Michael Ristow’s work is fueling a lot of bad press for antioxidants: is there an answer?

It is ironic that Michael Ristow is so worried about our taking antioxidant vitamins and interfering with the deployment of our own antioxidant defenses. Why ironic? Because our defenses are so poor. They are poor under ordinary oxidative stress and they are totally inadequate when we are put under serious oxidative stress, and we poor creatures cannot even synthesize more vitamin C to maintain that weak defense strategy.

Clearly, we should work with those defenses if we can, but at any rate work around those defenses, and make them much better. And we will no doubt bungle our way to a better system than what nature has selected for, because nature’s investment in self-preservation, maintenance, and repair is always less than its investment in growth and reproduction.

Antioxidants do so many good things for the body besides provide free radical protection. Thus, it is in our health interest to add these supplements to our diet. Previously, a downside of taking boatloads of antioxidants was revealed when it was shown that this overdose of antioxidants can interfere with signaling that uses free radicals (like nitric oxide, so critical to keeping blood vessels dilated and our blood pressure in a healthy range). More recently, Michael Ristow’s work has shown that taking antioxidants can interfere with the hormetic benefit that free radicals can give us via inductions of various genes, including of course our powerful antioxidant enzyme genes.

Can we have our cake, consisting of the many other benefits from antioxidant nutrients like vitamin C, vitamin E, vitamin A, vitamin D, vitamin K, thiamine, CoQ10, lipoic acid, bioflavonoids, vitamin B3, melatonin (including its precursors and its derivatives), beta-alanine [used to make carnosine], taurine, etc., and eat it too?

Maybe – there are at least three things to try to circumvent the Ristow limitations:

  1. Intermittent supplementation. Take occasional vacations from antioxidant supplements and exercise sufficiently hard to induce our antioxidant enzymes to near the maximum healthy level.
  2. Occasional extreme exercise to overwhelm the sum total of all of our antioxidant defenses.
  3. Supplements (taurine et al?) that inhibit the formation of free radicals in the first place. If free radicals formation is successfully inhibited, who needs antioxidant enzymes or antioxidant vitamins?

Note that neither of these will work if (1) antioxidant enzymes decay rapidly after antioxidant supplementation re-commences and (2) if the antioxidants themselves are not inhibiting induction of defenses by virtue of their antioxidant actions, but by direct changes in gene expression that have a net effect of inhibiting induction of hormetic defenses such as the antioxidant enzymes.

An example of Ristow’s work (the whole paper is available for free online):

Consider this argument, a bit of a straw man – using too high a vitamin E dose (almost certainly would compromise health by interfering with vitamin K) and way too low a vitamin C dose, and not using multiple doses of antioxidants throughout the day, as Pauling did with vitamin C, and using only vitamins C and E (when there are much better cocktails to take?), is neither good nor smart antioxidant supplement protection. Moreover, the subjects are unsuitable in that neither their complete nutritional status nor their habits/lifestyles are defined. Supplements do not work in isolation – to have a benefit, antioxidant and beyond, supplements require that every other essential and conditionally essential nutrient be in place at optimal levels. The conclusion to this straw man argument in this article is not quite warranted, but it is illustrative of what I believe is a real handicap that that devil, dialectical nature, has given us. Note also the contradiction between the title, which is absolute, “antioxidants prevent…,” and the weak and probabilistic conclusion “supplementation with antioxidants may preclude…”

Proc Natl Acad Sci U S A. 2009 May 26;106(21):8665-70. doi: 10.1073/pnas.0903485106. Epub 2009 May 11.

Antioxidants prevent health-promoting effects of physical exercise in humans.

Author information

  • 1Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena D-07743, Germany. mristow@mristow.org


Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic, euglycemic clamp in previously untrained (n = 19) and pretrained (n = 20) healthy young men. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome-proliferator-activated receptor gamma (PPARgamma), and PPARgamma coactivators PGC1alpha and PGC1beta only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.


ClinicalTrials.gov NCT00638560.

[PubMed – indexed for MEDLINE]

Free PMC Article



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