Are You Getting Enough of These Key Nutrients for Cancer Prevention?

Vitamin D

The primary source of vitamin D is sun exposure. After entering our body, vitamin D converts to 25-hydroxy-vitamin D (calcidiol) in the liver and then to its active form, 1,25-dihydroxy-vitamin D (calcitriol) in the kidneys. Vitamin D is well known for its crucial function in bone health. We are now also recognizing its other roles in human health, such as increasing intestinal calcium absorption and regulating cellular growth. Studies also have shown an association between higher blood levels of 25-hydroxy-vitamin D and reduced risk of various cancers, such as colon, breast, prostate, and ovarian cancer (Garland et al., 2006).

So, what are the mechanisms here? Vitamin D and its metabolites have been shown to inhibit tumor angiogenesis, stimulate mutual adherence of cells, and enhance intercellular communication, thereby strengthening the inhibition of proliferation. Vitamin D metabolites can help maintain a normal calcium gradient in the colon epithelial crypts. High serum levels of 25(OH)D are associated with decreased proliferation of noncancerous but high-risk epithelial cells in the colon. 1,25(OH)2D inhibits mitosis of breast epithelial cells. Moreover, 1,25(OH)2D enhances the pulsatile release of ionized calcium from intracellular stores that induces terminal differentiation and apoptosis.

Considering vitamin D deficiency is prevalent due to insufficient sun exposure and limited food sources, I highly recommend oral vitamin D3 supplementation. The dosage must be individualized based on marker 25(OH)D serum level. The National Academy recommends a daily vitamin D intake of 400 to 800 IU with a tolerable upper intake level of 1000 to 4000 IU daily, depending on age from birth to > 70. Depending on the serum 25(OH)D levels, a higher dosage often is needed.

Serum concentrations of 25(OH)D associated with deficiency haven't been identified. However, an expert committee of the Food and Nutrition Board at the National Academies concluded that serum 25(OH)D concentrations < 30 nmol/L indicate vitamin D deficiency. Levels of 50 nmol/L or more are generally sufficient. However, a level of > 75 nmol/L may be necessary for clinical practice to optimize vitamin D's beneficial health effect on bone, calcium, and muscle metabolism (Vitamin D - Health Professional Fact Sheet, n.d.). Foods rich in vitamin D include cod liver oil, trout, salmon, mushroom, vitamin D-fortified milk, etc.

Selenium

Selenium (Se), as an essential trace element, plays a role in many critical biological processes, including thyroid function, redox signaling, immune function, detoxification, and antioxidant activity. These effects are primarily mediated by over 25 encoded selenoproteins, with glutathione peroxidases (involved in antioxidant action and sperm motility) and thioredoxin reductases (involved in intracellular redox regulation and signaling) being the most studied. Se has multiple immune-stimulant effects, from increasing activated T-cells and natural killer cell activity to enhancing lymphocyte-mediated tumor cytotoxicity. It affects cellular processes and molecular pathways involved in the anti-cancer and antitumor effects (EVANS et al., 2017). However, there is a challenge with using Se for cancer patients in conjunction with chemo and radiotherapy, which is to identify the balance between mitigating treatment-induced tissue toxicities and compromising chemo-radiation therapy's antitumor effects. The optimal form and dose of Se to go along with chemotherapy or radiotherapy remain unclear. 

Animal studies have shown that the organic forms of Se, such as Se-methyl-selenocysteine and L-selenomethionine, are more effective and safer than the inorganic forms, such as sodium selenite, which are more genotoxic. The RDA recommendation for Se's daily intake set by National Academies ranges from 15 to 70 mcg, depending on age, mainly to prevent deficiency. The tolerable upper intake level is 45 to 400 mcg daily, depending on age. Selenium can be obtained from foods such as Brazil nuts. Consuming 2-4 Brazil nuts daily should provide sufficient selenium the body requires.

Vitamin E

Vitamin E is a group of fat-soluble antioxidants. There are different forms of vitamin E, including α-tocopherols (αT), being the primary dietary source, and other lesser-known forms such as γ-tocopherol (γT), δ-tocopherol (δT), γ-tocotrienol (γT3), and δ-tocotrienol (δT3).

Even though αT supplementation has been predominant, it failed to show cancer-preventive effects in clinical studies and was reported to increase prostate cancer risk. Accumulating preclinical studies suggest that the forms of vitamin E are critically important factors for cancer prevention. Mechanistic and cell-based studies have shown that compared to αT, the lesser-known forms (γT, δT, γT3, and δT3) have a much more potent effect in blocking cancer-promoting pathways, inhibiting cancer cell proliferation, and inducing cancer cell apoptosis. These forms of vitamin E are readily metabolized and have more potent anti-inflammatory and anti-cancer effects than unmetabolized versions.

The effectiveness of vitamin E also depends on the stage and severity of tumorigenesis. γT, δT, and a mixture of tocopherols with 59.3% γ-T, 25.4% δ-T, 13.5% α-T and 1.6% β-T (γTmTs) have been shown to be effective in preventing early-stage cancer progression but only provide modest protection of more aggressive and advanced stages of cancer. Studies suggest that γT, δT, and γTmTs significantly suppress tumorigenesis if the intervention starts before initiating carcinogenesis. Contrarily, they seemed less effective if supplementation was commenced after the cancer had progressed (Yang et al., 2020).

The RDA for daily vitamin E intake defined by National Academies ranges from 4 – 19 mcg in the form of αT, depending on age from birth to > 70. However, recent clinical studies show that vitamin E tocotrienol isomers are superior to tocopherols. In human studies involving pancreatic cancer patients and healthy volunteers, δT3 at 100 to 3200 mg per day for two weeks did not show side effects. The tolerable upper intake level is 0 to 1000 mg daily, depending on age from birth to > 70. Foods rich in vitamin E include sunflower seeds, wheat germ oil, almonds, and other nuts.

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References:

EVANS, S. O., KHAIRUDDIN, P. F., & JAMESON, M. B. (2017). Optimising Selenium for Modulation of Cancer Treatments. Anti-cancer Research, 37(12).

Garland, C. F., Garland, F. C., Gorham, E. D., Lipkin, M., Newmark, H., Mohr, S. B., & Holick, M. F. (2006). The Role of Vitamin D in Cancer Prevention. American Journal of Public Health, 96(2), 252. https://doi.org/10.2105/AJPH.2004.045260

Vitamin D - Health Professional Fact Sheet. (n.d.). Retrieved October 11, 2022, from https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

Yang, C. S., Luo, P., Zeng, Z., Wang, H., Malafa, M., & Suh, N. (2020). Vitamin E and Cancer Prevention: Studies with different forms of tocopherols and tocotrienols. Molecular Carcinogenesis, 59(4), 365. https://doi.org/10.1002/MC.23160