November 30, 2006 (Chicago, IL) – There are robust data to support the cardiovascular health claims made by manufacturers of some nutritional supplements, but for others the evidence is shaky at best, delegates heard earlier this month at the American Heart Association 2006 Scientific Sessions.
In a seminar entitled, "The science behind popular nutrition claims," a host of experts presented a roundup of the research on a number of substances claimed to "help maintain a healthy heart."
While some claims made for plant stanols and sterols, lipoic acid, and coenzyme Q10 appear to have a basis, the data on green tea, policosanols, and folic acid are equivocal, and there is little evidence for any benefit of vitamin E, the researchers said.
Stanols/sterols lower LDL, but no evidence that policosanols do
Dr Alice H Lichtenstein (Tufts University, Boston, MA) explained that plant stanols and sterols are the fat-soluble fractions of grains, seeds, root stems, and branches and are analogous to cholesterol in animals. Most people eat around 100 to 300 mg per day of such substances, but vegetarians consume more, up to 500 mg per day, she said.
"It is remarkable how consistent the impact of plant stanols is," she noted. "Although they need to be taken every day, data [1,2] have shown that maximal doses of 2 to 3 g per day seem to reduce LDL cholesterol by about 10%."
There is just one small concern, she said, namely that these substances might decrease the absorption of some fat-soluble vitamins. In fact, this has been demonstrated for only one--beta-carotene--and it is not clear what the clinical impact of this is, she noted.
Dr Peter JH Jones (McGill University, Montreal, Quebec) discussed the evidence for policosanols, waxy substances found in sugar cane--the most prevalent of which is known as octacosanol--that are also claimed to lower cholesterol.
Jones explained that much of the early work on policosanols, which claimed the benefits, was done in Cuba, but there came a realization that these findings needed to be confirmed by independent laboratories.
Four recently published human trials have found no effect of policosanols on LDL cholesterol [3-6].
"So how do we explain this disparity?" he wondered. "There's a possibility that baseline dietary intakes vary, or that there are genetic differences across populations in lipid metabolism--but then again, statins work across all populations, so why shouldn't policosanols?"
In addition, no molecular mechanism to explain an effect of policosanols on cholesterol has been defined, he noted. "Until these disparities are explained, policosanols cannot be recommended," he concluded.
Lipoic acid for diabetic neuropathy? Coenzyme Q10 for HF?
Dr Ishwarlal Jialal (University of California Davis Medical Center, Sacramento) told the audience the data on lipoic acid in humans are "very confusing, but there is one condition in which it clearly is of benefit--diabetic neuropathy."
However, he said, there is still no consensus on the optimum dose--which could be anywhere between 200 and 1800 mg/day--and more work needs to be done on the best form of lipoic acid to be used as a nutritional supplement.
Jialal also discussed coenzyme Q10, also known as ubiquinone, ubiquinol, and ubidecarenone. Studies looking at the use of this supplement show no clear benefit in cardiovascular disease and no definitive effect in reducing myalgias in patients taking statins, he said. In addition, patients taking warfarin need to exercise caution when taking coenzyme Q10.
But there is evidence of benefit in oneindication, heart failure, he said, citing a meta-analysis in which coenzyme Q10 had shown some improvement in ejection fraction [7].
But "much more research needs to be done in heart failure, using state-of-the-art techniques such as echocardiography to assess functional outcomes," he added. "Coenzyme Q10 is expensive, it's sold to everyone, and patients take it whether or not it affords them benefit.
"We particularly need to answer the question of whether this will work in heart-failure patients resistant to conventional drugs such as beta blockers," he noted.
Vitamin E gone to seed; folic acid on shaky ground
Jialal ended his talk by assessing the evidence for vitamin E (alpha-tocopherol). The majority of trials involving vitamin E have been negative, he said, but one study published in 2005 [8], which was the longest-duration vitamin study ever conducted, "went against the overwhelming data," showing a reduction in cardiovascular death (p=0.03) and a "tremendous effect in older women (p=0.009)," he noted.
However, "the totality of evidence does not support supplementation with vitamin E for the prevention and/or treatment of cardiovascular disease," he concluded, adding that there is "a general movement against antioxidants such that it is almost impossible now to get funding for such studies."
Dr Eric Rimm (Harvard University, Cambridge, MA) talked about folic acid and vitamin B6 . While much observational data suggested a benefit of B6 and folate via their homocysteine-lowering effects, major secondary-prevention studies have failed to replicate this, he noted.
However, Rimm believes there may be a benefit of folic acid in certain susceptible populations, as suggested by subanalyses of the large intervention trials. "B vitamins clearly lower homocysteine, and homocysteine increases the risk of coronary heart disease," he stated.
Green tea: The jury is still out
Finally Dr David J Maron (Vanderbilt University, Nashville, Tennessee) said the data on green tea were mixed, but claims of its efficacy are founded on its well-documented antioxidant and anti-inflammatory effects.
He explained that all types of tea are derived from the same plant--Camellia sinensis--and that black tea is fermented, oolong tea is partially fermented, and green tea is not fermented.
One meta-analysis found an 11% reduction in MI for every additional three cups per day [9], but he noted heterogeneous results among the studies--eg, an increased risk of CHD in a UK trial, an increased risk of stroke in a study done in Australia, but reductions in risk in continental Europe.
The largest study ever conducted on green tea--the Ohsaki study--was recently published in the Journal of the American Medical Association [10], he noted, and it found a reduction in deaths from stroke, but not coronary heart disease, in those who drank five or more cups per day compared with those who had less than one. And the benefits were particularly noticeable in women.
But this is observational data, Maron noted, adding that the only four intervention studies that have been conducted have found no evidence of benefit with tea itself or green-tea extracts such as theaflavin.
"We have no credible scientific evidence to support these health claims," he said. Despite this, and despite the FDA issuing a letter of denial for a claim made by the world's largest green-tea manufacturer earlier this year, there are still myriad advertisements touting the benefits of tea, he noted with exasperation.
"Ideally, we need long-term intervention trials," he concluded, adding that the same can be said for red wine and chocolate. "Stay tuned."
Miettinen TA, Puska P, Gylling H, et al. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med 1995; 333: 1306.
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Lin Y, Rudrum M, van der Wielen RP, et al. Wheat germ policosanol failed to lower plasma cholesterol in subjects with normal to mildly elevated cholesterol concentrations. Metabolism 2004 Oct; 53: 1309-1314.
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Sander S, Coleman CI, Patel AA, et al. The impact of coenzyme Q10 on systolic function in patients with chronic heart failure. J Card Fail 2006: 12:464-472.
Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: The Women’s Health Study: a randomized controlled trial. JAMA 2005; 294: 56-65.
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Kuriyama S, Shimazu T, Ohmori K, et al. Green tea consumption and mortality due to cardiovascular disease, cancer and all causes in Japan. The Ohsaki study. JAMA 2006; 296:1255-1265.
Heartwire from Medscape © 2006
Cite this: Lisa Nainggolan . Evidence Lacking for Most Nutraceuticals - Medscape - Nov 30, 2006.
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