August 3rd, 2011
Recommended Reading: A Critical (and Funny) View of Antioxidants
Larry Husten, PHD
“Antioxidants don’t work, but no one wants to hear it,” writes Kent Sepkowitz, an infectious diseases specialist at Memorial Sloan-Kettering, in Slate. Sepkowitz reviews the sparse scientific knowledge about antioxidants and then discusses the difficulties faced by physicians who “were slow to jump onto the antioxidant bandwagon and are slower still to jump off.”
“Few medical remedies have a more sterling reputation” than antioxidants, he writes, but
there is a wee small problem in our ongoing anti-oxidize-athon: As it turns out, we have no evidence that antioxidants are beneficial in humans. (Though if you’re a Sprague-Dawley rat, there’s hope.)
Sepkowitz explains to Slate readers that a free radical isn’t “a fiery Berkeley politico” and observes that if physicians try to warn their patients about the lack of evidence “it’s like we’re denying the benefits of sunshine and fresh air.” Citing evidence is fruitless, he says:
…double-blinded medical studies are counterbalanced, in America, by a parallel system of peer review in the form of a nonstop confab of health-themed talk shows, print magazines, and blogs.
3 Responses to “Recommended Reading: A Critical (and Funny) View of Antioxidants”
NEJM Journal Watch — Recent Cardiology Articles- Cardiovascular Outcomes of Tirzepatide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity
- To Lower Stroke Risk in Patients Undergoing Atrial Fibrillation Ablation, Is a Device or a Medication Better?
- Intensive vs. Standard Blood Pressure Lowering in Patients with Diabetes
- Anticoagulation in Patients with Cancer-Associated Pulmonary Embolism: How Long Is Long Enough?
- Spironolactone Use After Percutaneous Intervention for Acute Myocardial Infarction
And there was a study of male smokers in Finland (? NEJM or JAMA) that put half of them on anti-oxidants and the other half on placebo, and the smokers taking anti-oxidants had a HIGHER incidence of lung cancer.
To put all “antioxidants” under the same tent and summarily dismiss them all as useless reveals profound arrogance as well as ignorance of the studies regarding antioxidants. The studies are totally inadequate to reach that broad a conclusion.
The lack of proof of value does not prove lack of value. I agree that blanket acceptance of antioxidants as being good without evidence is foolish; to dismiss the possibility of benefit with the current limited evidence is equally foolish.
Competing interests pertaining specifically to this post, comment, or both:
I like blueberries and spinach.
Antioxidants do “work,” but in their physiological roles, not necessarily as pharmacological agents with specific targets, as we unjustly demand. The problem is not with the antioxidants, but with our lack of understanding about the bewildering complex biochemical pathways that are yet to be discovered. Our knowledge, although we believe it is advanced, is simultaneously primitive, and our view of on-off switches and biomarker criteria defining disease and treatment is also sometimes misguided (as illustrated by the disparities between actual practice and the results of recent outcome studies). Particularly with respect to the current degenerative “diseases of civilization”, the silent incubation periods of decades are only now being appreciated.
Nutritional building blocks have their own “purpose” and “agenda.” By and large, their distribution in tissues is particular with multiple effects, and both are currently well beyond our control. We have identified some beneficial effects, and when this happens during the pathogenesis of a disease, we immediately assign a putative therapeutic role. This is fool’s gold, which rarely pans out. We should still be humbled by the adage that Mother Nature is the ultimate biochemist, and she has been at it longer than we have.
Commercial interests only add to the simplistic misbeliefs generally repeated on the internet. One example is the antioxidant property of polyphenols—few realize many these substances are rapidly excreted and most likely serve roles in regulating signaling.
Diabetes is a disease marked by intense oxidative stress which ultimately causes glucose mishandling. There is actually a well-developed literature supporting the benefits of blueberries in diabetics and those with metabolic syndrome. The pathways involved in the pathogenesis of DM2 and the properties of blueberries are far from understood.
CHD is characterized by vascular oxidative stress at a fundamental level. Long-chain omega-3 PUFA causes multiple beneficial changes in cell signaling that relate to CHD molecular pathology. We do not understand either one.
So let’s stop expecting blueberries to do the job of metformin, or omega-3s to do the job of statins. Instead, we should be thankful we have all of them, and use them wisely. Eat leafy greens and some nuts rather than grumble about the lack of proof vitamin E cures heart disease.
The pursuit of proof—or lack thereof—of such relationships sometimes takes surprising forms. Giving a small amount of omega-3s or vitamin E or D to patients taking multiple prescription drugs with essentially end-stage heart, kidney, or neurological disease and searching for improvements in outcomes after a short period of time is unrealistic and fails to discount extensive gaps in our knowledge.
The problem is not only our expectations concerning antioxidants, but also the general inability to sustain antioxidant intake or other dietary/lifestyle improvements for even a minute fraction of the period during which degenerative disease develops. Not only are some beliefs mistaken, habits atrocious, but perceptions as well. Patients know when they last ate a few blueberries, but cannot—or will not—accurately relate the frequency or size of their fast-food junk meals during the week.
There is nothing wrong with antioxidants. The problem is with us.
William B: A spinach salad followed by blueberries covered by pomegranate syrup sounds good at the moment. Of course, with a glass of polyphenol-laden red wine to help prevent peroxidation of my omega-3s (Cazzola R, Cestaro B. Red wine polyphenols protect n-3 more than n-6 polyunsaturated fatty acid from lipid peroxidation. In press. Food Research International. doi:10.1016/j.foodres.2011.07.029)
Richard Kones MD