Low-dose resveratrol as a calorie restriction mimetic

Resveratrol, a natural product derived from grape skins and other plant sources, is widely (but not universally) believed to be an activator of the longevity assurance genes known as sirtuins. Despite some debate about its mechanism of action, the compound has received a great deal of attention as a possible pharmaceutical remedy for diseases of aging such as late-onset diabetes.

Most famously, resveratrol has been reported to increase the median lifespan of mice fed a high-fat diet, but that study has been subject to numerous criticisms. The diet in question was so unhealthy it would have made Morgan Spurlock blush, raising questions about its fairness as a model even for the most deranged Western diet. Furthermore, the quantity of resveratrol administered to the mice in the study corresponded to something like 1000 bottles of red wine per day. A skeptical reader could fairly claim that such a study, in which ridiculously high doses of a compound have an effect on an obscenely unhealthy animal, teaches us exactly nothing about what manageable doses of the same compound might accomplish in reasonably healthy people (which is, arguably, the point).

So: do manageable doses of resveratrol have health benefits — specifically, with respect to diseases of aging or aging itself? The first evidence in the affirmative has recently been published by Barger et al., who demonstrate that mice eating a normal ad libitum calorie-controlled* diet supplemented with resveratrol (at a much lower dose than in previous studies) undergo many of the same transcriptional changes as animals undergoing caloric restriction (CR):

A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice

Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg/kg per day), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging, and prevent age-related cardiac dysfunction. Dietary resveratrol also mimics the effects of CR in insulin mediated glucose uptake in muscle. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR.

In addition to altered gene expression, the resveratrol-treated mice also exhibit delays in aging parameters (cardiovascular, endocrinological, metabolic) comparable to those caused by CR. The physiological and gene expression changes are observed in multiple tissues; taken together, they strongly support the hypothesis that resveratrol acts as a CR mimetic. Based on patterns of SIRT1 activity, however, the authors conclude that a subset of these changes (specifically, the delay in age-related cardiac decline) are not due to activation of SIRT1 by resveratrol.

The next question: Given that resveratrol and CR stimulate similar transcriptional changes, and that resveratrol yields some of the same physiological benefits as long-term CR, does low-dose resveratrol also have a favorable effect on median or maximum longevity? Based on these findings, I know how I’d bet, but for the ultimate answer, we’ll have to wait for the next paper.

* See Jamie Barger’s comment below.


  1. Hi Chris,

    Nice write-up. I just wanted to clarify one point. Our control (and resveratrol-treated) mice are not fed ad lib, we feed them a controlled caloric intake (84 kcal/day) which is ~10% lower than ad lib intake. The primary reason we use this protocol is that it prevents obesity in the mice, thus our “Young Control” vs. “Old Control” comparisons represent the effects of primary aging. It seems like a minor point, but as you point out, this highlights a major distinction between the earlier studies with resveratrol in mice and our recent study.

  2. I just started taking 100 mg of resveratrol (Longevinex) twice a day with my morning and noon meals. I suffer from insulin insensitivity, (metabolic sydrome) the precursor to type two diabetes. What I immediately noticed is that I no longer experience tiredness after consuming carbs.

    It will be interesting to see what my insulin levels look like after my next Glucose Tolerance Test. I’ve been taking metaformin by prescription to improve my insulin sensitivity, but haven’t seen much effect.

  3. OK, Ouroboros, how would you bet?

    I’m betting my life, so how about sharing some well-informed opinion?

    I really enjoy reading your work. You make me see the inside of the lab! Thanks.


  4. I don’t currently take any form of resveratrol, though as I’ve commented before, this is mostly because I don’t trust the people who sell it, and I’m not sure what I’d be getting.

    I’d certainly want to avoid high doses, regardless of the vendor; I’m concerned by reports about malabsorption and chelation issues — though I’m having a hard time tracking down reputable sources on these points.

  5. Hi,

    I need some help of the well informed people from this forum.

    My mother is diagnosed breast cancer one month ago. She was taking Resveratrol (50 mg), for one year now. She has to do chemotherapy in the next 6 months.

    Do you think it is good for she to continue taking Resveratrol, and if so, to maybe increase the dosis (like to take Longevinex)?

    I live in Austria and it is not very popular to ask such questions the physicians.

    Thanks a lot!


  6. Mir, I think that asking for medical advice on blogs is a bad idea, generally speaking. I’m sorry if it’s tough to ask Austrian doctors about stuff like this, but I still think it’s your best bet.

    The best answer I can give you is that it’s unlikely that anyone has carefully studied effect of resveratrol on specific chemotherapeutic agents, so any answer you get from anyone is likely to say more about their own prejudices than anything else.

    For my part, I think resveratrol is a basically innocuous substance at such low doses, and that it’s unlikely to interfere with any modern chemotherapy, and that if it makes your mom feel better to take it then she should keep on taking it. I have no advice about specific formulations or whether higher doses would be useful or harmful. I don’t think anyone knows.

  7. ouroboros,

    I aswered, but the entry did not show up in the blog.

    Thank you for your advice.


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