What does science say about the controversial role of Vitamin E??
Vitamin E is a fat-soluble vitamin which is carried in chylomicrons and LDL cholesterol to tissues. It was discovered that inhibition of this vitamin caused the abortion of rat offspring and decreased sperm motility. It was named Tocopherol and found to be a series of chemicals including tocopherol and tocotrienol with alpha, beta, gamma and delta (decreasing in order of potency) subgroups. There is also a synthetic form of all-rac-alpha-tocopherol. Some forms of vitamin E have been found to have antioxidant properties and are thought to have a protective effect against various diseases, including cancer, cardiovascular disease, and Alzheimer’s disease. However, trials with vitamin E supplementation for cancer and disease treatments have mainly been inconclusive and some studies have suggested that vitamin E supplementation may be ineffective or even harmful in certain populations. Due to much controversy surrounding the precise role of this vitamin on health, more research is needed to evaluate its precise role and therapeutic potential (Brigelius-Flohé, 2021).
The role of vitamin E in the prevention of disease has been a topic of scientific debate for many years. This is because there are 8 different species of the vitamin, some of which go into tissues and some do not, there is the synthetic and natural form, the conversion of the vitamin, and the level of degradation or conjugation, all of which are confounders in the roles of vitamin E and its application. It is mainly found in the diet in Wheat germ oil, Sunflower seeds, Almonds, Peanut butter, Olive oil, Spinach, Broccoli and kiwifruit.
One of the earliest studies to investigate the potential health benefits of vitamin E was the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) trial (Ahn et al., 2008), which was conducted in Finland in the 1990s. Strengths of this study are the size of the study and that it was a double-blinded, placebo-randomised controlled trial with high adherence (90% of participants took their prescribed supplement). Weaknesses are that it only used unhealthy participants and that there was a lack of diversity in the study as it was the trial enrolled primarily white men, which limits the generalizability of the results to other racial or ethnic groups. The study involved over 29,000 male smokers and found that supplementation with vitamin E reduced the risk of prostate cancer by RR:1.32 and lung cancer by RR:1.23. However, the study also found that vitamin E supplementation increased the risk of hemorrhagic stroke by RR:1.22.
More recently there was the Prevention SELECT (Selenium and Vitamin E Cancer Trial) (Klein et al., 2011) study. This involved over 35,000 men (a strength of the study being the cohort size and that it was a randomized controlled trial with a control group and was conducted over a long time period in one geographic location (so the control group was matched to minimize confounding) with a high adherence rate of 80% in participants) in the United States, found that supplementation with vitamin E did not reduce the risk of prostate cancer and may even increase the risk of prostate cancer in some men. The trial found that participants who received vitamin E supplements had a slightly higher risk of developing prostate cancer, as well as a slightly higher risk of developing diabetes. This highlights the potential risks associated with high-dose vitamin E supplementation. Weaknesses of the study are that it was only in men over 50 with no history of prostate cancer and so the findings may not be populationally representative for those of other sexes, ages or racial and ethnic groups. The study also found that vitamin E supplementation did not reduce the risk of other types of cancer or cardiovascular disease.
The CHOAS, (Stephens et al., 1996) or Cambridge Heart Antioxidant Study was a randomized controlled trial conducted in the United Kingdom to investigate the effects of vitamin E supplementation on cardiovascular disease (CVD) outcomes in patients with coronary artery disease. The trial enrolled over 2,000 patients and was conducted from 1993 to 1999. This found that patients who received 400 IU/day of vitamin E had a significantly lower risk of non-fatal myocardial infarction (heart attack) and cardiovascular death compared to patients who received a placebo. However, there was no significant difference between the groups in the incidence of overall cardiovascular events or all-cause mortality. Strengths of this study are that it was a randomized control trial with double-blinding, with over 2000 participants and a long duration. Cons of the study are that it enrolled only patients with coronary artery disease, which limits the generalizability of the results to other populations, such as healthy individuals or patients with other types of CVD. It also used a very high dose of Vitamin E which may not represent the true impact of vitamin E on health.
In addition to these studies, several meta-analyses have been conducted to evaluate the overall evidence for the health benefits of vitamin E (Lee et al., 2005) Another meta-analysis published in the Cochrane Database of Systematic Reviews in 2012 found that vitamin E supplementation did not reduce the risk of Alzheimer’s disease or cognitive decline (Farina et al., 2017).
Despite the conflicting evidence, some studies have suggested that vitamin E may still have a role in the prevention of disease. For example, a study published in the (Jenkins et al., 2018) Journal of the American College of Cardiology in 2018 found that vitamin E supplementation reduced the risk of cardiovascular disease in women with diabetes.
In conclusion, the role of vitamin E in the prevention of disease is still a topic of scientific debate (Brigelius-Flohé, 2021). While some studies have suggested that vitamin E supplementation may be beneficial in reducing the risk of certain diseases, other studies have found no evidence of health benefits or even potential harm. What is clear is that there are many confounding factors impacting the role of this key vitamin linked to the form of vitamin E you take (whether tocopherol or tocotrienol or alpha, beta, gamma or delta form or synthetic all-rac-alpha tocopherol), the dosage, how it is absorbed (whether you absorb it with enough chylomicrons or LDL cholesterol), the individual health status, age, sex and ethnicity of the person who absorbs it, and the desired health come from its application. With research showing potential links for the treatment of pre-eclampsia, cancer, delaying ageing, neuropathy, myopathy and steatitis (inflammation of fat tissue), there is a huge therapeutic potential for this vitamin.
Copyright Laura Campbell 08/04/2023 (written as a masters report essay and converted into article)
Ahn, J., Moslehi, R., Weinstein, S. J., Snyder, K., Virtamo, J., & Albanes, D. (2008). Family history of prostate cancer and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Int J Cancer, 123(5), 1154–1159. https://doi.org/10.1002/ijc.23591
Brigelius-Flohé, R. (2021). Vitamin E research: Past, now and future. Free Radic Biol Med, 177, 381–390. https://doi.org/10.1016/j.freeradbiomed.2021.10.029
Farina, N., Llewellyn, D., Isaac, M. G., & Tabet, N. (2017). Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database Syst Rev, 1(1), Cd002854. https://doi.org/10.1002/14651858.CD002854.pub4
Jenkins, D. J. A., Spence, J. D., Giovannucci, E. L., Kim, Y.-i., Josse, R., Vieth, R., Mejia, S. B., Viguiliouk, E., Nishi, S., Sahye-Pudaruth, S., Paquette, M., Patel, D., Mitchell, S., Kavanagh, M., Tsirakis, T., Bachiri, L., Maran, A., Umatheva, N., McKay, T., . . . Sievenpiper, J. L. (2018). Supplemental Vitamins and Minerals for CVD Prevention and Treatment. Journal of the American College of Cardiology, 71(22), 2570–2584. https://doi.org/doi:10.1016/j.jacc.2018.04.020
Klein, E. A., Thompson, I. M., Jr., Tangen, C. M., Crowley, J. J., Lucia, M. S., Goodman, P. J., Minasian, L. M., Ford, L. G., Parnes, H. L., Gaziano, J. M., Karp, D. D., Lieber, M. M., Walther, P. J., Klotz, L., Parsons, J. K., Chin, J. L., Darke, A. K., Lippman, S. M., Goodman, G. E., . . . Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Jama, 306(14), 1549–1556. https://doi.org/10.1001/jama.2011.1437
Lee, I.-M., Cook, N. R., Gaziano, J. M., Gordon, D., Ridker, P. M., Manson, J. E., Hennekens, C. H., & Buring, J. E. (2005). Vitamin E in the Primary Prevention of Cardiovascular Disease and CancerThe Women’s Health Study: A Randomized Controlled Trial. Jama, 294(1), 56–65. https://doi.org/10.1001/jama.294.1.56
Stephens, N. G., Parsons, A., Schofield, P. M., Kelly, F., Cheeseman, K., & Mitchinson, M. J. (1996). Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet, 347(9004), 781–786. https://doi.org/10.1016/s0140-6736(96)90866-1