Plant extracts

Resveratrol At 2.4 mg: Absorbed, Then Almost Entirely Changed

The panel prints 12 mg of resveratrol extract. The arithmetic on the panel page turns that into 2.4 mg of resveratrol. This article asks what happens to 2.4 mg once it is swallowed, and what the trials that used far more can and cannot carry across.

What the row actually contains

The line on the Supplement Facts panel reads Resveratrol Extract (Std. 20% from Polygonum Cuspidatum), 12 mg. Two numbers are printed and a third can be worked out. Twelve is the weight of the material in the capsule. Twenty per cent is the share of that material the maker says is resveratrol. Twelve multiplied by 0.20 is 2.4, so one capsule carries about 2.4 mg of the compound the name refers to.

That multiplication is the same one the panel page applies to the konjac and turmeric rows, and it is worth noticing what it does not do. It does not describe the remaining 9.6 mg. The label says the extract was standardised to a resveratrol content; it does not say what the rest of a knotweed root extract is, and this website will not guess. What can be said is that the compound on the front of the row is present at roughly a fortieth of the figure most of the trials below used.

The other reason to start with the arithmetic is that resveratrol is the row on this panel where the distance between the name and the amount is widest to a reader who does not multiply. A reader who sees 12 mg has one impression. A reader who sees 2.4 mg has another. Both are describing the same capsule.

Where the extract comes from

Polygonum cuspidatum is the plant more commonly called Japanese knotweed, a tall, fast-growing perennial whose root is a commercial source of resveratrol. Resveratrol is a stilbene, a polyphenol that plants make in response to stress, and it is the compound usually credited to red wine and grape skins in popular writing. The knotweed root is used as the raw material because it holds far more of it than grapes do, which is the whole point of buying an extract rather than a fruit.

This is worth saying plainly because the plant name on the label is the only place the source appears. The ingredients page names it as Japanese knotweed, and the panel names it by its botanical name. Neither says which part of the plant or what solvent was used, and neither needs to for the arithmetic above, which depends only on the percentage.

The absorption study, in detail

The most useful single paper for a small oral dose is Walle 2004, an absorption and metabolism study in six human volunteers. The team gave each person resveratrol labelled with carbon-14, once by mouth and once intravenously, so that every fragment of the compound could be followed whatever it turned into.

The oral dose was 25 mg, which the authors describe as a dietary-relevant amount. Three findings matter here.

• Absorption was high. At least 70% of the oral dose was absorbed.
• Circulating material was large but almost none of it was resveratrol. Peak plasma levels of resveratrol and its metabolites together were 491 ± 90 ng/ml, about 2 µM, with a half-life of 9.2 ± 0.6 hours. Yet only trace amounts of unchanged resveratrol, under 5 ng/ml, could be detected.
• The body changed it fast. Most of the dose was recovered in urine, and the analysis found three routes: sulfate conjugation, glucuronic acid conjugation, and hydrogenation of the aliphatic double bond, the last likely produced by gut bacteria. Very rapid sulfation in the intestine and liver appeared to be the rate-limiting step.

The title of the paper puts it in one line: high absorption, very low bioavailability. Both halves are true at once, and they are only contradictory if bioavailability is taken to mean the share of the dose that was absorbed rather than the share that reaches the blood as the original compound.

What high absorption and low bioavailability mean together

The authors do not conclude that resveratrol does nothing. They note that the compound accumulates in epithelial cells along the aerodigestive tract and that some of the metabolites may themselves be active, so the picture is unsettled rather than closed. What the study does settle is a narrower point that matters for a label: the amount swallowed and the amount of the original compound in the blood are different numbers, and the second is much smaller than the first.

Apply that to this capsule and two things follow. First, the printed 2.4 mg is an upper bound on what could ever reach the blood as unchanged resveratrol, because it is the whole amount before any conjugation. Second, this desk will not scale the 25 mg result down to 2.4 mg and quote a plasma figure, because the relationship between dose and circulating level is not guaranteed to be a straight line, and a straight line is the only thing a simple division would assume.

The dose subgroup in the diabetes trials

Zhu 2017 pooled randomised trials of resveratrol in people with type 2 diabetes. It found nine trials with 283 participants in all. Fasting plasma glucose fell by 0.29 mmol/l and fasting insulin by 0.64 U/mL, and blood pressure and an insulin resistance index also improved. Changes in HbA1c and in LDL and HDL cholesterol were negligible.

The detail that matters for this capsule is a subgroup analysis. The authors compared trials giving less than 100 mg a day with trials giving 100 mg a day or more, and found a significant difference in fasting glucose, with the higher-dose group presenting the more favourable results. Read plainly, the pooled benefit came from the trials that used the larger amounts.

Put 2.4 mg beside a 100 mg line and the ratio is about 42 to 1. The capsule does not sit near the boundary of that subgroup split. It sits on the far side of the smaller group, far below where the comparison was even drawn. Everything in the pooled result belongs to people with type 2 diabetes taking a much larger amount, which is a different group at a different dose.

What the umbrella review concluded

Zeraattalab-Motlagh 2021 is an umbrella review, a review of reviews, published in the American Journal of Clinical Nutrition. It gathered eleven meta-analyses in type 2 diabetes covering 29 outcomes and 1,476 people, seventeen in metabolic syndrome covering 26 outcomes and 727 people, and ten in non-alcoholic fatty liver disease covering 24 outcomes and 271 people.

Its own summary is measured. Resveratrol had beneficial effects on some outcomes, among them blood pressure, lipid profile, glycaemic control and insulin resistance in diabetes, waist circumference in metabolic syndrome, and body weight and inflammation markers in fatty liver disease. But for almost all outcomes the size of the effect was trivial, the certainty of the evidence was very low to low, or too few trials existed. The one outcome with a clinically important effect was HbA1c in the short term, under twelve weeks, where six trials gave a mean difference of −1.05% with a wide interval and moderate certainty, and even that was qualified by short follow-up and small samples.

The conclusion the authors reach is the sentence to carry: current evidence does not support supplementation with resveratrol for the management of cardiometabolic risk factors in patients with type 2 diabetes, metabolic syndrome and fatty liver disease. That is a conclusion about trials at trial doses, in patients. It is the strongest available statement about the ingredient, and it is not favourable, before the dose on this label is even considered.

The trial that measured metabolic rate

The panel sits under a product sold in a metabolism category, so the most directly relevant trial is the one that measured metabolic rate itself. Timmers 2011 gave eleven healthy, obese men either placebo or 150 mg a day of resveratrol in a randomised, double-blind crossover for thirty days.

Resveratrol significantly reduced sleeping and resting metabolic rate. In muscle it activated AMPK and raised SIRT1 and PGC-1α protein, and it improved mitochondrial respiration on a fatty acid substrate. It also lowered intrahepatic lipid, circulating glucose, triglycerides, alanine aminotransferase and inflammation markers, lowered systolic blood pressure and improved a HOMA index. The authors describe the pattern as mimicking calorie restriction.

Two things need to travel with those results. The direction on metabolic rate was down, not up, which is why no page on this website calls resveratrol a metabolism booster. And the dose was 150 mg a day, about sixty-three times what this capsule carries, in eleven men for a month. Nothing from that trial transfers to 2.4 mg in either direction.

The doses, side by side

The figures above sit in different papers, so they are easy to lose. Laid in one table they show the same thing from every direction.

The ratios divide the trial figure by 2.4 mg. They compare amounts of the compound, not effects, and no trial has tested the capsule.

What this desk will not say

Resveratrol is the most quoted name in this family of ingredients, and it is easy to oversell in either direction.

• That 2.4 mg of resveratrol does anything measurable. No trial used an amount near it, and the nearest boundary in the pooled data sits about forty times higher.
• That resveratrol raises metabolic rate. The one trial here that measured it found it fell, at a dose sixty-three times larger.
• That the small amount is harmful. Nothing cited here suggests that, and the reason to write this article is precision, not alarm.
• That the remaining 9.6 mg of extract is anything in particular. The label does not describe it.
• That the absorbed portion is the active portion. The absorption study shows most of an absorbed dose circulating as conjugates, and whether those act is not settled.

What can be said is on the table above: the label prints a weight and a percentage, the percentage gives 2.4 mg, and that is the amount of the compound in the capsule. The ingredients page gives every other row the same treatment, and the eleven-amounts article sets all of them against the research in one place. Two other small rows get the same reading in the berberine article and the mangosteen and prickly pear article.