Resveratrol and Humans: What a New Study Could Mean

Juvenon Health Journal volume 9 number 8 august 2010
By Benjamin V. Treadwell, Ph.D.

Consider the questions of which vitamin / herbal supplements to take or whether to take them at all. Do we look to health professionals, who can’t seem to agree among themselves, for the answers? Should we combine their supplement advice with research, although much of it hasn’t progressed beyond cellular or animal studies?

Let’s take a closer look at a plant-derived supplement, resveratrol, as an example of the promising evolution of available information. From TV news to Internet blogs to scientific journals, resveratrol has gotten a lot of coverage for its reported health benefits. Although the published research is copious, the vast majority of the work was carried out in vitro or with yeast, worms, fruit flies, mice, rats and monkeys.

“Published results from human studies have been limited until recently.”

Published results from human studies have been limited until recently. (See Juvenon Health Journal, Volume 9, Number 4, “Resveratrol: New Evidence for a Human Health Benefit.”) In June of this year, a research team from New York presented some potentially significant new human findings. (See this issue’s “Research Update.”) But before we review their study, allow me to provide some context.

The Primary Plant
Although there are many sources for resveratrol, such as the skin of red grapes, the Japanese knotweed plant (Polygonum cuspidatum) seems to be the most common, due to the plant’s ubiquitous nature and relatively high resveratrol content. If you examine the label on a bottle of resveratrol, you’ll probably find the supplement is purified from a knotweed extract. A PCE, Polygonum cuspidatum extract, was also the source of the polyphenol for the New York study.

Purest Compounds vs. Most Potent Remedy
The intriguing nature of much of the research on many plant-derived supplements, as compared to chemically synthesized nutrients such as many vitamins, is the lack of absolute knowledge of how many substances the plant supplement contains. The New York researchers’ extract was a partially purified preparation of resveratrol, containing 20% resveratrol (dry weight percentage) and 80% numerous other plant compounds.

The investigators could not ascribe the PCE’s effects to one particular component. In fact, they suggested their results, considered impressive, might have been the consequence of several plant nutrients (resveratrol and others), acting together. If the team had used a highly purified preparation of resveratrol, the results might have been very different. (But would they have been better?)

“Japanese knotweed plant (Polygonum cuspidatum) may be the most common resveratrol source.”

PCE Study Design
There were 20 human subjects for the New York researchers’ six-week experiment, average age 35 and all in excellent health. One group of 10 was asked to take a capsule each day containing 200 mg of the PCE. The other 10 participants were given a similar-looking capsule, which contained 200 mg of an inert substance, a placebo.

Blood was drawn from each subject at the start of the study and at one-, three- and six-week intervals. The blood was separated into serum and cells. The cells were further separated by centrifuging to obtain a population of those involved in immune response, mononuclear cells.

PCE’s Promising Results
Compared to levels present at the start of the study, the subjects taking the PCE capsule demonstrated a striking decrease in serum levels of C-reactive protein (CRP) and TNF-alpha. These two markers of inflammation have been associated with many disease states, such as atherosclerosis, diabetes, cancer, and neurodegenerative diseases of aging. The group taking the placebo showed no change; their markers of inflammation remained high.

“Markers of inflammation, previously associated with many disease states, decreased in the PCS group.”

Examination of the isolated white blood cells, the mononuclear cells (cells with a specific mission to elicit an inflammatory response) during the six-week PCE treatment, also showed a significant decrease in several markers of inflammation, including one known as the master regulator of inflammation, NF-kB. Again, the subjects taking the placebo showed no change. There were several other markers of inflammation, associated with insulin resistance and diabetes, which were also significantly lower in the PCE subjects.

Motivating More Human Studies
Although the reported results of this study are impressive, its limitations call for longer and broader-based experiments. With the small number of subjects, statistical significance is less than ideal. Because the subjects were age matched (35 plus-or-minus five years), extrapolating the results to other age groups would be difficult. And, since the study lasted a relatively short six weeks, there’s the possibility that the PCE’s effects may not be durable.

Perhaps more importantly, I believe the New York team’s research may be a catalyst for significant related work. As they suggested, further analysis may demonstrate that multiple nutrients are required to produce the impressive anti-inflammatory results. It may be that resveratrol is just one of several plant compounds involved and, to produce its positive health effects, it requires the cooperative action of additional plant nutrients contained in the PCE. In other words, the highest purity resveratrol may not produce the greatest (and media-highlighted) health benefits!

Recently, a research team from the State University of New York and Kaleida Health, both in Buffalo, designed an experiment to determine the effects of a plant extract, containing resveratrol, on oxidative and inflammatory stress in normal humans. The group’s interest was motivated by previous animal and cell-culture resveratrol studies, which had demonstrated significant positive health effects, and the lack of corresponding human in vivo data.

The team published their methodology and results in “An Antiinflammatory and Reactive Oxygen Species Suppressive Effects of an Extract of Polygonum Cuspidatum Containing Resveratrol” in the Journal of Clinical Endocrinology & Metabolism.

The plant extract (PCE) was made from Polygonum cuspidatum (Japanese knotweed). The six-week study involved two groups of 10 subjects each, all of normal weight and healthy. One group received capsules containing 200 mg of the PCE. The other took similar capsules containing 200 mg of an inert substance, the placebo.

Blood samples, drawn at the start of the study and at one-, three- and six-week intervals, were centrifuged and serum collected. The blood cells were further refined to obtain a pure population of mononuclear cells, the type of cell normally involved in initiating an inflammatory response.

After six weeks, markers of inflammation, TNF alpha and CRP, in serum samples from the PCE-capsule group were lower than at the beginning of the study. The placebo group showed no decrease. Similarly, there was less expression, in the PCE group’s isolated mononuclear cells, of markers of inflammation, NF-kB and the enzyme p47nox. A number of additional markers, involved in promoting insulin resistance, were also reduced in the PCE group, but not in the placebo group.

The investigators concluded these results suggest the PCE, containing resveratrol, has a comprehensive suppressive effect on oxidative and inflammatory stress in humans. They qualified their conclusions by recommending 1) longer studies to ensure that the effect is durable and 2) studies to identify which component of the extract is responsible and whether higher doses will produce greater effects.

The team also acknowledged the relatively small number of subjects in their study (larger groups would increase statistical significance). And, because their results imply that PCE may be a potential insulin sensitizer, they suggested testing this theory on an insulin-resistant population.

This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

Dr.Treadwell answers your questions.

question: I recently heard that taking calcium supplements after age 60 is not good and can cause organ problems. The report said it was better to get calcium from food, especially if you are older. Is this a new discovery? I have taken calcium supplements for several years and am 65 years old. – 

answer: Since the body no longer stores calcium after age 30-35, getting the mineral from other sources, as we age, is essential. The recent report, to which I believe you’re referring, is preliminary and its conclusions may be based on insufficient evidence. Although relying on diet would be ideal, many of us have been taking calcium supplements with seemingly excellent results.

It is also noteworthy that the subjects in this study were not taking magnesium along with the calcium. Other studies have demonstrated that magnesium aids in calcium absorption and a combination of these two minerals, along with vitamin D, helps maintain bone strength and density. Magnesium has also been shown to benefit cardiovascular health.