An Example of Dietary Supplements Doing Nothing

Dietary supplements of the sort sold in stores are largely useless, and those that do provide benefits have a far smaller effect than either exercise or calorie restriction. Past the point of maintaining something along the lines of the Reference Daily Intake, such as is provided by a multivitamin produce, the balance of evidence suggests that most of these supplements do little for long term health and longevity. In many cases modest extension of life observed in some animal studies (not not in others) can be explained away by inadvertent calorie restriction or other artifacts. In the case of antioxidant supplements the current consensus is that these in fact harm beneficial processes that depend upon the use of low levels of oxidants as signals.

Here is a study to show that a range of currently popular supplements do absolutely nothing to various measures of human metabolism:

Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up.

The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement.

The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals.



I really hate these "supplements do nothing" studies, and the articles reporting them.

We already know these supplements work in vitro, or in animals, or in other studies. And we understand the mechanisms by which they are supposed to work. If you look at the data from this study, I don't see anything that strongly contradicts the previous studies.

We're not talking about homeopathy or reiki here.

The control group in this study was given a wide range of vitamin and mineral supplements, and they improved pretty much across the board from their baselines (even though they were aging). Most people don't get the RDI of vitamins and minerals, and it hurts their health, and they should be taking multivitamin supplements.

The "supplement" group also improved relative to the control group, just not enough to be statistically significant.

The doses in the study are lower than what people often use.

Half these supplements are intended for protecting the brain and improving cognitive function, but they didn't measure cognitive function or anything about the brain.

Telling people not to take nutrients like fish oil seems irresponsible to me, without better evidence than this.

Posted by: Carl at September 6th, 2013 8:28 AM

Not sure I'd rate many of those suppliments as 'popular'. Fish oil, yes, but cinnamon bark extract? Huh? None are vitamins and both groups took a multivitamin anyway. Sounds like a study that shows your herbs and spice rack doesnt improve your health.

Posted by: Wayne at September 6th, 2013 8:55 AM

Overall it does seem there was little effect from this 6-month intervention in relatively healthy people, but I couldn't believe it when I read this: "Both the SUP [supplemented] and CON [control] groups took a daily multivitamin/mineral supplement."

The supplement they specified contains about 20 confounding ingredients, including some that are probably not so good for most people, such as iron and copper.

Posted by: John at September 7th, 2013 11:38 AM

This study is an example of the scurrilous type of research being done to intentionally smear dietary supplements. The researchers involved should be embarrassed for their disregard for the current science on aging in what appears to be intentional over-dosing of human subjects with the intent to prove dietary supplements are of worthless value.

First, dietary deficiencies for essential nutrients (lettered vitamins, esential minerals)should have been pre-determined and then measured following supplementation. You cannot fix something that isn't broken. Even then, if improvements were not noted among deficient individuals, this may be due to (a) inadequate supplementation; (b) poor absorption due to lack of stomach acid; (c) blockage of absorption my medications, refined sugars, or lack of delivery due to poor bile flow, etc.

Second, it would have been better to utilize recognized markers of longevity rather than markers of disease, such as labile iron or red blood cell width, or possibly even ferritin (iron storage).

Third, the current science on aging points to calorie restriction as a model for anti-aging effects and healthspan prolongation, with polyphenols like those used in this study as molecular mimics of food deprivation.

However, calorie restriction per se does not explain why the rate of aging is nil during youthful growth, progressive once full-growth is achieved, and flat in late adulthood. I submit that the rate of aging is determined by overmineralization which can be achieved by reduction of food intake, not necessarily by calories. During childhood growth there is acute need for minerals for bone (calcium), collagen (copper) and red blood cell production (iron). Overmineralization does not generally occur during the growth years. Once full growth is achieve, overmineralization begins, first in males and later with the change of lifein females when iron losses cease with cessation of menstruation.

There is considerable evidence for this in the medical literature which I have cited in a report entitled The Overmineralization Theory of Aging. ( )

Fourth, the dietary supplement regimen emplyed in this study largely consisted of polyphenols, 5400 mg in all, which are known to produce a U-shaped or J-shaped risk curve both in red wine and in the laboratory when individual polyphenols are employed.

Generally, no supplemental intake of concentrated sources of polyphenols --wine (which provides ~1000-fold greater polyphenols than grape juice) or supplements, produces no longevity effects. Alcohol abstainers (tea totalers) do not live longer than modest wine drinkers.

Among wine drinkers and in animal studies where polyphenols were employed, modest dosage (3-5 five-ounce glasses of red wine providings 60 mg polyphenols per glass, or 180-300 mg, or 100-350 mg of resveratrol in animal studies) produces beneficial effects, largely due to preconditioning effects produced by hormesis.

Polyphenols not only chelate and control minerals and favorably switch genes, but are initially perceived by the body as a biological stressor, thus activating endogenous (internal) enzymatic antioxidants (glutathione, catalase, SOD, heme oxygenase, adenosine).

Modest dosage produces an anti-oxidant effect (for example, low-dose resveratrol binds to copper, producing antioxidant effects) while high doses produce a pro-oxidant effect (mega-dose resveratrol releases copper).

The researchers involved in the design of this study, as have others who have preceded them, disregard the known hormesis effect and provide a pro-oxidant non-hormetic dose (equivalent to ~74.25 mg/kilogram of body weight for 70 kilo/160 lb human).

A pro-oxidant dose would be more appropriate for treatment of cancer or infection under the supervision of a physician. However, even then, a 5000 mg dose of resveratrol induced rapid kidney failure among multiple myeloma patients and the study had to be halted. This was likely due to pooling of resveratrol in the kidneys prior to excretion (Sirtris Pharmaceuticals study, SRT501 drug, unpublished).

Such overdoses of polyphenols are known to produce frontal headaches (likely from induced anemia, particularly in menstruating females who are deficient in iron), anxiety reactions, skin rash and flu-like symptoms.

In addition to the polyphenols employed in this study, carnitine and lipoic acid also control iron and represent over-chelation.

The contention that these polyphenols are not biologically available due to liver metabolization is another myth created by biologists who want to develop drug analogs over dietary supplements.

However, a recently published study shows that liver metabolites of resveratrol exhibited equal and comparable degree of biological activity as free unbound resveratrol.(

The immediate bioavailability of resveratrol and other polyphenols may be enhanced by accompaniment with other natural molecules (quercetin, piperine), but eventually all are detoxified by the liver (conjugated with glucuronate and sulfate) because they are perceived as a potential biological threat, which is why they are detoxed in the first place.

Resveratrol and other polyphenols are released from glucuronate by the enzyme glucuronidase, which is abundant at the site of inflammation, infection and malignancy. Therefore, resveratrol and other polyphenols are delivered in free unbound form at the right time and place via "nature's drug delivery system." Some Rx drugs are pre-gluconidated for this very purpose.

Furthermore, calorie restriction and resveratrol may activate the same genes but health benefits may only be measurable among unhealthy individuals. ( )

If biologists had intentionally set out to intentionally overdose human subjects with polyphenols and to negate the known hormesis effects and measure disease markers rather than longevity markers, they couldn't have done a better job. -- Bill Sardi, Resveratrol Partners LLC

Posted by: Bill Sardi at September 8th, 2013 5:57 PM

Why can I not access this paper? Has it been pulled off the net? Call it crazy, but I'd like to actually see the results before accepting the authors' conclusions or making any comments.

Posted by: Walter Crompton at October 14th, 2013 12:18 PM

@Walter Crompton: They bumped it to the next issue, apparently, which changed the URL. I've fixed that, so the link should work now.

Posted by: Reason at October 14th, 2013 3:29 PM

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