Gamma-tocopherol is the form of vitamin E that is one of the most important neutralisers of the reactive nitrogen species (RNS) — it is the most abundant form of vitamin E in the American diet (from the soybean oil, the corn oil, the walnuts, and the pecans), and it is the primary defender against the nitrosative stress and the chronic inflammation that are associated with the elevated reactive nitrogen species (peroxynitrite, nitrogen dioxide, nitrite). While the alpha-tocopherol is the most important interceptor of the reactive oxygen species (ROS) and the primary defender against the LDL oxidation, the gamma-tocopherol is the most important interceptor of the reactive nitrogen species and the primary defender against the nitrosative stress — and this unique and complementary role of the gamma-tocopherol makes it one of the most important and most underappreciated forms of vitamin E for the prevention of the chronic inflammatory diseases, the cardiovascular disease, and the prostate cancer. Gamma-tocopherol neutralises the reactive nitrogen species by reacting with the peroxynitrite to form the 5-nitro-gamma-tocopherol, which is a stable and biologically inactive product that is excreted in the urine — this direct chemical reaction between the gamma-tocopherol and the peroxynitrite is the primary mechanism by which the gamma-tocopherol prevents the nitrosative stress and protects the cells from the reactive nitrogen species-induced damage. Without adequate gamma-tocopherol and RNS neutralisation, the nitrosative stress accumulates, the chronic inflammation develops, and the prostate dysfunction and the cardiovascular disease progress — the hallmark of the gamma-tocopherol deficiency and of the nitrosative stress states that are associated with the prostatitis, the benign prostatic hyperplasia (BPH), the prostate cancer, and the atherosclerosis.
Gamma-Tocopherol and the Prostate Health
Gamma-tocopherol supports the prostate health primarily through its neutralisation of the reactive nitrogen species and through its inhibition of the cyclooxygenase-2 (COX-2) and the prostate-specific antigen (PSA) expression — these are the two primary mechanisms by which the gamma-tocopherol prevents the prostatitis, the BPH, and the prostate cancer, and they are the reason why the gamma-tocopherol (and not the alpha-tocopherol) has been consistently associated with the reduced risk of the prostate cancer in the observational studies. The gamma-tocopherol inhibits the COX-2 expression (through its inhibition of the NF-κB pathway), and it thereby reduces the production of the prostaglandins (particularly the PGE2) that are responsible for the prostate inflammation, the pain, and the growth of the prostate tissue. The gamma-tocopherol also reduces the PSA expression (through its anti-inflammatory and its antioxidant effects), and it thereby slows the progression of the BPH and reduces the risk of the prostate cancer. The combination of the RNS neutralisation, the COX-2 inhibition, and the PSA reduction makes the gamma-tocopherol one of the most important and most specific nutrients for the prostate health — and it explains why the gamma-tocopherol supplementation has been shown to reduce the risk of the prostate cancer by 30-40% in the ATBC trial and in the Health Professionals Follow-Up Study.
The clinical importance of the gamma-tocopherol for the prostate health is underscored by the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) trial — a study in over 29,000 male smokers found that the gamma-tocopherol levels (in the highest quartile) were associated with a 30-40% reduced risk of the prostate cancer, compared to the lowest quartile — demonstrating the potent and clinically meaningful prostate-protective effect of the gamma-tocopherol in a large population of male smokers.
Practical Application
For general gamma-tocopherol supplementation for the reactive nitrogen species neutralisation and for the prostate health, the evidence-based approach is to supplement with 50-200mg of gamma-tocopherol daily (as the mixed tocopherol supplement that contains both the alpha-tocopherol and the gamma-tocopherol in a ratio of approximately 1:1 to 1:2 — the mixed tocopherol formula is preferred over the isolated gamma-tocopherol because it provides both the alpha-tocopherol for the ROS neutralisation and the gamma-tocopherol for the RNS neutralisation, and because the high-dose alpha-tocopherol alone may actually reduce the gamma-tocopherol levels by competing for the hepatic alpha-tocopherol transfer protein). The gamma-tocopherol should be taken with the alpha-tocopherol (at a ratio of approximately 1:1 to 1:2, as the mixed tocopherol formula) for the comprehensive vitamin E coverage and for the maximum antioxidant protection against both the ROS and the RNS. The gamma-tocopherol is generally well-tolerated with no significant adverse effects at the doses that are used for the RNS neutralisation (up to 400mg daily of the mixed tocopherol). For comprehensive reactive nitrogen species neutralisation and prostate health, gamma-tocopherol pairs well with the alpha-tocopherol (as the mixed tocopherol formula — which provides both the alpha-tocopherol for the ROS neutralisation and the gamma-tocopherol for the RNS neutralisation — the mixed tocopherol formula is the most effective and most evidence-based approach for the comprehensive vitamin E coverage and for the maximum antioxidant protection), with the selenium (which is a cofactor for the glutathione peroxidase and which works synergistically with the gamma-tocopherol for the antioxidant defence and for the prevention of the nitrosative stress — the combination of the gamma-tocopherol and the selenium is one of the most effective combinations for the prevention of the prostate cancer and for the protection of the cardiovascular system from the nitrosative stress), with the lycopene (which is the most important carotenoid for the prostate health and which works synergistically with the gamma-tocopherol for the prevention of the BPH and of the prostate cancer — the combination of the gamma-tocopherol and the lycopene is one of the most effective combinations for the prostate health and for the reduction of the prostate cancer risk), and with the zinc (which is the most important mineral for the prostate function and which works synergistically with the gamma-tocopherol for the prevention of the prostatitis and for the maintenance of the prostate health — the combination of the gamma-tocopherol and the zinc is one of the most effective combinations for the prevention of the BPH and for the reduction of the lower urinary tract symptoms in men with the prostate enlargement).
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