Vitamin E is a fat-soluble vitamin with several forms, but alpha-tocopherol is the only one used by the human body. Its main role is to act as an antioxidant, scavenging loose electrons—so-called “free radicals”—that can damage cells. The DV for vitamin E is 15 mg for adults (22 IU daily).
90 percent of Americans have diets that contain less than the recommended intake of vitamin E.
Natural vs. Synthetic Vitamin E
Alpha-tocopherol is the most biologically active form of vitamin E, and its natural form consists of one isomer. In contrast, synthetic alpha-tocopherol contains eight different isomers, of which only one (about 12 percent of the synthetic molecule) is identical to natural vitamin E. The other seven isomers range in potency from 21 percent to 90 percent of natural d-alpha-tocopherol.
Synthetic Vitamin E
dl-α-Tocopheryl acetate
dl-α-Tocopheryl succinate
dl-α-Tocopherol
Natural Vitamin E
d-α-Tocopheryl acetate
d-α-Tocopheryl succinate
d-α-Tocopherol
Vitamin E is added to supplements, multivitamins, breakfast cereals, fruit juices, foods, cosmetic products, and sunscreen often in the form of α-tocopherol, which could be synthetic or natural, and it's often synthetic unless the label states it is a natural form of vitamin E or is labeled as d-α-Tocopherol.
Tocopherols and Tocotrienols
There are many different types of Vitamin E in the form of tocopherols and tocotrienols. Tocotrienols differ from tocopherols in that they have an unsaturated side chain. The various forms of vitamin E are not interconvertible in humans and do not behave the same metabolically.
alpha (α)-, beta (β)-, gamma(γ)-, and delta(δ)-tocopherol.
alpha (α)-, beta (β)-, gamma(γ)-, and delta(δ)-tocotrienol.
Vitamin E acetate and succinate
Alpha-tocopheryl acetate (αTOL or αTOA)
Alpha-tocopheryl succinate (αTOS): obtained by the esterification of αTOL, is a more stable powder form of αTOL, since the succinate group protects.
Despite their similar chemical structures, αTOS differs in activity from αTOL.
For example, αTOS is redox-insensitive prior to being cleaved to αTOL by esterases. In contrast to αTOL, αTOS induces growth suppression, cell cycle arrest, and/or apoptosis in a wide range of cancer cells.
Alpha-tocopheryl succinate, in contrast to alpha-tocopherol and alpha-tocopheryl acetate, inhibits prostaglandin E.{ref}
Studies on Vitamin E and cancer
Vitamin E promotes breast cancer cell proliferation by reducing ROS production and p53 expression
https://pubmed.ncbi.nlm.nih.gov/27383327
Antioxidants accelerate lung cancer progression in mice
https://pubmed.ncbi.nlm.nih.gov/24477002/
"NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect. Thus, antioxidants accelerate tumor growth by disrupting the ROS-p53 axis."
Vitamin E intake and the lung cancer risk among female nonsmokers: a report from the Shanghai Women’s Health Study.
" We prospectively investigated the associations between tocopherol intake from diet and from supplements with lung cancer risk among 72,829 Chinese female nonsmokers aged 40-70 years and participating in the Shanghai Women’s Health Study (SWHS)"
"After 12.02 years of follow-up, 481 women were diagnosed with lung cancer. Total dietary tocopherol was inversely associated with lung cancer risk among women meeting dietary guidelines for adequate intake (AI) of tocopherol (14 mg/day or more: HR: 0.78; 95% CI 0.60-0.99; compared to the category less than AI). The protective association between dietary tocopherol intake and lung cancer was restricted to women exposed to side-stream smoke in the home and workplace (HR=0.53 (0.29-0.97), p-trend = 0.04). In contrast, vitamin E supplement use was associated with increased lung cancer risk (HR: 1.33; 95% CI 1.01-1.73), more so for lung adenocarcinoma risk (HR: 1.79; 95% CI 1.23-2.60). In summary, dietary tocopherol intake may reduce the risk of lung cancer among female non-smokers, however supplements may increase lung adenocarcinoma risk and requires further investigation."
Vitamin E is a complete tumor promoter in mouse skin
https://academic.oup.com/carcin/article-abstract/14/4/659/278071
Nrf2 Activation Promotes Lung Cancer Metastasis by Inhibiting the Degradation of Bach1
https://www.cell.com/cell/fulltext/S0092-8674(19)30631-2
BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis
https://www.cell.com/cell/fulltext/S0092-8674(19)30633-6
"Vitamin E promotes KRAS-driven lung cancer metastasis"
Vitamin E Update: Gamma-tocopherol, Not Alpha-tocopherol, Inhibits Cancer Cell Growth
https://www.rejuvenation-science.com/research-news/vitamin-e/n-vitamin-e-alpha-gamma-cancer
γ-Tocotrienol-induced endoplasmic reticulum stress and autophagy act concurrently to promote breast cancer cell death
https://cdnsciencepub.com/doi/10.1139/bcb-2014-0123
"In summary, these finding demonstrate that γ-tocotrienol-induced ER stress and autophagy occur concurrently, and together act to promote human breast cancer cell death."
Tocotrienols Modulate Breast Cancer Secretomes and Affect Cancer-Signaling Pathways in MDA-MB-231 Cells: A Label-Free Quantitative Proteomic Analysis
https://www.tandfonline.com/doi/abs/10.1080/01635581.2019.1607407
Note, the mechanism of action is the induction of autophagy.
Effect of tocotrienols on the growth of a human breast cancer cell line in culture
https://link.springer.com/article/10.1007/BF02536615
"The tocotrienol-rich fraction (TRF) of palm oil consists of tocotrienols and some α-tocopherol (α-T). Tocotrienols are a form of vitamin E having an unsaturated side-chain, rather than the saturated side-chain of the more common tocopherols. Because palm oil has been shown not to promote chemically-induced mammary carcinogenesis, we tested effects of TRF and α-T on the proliferation, growth, and plating efficiency (PE) of MDA-MB-435 estrogen-receptor-negative human breast cancer cells. TRF inhibited the proliferation of these cells with a concentration required to inhibit cell proliferation by 50% of 180 μg/mL, whereas α-T had no effect at concentrations up to 1000 μg/mL as measured by incorporation of [3H]thymidine. The effects of TRF and α-T also were tested in longer-term growth experiments, using concentrations of 180 and 500 μg/mL. We found that TRF inhibited the growth of these cells by 50%, whereas α-T did not. Their effect on the ability of these cells to form colonies also was studied, and it was found that TRF inhibited PE, whereas α-T had no effect. These results suggest that the inhibition is due to the presence of tocotrienols in TRF rather than α-T."
Palm tocotrienols cause cleavage of poly-(ADP)-ribose polymerase enzyme and down-regulation of cyclooxygenase-2 protein level in human breast cancer cells
Vitamin E Succinate Promotes Breast Cancer Tumor Dormancy
https://www.sciencedirect.com/science/article/abs/pii/S0022480400959481
"Conclusions. VES inhibits the growth of breast cancer cells in vitro and in vivo. This is the first report of VES inhibition of established tumor growth in vivo. The mechanism of VES's in vivo effects may involve inhibition of tumor angiogenesis since VES inhibits VEGF gene expression."
Synergies
Synergistic anticancer effects of combined γ-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFκB signaling
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878915/
"These results demonstrate that combined treatment with low doses of γ-tocotrienol and celecoxib synergistically inhibited the growth of highly malignant +SA mammary epithelial cells in culture."
"Combined treatment with 0.25 μM γ-tocotrienol (subeffective dose) and 2.5–20 μM celecoxib, or combined treatment with 2.5 μM celecoxib (subeffective dose) and 0.25–2.0 μM γ-tocotrienol caused a greater reduction in +SA cell growth as compared to cells treated with corresponding doses of γ-tocotrienol or celecoxib alone. Additional studies showed that the synergistic antiproliferative effects of these combined treatments were associated with reduction in COX-2, but not COX-1 levels, and a corresponding suppression in PGE2 synthesis and decrease in Akt and NFκB activation."
γ-Tocotrienol upregulates aryl hydrocarbon receptor expression and enhances the anticancer effect of baicalein
https://pubmed.ncbi.nlm.nih.gov/27055589/
"The co-treatment with γ-T3 and baicalein enhanced the anti-proliferative activity of baicalein, accompanied by the downstream events of AhR-activation induced by baicalein. These data suggest that γ-T3 upregulates AhR expression and enhances its sensitivity to baicalein."
Synergistic inhibition of cancer cell proliferation with a combination of δ-tocotrienol and ferulic acid
https://pubmed.ncbi.nlm.nih.gov/25285637/
"We investigated the synergistic inhibitory effects of its components, particularly δ-tocotrienol (δ-T3) and ferulic acid (FA), against the proliferation of an array of cancer cells, including DU-145 (prostate cancer), MCF-7 (breast cancer), and PANC-1 (pancreatic cancer) cells. The combination of δ-T3 and FA markedly reduced cell proliferation relative to δ-T3 alone, and FA had no effect when used alone. Although δ-T3 induced G1 arrest by up-regulating p21 in PANC-1 cells, more cells accumulated in G1 phase with the combination of δ-T3 and FA. This synergistic effect was attributed to an increase in the cellular concentration of δ-T3 by FA. "
α-Tocopherol succinate enhances pterostilbene anti-tumor activity in human breast cancer cells in vivo and in vitro
https://www.oncotarget.com/article/23390/text/
Tocotrienol combination therapy results in synergistic anticancer response