One of the latest sensational headlines proclaimed that supplemental Vitamin E causes cancer, but to put it mildly this headline is very misleading.
How and When Vitamin E Can Accelerate Cancer Growth
A recent study showed that, in abnormal cells, vitamin E and NAC (n-acteyl-cysteine, another antioxidant) can dampen the p53 DNA damage response, meaning the tumor suppressor gene (p53) does not get activated because there is little oxidation/nitration to stimulte the response.
It is important to understand that reducing DNA damage in normal healthy cells is a good thing since DNA damage is a cancer initiator. However, cancer cells may use supplemental antioxidants to their advantage because it allows them to continue to override these important checkpoints thereby promoting the survival of these abnormal cells.
Giving Mice with Cancer 5 to 50 Times The RDA in Vitamin E
The ability of supplemental antioxidants to promote the survival of cancer cells in mice was demonstrated recently. Researchers fed mice with lung cancer between 5 and 50 times the RDA of an isolated form of vitamin E and it accelerated the cancer growth. They showed the mechanism of this tumor acceleration was that p53 was not getting activated due to the quenching of reactive oxygen species by the vitamin E. As a consequence, that important tumor suppressor checkpoint did not get activated and cancer cell death was not initiated.
At the same time let’s keep in mind that the same dose of Vitamin E and N-acetyl-cysteine given to normal mice without cancer, did not initiate cancer. In fact, it did the opposite. It reduced DNA damage, a well-known initiator of cancer. This is a perfect demonstration of how the effects of supplemental vitamins are context-dependent and generalizations should not be made.
Vitamin E can prevent DNA damage, which is a good thing if you do not already have cancer since DNA damage is a well-known cancer initiator. However, if you already have cancer DNA damage can activate any functional tumor suppressor genes, which can kill the cancer cell.
This may also serve another lesson: more is not always better.
Endogenous Antioxidants: Even Our Bodies Produce Them
Exogenous Antioxidants aka Dietary Antioxidants
These antioxidants come from foods and supplements. Vitamin E is one of the many dietary antioxidants and is critical for optimal health. Vitamin E comes from plants, and there are at least 8 different forms (alpha, beta, gamma, and delta), which are present as either tocopherols or tocotrienols.
There are two major forms of vitamin E in the body:
Alpha Tocopherol - found in the largest quantity in the body, and the most potent at stopping reactive oxygen species.
Gamma Tocopherol - second most abundant, and important for inhibiting reactive nitration oxidants. Gamma Tocopherol also inhibits cyclooxygeanse activity (otherwise known as COX), which generates inflammatory chemicals.
Although both alpha and gamma tocopherol prevent the oxidation of lipids (fats), DNA, and proteins -- ONLY gamma tocopherol prevents damaging reactive nitrogen oxidants and affects the COX pathway that creates inflammatory chemicals.
Moreover, taking high doses (such as 400 IU a day) of alpha tocopherol in isolation actively depletes levels of gamma tocopherol. Because alpha tocopherol is the most abundant in tissues and in plasma, it happens to be the major form that is found in supplements... usually to the exclusion of all else within the Vitamin E family.
The take home message is that if you choose to supplement Vitamin E always take a form with mixed tocopherols including plenty of Gamma Tocopherol.
Selenium and Vitamin E taken Together
A study showed that the men supplementing with the 400 IU/day of alpha-tocopherol alone had an 18% increased risk of prostate cancer; however, this risk was ameliorated when the participants were co-administered the same dose (400 IU) of the alpha-tocopherol along with 200 micrograms of selenium. The most recent follow-up found that only the men with the lowest selenium levels at baseline were at risk for increased prostate cancer after alpha-tocopherol supplementation [4].
Selenium is required for the function of about 25 different proteins including glutathione peroxidase (one of the big three endogenous antioxidants produced in your body that requires selenium). One of these proteins (selenoprotein P) which require selenium is an enzyme that detoxifies reactive nitrogen oxidants.
Since protection against reactive nitrogen oxidants is one of the specific functions of gamma tocopherol this might be the mechanism by which selenium can protect against prostate cancer in men that supplemented with a high dose of alpha tocopherol (which depleted their gamma tocopherol).
Studies have also found that higher vitamin E levels are associated with a lower risk for prostate cancer. In a case-controlled study looking at serum levels of alpha, gamma, and selenium and the prostate, it was found that those with the highest levels of serum gamma tocopherol was associated with a five-fold decrease in prostate cancer.
Summary
Both reactive oxygen species and reactive nitrogen species are being produced inside your cells every single day. These damaging byproducts of normal metabolism and immune activation wreak havoc on your DNA, proteins, and cell membranes, which lead to diseases of aging such as cancer and neurodegeneration.
Having the appropriate amount and combination of antioxidants can prevent this damage from occurring in normal cells. However, taking mega doses of vitamin E in the presence of cancer may have negative consequences because it prevents the reactive oxygen species from activating tumor suppressor genes that kill cancer cells.
Selenium and Vitamin E
Selenium has been shown to be protective against cancer, and while alpha tocopherol is important, if you're both deficient in selenium AND depleting your gamma tocopherol levels then the additional inflammation may be just enough to tip you over the edge into a diseased state.
According to NHANES survey, 60% of the US population does not meet the requirement of minimum levels of alpha tocopherol, which is 22.4 IU/day.
This is compared to about 6% of the population that does not meet the requirement for selenium. The RDA for selenium is 55 micrograms/day. There are about 25 different proteins that require selenium and this RDA is based on the amount needed to maintain maximal activity of glutathione peroxidase.
Other data indicates that 55 micrograms per day may not be enough to maintain maximal activity of some other selenium-dependent enzymes. Most people in the US are not meeting their requirements for vitamin E and should probably try to increase their consumption of foods that contain all forms of vitamin E like almonds, pecans, wheat germ, and avocados.
If you do choose to supplement Vitamin E use a supplement that contains all forms of tocopherols including plenty of gamma tocopherol. Also consider taking an optimal dose (200 micrograms per day) of a preferred form of selenium like the Selenoexcell (if taking a multiple vitamin count the micrograms of selenium contained there – you do not need more than 200 micrograms). If you want to avoid supplementation Brazil nuts are VERY high in bioavailable selenium – just one to two per day is all you need!
