Gamma-Tocopherol and Metabolic Syndrome

by | Jan 12, 2016 | 2012, Metabolic Syndrome, Pancreatic Health, Vitamin E

Written by Chrystal Moulton, Staff Writer. Gamma-tocopherol more effectively decreased C reactive protein (a marker of oxidative stress)  by 30% more than alpha-tocopherol.

Metabolic syndrome refers to a group of risk factors that significantly increases the risk of developing chronic diseases such as coronary heart disease, diabetes, and stroke. These factors are high blood pressure, large waistline (excess fat in abdominal region), high fasting blood sugar, low HDL, and high triglycerides. Any 3 of these risk factors are required for a diagnosis of Metabolic Syndrome. (1) Another likely factor in the development of chronic disease is oxidative stress. This refers to an imbalance in the presence of free radical molecules in the body that cause cellular damage and antioxidants (a.k.a. free radical scavengers) that defends against them. One of the most powerful antioxidants naturally found in foods is vitamin E. The most common supplement form of vitamin E is alpha-tocopherol, which is effective in reducing inflammation and oxidative stress. (2,3) However, several long-term studies on the effects of alpha-tocopherol in relation to chronic illnesses have shown no benefit. (4-6) Researchers wonder if the null results may be due to alpha-tocopherol’s affect on other forms of vitamin E naturally present in the body. Clinical trials have shown that alpha-tocopherol supplementation decreases gamma-tocopherol levels within the body. (7,8) Furthermore, studies with gamma-tocopherol have demonstrated that increased levels of gamma-tocopherol in the body is associated with lower mortality and a reduction in the incidence of metabolic syndrome and chronic diseases. (9-11) In the current study (12), researchers tested whether gamma-tocopherol alone or in combination with alpha-tocopherol was more effective against markers of oxidative stress and inflammation in subjects with metabolic syndrome.

Eighty participants who were not taking vitamin E were recruited to this study. Participants had to have 3 of 5 symptoms related to metabolic syndrome:

  1. Waist circumference= >40 inches for men , >35 inches for women
  2. Triglycerides= >150mg/dl
  3. Blood pressure= >130/80 mm Hg
  4. Fasting glucose= >100mg/dl
  5. HDL= <40mg/dl in men, <50mg/dl in women

The study was a randomized, placebo-controlled trial. Individuals were assigned to receive 800 mg/d of alpha-tocopherol, 800 mg/d of gamma-tocopherol, 800 mg each of alpha and gamma- tocopherol /day, or placebo for 6 weeks. Participants were instructed to take 2 capsule/day with a meal. Fasting blood and 24-hour urine sample was taken at baseline and after the end of the trial. Researchers measured for markers of oxidative stress and inflammation including urinary nitrotyrosine, cytokines (IL-1b, TNF-alpha, IL-6), and C-reactive protein. The amount of alpha and gamma-tocopherol in plasma along with their metabolites were also measured.

Table 1. Results from Study

 

Placebo

Α-tocopherol

G-Tocopherol

A & G-Tocopherol
0 weeks 6weeks 0 weeks 6weeks 0 weeks 6weeks 0 weeks 6weeks
TNF (ng/L) 0.31 0.39 0.27 0.23* 0.26 0.24 0.28 0.14*‡
Lipid Peroxides (µM) 3.3±1.2 3.2±1.2 3.5±1.0 2.1±1.0*‡ 3.4±1.2 2.0±0.6*‡ 3.5±1.2 1.9±0.6*‡
CRP (mg/L)ª ~4.2 ~4.0 ~6.0 ~5.0** ~5.0 ~3.5** ~6.0 ~3.5†
Urine Nitrotyrosineª (μmol/mg Creatinine) ~5.0 ~4.0 ~7.0 ~7.0 ~5.0 ~3.0† ~11.0 ~5.0†

*p<0.05 compared to baseline; ‡ p<0.05 compared to baseline and placebo. ª estimated median values obtained from graphs. † p<0.02 compared to placebo; **p<0.001 compared to baseline.

After 6 weeks of supplementation, C-reactive protein levels were significantly lower for all supplemental groups compared to baseline (p<0.001). The combination of alpha and gamma-tocopherol, however, significantly lowered C-reactive protein compared to both baseline results and placebo (p<0.02). Median reduction was 15%. Alpha-Tocopherol alone and in combination with gamma-tocopherol significantly decreased TNF-alpha levels in the blood (p<0.05). Markers of oxidative stress including lipid peroxides were also significantly reduced by all treatments compared to placebo (p<0.01). Nitrotyrosine levels in urine were significantly lowered by gamma-tocopherol treatment alone and in combination with alpha-tocopherol (p<0.02). However, alpha-tocopherol alone had no effect on nitrotyrosine levels. Alpha and gamma-tocopherol levels were significantly increased after 6 weeks of supplementation. However, plasma gamma-tocopherol was decreased by 37% following alpha-tocopherol supplementation. Furthermore, gamma-tocopherol increase was significantly lower with the alpha-gamma combination compared to gamma-tocopherol levels post-supplementation (p<0.001). Gamma-tocopherol supplementation, however, did not significantly change plasma concentration alpha-tocopherol.

Source: Seralini, G.-E, et al. Long term toxicity of Roundup herbicide and a Roundup-tolerant genetically modified maise. Food Chem Toxicol. (2012), http://dx.doi.org/10.1016/j.fct.2012.08.005

© 2012 Elsevier Inc. All rights reserved.

Posted May 7, 2014.

Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.

References:

  1. What Is Metabolic Syndrome? NIH National Heart, Lung, and Blood Institute. Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/ms/. Accessed April 30, 2014.
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  3. Singh U, Devaraj S, Jialal I. Vitamin E, oxidative stress, and inflammation. Annu Rev Nutr. 2005;25:151-74.
  4. Shekelle PG, et al. Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease. J Gen Intern Med. 2004 Apr;19(4):380-9.
  5. Lee IM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA. 2005 Jul 6;294(1):56-65.
  6. Lonn E, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005 Mar 16;293(11):1338-47.
  7. Huang HY, Appel LJ. Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. J Nutr. 2003 Oct;133(10):3137-40.
  8. Handelman GJ, et al. Oral alpha-tocopherol supplements decrease plasma gamma-tocopherol levels in humans. J Nutr. 1985 Jun;115(6):807-13.
  9. Jiang Q. Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radic Biol Med. 2014 Apr 3. pii: S0891-5849(14)00152-X
  10. Jiang Q, Ames BN. Gamma-tocopherol, but not alpha-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats. FASEB J. 2003 May;17(8):816-22.
  11. Wagner KH, Kamal-Eldin A, ElmadfaI. Gamma-tocopherol–an underestimated vitamin? Ann Nutr Metab. 2004;48(3):169-88
  12. Devaraj S, et al. Gamma-tocopherol supplementation alone and in combination with alpha-tocopherol alters biomarkers of oxidative stress and inflammation in subjects with metabolic syndrome. Free Radic Biol Med. 2008 Mar 15;44(6):1203-8.