Vitamin E

What Is It?

Vitamin E is a fat-soluble nutrient naturally present in many common household foods$^{1}$. Although vitamin E exists in eight different chemical forms, alpha-Tocopherol is most biologically relevant to us as it is found in higher blood concentrations$^{2,3}$. Therefore, ‘vitamin E’ will specifically refer to ‘alpha-Tocopherol’ throughout this article. As an antioxidant, vitamin E has the potential to reduce levels of reactive oxygen species (ROS), which may be beneficial in conditions where inflammation is an underlying factor, most notably cardiovascular disease and cancer$^{2}$. 

What Are Its Other Names?

Vitamin E, or alpha-Tocopherol, is sometimes referred to as D-alpha-Tocopherol, (+)-alpha-Tocopherol, or RRR-alpha-Tocopherol. However, it is also known as 5,7,8-Trimethyltocol$^{4}$. The IUPAC name for vitamin E is (2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-ol$^{4}$.

What Foods Have It?

Note: The above data was obtained from the U.S. Department of Agriculture FoodData Central$^{5}$. It is important to note that there may be significant variation in vitamin E content based on a diverse range of factors.

What Are Its Main Benefits?

Benefits for Cancer Prevention  Vitamin E has been shown to be effective in scavenging free radicals to protect cells from oxidative damage, which is a significant driver of inflammation (see ‘What Are Its Mechanisms of Action?’ for more details)$^{6}$. This makes vitamin E a potentially effective agent against diseases like cancer. In one systematic review, it was reported that vitamin E supplementation was associated with a reduction in breast cancer risk$^{7}$. While these findings may be promising, it is worth noting that other studies have found no relationship between vitamin E supplementation and other types of cancer$^{8}$. In fact, in some cases, vitamin E supplementation led to an increased risk of certain cancer types instead (see ‘What Are its Main Drawbacks’ for more details).  Benefits for Side-Effects of Cancer Treatment  In addition to reducing the risk of breast cancer, vitamin E supplementation has also been demonstrated to improve the side effects associated with breast cancer treatment, specifically radiation therapy. During the process of radiation therapy, ionizing radiation may damage healthy cells in the vicinity of a tumour, leading to inflammation and an array of side effects like lymphedema (swelling caused by fluid-up) and fibrosis (scarring of soft tissues)$^{9}$. In one randomized controlled trial involving 24 breast cancer patients who had previously undergone radiation therapy, it was reported that the co-administration vitamin E and Pentoxifylline -- a drug commonly prescribed for peripheral artery disease and explored for cancer treatment -- led to a statistically significant reduction in the severity of radiation-induced fibrosis$^{10,11}$. Furthermore, a separate randomized controlled trial in 83 breast cancer patients found that the co-administration of these two compounds was effective in improving radiation-induced side effects$^{12}$. However, given that these studies investigated the effects of vitamin E in combination with Pentoxifylline, these benefits on the side effects of cancer treatment cannot be attributed to vitamin E alone, thus necessitating further investigation. 

What Are Its Main Drawbacks?

Potential Adverse Events While the use of vitamin E supplements is generally safe, several studies investigating its role in cardiovascular disease prevention have found a positive association between vitamin E consumption and haemorrhagic stroke risk$^{13,14}$. Besides haemorrhagic stroke, long-term vitamin E supplementation is also associated with thrombophlebitis, a condition that leads to the formation of blood clots in the veins, usually in the legs$^{15,16}$. Furthermore, the same study also reported that vitamin E may also cause gastrointestinal symptoms, increased blood pressure, and fatigue in some patients, but these findings are not so well characterized$^{17}$.  Possible Drug Interactions  Vitamin E has been reported to interfere with the body’s blood clotting abilities$^{17}$. Therefore, it is important to exercise caution before using anticoagulant drugs, such as warfarin, in combination with vitamin E$^{18}$. 

Potential Cancer-Promoting Effects As discussed in ‘What Are Its Main Benefits: Benefits for Cancer Prevention’, some studies have linked vitamin E supplementation to an increased risk of certain cancers, including prostate and colorectal cancer$^{19,20}$. In a study involving 35,533 healthy male volunteers, it was found that vitamin E was associated with a statistically significant increase in prostate cancer risk$^{19}$. Similarly, a separate randomised controlled trial within the larger Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study found that vitamin E consumption resulted in an increased risk of colorectal adenomas$^{20}$. However, it is important to note that participants in the alpha-Tocopherol group underwent more colonoscopies, potentially leading to a higher detection rate of colorectal adenomas compared to the beta-carotene group$^{20}$. Therefore, while some evidence suggests a potential link between vitamin E and increased cancer risk, further research is still needed to fully understand this relationship. Overall, it is important to speak with a healthcare provider to understand the suitability of vitamin E supplementation for your individual needs.

What Are Its Mechanisms of Action?

1. Reduction of Oxidative Stress: Oxidative stress, characterized by the imbalance of reactive oxygen species (ROS), is a key driver of inflammation and cancer$^{21}$. Vitamin E has been shown to possess powerful antioxidant properties as it is able to neutralize ROS and thus terminate free radical chain reactions$^{3,6}$. Additionally, vitamin E can indirectly reduce oxidative stress by activating NF-E2-related Factor 2 (Nrf2) which mediates the transcription of antioxidant proteins$^{3,22}$. The accumulation of ROS has detrimental consequences to cells as it can lead to DNA damage and consequently, cancer$^{23}$. Vitamin E’s twofold nature as a direct and indirect antioxidant thus renders it potentially useful in the fight against cancer.
2. Inhibition of PI3K/Akt Pathway: Beyond oxidative stress, vitamin E has also been shown to suppress the PI3K/Akt pathway which promotes cellular proliferation and cell survival$^{3,24}$. Vitamin E accomplishes this by activating an important tumour suppressor known as protein phosphatase 2A (PP2A), which deactivates the Akt protein, consequently terminating PI3K/Akt signalling$^{3,25}$. This has beneficial effects in cancer prevention because sustained proliferative signalling is an important hallmark of cancer cells$^{26}$.
3. Induction of Apoptosis: Vitamin E supplementation has also been reported to upregulate tumour necrosis factors (TNF), namely TNF-α and TNF-β$^{27}$. TNF exerts its anticancer activities by activating the c-Jun N-terminal kinase (JNK) which leads to cell death$^{28}$. However, it is important to highlight that TNF can also activate a contrasting pathway that drives cancer development, known as the Nuclear Factor Kappa-B (NF-κB) pathway$^{28}$. Therefore, more investigation is needed to characterize the relationship between vitamin E consumption and the induction of apoptosis. 

What Are Typical Doses and Durations?

Dosage

Clinical studies investigating the role of vitamin E in cancer prevention have employed a range of treatment doses. Across all studies, vitamin E was administered orally, either as capsules, powder or in the form of vitamin E-containing foods like vegetable juices and walnuts$^{29-32}$. Studies that administered vitamin E in the form of capsules typically expressed doses as mg/day or IU, with doses ranging from 50 mg/day to 300 mg/day, or 400 IU to 800 IU$^{29,33-35}$. Meanwhile, there were also studies that investigated the association between natural vitamin E intake and cancer prevention, in which case the subjects’ natural dietary intakes was assessed and no treatment dose was administered$^{36}$.  Duration The treatment duration for most clinical studies examining the anticancer effects of vitamin E were highly varied, lasting anywhere between several weeks to several years$^{30,37}$. Studies that lasted a few weeks to months typically explored the effects of vitamin E in combination with chemotherapy$^{33}$. There were also a number of studies that lasted a period of a few years with a follow-up, and these studies typically looked at the effect of a vitamin E-rich diet on cancer prevention$^{38}$. 

Summary of Data

Summary of clinical trials that administered alpha-Tocopherol on its own. A total of 3 studies that fit this criteria were identified from the PubMed database:

Summary of clinical trials that examined the anticancer effects of alpha-Tocopherol as part of a multivitamin or multi-antioxidant supplement. A total of 7 studies that fit this criteria were identified from the PubMed database:

Summary of clinical trials that administered alpha-Tocopherol as an adjuvant to cancer treatment. A total of 4 studies that fit this criteria were identified from the PubMed database:

Summary of results that examined the effects of alpha-Tocopherol as part of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study. A total of 15 studies that fit this criteria were identified from the PubMed database:

Below are links to detailed alpha-Tocopherol human clinical trial study notes analyzed by Anticancer.ca.

📄 Detailed alpha-Tocopherol (administered alone) human clinical trial study notes analyzed by Anticancer.ca

📄 Detailed alpha-Tocopherol (as a multivitamin or multi-antioxidant supplement) human clinical trial study notes analyzed by Anticancer.ca

📄 Detailed alpha-Tocopherol (as an adjuvant to cancer treatment) human clinical trial study notes analyzed by Anticancer.ca

📄 Detailed alpha-Tocopherol (as part of ATBC study) human clinical trial study notes analyzed by Anticancer.ca

References

1. Vitamin E: Overview, uses, side effects, precautions, interactions, dosing and reviews. WebMD Available at: https://www.webmd.com/vitamins/ai/ingredientmono-954/vitamin-e. (Accessed: 2nd December 2024)
2. Office of dietary supplements - vitamin E. NIH Office of Dietary Supplements Available at: https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/. (Accessed: 2nd December 2024)
3. Ju, J. et al. Cancer-preventive activities of Tocopherols and Tocotrienols. Carcinogenesis 31, 533–542 (2009).
4. Alpha-Tocopherol. National Center for Biotechnology Information. PubChem Compound Database Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Alpha-Tocopherol#section=Depositor-Supplied-Synonyms. (Accessed: 2nd December 2024)
5. FoodData Central. U.S. Department of Agriculture. Available at: https://fdc.nal.usda.gov/fdc-app.html#/?component=1122 (Accessed: 2nd December 2024)
6. Xin, J. et al. Association between circulating vitamin E and ten common cancers: Evidence from large-scale Mendelian randomization analysis and a longitudinal cohort study. BMC Medicine 20, (2022).
7. de Oliveira, V. A. et al. Consumption and supplementation of vitamin E in breast cancer risk, treatment, and outcomes: A systematic review with meta-analysis. Clinical Nutrition ESPEN 54, 215–226 (2023).
8. Wang, L. et al. Vitamin E and C supplementation and risk of cancer in men: Posttrial follow-up in the physicians’ health study II randomized trial. The American Journal of Clinical Nutrition 100, 915–923 (2014).
9. Canadian Cancer Society / Société canadienne du cancer. Side effects of radiation therapy. Canadian Cancer Society Available at: https://cancer.ca/en/treatments/treatment-types/radiation-therapy/side-effects-of-radiation-therapy. (Accessed: 18th January 2025)
10. Nieder, C., Zimmermann, F. B., Adam, M. & Molls, M. The role of Pentoxifylline as a modifier of radiation therapy. Cancer Treatment Reviews 31, 448–455 (2005).
11. Delanian, S., Porcher, R., Balla-Mekias, S. & Lefaix, J.-L. Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis. Journal of Clinical Oncology 21, 2545–2550 (2003).
12. Magnusson, M. et al. Pentoxifylline and vitamin E treatment for prevention of radiation-induced side-effects in women with breast cancer: A phase Two, double-blind, placebo-controlled randomised clinical trial (PTX-5). European Journal of Cancer 45, 2488–2495 (2009).
13. Sesso, H. D. Vitamins E and C in the prevention of cardiovascular disease in men. JAMA 300, 2123 (2008).
14. Pastori, D. et al. Vitamin E serum levels and bleeding risk in patients receiving oral anticoagulant therapy: A retrospective cohort study. Journal of the American Heart Association 2, (2013).
15. Roberts, H. J. Thrombophlebitis associated with vitamin E therapy. Angiology 30, 169–177 (1979).
16. Thrombophlebitis. Mayo Clinic Available at: https://www.mayoclinic.org/diseases-conditions/thrombophlebitis/symptoms-causes/syc-20354607. (Accessed: 18th January 2025)
17. Roberts, H. J. Thrombophlebitis associated with vitamin E therapy. Angiology 30, 169–177 (1979).
18. Vitamin E. Memorial Sloan Kettering Cancer Center Available at: https://www.mskcc.org/cancer-care/integrative-medicine/herbs/vitamin-e#references-1. (Accessed: 18th January 2025)
19. Klein, E. A. et al. Vitamin E and the risk of prostate cancer. JAMA 306, 1549 (2011).
20. Malila, N. et al. The effect of alpha-tocopherol and beta-carotene supplementation on colorectal adenomas in middle-aged male smokers. Cancer Epidemiology, Biomarkers & Prevention 6, 489–493 (1999).
21. Hussain, T. et al. Oxidative stress and inflammation: What polyphenols can do for us? Oxidative Medicine and Cellular Longevity 2016, (2016).
22. Shelton, P. & Jaiswal, A. K. The transcription factor nf‐e2‐related factor 2 (NRF2): A Protooncogene? The FASEB Journal 27, 414–423 (2012).
23. Auten, R. L. & Davis, J. M. Oxygen toxicity and reactive oxygen species: The Devil is in the details. Pediatric Research 66, 121–127 (2009).
24. Glaviano, A. et al. PI3K/AKT/mtor signaling transduction pathway and targeted therapies in cancer. Molecular Cancer 22, (2023).
25. Nadel, G. et al. GqPCR-stimulated dephosphorylation of AKT is induced by an IGBP1-mediated PP2A switch. Cell Communication and Signaling 20, (2022).
26. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: The next generation. Cell 144, 646–674 (2011).
27. Tucker, J. M. & Townsend, D. M. Alpha-tocopherol: Roles in prevention and therapy of human disease. Biomedicine & Pharmacotherapy 59, 380–387 (2005).
28. Wang, X. & Lin, Y. Tumor necrosis factor and cancer, buddies or foes? Acta Pharmacologica Sinica 29, 1275–1288 (2008).
29. Mooney, L. A. et al. Antioxidant vitamin supplementation reduces benzo(a)pyrene-DNA adducts and potential cancer risk in female smokers. Cancer Epidemiology, Biomarkers & Prevention 14, 237–242 (2005).
30. The alpha-tocopherol, beta-carotene lung cancer prevention study: Design, methods, participant characteristics, and compliance. Annals of Epidemiology 4, 1–10 (1994).
31. Rock, C.L. et al. Responsiveness of carotenoids to a high vegetable diet intervention designed to prevent breast cancer recurrence. Cancer Epidemiology, Biomarkers & Prevention 8, 617-23 (1997).
32. Spaccarotella, K. J. et al. The effect of walnut intake on factors related to prostate and vascular health in older men. Nutrition Journal 7, (2008).
33. Misirlioglu, C. H., Demirkasimoglu, T., Kucukplakci, B., Sanri, E. & Altundag, K. Pentoxifylline and alpha-tocopherol in prevention of radiation-induced lung toxicity in patients with lung cancer. Medical Oncology 24, 308–311 (2007).
34. Goodman, M.T. et al. Effects of beta-carotene and alpha-tocopherol on bleomycin-induced chromosomal damage. Cancer Epidemiology, Biomarkers & Prevention 2, 113-7 (1998).
35. Tam, L.S. et al. Effects of vitamins C and E on oxidative stress markers and endothelial function in patients with systemic lupus erythematosus: a double blind, placebo controlled pilot study. Journal of Rheumatology 2, 275-82 (2005).
36. Nouraie, M. et al. Fruits, vegetables, and antioxidants and risk of gastric cancer among male smokers. Cancer Epidemiology, Biomarkers & Prevention 14, 2087–2092 (2005).
37. Chitra, S. & Shyamaladevi, C. S. Modulatory action of α-tocopherol on erythrocyte membrane adenosine triphosphatase against radiation damage in oral cancer. The Journal of Membrane Biology 240, 83–88 (2011).
38. Malila, N. et al. Dietary and serum α-tocopherol, β-carotene and retinol, and risk for colorectal cancer in male smokers. European Journal of Clinical Nutrition 56, 615–621 (2002).

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• Vitamin E
• What Is It?
• What Are Its Other Names?
• What Foods Have It?
• What Are Its Main Benefits?
• What Are Its Main Drawbacks?
• What Are Its Mechanisms of Action?
• What Are Typical Doses and Durations?
• Summary of Data
• References
• About This Article
• Disclaimer