Life Extension Magazine®

Issue: Feb 1998

New research on the benefits of gamma tocopherol, and more.

Scientifically reviewed by: Dr. Gary Gonzalez, MD, on January 2021.


Gamma Tocopherol Complements Alpha Tocopherol

Gamma-Tocopherol traps mutagenic electrophiles such as NO(x) and complements alpha-tocopherol: Physiological implications
Christen S.; Woodall A.A.; Shigenaga M.K.; Southwell-Keely P.T.; Duncan M.W.; Ames B.N.
Proceedings of the National Academy of Sciences of the United States of America (USA), 1997, 94/7 (3217-3222)

Peroxynitrite, a powerful mutagenic oxidant and nitrating species, is formed by the near diffusion-limited reaction of NO and O2 during activation of phagocytes. Chronic inflammation induced by phagocytes is a major contributor to cancer and other degenerative diseases.

We examined how gamma-tocopherol (gammaT), the principal form of vitamin E in the United States diet, and alpha-tocopherol (alphaT), the major form in supplements, protect against peroxynitrite-induced lipid oxidation. Lipid hydroperoxide formation in liposomes (but not isolated low-density lipoprotein) exposed to peroxynitrite or the NO and O2 generator SIN-1 (3-morpholinosydnonimine) was inhibited more effectively by gammaT than alphaT. More importantly, nitration of gammaT at the nucleophilic 5-position, which proceeded in both liposomes and human low density lipoprotein at yields of similar-50% and similar-75%, respectively, was not affected by the presence of alphaT.

These results suggest that despite alphaT's action as an antioxidant, gammaT is required to effectively remove the peroxynitrite-derived nitrating species. We postulate that gammaT acts in vivo as a trap for membrane-soluble electrophilic nitrogen oxides and other electrophilic mutagens, forming stable carbon-centered adducts through the nucleophilic 5-position, which is blocked in alphaT. Because large doses of dietary alphaT displace gammaT in plasma and other tissues, the current wisdom of vitamin E supplementation with primarily alphaT should be reconsidered.

Dietary Restriction, Survival and Disease
The effect of dietary restriction of varying duration on survival, tumor patterns, immune function, and body temperature in B10C3F1 female mice.
Cheney KE, Liu RK, Smith GS, Meredith PJ, Mickey MR, Walford RL.
J Gerontol (1983 Jul) 38(4):420-30

Seven groups of mice were maintained on different dietary programs varying with respect to restriction at various stages of life. Restriction was associated with less age-related decline in T-dependent immunological function and a slight but significant lowering of body temperature.

The best mean and maximum survival and the lowest late-life mortality rate was found in the group restricted throughout life, but restriction during any part of the life span enhanced survival to some degree. The mean life spans of tumor-bearing animals tended to be greater in restricted than in non-restricted groups, corresponding to an age-decelerating effect.

Tumor frequency varied with the period of life during which restriction took place and was not always decreased in restricted animals. These latter results suggest that the mechanisms whereby dietary restriction influences the aging rate and tumor susceptibility may not be entirely identical.

Dietary Restriction and Learning

Dietary restriction benefits learning and motor performance of aged mice.
Ingram DK, Weindruch R, Spangler EL, Freeman JR, Walford RL.
J Gerontol (1987 Jan) 42(1):78-81

Female C3B10RF1 mice maintained on either a control (approximately 95 kcal/week) or restricted (approximately 55 kcal/week) diet since weaning were tested in a behavioral battery at 11 to 15 or 31 to 35 months of age (middle-aged vs. aged). Age-related declines observed among control groups in tests of motor coordination (rotorod) and learning (complex maze) were prevented by the restriction regime. In addition, diet restriction increased locomotor activity in a runwheel cage among mice of both ages but did not affect exploratory activity in a novel arena.

Influenza and Dietary Restriction

Influences of dietary restriction on immunity to influenza in aged mice.
Effros RB, Walford RL, Weindruch R, Mitcheltree C.
J Gerontol (1991 Jul) 46(4):B142-7

Our previous studies of the immune response of aged mice inoculated with influenza A virus revealed age-related decreases in antigen-specific cytotoxic T-lymphocyte function (CTL), T-cell proliferation, IL-2 production, antigen presentation, and antibody production.

Because dietary restriction (DR) of rodents has been shown to extend maximum life span, delay the onset of tumors, and improve many immunologic parameters in aged animals, we tested the effect of such a regimen on the immune response to the influenza virus.

We report that DR significantly inhibited the age-related decline in antigen presentation and T-cell proliferation. It also reduced the decline in antibody production to the virus. This is the first demonstration of improved immunity to an actual infectious agent resulting from DR. The improvement appears to be on a number of levels and to reflect more than one operative mechanism.

C. Elegans, Longevity and Daf-2

Daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans
Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G.
Science (1997 Aug 15) 277(5328):942-6,

A C. elegans neurosecretory signaling system regulates whether animals enter the reproductive life cycle or arrest development at the long-lived dauer diapause stage. Daf-2, a key gene in the genetic pathway that mediates this endocrine signaling, encodes an insulin receptor family member.

Decreases in daf-2 signaling induce metabolic and developmental changes, as in mammalian metabolic control by the insulin receptor. Decreased daf-2 signaling also causes an increase in life span. Life span regulation by insulin-like metabolic control is analogous to mammalian longevity enhancement induced by caloric restriction, suggesting a general link between metabolism, diapause, and longevity.

Congestive Heart Failure and Coenzyme Q10

Refractory congestive heart failure successfully managed with high dose coenzyme Q10 administration
Sinatra S.T.,
Molecular Aspects of Medicine (United Kingdom), 1997, 18/SUPPL. (S299-S305)

Coenzyme Q10 (CoQ10) is a critical adjuvant therapy for patients with congestive heart failure (CHF), even when traditional medical therapy is successful. Adjunctive therapy with Q10 may allow for a reduction of other pharmacological therapies, improvement in quality of life, and a decrease in the incidence of cardiac complications in congestive heart failure.

However, dosing, clinical application, bioavailability and dissolution of CoQ10 deserve careful scrutiny whenever employing the nutrient. The assessment of blood levels in 'therapeutic failures' appears warranted.

CoQ10 and Skeletal Muscle Energy Metabolism

Effects of oral supplementation of coenzyme Q10 on 31P-NMR detected skeletal muscle energy metabolism in middle-aged post-polio subjects and normal volunteers
Mizuno M.; Quistorff B.; Theorell H.; Theorell M.; Chance B.,
Molecular Aspects of Medicine (United Kingdom), 1997, 18/SUPPL. (S291-S298)

The effects of oral supplementation of 100 mg coenzyme Q10 (CoQ10) for 6 months on muscle energy metabolism during exercise and recovery were evaluated in middle-aged post-polio (n=3) and healthy subjects (n=4) by the use of phosphorus-31 nuclear magnetic resonance spectroscopy. The metabolic response to isometric plantar flexion at 60% of maximal voluntary contraction force (MVC) for 1.5 minutes was determined in gastrocnemius muscles before, after 3 months and 6 months of CoQ10 supplementation.

The MVC of plantar flexion was unchanged following CoQ10 supplementation. The resting P(i)/PCr ratio in gastrocnemius muscles of all subjects decreased after 3 months and 6 months CoQ10 (P 0.05). The post-polio individuals showed a progressive decrease in this ratio, while less pronounced changes were observed in the control subjects.

Similarly, the post-polio individuals showed a lower P(i)/PCr ratio at the end of 60% MVC in both 3 month and 6 month CoQ10, whereas no change in the ratio was observed in the control subjects. A less pronounced decrease in muscle pH was observed at the end of 60% MVC in both 3 month and 6 month CoQ10 in the post-polio individuals, but not in the control subjects. No systematic difference in end-exercise ATP was observed between the three phases in both groups.

The half-time of recovery for PCr decreased in all subjects after 6 months of CoQ10 supplementation (P 0.05).

The results suggest that CoQ10 supplementation affects muscle energy metabolism in post-polio individuals to a greater extent than in control subjects. The mechanism for this effect is not clear, but may involve an effect of CoQ10 on peripheral circulation in the calf muscles, its action in mitochondrial oxidative phosphorylation and/or its antioxidant potential.

Exercise Performance and Coenzyme Q10
The effect of coenzyme Q10 on the exercise performance of cross-country skiers
Ylikoski T.; Piirainen J.; Hanninen O.; Penttinen J.
Molecular Aspects of Medicine (United Kingdom), 1997, 18/SUPPL. (S283-S290)

Coenzyme Q10, supplementation (Bio-Qinon Pharma Nord, 90 mg/day) was studied in a double-blind cross-over study of 25 Finnish top-level cross-country skiers. With CoQ10 supplementation, all measured indexes of physical performance (AET, ANT and VO2Max) improved significantly.

During verum supplementation, 94% of the athletes felt that the preparation had been beneficial in improving their performance and recovery time vs. only 33% in the placebo periods.

CoQ10, Alpha Tocopherol, and Liver Damage
T-2 toxin-induced DNA damage in mouse livers: The effect of pretreatment with coenzyme Q10 and alpha-tocopherol
Atroshi F.; Rizzo A.; Biese I.; Veijalainen P.; Antila E.; Westermarck T.,
Molecular Aspects of Medicine (United Kingdom), 1997, 18/SUPPL. (S255-S258)

Active oxygen species are reported to cause organ damage. This study was therefore designed to determine whether oxidative stress contributed to the initiation or progression of hepatic DNA damage produced by T-2 toxin.

The aim of the study was also to investigate the behavior of the antioxidants coenzyme Q10 (CoQ10), and alpha-tocopherol (vitamin E) against DNA damage in the livers of mice fed T-2 toxin. Treatment of fasted mice with a single dose of T-2 toxin (1.8 or 2.8 mg/kg body weight) by oral gavage led to 76% hepatic DNA fragmentation. T-2 toxin also decreased hepatic glutathione (GSH) levels markedly. Pretreatment with CoQ10 (6 mg/kg) together with alpha-tocopherol (6 mg/kg) decreased DNA damage. The CoQ10 and vitamin E showed some protection against toxic cell death and glutathione depletion caused by T-2 toxin. Oxidative damage caused by T-2 toxin may be one of the underlying mechanisms for T-2 toxin-induced cell injury and DNA damage, which eventually lead to tumorigenesis.

CoQ10 Therapy for Myocardial Ischemia
The mechanisms of coenzyme Q10 as therapy for myocardial ischemia reperfusion injury
Whitman G.J.R.; Niibori K.; Yokoyama H.; Crestanello J.A.; Lingle D.M.; Momeni R. G.J.R. Whitman.
Molecular Aspects of Medicine (United Kingdom), 1997, 18/SUPPL. (S195-S203)

It has been hypothesized that CoQ10 pretreatment protects myocardium from ischemia reperfusion (I/R) injury by its ability to increase aerobic energy production as well as its activity as an antioxidant. Isolated hearts from rats pretreated with either CoQ10 20 mg/kg i.m. and 10 mg/kg i.p. or vehicle 24 hours and 2 hours prior to the experiment, were subjected to 15 min of equilibration (EQ), 25 min of ischemia, and 40 min of reperfusion (RP).

Developed pressure, plus or minus dp/dt, myocardial oxygen consumption, and myocardial aerobic efficiency (DP/MVO2) were measured. 31P NMR spectroscopy was used to determine ATP and PCr concentrations. Lucigenin-enhanced chemiluminescence of the coronary sinus effluent was utilized to determine oxidative stress through the protocol.

CoQ10 pretreatment improved myocardial function after ischemia reperfusion. CoQ10 pretreatment improved tolerance to myocardial ischemia reperfusion injury by its ability to increase aerobic energy production, and by preserving myocardial aerobic efficiency during reperfusion. Furthermore, the oxidative burst during RP was diminished with CoQ10. Similarly it was hypothesized that CoQ10 protected coronary vascular reactivity after I/R via an antioxidant mechanism. Utilizing a newly developed liposomal CoQ10 preparation given i.v. 15 min prior to ischemia, ischemia reperfusion was carried out on Langendorff apparatus as previously described. Just prior to ischemia and after RP, hearts were challenged with bradykinin (BK) and sodium nitroprusside (SNP) and change in coronary flow was measured. CoQ10 pretreatment protected endothelial-dependent and endothelial-independent vasodilation after I/R.

We conclude that CoQ10 pretreatment protects coronary vascular reactivity after I/R via OH radical scavenger action.