Vitamin E is an antioxidant nutrient that we get through food sources or supplements. However, Vitamin E supplementation has shown differential impact in different cancers. Vitamin E has shown increased risk of prostate and brain cancers, no impact on lung cancer and benefits in Ovarian cancer. This differential effect could be linked to genetic variation in individuals based on variations in how Vitamin E is processed in the body. Excessive Vitamin E supplementation can cause harm due to excessive bleeding and stroke. Therefore, it is best to increase Vitamin E through food sources as part of a healthy diet or nutrition for cancer, rather than taking supplements.
Many people believe that taking vitamins and supplements can help with reducing the risk of many chronic health conditions and improve their overall well-being. However, there are many clinical studies that are showing that benefits of vitamins and supplements are context specific and in many cases they do not provide any benefit and could even be harmful. Vitamin E is one such nutrient that is popular for its varied health benefits and besides being part of many foods that we eat as part of our diet/nutrition, is taken as a supplement for an added dose and benefit. We will examine the sources, benefits and risks associated with excessive Vitamin E supplementation in cancer diet/nutrition.
Vitamin E is a group of fat soluble antioxidant nutrients found in many foods and also taken as a supplement individually or part of multi-vitamin supplementation, for its many health benefits. Vitamin E essentially is made of two groups of chemicals: tocopherols and tocotrienols. The antioxidant properties of Vitamin E help in protecting our cells from damage caused by reactive free radicals and oxidative stress. Hence, food sources and supplements of Vitamin E provide numerous health benefits ranging from skin-care to improved heart and brain health.
Sources of Vitamin E
Vitamin E rich food sources include corn oil, vegetable oils, palm oil, almonds, hazelnuts, pinenuts, sunflower seeds, besides many other fruits and vegetables that we consume in our diet. Tocopherols are the major sources of Vitamin E in our diet and supplements when compared to tocotrienols. Foods that have higher tocotrienol are rice bran, oats, rye, barley and palm oil.
Risk – Benefit association of Vitamin E with Cancer
Antioxidant properties of Vitamin E can help with reducing harmful oxidative stress and damage in our cells. Aging causes a reduction in the inherent antioxidant capacity of our bodies, thus Vitamin E helps with anti-aging effects. It is associated with reducing risk of chronic and aging related disorders such as cardiovascular, diabetes and even having anti-cancer impact. Studies in cancer cells and animal models have shown a beneficial impact of Vitamin E supplementation on prevention of cancer. Multiple clinical trials have evaluated the association of Vitamin E supplement use in cancer patients and have shown varied effects ranging from benefit, to no impact, to harm, in different cancers.
In this blog we will summarize some of these clinical studies that highlight that Vitamin E use as part of nutrition/diet is beneficial in some cancers while it is associated with a negative impact in other cancer types. Therefore, benefits vs. risk of the use of Vitamin E sources in cancer diet/nutrition is context dependent and varies with cancer type and treatment.
Benefits of Vitamin E in Ovarian Cancer
Ovarian cancer diagnosis usually occurs at a later, more advanced stage, because early stages of this cancer rarely cause any symptoms. During later stages of ovarian cancer, the symptoms such as weight-loss and abdominal pain, which are generally non-specific, start showing up and these usually do not raise much alarm. It is due to these reasons that women are diagnosed with ovarian cancer at much later stages, with a five year survival rate of 47% (American Cancer Society). Ovarian cancer patients are treated with chemotherapy treatments that many do not respond to. One of the most common targeted therapies used for ovarian cancer works by starving the tumor cells by preventing the growth of new blood vessels that are vital for the transport of nutrients to the rapidly growing tumor.
In the context of ovarian cancer, Vitamin E compound tocotrienol has shown benefits when used in combination with the standard of care (SOC) drug (humanized anti-VEGF monoclonal antibody) in patients who were resistant to chemotherapy treatment. Researchers in the Department of Oncology in Vejle Hospital, Denmark, studied the effect of the tocotrienol subgroup of Vitamin E in combination with the SOC drug in ovarian cancer patients that did not respond to chemotherapy treatments. The study included 23 patients. Combination of tocotrienol with the SOC drug showed very low toxicity in the patients and had a 70% disease stabilization rate. The median overall survival recorded for this phase II trial was much higher compared to the current literature. (Thomsen CB et al, Pharmacol Res., 2019) This study supports the anti-cancer effect of delta-tocotrienol subgroup of Vitamin E in multiresistant ovarian cancer, but the same is not established for tocopherols.
Risk of Vitamin E in Brain Cancer
A study based in different neuro oncology and neurosurgery departments across US hospitals analyzed structured interview data from 470 patients that was conducted following diagnosis of brain cancer glioblastoma multiforme (GBM). The results indicated that a significantly large number of these patients (77%) reported randomly using some form of complementary therapy like vitamins or natural supplements. Surprisingly, Vitamin E users had a higher mortality when compared to those that did not use Vitamin E supplements. (Mulphur BH et al, Neurooncol Pract., 2015)
In another study from Umea University, Sweden and Cancer Registry of Norway, the researchers took a different approach on determining risk factors for brain cancer, glioblastoma. They took serum samples up to 22 years prior to glioblastoma diagnosis and compared the metabolite concentrations of serum samples of those that developed the cancer from those that did not. They found significantly higher serum concentration of Vitamin E isoform alpha-tocopherol and gamma-tocopherol in cases that developed glioblastoma. (Bjorkblom B et al, Oncotarget, 2016)
Risk of Vitamin E in Prostate Cancer
A very large Selenium and Vitamin E Cancer Prevention Trial (SELECT) done at 427 sites in the United States, Canada and Puerto Rico on over 35,000 men to assess the risk-benefit of Vitamin E supplementation. This trial was done on men who were 50 years or older and who had low prostate specific antigen (PSA) levels of 4.0 ng/ml or less. Compared to those who did not take Vitamin E supplements (Placebo or reference group), the study found an absolute increase in the risk of prostate cancer in those taking vitamin E supplements. Hence, the supplementation with Vitamin E in the diet/nutrition is associated with an increased risk of prostate cancer among healthy men. (Klein EA et al, JAMA, 2011)
No effect of Vitamin E in Lung Cancer
In the alpha-tocopherol, beta-carotene cancer prevention study done on male smokers over 50 years old, they found no reduction in the incidence of lung cancer after five to eight years of dietary supplementation with alpha-tocopherol. (New Engl J Med, 1994)
Benefit/Risk of Vitamin E in Cancer is linked to individual genetic variation
A recent study analyzed the varying effects of Vitamin E impact on different cancers, and has indicated that the cancer protective effects of Vitamin E sources were different in individuals due to differences in an enzyme that processes Vitamin E in the body. Catechol-o-methyltransferase (COMT) is the enzyme that processes Vitamin E in our body. Each individual can have a specific variant of COMT, with one variant having very high activity of COMT, while the other variant having a low activity and some could have a copy of each and therefore have moderate activity of COMT.
The study found that using excessive Vitamin E sources in individuals with the high activity variant of COMT put them at a disadvantage for a higher cancer risk. In individuals with the lower activity variant of COMT who took Vitamin E supplements, Vitamin E supplementation was beneficial and lowered their risk of cancer by 15% compared to their counterparts with the same low activity COMT variant who did not take the Vitamin E supplement.
Hence, as per this analysis, the variation in Vitamin E cancer preventative effects may be more linked to the genetic makeup of the individual in terms of how Vitamin E is processed in the body. (Hall, KT et al, J National Cancer Inst., 2019) This variation called pharmacogenetics is well known in responses to different drugs based on the genetic variations in individuals. This has now been found for processing of Vitamin E sources and could be relevant for other nutrient sources used in cancer nutrition/diet as well..
The daily recommended dose for Vitamin E is 15 mg. Exceeding this amount can lead to serious side-effects such as increased risk of bleeding and hemorrhagic stroke, besides the above risk factors linked to increased association with prostate cancer and glioblastoma, as reported in clinical studies.
One reason why the excessive Vitamin E antioxidant supplementation can be harmful is because it could disrupt the fine balance of maintaining the right level of oxidative stress in our cellular environment. Too much oxidative stress can cause cell death and degeneration but too little oxidative stress can also interfere with the inherent antioxidant capacity that in turn leads to other consequential changes. One such change is a decrease in a key tumor suppressor gene called P53, that is considered the guardian of the genome, thus increasing the probability of developing cancer. (Sayin VI et al, Sci Transl Med., 2014)
Hence, excessive supplementation of Vitamin E (especially in a diet for your cancer) may be too much of a good thing! It’s best to increase your Vitamin E intake through eating more of the Vitamin E rich food sources rather than through using high dose Vitamin E supplements, unless recommended by your doctor.
Cancer patients often have to deal with different chemotherapy side effects which affect their quality of life and look out for alternative therapies for cancer. Taking the right nutrition and supplements based on scientific considerations (avoiding guesswork and random selection) is the best natural remedy for cancer and treatment related side-effects.