In similar articles in the New York Times, science writers Nicholas Wade (2009) and Gretchen Reynolds (2010) have reported on the complex nature of responses to antioxidant supplements used to prevent injury with exercise, and cited several scientific studies suggesting that more may not be better. These studies show that high dose antioxidants can indeed prevent the expected rise in free radicals in injured muscle -- but these same high dose antioxidants can prevent activation of protective systems that adapt to the injury -- which in turn may cause harm over the long term.

Might there be any similar concerns about the long term use of antioxidant supplements in Huntington's disease? Is there potential for harm?

Animal exercise-antioxidant study: In the study cited in the New York Times, two groups of rats were exercised on small treadmills: The first group had received no additional supplements, while the other group received high doses of Vitamin E and C. In those animals given no additional supplements, free radical levels in exercised muscles increased; but also in addition to free radicals, levels of protective factors and blood flow increased, and a pro-health decrease in muscle insulin resistance occurred. Insulin resistance is detrimental to metabolic cell systems. In those animals given high dose antioxidants, while levels of free radicals decreased, there was no increase in levels of protective factors or increase in blood flow, or improvements in insulin resistance [Copp SW 2009].

Human exercise-antioxidant study: In subsequent human study other scientists have shown that exercise and its associated production of free radicals in muscle promoted the same pro-health decrease in systemic insulin resistance, or that affecting the whole body. And importantly similar to earlier rat studies, this beneficial effect of exercise in humans is blunted by high dose antioxidants [Ristow M 2009].

It appears that the body adapts to intermittent muscle injury in ways that can promote health and improve cell metabolism, and that this adaptation is negatively altered by high dose antioxidants.

What about antioxidant use in Huntington's? These findings with vitamin E and C in studies of exercise may, or may not have relevance for use of these or other high dose antioxidants for Huntington's. However, exercise is postulated to be helpful in HD animal models [Pang TY 2006] , and in human HD positively correlates with delay of disease onset in HD individuals [Trembath MK 2010]. Therefore it is reasonable to postulate that high dose antioxidants vitamin E and C may impair the benefit of exercise for those with HD. It is also known that insulin resistance is a metabolic stressor that occurs in HD and correlates with disease progression [Lalić NM 2008]. The beneficial metabolic response to exercise by decreasing insulin resisitence may be impaired by antioxidant use in HD.

It is also unknown what effects high dose creatine or coenzyme Q-10 might have on human free radical response in muscles of individuals with or without the HD gene expansion. Off course, the antioxidant effect on intermittent free radical production related to exercise may be very different from the effects on chronic low level free radical production that occurs in HD.

Editor's comment: The human body, whether in health or disease is immensely complex. There are millions of cell interactions that form a delicate balance between life and death processes. It is highly unlikely that any cell process works in isolation. So, if a medicine is designed to target a process believed to be harmful, that same medicine may prevent an adaptive "health" response, which in the long run may cause harm.

At least in the exercise model, high dose antioxidants may promote harm by interfering with protective adaptive responses. My opinion for use of high dose antioxidants in HD? Because there is potential for harm, I'd advise against them outside of a clinical trial.

References

Copp SW, Ferreira LF, Herspring KF, Hirai DM, Snyder BS, Poole DC, Musch TI. The effects of antioxidants on microvascular oxygenation and blood flow in skeletal muscle of young rats. Exp Physiol. 2009 Sep;94(9):961-71. doi: 10.1113/expphysiol.2009.048223. Epub 2009 Jun 5. PubMed abstract

Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Blüher M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. 2009 May 26;106(21):8665-70. doi: 10.1073/pnas.0903485106. Epub 2009 May 11. PubMed abstract

Pang TY, Stam NC, Nithianantharajah J, Howard ML, Hannan AJ. Differential effects of voluntary physical exercise on behavioral and brain-derived neurotrophic factor expression deficits in Huntington's disease transgenic mice. Neuroscience. 2006 Aug 25;141(2):569-84. Epub 2006 May 22. PubMed abstract

Trembath MK, Horton ZA, Tippett L, Hogg V, Collins VR, Churchyard A, Velakoulis D, Roxburgh R, Delatycki MB. A retrospective study of the impact of lifestyle on age at onset of Huntington disease. Mov Disord. 2010 Jul 30;25(10):1444-50. doi: 10.1002/mds.23108. PubMed abstract

Lalić NM, Marić J, Svetel M, Jotić A, Stefanova E, Lalić K, Dragasević N, Milicić T, Lukić L, Kostić VS. Glucose homeostasis in Huntington disease: abnormalities in insulin sensitivity and early-phase insulin secretion. Arch Neurol. 2008 Apr;65(4):476-80. doi: 10.1001/archneur.65.4.476. PubMed abstract