Antioxidants prevent health-promoting effects of physical exercise in humans

Awhile back I noted a paper which showed that vitamin C abolished endurance training effects. It turns out that vitamin C isn't the only substance that will do this: Antioxidants prevent health-promoting effects of physical exercise in humans. This from the PNAS, a high-impact journal; this study isn't shoddy work, in other words.

The experimenters took two groups of young men, previously trained with endurance exercise, and previously untrained. Each group in turn was randomized to receive antioxidant supplements in the form of 400 IU vitamin E and 1000 mg vitamin C daily, or placebos. Then the men underwent 4 weeks of training, 5 days a week, including biking, running, and circuit training.

The result: those who had taken antioxidants saw no, repeat, no health benefits from exercise. The measurements done were of insulin sensitivity, TBARS (a measure of oxidative stress), and several others. In each of them, those who exercised, and did not take antioxidants, regardless of whether they had trained previously or not, saw an increase in insulin sensitivity, a decrease in TBARS, and so on, while these effects were abolished in those who took the antioxidants. Further, the promotion of muscle antioxidant defenses which is normally promoted by exercise was prevented by supplementation.

From the paper:

Most importantly, these changes in gene expression and the increase in insulin sensitivity following physical exercise are almost completely abrogated by daily ingestion of the commonly used antioxidants vitamin C and vitamin E. Thus, antioxidant supplementation blocks many of the beneficial effects of exercise on metabolism.

What are the larger implications here? What about that high fruit and vegetable intake that we are constantly told is so good for us? this is where it gets very interesting:

If transient increases in oxidative stress are capable of counteracting insulin resistance in humans, it is possible that preventing the formation of ROS by, for example, antioxidants might actually increase, rather than decrease, the risk of type 2 diabetes. While this remains to be determined, one metaanalysis of previously published studies (27) suggests that high dietary intake of fruits and vegetables, a source of antioxidants but also of numerous other bio-active compounds, may actually decrease the risk for type 2 diabetes. Nevertheless, and as stated by Hamer and Chida (27), all larger intervention trials evaluating the diabetes-preventive potential of defined antioxidant supplements have been unable to find any positive effects of supplementation (28–30). Moreover, antioxidant use in type 2 diabetics has been linked to increased prevalence of hypertension (31) and use of antioxidant supplements has recently been proposed to increase overall mortality in the general population (32). Taken together, these previously published findings tentatively suggest that fruits and vegetables may exert health-promoting effects despite their antioxidant content and possibly due to other bio-active compounds. [...]

Free radicals causing oxidative stress are an inevitable by-product of mitochondrial metabolism and have been proposed to exert repetitive damage to individual cells of the body promoting increased disease prevalence and aging (33). However, and in specific regard to exercise, antioxidants were incapable of further extending exercise-induced lifespan extension in rats (26). Repeated exposure to sublethal stress has been proposed to cumulate in enhanced stress resistance and ultimately increased survival rates due to a process named hormesis. By analogy, for sublethal ROS-dependent processes emanating from the mitochondria, the term “mitohormesis” was recently proposed on a hypothetical basis (34). Evidence for this novel concept has been provided in model organisms such as nematodes (15) and rats (17), and the current study would extend the concept of mitohormesis to the amelioration of insulin resistance in humans, suggesting that potential harmful ROS may exert health promoting effects via defined molecular intermediates (Fig. 3). [...]

Taken together, we find that antioxidant supplements prevent the induction of molecular regulators of insulin sensitivity and endogenous antioxidant defense by physical exercise. Consistent with the concept of mitohormesis, we propose that transiently increased levels of oxidative stress reflect a potentially health-promoting process at least in regards to prevention of insulin resistance and type 2 diabetes mellitus. [My emphases.]

Reference was made above to nematodes, in this case the famous Caenorhabditis elegans, the subject of Cynthia Kenyon's longevity experiments. In the study referenced above:

Reduced glucose availability promotes formation of reactive oxygen species (ROS), induces catalase activity, and increases oxidative stress resistance and survival rates, altogether providing direct evidence for a hitherto hypothetical concept named mitochondrial hormesis or "mitohormesis." Accordingly, treatment of nematodes with different antioxidants and vitamins prevents extension of life span. In summary, these data indicate that glucose restriction promotes mitochondrial metabolism, causing increased ROS formation and cumulating in hormetic extension of life span, questioning current treatments of type 2 diabetes as well as the widespread use of antioxidant supplements. [Link.]

My takeaway on all this: low carb diets promote health and longevity by, among other things but perhaps mainly, increasing insulin sensitivity, and along with it, decreasing inflammation. This is the lesson from Kenyon's worm experiments, in which insulin signaling is disrupted, causing the worms to have up to a 6-fold increase in longevity. But antioxidants appear to completely abolish this activity related to insulin signaling.

There have been many arguments on both sides of the antioxidant debate, but this one I find very convincing, enough so that it appears that antioxidants are bad for your health.