High Doses Of Vitamin E Boost Rat Survival Rate 40%; Brain Function, Neuromuscular Gains

Their just-published paper shows that using vitamin Esupplementation physiologically comparable to recent human experiments inAlzheimer’s Disease patients, resulted in these major findings:

• male mice showed a 40% increase in median lifespan (to 85 ± 4 weeks from 61 ± 4).

• 17% increase in maximal lifespan (to 136 weeks from 116 weeks).

• increases in the ability to perform tests measuring neuromuscular performance (high-wire tightrope) and cognitive exploratory activity (T-maze); the increases on both tests ranged 9%-24% at 52 weeks, and 28%-45% at 78 weeks of age.

• brain alpha-tocopherol content increased 2.5-fold in male mice taking vitamin E.

• vitamin E supplementation offset various measures of mitochondrial function loss in a range of 37%-66% at the 52- and 78-week test points.

• all results were significant to a greater than 99% confidence level.

The paper “Vitamin E at high doses improves survival,neurological performance and brain mitochondrial function in aging malemice” appears online in the American Journal of Physiology-Regulatory,Integrative and Comparative Physiology, published by the AmericanPhysiological Society. Research was by Ana Navarro, Carmen Gomez,Maria-Jesus Sanchez-Pino, Hipolito Gonzalez and Manuel J. Bandez of the University of Cadiz, Spain, and Alejandro D. Boveris and Alberto Boverisof the University of Buenos Aires.

Results seen supporting ‘free radical’ theory ofaging

Alberto Boveris, professor at the University of BuenosAires, said the results of these extended experiments “are in line with thefree radical theory of aging put forward by Gerschman and Harman in the1950s. Our results show a significant negative correlation between themitochondrial content of the oxidation products of free-radical mediatedreactions and mitochondrial enzymatic activities.

“Moreover, brain mitochondrial enzymatic activitieswere linearly related to mice success in the tests of neuromuscular functionand of exploratory and cognitive activity and to the maximal mice lifespan,” Boveris reported. He noted that the amount of vitamin Esupplementation was metabolically and physiologically similar to the1200-2000mg. daily dosage for two to three years used in two Alzheimer’sDisease experiments involving over 400 patients without adverse effects.

The paper observes that the “study shows the beneficialeffects of high doses of vitamin E on the median and maximal lifespan ofmale mice, an effect that is parallel to a beneficial effect on the declineof neurological performance and mitochondrial function associated withaging.” It said the “marked increase” in median lifespan and the moderaterise of maximal lifespan “is properly described as a delay in the onset ofthe almost linear decay in mice survival.”

The mice used in the experiment, the CD-1/UCadiz, are asenescence accelerated strain with a median lifespan of 60-70 weeks andmaximal lifespan of 100-120 weeks. Vitamin E supplementation of the testgroup began at age 28 weeks.

Role of vitamin E as antioxidant; support for‘specificity’ concept

The researchers noted that the “mitochondrial contentof lipid protein oxidation products, an indication of free-radical mediatedreactions and oxidative damage, was increased in the brain and liver ofaging mice, and the effect was partially [and significantly] prevented byvitamin E. The protein carbonyl content of brain mitochondria, taking28-week-old mice as reference, increased 33%-69% at 52 and 76 weeks, andthis increase was markedly prevented (76% and 65%) by vitamin Esupplementation” measured at the two age points.

Vitamin E supplementation was “able to prevent thedecrease in the activities of brain enzymes that are mitochondrial markersof aging: mtNOS (by 95%), Mn-SOD (by 60%), and NADH-cytochrome c reductaseand cytochrome oxidase activity” by 35%, the paper said

“The activities of the inner membrane bound mtNOS andof the matrix enzyme MnSOD in brain and liver mitochondria also decreasedupon aging, in agreement with earlier reports and with the concept ofspecificity rather than randomness in the inactivation of mitrondrialenzymes,” according to the paper. “The activity of mtNOS was decreased by44%-66% and Mn-SOD by 28%-50% at 52-78 weeks of mice age, effects that weremarkedly prevented by vitamin E supplementation,” it added.

Clues to mitochondrial dysfunction -- and next steps

Finally, the authors noted two “interestingcorrelations”: The first is the inverse relationship between oxidativedamage and enzymatic activities in the brain and liver, “which are due tooxidized and damaged proteins, and not to a direct inhibitory effect oflipid oxidation products (ie., malonaldehyde) due to the high dilution ofthe enzymes in the assays” where the reduced rates occurred. The secondcorrelation shows “that decreased electron transfer rates and limitedrespiration and energy supply are the basis of the mitochondrial dysfunctionin aging and that mitochondrial dysfunction is the pacemaker of the declinein neurological performances which has a determinant role in survival.”

• Further studies are needed to find the threshold for vitamin E “doses that provide beneficial effects in the neurological function in aging mammals,” the study noted.

• Boveris said the team has completed studies on the role of calorie reduction (CR), “which could yield interesting results especially in comparison with similar, but much longer, rhesus monkey studies being carried out by Richard Weindruch at the University of Wisconsin-Madison on CR and oxidative stress.”

The paper “Vitamin E at high doses improves survival,neurological performance and brain mitochondrial function in aging malemice” appears in the online edition of the American Journal ofPhysiology- Regulatory, Integrative and Comparative Physiology,published by the American Physiological Society. Research was by AnaNavarro, Carmen Gomez, Maria-Jesus Sanchez-Pino, Hipolito Gonzalez andManuel J. Bandez of the Department of Biochemistry and Molecular Biology,School of Medicine, University of Cadiz, Spain; and Alejandro D. Boveris andAlberto Boveris of the Laboratory of Free Radical Biology, School ofPharmacy and Biochemistry, University of Buenos Aires, Argentina.

Research was supported by grants from Ministeriode Sanidad y Consumo de España, and by Plan Andaluz de Investigación.