# Resveratrol

Category: Drugs & Compounds

Resveratrol is a stilbenoid phytoestrogen that Ray Peat consistently identified as a dangerous molecule masquerading as an anti-aging therapy, primarily through its fraudulent association with the sirtuin genes and calorie restriction mimetics. Peat argued that the entire…

9 passages · 3 authors · 2009–2021 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/resveratrol

## Synthesis

**Resveratrol** is a stilbenoid phytoestrogen that Ray Peat consistently identified as a dangerous molecule masquerading as an anti-aging therapy, primarily through its fraudulent association with the **sirtuin genes** and calorie restriction mimetics. [Source 1, 4] Peat argued that the entire premise of resveratrol as a longevity drug rests on the discredited *rate of living theory*, which wrongly assumes that a lower metabolic rate extends lifespan, and on a fundamental misunderstanding of yeast biology where increased cell division—analogous to cancer in humans—was misinterpreted as longevity. [Source 1, 2] He noted that resveratrol is structurally similar to the synthetic estrogen **diethylstilbestrol (DES)**, a notoriously toxic and carcinogenic pharmaceutical, and that its effects in yeast are simply the result of overdosing an estrogen-sensitive organism to increase its fertility. [Source 2, 4]

The molecular mechanism promoted by resveratrol advocates involves the activation of the Sir2/SirT1 gene, a "silent information regulator" that suppresses protein production as a stress response. [Source 2] Peat warned that this process of turning off genes in a human moves the organism toward a spore-like, hibernating state, and critically, two of the proteins silenced by sirtuins are **klotho**, an anti-aging phosphate-regulating protein, and **P53**, a crucial tumor-suppressor protein. [Source 2] He further highlighted that resveratrol suppresses mitochondrial respiration, inhibits the formation of the protective hormone **progesterone** within mitochondria, and interferes with the ability of pancreatic beta cells to secrete insulin. [Source 3] In direct opposition, Peat pointed to **niacinamide** as a substance that protects mitochondrial respiration, extends the replicative lifespan of human cells in vitro, and was once explicitly warned against by resveratrol promoters for antagonizing sirtuins and supposedly accelerating aging. [Source 3, 6]

Georgi Dinkov has extended this critique by detailing the commercial failure and toxicity of resveratrol, noting that GlaxoSmithKline's $720 million acquisition of David Sinclair's company Sirtris ended abruptly when clinical trials for kidney failure resulted in an increased number of deaths in the treatment group, leading to the immediate halt of all research. [Source 5, 8, 9] Dinkov explained that while resveratrol can raise NAD levels, it does so pathologically by *speeding up glycolysis* and generating lactic acid, effectively promoting a cancer metabolism by using pyruvate as an emergency oxidant rather than supporting proper oxidative phosphorylation through the Krebs cycle. [Source 7] He emphasized that all stilbenoids are potent phytoestrogens that destabilize the cell, making it divide faster and enter a state primed for mutation. [Source 8, 9]

Peat also documented that resveratrol's supposed benefits are contradicted by direct experimental evidence, including a study showing it reduced the ability of human keratinocytes to divide, an effect that by the rate-of-living theory's own definitions would constitute *premature aging*. [Source 3] He observed that the metabolic depression expected from resveratrol—slowed heart rate and lowered body temperature—was only transient in mice, but that the treatment permanently reduced their endurance on a treadmill. [Source 4] The broader cultural acceptance of resveratrol, Peat argued, was manufactured by a culture permeated by genetic determinism and amplified by mass media, obscuring the reality that calorie restriction's effects involve hundreds of genes and that increased SirT1 activity might actually contribute to cancer and Alzheimer's disease. [Source 1, 4]

## People also ask

### How does resveratrol affect mitochondrial function and energy production?

Peat argued that resveratrol suppresses mitochondrial respiration and inhibits progesterone formation within mitochondria, while Dinkov noted it pathologically raises NAD by speeding up glycolysis and generating lactic acid rather than supporting proper oxidative phosphorylation.

### Why did Ray Peat consider resveratrol similar to the drug DES?

Peat observed that resveratrol is structurally similar to the synthetic estrogen diethylstilbestrol, a notoriously toxic and carcinogenic pharmaceutical, and that its effects in yeast result from overdosing an estrogen-sensitive organism to increase fertility.

### What happened when resveratrol was tested in human clinical trials?

Georgi Dinkov reported that GlaxoSmithKline halted all resveratrol research after clinical trials for kidney failure resulted in an increased number of deaths in the treatment group, ending the company's $720 million investment.

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## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — Resveratrol, rate of living, CO2, and aging

Ray Peat · Newsletter · Sep 2009

> # Resveratrol: Rate of Living, CO2, and Aging
>
> [references]
>
> A year ago GlaxoSmithKline bought Sirtris, a company focusing on the biological effects of resveratrol, for $720,000,000. Harvard Medical School’s website, and broadcasts by Barbara Walters and Morley Safer have publicized resveratrol as a longevity-increasing drug, and millions of people are spending large amounts of money for resveratrol capsules.
>
> The main claim being made about resveratrol is that it can mimic the anti-aging effects of calorie restriction, without having to restrict food consumption. This involves silencing genes, blocking their production of RNA and protein.
>
> The mass media and some medical journals aren’t giving a balanced description of the biological effects of resveratrol, but many biologists are being influenced too, by the same simple arguments that the television reporters summarized. The academic biology culture, the medical culture, and the basic American culture itself, are all permeated by the idea of genetic determinism, so when a DNA molecule in yeast is identified as the “anti-aging gene,” and a molecule is found that activates it, that molecule, or something similar, seems to them clearly to be an anti-aging drug.
>
> Part of the cultural framework that makes it easy to sell that idea is the old “rate of living” theory of aging, the idea that we have only so many heartbeats in a lifetime, that we can use only so many calories and so much oxygen in a lifetime, and that organisms with a low metabolic rate therefore live longer than those with a high metabolic rate. The rate of living theory is closely related to the “wear and tear” theory of aging, that our bodies are (except for our germ cells) made up of “post-mitotic cells,” unable to continue dividing once growth is complete, and so must die when those cells are “worn out.” By the middle of the 20th century, those ideas had been disproved in many ways, but in the 1960s Leonard Hayflick renewed for a time the doctrine of aging as the wearing out of unrenewable cells, with his doctrine that somatic cells (non-germ cells) have an absolute limit of 50 replications. Producing cloned animals from somatic cells, and the subsequent excitement about stem cells, made that theory obsolete (again).

### Source 2 — Longevity

Ray Peat · Interview · Apr 12, 2014 · https://www.youtube.com/watch?v=XEgfGJ4BAGk

> **Ray Peat:** Yeah, in calorie restriction the organism has to do something to survive and so it starts shutting down, turning off the genes. The initials stand for "Silent Information Regulators", "SIR". In yeasts, starvation or stress will turn those on and turn off genes and in animal cells they do the same thing, but how they got to be so interesting is that a group at Harvard was arguing that longevity in yeast corresponded to long life in humans. But in single-celled organisms, what they were saying was, rapid and continued cell division - the equivalent would be cancer in a human rather than long life - and from the ability to stimulate rapid and prolonged cell division in yeasts, they argued that resveratrol, which is related chemically, very closely to DES (diethylstilbestrol), a simple synthetic oestrogen, resveratrol is a natural stilbene-type substance found in grapes. It does have oestrogenic activity and yeasts are especially sensitive - yeasts produce oestradiol just like humans - and so yeast is being given basically an over-dose of oestrogen so it is more fertile. In humans that same sort of over-dose isn't desirable. In that process of turning off genes, when you do it in a human, you are moving towards the spore-like or hibernating state of not producing proteins, and two of the very important proteins that get turned off by the sirtuins, include klotho - the phosphate-regulating protein that, when it's turned off, you get very rapid ageing and degeneration of all of the tissues - and another protein or enzyme, P53 protein, is a tumour-suppressor protein. And so you definitely don't want to just blindly turn off proteins in defence.

### Source 3 — Resveratrol, rate of living, CO2, and aging

Ray Peat · Newsletter · Sep 2009

> It protects nerves, vascular cells, insulin-producing cells in the pancreas, and a variety of other types of cell from cell death produced by lack of oxygen, excitotoxicity, endotoxin, and a variety of stressors and toxins. (Niacinamide acts in many ways as a negation of resveratrol; for example, resveratrol interferes with the ability of the beta cells to secrete insulin [Szkudelski, 2007]).
>
> Niacinamide protects mitochondrial respiration from many of the age-related factors that can damage mitochondria and decrease energy production. Lipopolysaccharide, the bacterial endotoxin, increases the production of the free radical nitric oxide, leading to the secretion of inflammatory mediators and the suppression of energy production by the mitochondria. These effects are blocked by niacinamide (Fukuzawa, et al., 1997). Calorie restriction also protects mitochondrial respiration, in yeasts (Lin, et al., 2002) and rats (Broderick, et al., 2002).
>
> The “replicative lifespan” of human cells in vitro is extended by treatment with niacinamide (Kang, et al., 2006).
>
> In an experiment with human keratinocytes in vitro, resveratrol had the opposite effect, reducing their ability to divide (Blander, et al., 2009). By the definitions of “aging” used by the advocates of the rate-of-living theory, this experiment suggests that resveratrol causes premature aging. Estrogen has a similar effect on keratinocytes. Resveratrol, nitric oxide, and estrogen, unlike niacinamide, suppress mitochondrial respiration. Resveratrol inhibits the formation of progesterone (Chen, et al., 2007), which is synthesized in mitochondria.
>
> The NIH researchers reported that the food deprived monkeys (contrary to their expectation) didn’t have a lower rate of metabolism, but many experiments done with a variety of very different animals through much of the last century found that a higher metabolic rate corresponded to increased longevity. Within a given species of bird or mammal, the higher rate of metabolism is often associated with a higher body temperature, and a long life span.

### Source 4 — Resveratrol, rate of living, CO2, and aging

Ray Peat · Newsletter · Sep 2009

> To the brewing industry, these effects of phytoestrogens are known to influence the biomass, but when the rate of growth is considered to represent aging, then increased biomass is equivalent to increased longevity.
>
> Anyone familiar with the last 40 years of yeast research would presumably know that phenolic phytoalexins are estrogenic, and that the growth of yeast is influenced by estrogenic substances, and also that estrogenic substances such as resveratrol could be very dangerous if consumed in exaggeratedly large amounts.
>
> Resveratrol is a stilbene, similar in structure to diethylstilbestrol, DES, the famously toxic-carcinogenic pharmaceutical. Estrogens affect all of the systems affected by resveratrol, and for 67 years, the estrogen industry has been telling the public that whatever estrogen does is beneficial---more than 200 medical conditions have been benefited by estrogen treatment, according to the medical literature/pharmaceutical advertising.
>
> Many people have been asserting that the reason calorie restriction can extend life is that it activates “the antiaging gene, Sir2.” A recent publication (Carrano, et al., 2009) from the Salk institute proposes that two other genes are responsible for calorie-restriction longevity in the roundworm, C. elegans.
>
> But restricting calories has a multitude of effects--Sir2 is only one of hundreds of genes that function differently in hunger-stressed animals. Calorie restriction is stressful, but the nature of that stress and the response to it depends on the whole situation, just as in any other challenging situation.
>
> One problem with the Sirtris scheme is that increased Sir2 activity shortens the actual chronological lifespan of non-dividing yeast (Kennedy, et al., 2005; Fabrizio, et al., 2005). In animals, increasing the activity of SirT1 might contribute to the development of cancer (Liu, et al., 2009). It might also be involved in Alzheimer’s disease, and the replacement of nerve cells in the brain with astrocytes or other glial cells. Gliosis can occur in normal aging, but inflammation can produce extreme degrees of fibrosis of the brain or spongy encephalopathy. Estrogens also have this effect of accelerating stem cell production of glial cells.

### Source 5 — Estrogen, Progesterone and Resveratrol with Georgi Dinkov

Georgi Dinkov · Interview · Sep 16, 2021

> **Georgi Dinkov:** than in the placebo group in a situation like that all ethical protocols call for an immediate shutdown of the studies and basically the studies disbanded right because death is a very serious the most serious serious adverse event essays as they call them in the industry so within within a year after this fiasco gsk quietly shut down surgeries and then i never heard anything about that company ever since i think the company was actually did actually fall but gsk bought it from david sinclair for 750 million dollars And I think a good portion of the money went to Harvard because Mr. Sinclair was at the time at Harvard. I think to this day he maintains some kind of a professorship at Harvard. He's not a full professor. He used to be, but I think he still either lectures or is somehow associated. He has a lab there or something like that. But anyways, so basically, he got $750 million, or at least a good portion of it, and then disappeared for a while. I mean, if you kind of check his publications, between 2007, which is when searchers were shut down, In 2015, 2016, there was not much in terms of scientific activity from this individual. There was no discussion of resveratrol. There were no publications. There were publications of resveratrol, but there were publications from rival pharmaceutical companies, and they basically called into question the very idea of resveratrol being effective for any of these conditions that Mr. Sinclair was saying it should be, right?

### Source 6 — Ray Peat KMUD: 12-10-13 Aging and Energy Full Interview

Ray Peat · Interview · Jan 25, 2017 · https://www.youtube.com/watch?v=DEdDTAyZuJU

> **Andrew Murray:** They said that some of the chemicals that were uncovered might be useful in the future.
>
> **Ray Peat:** At the time, the people promoting resveratrol through that company as an anti-aging chemical were warning that niacinamide antagonized resveratrol and lowered the sirtuins. Therefore, niacinamide would accelerate aging. But I think now they've changed their story. At that time, five years ago, it was very clear that niacinamide greatly extended cell life, just a tremendous increase in human cell longevity in vitro. And it's very safe, so it can be used in all of these epigenetic problems, Parkinson's disease, Alzheimer's disease, various types of cancer and so on. And it's interesting that all of these substances that have been known, some of them for thousands of years, as anti-inflammatory drugs, they all turn out to work in the same direction, protecting us from over-methylation and over-removal of the... acetyl groups from the histones.
>
> **Andrew Murray:** Okay, hold it there, Dr. Peat. We've got a couple more callers, so let's take the next caller. You're on the air, and where are you from?

### Source 7 — Georgi Dinkov: more is not better, Russian spies, sanity, orthorexia, NAD, D3 and how to drink vodka

Georgi Dinkov · Interview · Jan 21, 2021 · https://www.youtube.com/watch?v=KSuhf6PS2jk

> **Georgi Dinkov:** Yeah, he got a $700 million payout. You can look it up. It's on Wikipedia. Type David Sinclair in Google. Look at his Wikipedia page. There's an entire section of how he built up surgeries, built up the hype about resveratrol, right? It attracted the attention. Now, a lot of the studies about raising NAD are legitimate, right? But resveratrol is really not a good way to do that because it is itself a potent phytoestrogen. It competes with estrogen for the estrogen receptors, and it activates with about the same affinity, with about the same strength. So you are taking a potent estrogen yourself by taking resveratrol. One of the most infamous drugs that was ever approved, Vioxx, which killed a number of people back in the early 2000s, it was subsequently withdrawn, is a very close structural analog of resveratrol. And a lot of the very powerful NSAIDs, non-steroid anti-inflammatory drugs that big pharma is working on, are based off of Vioxx. More of them are still coming and about to be approved. And resveratrol and those drugs all share the same structure. It's called a still being. All still beings, they exist in nature uniformly. They're widely distributed in nature in almost every plant. They're all estrogenic. They're all phytoestrogens. So taking resveratrol will raise your NAD levels by speeding up glycolysis. By speeding up glycolysis, yes. But the glycolysis generates NAD by generating lactic acid. So you don't want to be speeding. The way to generate NAD properly is by having the NADH, which is the reduced version, properly oxidized through the Krebs cycle and the electron transport chain. If resveratrol is only accelerating glycolysis, glycolysis can also generate NAD back from NADH, but it uses pyruvate as an emergency oxidant, and pyruvate oxidizes NADH back to NAD and creates lactic acid. Pyruvate turns into lactic acid. And all estrogens...

### Source 8 — Another View of Evolution [Generative Energy #14]

Danny Roddy · Interview · Nov 25, 2015 · https://www.youtube.com/watch?v=pdF33V5kQr8

> **Georgi Dinkov:** he had the patents, all the patents on resveratrol and he had a special more bioavailable version related to the micronized issue that we talked about before. And then GlaxoSmithKline started a clinical trial with resveratrol on kidney failure because it's believed that the SIRT1 gene is involved in kidney failure. And then I think a significant percentage of the people on the trial died. So the trial was not only immediately halted, GSK, GlaxoSmithKline, essentially pulled the plug on all future resveratrol research as far as they're concerned. And the reason I bring this up is because you see that, first of all, this is a chemical that was supposed to act on a specific gene and have a very specific action. It didn't. First of all, basically the genome, even if you believe in neo-Darwinism, it's not structured to have one-on-one correspondence. And if you, let's say, if you activate or you silence one gene, you only affect or silence one protein. It's just not how it works. All the genes at the very least seem to be involved in a very complex network. then the relationship is is basically for all four possibilities one too many one to one many to one and many too many so so all of these genes form and they form dynamically they form networks one gene can turn off many others or can be turned off or owned by many others All of these genes can simultaneously affect each other. So in light of such complexity, basically this points to the fact that trying to reduce this to single gene-slash-protein interactions is probably not feasible, or at least not computationally feasible right now, even if in theory it did work. It's just not feasible right now. And by the way, again, to remind you, resveratrol is an estrogen. So the most publicized genetic therapy based on a naturally found estrogen was an abysmal failure. And I'm not surprised. Basically, estrogen has a very... very pronounced effect on the genome.

### Source 9 — #17: Progesterone/DHEA Study Results, Field Biology, NAFLD, and Vitamin E with Georgi Dinkov

Georgi Dinkov · Interview · Feb 21, 2020 · https://open.spotify.com/episode/2Ari0W9sBDaSeJPiyQo5nb

> **Georgi Dinkov:** and started several clinical trials. And in three of these trials, there were increased number of deaths in the active group. And as a result, GSK, GlaxoSmithKline, stopped those trials and eventually ran that search risk company to the ground. So even the large pharmaceutical company decided that resveratrol is a no-go. So that should tell you enough. Big money says no to resveratrol. And they tried it, believe me. It's not like they didn't want to try and they didn't want to turn it into a drug. They did everything they could, but it started killing people and they decided the legal risk wasn't worth it.

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