National Institutes of Health: How Resveratrol Works

Resveratrol, a compound found most famously in red wine, is the subject of a Feb. 13, 2012 news release by the National Institutes of Health. The NIH reports on a new study that identified the precise biochemical mechanism in the body that seems to be responsible for resveratrol’s ability to mitigate the harmful health effects of a high-fat diet.

One of the earliest reasons for scientific interest in resveratrol was the perception that people who drank a lot of red wine could also eat a relatively high fat diet, yet still have a rather low risk of cardiovascular disease. (This was the so-called “French paradox,” much discussed in the US media in the early 1990s.) The current NIH-supported study found evidence that resveratrol affects specific biochemical pathways that block the ill effects of a high-fat diet, such as obesity, glucose intolerance, and, potentially, the development of Type 2 diabetes. (Type 2 diabetes, in turn, is a risk factor for coronary heart disease.)

This NIH-supported study follows a pattern we’ve often seen before: the health benefits of a natural product are noted in general population studies, and eventually laboratory science allows us to home in on the exact mechanisms by which the natural substance works. Needless to say, we’re all for this kind of research to confirm and refine our knowledge of supplements!

Read more about the resveratrol study at:
http://www.nih.gov/researchmatters/february2012/02132012resveratrol.htm

You can find resveratrol in two forms at the NYBC. (Resveratrol Synergy adds some of the additional parts of the grape that are thought to have health benefits, and combines those with green tea extract, another food extract that researchers believe may have health benefits.)

Resveratrol
Resveratrol Synergy

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DHEA and depression

Here are citations for two well-designed recent studies on DHEA and depression. The first was undertaken by the NIH/National Institute of Mental Health and used DHEA as the sole therapy with a group of men and women aged 45 to 65 who were experiencing major or minor midlife-onset depression. The researchers concluded that DHEA was an effective treatment for this group. Note: a further item of interest is that DHEA therapy was also found to be associated with improvement in sexual function. (Contrast with certain prescription anti-depressants, which shall remain nameless!)
The second study, by Judith Rabkin et al. at Columbia Univ., focused on people with HIV and examined DHEA as a therapy for non-major depression, especially among a group that was not in the best physical health. The finding: DHEA was an effective and useful therapy under these conditions.
For more information on DHEA, including recommendations for use, see the NYBC
description of

DHEA – Douglas Laboratories

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Source: Arch Gen Psychiatry. 2005 Feb;62(2):154-62.

Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression.

Authors: Schmidt PJ, Daly RC, Bloch M, Smith MJ, Danaceau MA, St Clair LS, Murphy JH, Haq N, Rubinow DR. Behavioral Endocrinology Branch, National Institute of Mental Health, Rockville, MD CONTEXT: Alternative and over-the-counter medicines have become increasingly popular choices for many patients who prefer not to take traditional antidepressants. The adrenal androgen and neurosteroid dehydroepiandrosterone (DHEA) is available as over-the-counter hormonal therapy and previously has been reported to have antidepressant-like effects. OBJECTIVE: To evaluate the efficacy of DHEA as a monotherapy treatment for midlife-onset depression. DESIGN: A double-blind, randomized, placebo-controlled, crossover treatment study was performed from January 4, 1996, through August 31, 2002.S ettings The National Institute of Mental Health Midlife Outpatient Clinic in the National Institutes of Health Clinical Center, Bethesda, Md.Patients Men (n = 23) and women (n = 23) aged 45 to 65 years with midlife-onset major or minor depression participated in this study. None of the subjects received concurrent antidepressant medications.Intervention Six weeks of DHEA therapy, 90 mg/d for 3 weeks and 450 mg/d for 3 weeks, and 6 weeks of placebo. MAIN OUTCOME MEASURES: The 17-Item Hamilton Depression Rating Scale and Center for Epidemiologic Studies Depression Scale. Additional measures included the Derogatis Interview for Sexual Functioning. Results were analyzed by means of repeated-measures analysis of variance and post hoc Bonferroni t tests. RESULTS: Six weeks of DHEA administration was associated with a significant improvement in the 17-Item Hamilton Depression Rating Scale and the Center for Epidemiologic Studies Depression Scale ratings compared with both baseline (P<.01) and 6 weeks of placebo treatment (P<.01). A 50% or greater reduction in baseline Hamilton Depression Rating Scale scores was observed in 23 subjects after DHEA and in 13 subjects after placebo treatments. Six weeks of DHEA treatment also was associated with significant improvements in Derogatis Interview for Sexual Functioning scores relative to baseline and placebo conditions.CONCLUSION: We find DHEA to be an effective treatment for midlife-onset major and minor depression.

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Source: American Journal of Psychiatry. 2006 Jan;163(1):59-66.

Placebo-controlled trial of dehydroepiandrosterone (DHEA) for treatment of nonmajor depression in patients with HIV/AIDS

Authors: Rabkin JG, McElhiney MC, Rabkin R, McGrath PJ, Ferrando SJ.
New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York

OBJECTIVE: Subsyndromal major depressive disorder is common among HIV-positive adults. This study was designed to assess the efficacy of dehydroepiandrosterone (DHEA) as a potential treatment. METHOD: One hundred forty-five patients with subsyndromal depression or dysthymia were randomly assigned to receive either DHEA or placebo; 90% (69 of 77) of the DHEA patients and 94% (64 of 68) of the placebo patients completed the 8-week trial. The primary measure of efficacy was a Clinical Global Impression improvement rating of 1 or 2 (much or very much improved) plus a final Hamilton Depression Rating Scale score <or=8. Outcome was assessed by using intent-to-treat analysis, followed by completer analysis. Safety was assessed by queries about side effects at every study visit plus measures of CD4 cell count and HIV RNA viral load at baseline and week 8. DHEA dosing was flexible (100-400 mg/day). RESULTS: On the basis of clinicians’ ratings, DHEA was superior in the intent-to-treat analysis, where the response rate was 56% (43 of 77) for the DHEA group versus 31% (21 of 68) for the placebo group. In the completer analysis, the response rate was 62% (43 of 69) for the DHEA group, compared to 33% (21 of 64) for the placebo patients. The number needed to treat was 4 on the basis of intent-to-treat data and 3.4 on the basis of completer data. Few adverse events were reported in either treatment group, and no significant changes in CD4 cell count or HIV RNA viral load were observed in either group.

CONCLUSIONS: Nonmajor but persistent depression is common in patients with HIV/AIDS, and DHEA appears to be a useful treatment that is superior to placebo in reducing depressive symptoms. The low attrition rate in this group of physically ill patients, together with requests for extended open-label treatment, reflect high acceptance of this readily available intervention.

Whatever happened to policosanols?

Several years ago, there was growing interest in policosanols, a newly identified supplement, as a cholesterol-lowering agent. Major international scientific journals published promising studies of this substance derived from sugar cane wax, and it was already being marketed in a number of countries by the Cuban manufacturer, which had also conducted all the major studies (hmmm…). As of 2005, the accumulation of evidence was so impressive that even the NIH decided to fund an investigation of policosanols to lower lipid levels in people with HIV on HAART.

So what happened to this once-promising supplement? The tale is told in a piece of investigative reporting that NYBC published in early 2007. Author: Sean-Michael Fleming, with additional contributions from George Carter and Jared Becker.

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While updating the NYBC website [in 2006], I encountered disturbing reports of new, damning studies of policosanols, once the cholesterol-lowering darling of the supplement world. After some investigation, I realized I had started down a trail of…international intrigue.



Policosanols (chemically speaking, a mix of different kinds of long-chain fatty acids) became the golden child of supplements in recent years, with dazzling promise of being able to lower LDL (“bad”) cholesterol up to 30% with negligible side effects – and at far less cost than prescription statins. They seemed a godsend for those on HAART (highly active antiretroviral therapy), who often struggle with cholesterol control. Described in many respected scientific journals worldwide, they had been tested successfully on thousands of people!

Studies of sugarcane-derived policosanols first emerged from Cuba in the mid-1990s. Interest grew as human trials confirmed the supplement’s effectiveness in treating dyslipidemia. (Dyslipidemia refers to abnormal blood fat levels: elevated “bad” cholesterol and triglycerides, and low HDL or “good” cholesterol; it is frequently the precursor of cardiovascular disease.)


The Cuban studies received a major seal of approval from German scientists reviewing them in the American Heart Journal in 2002. Surveying over 20 published studies, the scientists declared the supplement to be “a fascinating new agent for the prevention and treatment of atherosclerotic disease.”
Meanwhile the sale of Cuban sugarcane policosanols – now patented – expanded to more than 40 countries, mainly in South America and the Caribbean. The Cuban version couldn’t be sold in the US due to the trade embargo, but a multitude of policosanol products appeared here as well. At NYBC we were enthusiastic about policosanol’s potential, and added it to our catalog in 2005.But doubts were surfacing. Studies of policosanols extracted from wheat germ and from rice failed to find an effect, though some claimed these forms did not contain the right balance of aliphatic alcohols (=policosanols).


In 2006 the German scientists who had given the Cuban studies high marks returned with results of their own rigorous trial of Cuban sugarcane policosanols, which found them no more effective than a dummy pill. Later in the year, Canadian researcher Dr. Peter Jones also reported a study using Cuban sugarcane policosanols that showed the supplement had no value in lowering cholesterol. (However, he used a 10 mg dose that may have been too low; others suggest the study was too short, being only 28 days long.)


Perhaps there was cause for skepticism from the start. Almost all the Cuban studies came from Dalmer Labs, which was connected to the nation’s Center for Scientific Research and then became the marketer of Cuba’s patented policosanols. No independent scientific verification took place outside of Cuba for years. And was it coincidence that the policosanol studies came out just when Cuba’s sugar industry was staggering under the loss of Soviet subsidies and a string ofbad harvests? Boosting sales of sugarcane derivatives became an acknowledged national goal, and would certainly be a good way to restore profitability to the island’s major cash crop.


We don’t yet know the full back-story to this “policontroversy.” At NYBC we are considering discontinuing policosanols, and would like to hear reactions from any member who has used them. In the meantime, we urge anyone interested in using them to do so at the beginning of bloodwork on a stable regimen. Then see if they work for you—or not. And please share your experiences with us.


With the promise of policosanols tarnished, what lipid-lowering alternatives to prescription drugs do people have? Fish oils continue to gain respect in scientific/medical communities in Europe and the US (see info about them on our new Supplement Fact Sheets – see “Resource Relaunch Revealed” in this issue). Dr. Jones sees a potentially bright future for plant sterols, which may significantly improve lipid profiles—we look forward to more study of these substances. Then there’s niacin, which despite the problem of “flushing/itching,” works very well for some people as a cholesterol-lowering agent (see detailed suggestions on our website).


Of course, nutritionists have long known about the moderate cholesterol-lowering effect of high-fiber foods like oatmeal. If you are trying to control your cholesterol, you should also understand that sugar intake, not just fat intake, influences your cholesterol level. And when monitoring cholesterol and cardiovascular risk, remember that the more recent focus has been not just on lowering “bad” cholesterol, but raising “good” cholesterol (which niacin does very well). And of course, making dietary changes and getting routine exercise are the first basis with which to start.


Thoughts? Comments? Any further information to offer us as we prepare to close the books on this once-promising supplement?