, and all-cause mortality.

A new study in Circulation: Heart Failure provides strong evidence that steroid use may weaken the heart and even lead to heart failure. The researchers performed echocardiographic exams on 12 weightlifters who took steroids and 7 evenly matched weightlifters who had not taken steroids.  Heart function of 10 of the 12 steroid-taking weightlifters was below the accepted limit of normal,  and many other measurements of the heart showed cause for concern in this group.

Here are the JAMA and AHA press releases:

Here is the JAMA release:

High Doses of B Vitamins Associated With Increased Decline in Kidney Function for Patients With Kidney Disease From Diabetes

CHICAGO – Patients with diabetic nephropathy (kidney disease caused by diabetes) who received high dose B-vitamin therapy experienced a more rapid decline in kidney function and had a higher rate of heart attack and stroke than patients who received placebo, according to a study in the April 28 issue of JAMA.

Diabetic nephropathy typically affects the network of tiny blood vessels in the glomerulus, a key structure in the kidney composed of capillary blood vessels, which is necessary for the filtration of the blood. “In addition to the personal burden, the societal burden of diabetic nephropathy is enormous, exceeding U.S. $10 billion in annual medical expenditures. Despite effective therapies to slow disease progression, approximately 40 percent of the estimated 21 million patients with diabetes in the United States develop overt nephropathy. New treatment approaches to this problem are needed,” the authors write.

According to background information in the article, several observational studies have shown a significant association between high concentrations of plasma total homocysteine and the risk of developing diabetic nephropathy, retinopathy, and vascular diseases, including myocardial infarction (MI; heart attack) and stroke. B-vitamin therapy (folic acid, vitamin B6, and vitamin B12) has been shown to lower the plasma concentration of homocysteine.

Andrew A. House, M.D., of the University of Western Ontario, and J. David Spence, M.D., of the Robarts Research Institute, London, Ontario, and colleagues conducted a study to examine whether B-vitamin therapy would slow the progression of diabetic nephropathy and prevent vascular events in 238 patients with type 1 or 2 diabetes. The randomized, placebo-controlled trial was conducted at five university medical centers in Canada between May 2001 and July 2007. Patients received single tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B6 (25 mg/d), and vitamin B12 (1 mg/d), or matching placebo. The primary outcome was change in radionuclide glomerular filtration rate (GFR; a measure of kidney function) between baseline and 36 months. Other outcomes included dialysis and a composite of heart attack, stroke, revascularization and all-cause death. Plasma total homocysteine was measured. Participants were followed-up for an average of 31.9 months.

Among the results, the researchers found that participants assigned to the B-vitamin group had a greater decrease in radionuclide GFR (and subsequently poorer kidney function) compared with the placebo group. Also, participants randomized to receive B vitamins had a significantly greater number of cardiovascular and cerebrovascular events, with the 36-month risk of a composite outcome, including heart attack, stroke, revascularization, and all-cause mortality that was double in the B-vitamin group, compared to the placebo group. There was no difference in requirement of dialysis.

Regarding plasma total homocysteine levels, at 36 months, participants in the B-vitamin group had an average decrease while participants in the placebo group had an average increase.

“Given the recent large-scale clinical trials showing no treatment benefit, and our trial demonstrating harm, it would be prudent to discourage the use of high-dose B vitamins as a homocysteine-lowering strategy outside the framework of properly conducted clinical research,” the authors conclude.
(JAMA. 2010;303[16]:1603-1609.)

Here is the AHA press release:

Study highlights:

• Long-term anabolic steroid use may weaken the heart more than previously thought.
• Steroid-related heart impairment is severe enough to potentially increase the risk of heart failure.
• The left ventricle, the heart muscle primarily responsible for pumping blood throughout the body, was significantly weaker among steroid users.

DALLAS, April 27, 2010 — Long-term anabolic steroid use may weaken the heart more than previously thought and may increase the risk of heart failure, according to research reported in Circulation: Heart Failure, an American Heart Association journal.

Anabolic-androgenic steroids mimic the naturally occurring testosterone, a muscle-building hormone that promotes male sexual characteristics.

“Anabolic steroids, in addition to being illegal, have important health consequences,” said Aaron L. Baggish, M.D., lead author of the study and instructor in the Department of Medicine at Massachusetts General Hospital in Boston. “I think for the first time we’re starting to realize that the heart is one of the organs that is negatively impacted by long-term steroid use.”

In the small study, investigators found that the left ventricle, the heart’s main pumping chamber, was significantly weaker during contraction (systolic function) in participants who had taken steroids compared to a group of similar non-steroid users.

A healthy left ventricle pumps out 55 percent to 70 percent of the blood that fills the heart (a measurement known as ejection fraction). Eighty-three percent of steroid users in the 12-person study had a low pumping capacity (ejection fraction less than 55 percent) that previous studies have linked to increased risk of heart failure and sudden cardiac death. In contrast, only one of the non-steroid users had a low ejection fraction.

Steroid users also exhibited impaired diastolic function, which is when the left ventricle relaxes and fills with blood. The researchers showed that ventricle relaxation among steroid users, as demonstrated by the left ventricle’s ratio of early-to-late blood filling, was reduced by almost half (0.93 compared with 1.80 among non-users). The left ventricle’s structure was similar in both steroid-users and non-users.

Baggish and his co-investigators used a technique known as Doppler echocardiography to examine the left ventricle’s function and structure. The test uses high-frequency sound waves, or ultrasound, to create moving pictures of the heart and its blood flow.

The steroid-using group included 12 male weight lifters, average age 40, who reported taking about 675 milligrams of steroids per week for nine years. The control group was seven age-matched, male weight lifters who reported no steroid exposure. Both groups had similar durations of past and current weight lifting and other physical activity, as well as similar cardiac risk factors other than steroid use. Although the users and non-users had comparable body-mass indices and body-surface areas, the steroid users had more muscle mass than the non-users.

Despite the small sample size, the statistically significant differences in heart function suggest a strong link between steroid use and heart impairment, said investigators who are conducting further studies to confirm their findings.

In previous studies, the precise effects of steroid use on heart dysfunction have been unclear. Part of the problem with conducting studies of steroid-related heart injury is that illegal anabolic steroid use is relatively recent. In the United States, these drugs first became widespread among athletes in the 1980s; so many steroid users from that era are now reaching the age when heart problems often surface.

“What we hope is that people start recognizing steroid use as a potential cause of heart disease and a cause of otherwise unexplained heart dysfunction in young people,” Baggish said.

Co-authors are: Rory B. Weiner, M.D.; Gen Kanayama, M.D., Ph.D.; James I. Hudson, M.D.; Sc.D.; Michael H. Picard, M.D.; Adolph M. Hutter, Jr., M.D.; and Harrison G. Pope, Jr., M.D.

Author disclosures are on the manuscript.

The National Institute on Drug Abuse partially funded the study.

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