Agnieszka Marosz, Dariusz Chlubek


The article presents the results of studies on potential risks associated with the abuse of vitamin supplements which until recently had been considered not only highly efficacious, but also completely safe. Particular consideration is given to vitamins A, E, D and C. The necessity to control the intake of vitamin supplements and even to strictly supervise the supply to high risk patients is highlighted.


vitamin supplements; vitamin A; vitamin C; vitamin D; vitamin E

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Peto R., Doll R., Buckley J.D., Sporn M.B.: Can dietary beta‑carotene materially reduce human cancer rates? Nature. 1981, 290 (5803), 201–208.

Graham S.: Diet and cancer. Am J Epidemiol. 1980, 112 (2), 247–252.

Lippman S.M., Benner S.E., Hong W.K.: Retinoid chemoprevention studies in upper aerodigestive tract and lung carcinogenesis. Cancer Res. 1994, 54, Suppl. 7, 2025–2028.

Greenberg E.R., Baron J.A., Stukel T.A., Stevens M.M., Mandel J.S., Spencer S.K. et al.: A clinical trial of beta carotene to prevent basal‑cell and squamous‑cell cancers of the skin. The Skin Cancer Prevention Study Group. N Engl J Med. 1990, 323 (12), 789–795.

Omenn G.S., Goodman G.E., Thornquist M.D., Balmes J., Cullen M.R., Glass A. et al.: Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996, 334 (18), 1150–1155.

Michaud D.S., Feskanich D., Rimm E.B., Colditz G.A., Speizer F.E., Willett W.C. et al.: Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts. Am J Clin Nutr. 2000, 72, 990–997.

Palozza P., Serini S., Trombino S., Lauriola L., Ranelletti F.O., Calviello G.: Dual role of β‑carotene in combination with cigarette smoke aqueous extract on the formation of mutagenic lipid peroxidation products in lung membranes: dependence on pO2. Carcinogenesis. 2006, 27, 2383–2391.

Krinsky N.I., Johnson E.J.: Carotenoid actions and their relation to health and disease. Mol Aspects Med. 2005, 26, 459–516.

Wertz K., Siler U., Goralczyk R.: Lycopene: modes of action to promote prostate health. Arch Biochem Biophys. 2004, 430, 127–134.

Rao A.V., Ray M.R., Rao L.G.: Lycopene. Adv Food Nutr Res. 2006, 51, 99–164.

Albanes D., Heinonen O.P., Huttunen J.K., Taylor P.R., Virtamo J., Edwards B.K. et al.: Effects of alpha‑tocopherol and beta‑carotene supplements on cancer incidence in the alpha‑tocopherol beta‑carotene cancer prevention study. Am J Clin Nutr. 1995, 62, Suppl. 6, 1427–1430.

Arora A., Willhite C.A., Liebler D.C.: Interactions of β‑carotene and cigarette smoke in human bronchial epithelial cells. Carcinogenesis. 2001, 22, 1173–1178.

Liu C., Russell R.M., Wang X.D.: Exposing ferrets to cigarette smoke and a pharmaco‑logical dose of β‑carotene supplementation enhance in vitro retinoic acid catabolism in lungs via induction of cytochrome P450 enzymes. J Nutr. 2003, 133, 173–179.

Kim J., Kim Y.: Animal models, carotenoids research and lung cancer prevention. Transl Oncol. 2011, 4 (5), 271–281.

Yu H., Rohan T.: Role of the insulin‑like growth factor family in cancer development and progression. J Natl Cancer Inst. 2000, 92, 1472–1489.

Liu B., Lee H.Y., Weinzimer S.A., Powell D.R., Clifford J.L., Kurie J.M. et al.: Direct functional interactions between insulin‑like growth factorbinding protein‑3 and retinoid X receptor‑α regulate transcriptional signaling and apoptosis. J Biol Chem. 2000, 275 (43), 33607–33613.

Kim Y., Lian F., Yeum K.J., Chongviriyaphan N., Choi S.W., Russell R.M. et al.: The effects of combined antioxidant (β‑carotene, α‑tocopherol and ascorbic acid) supplemen‑tation on antioxidant capacity, DNA single‑strandbreaks and levels of insulin‑like growth factor‑1/IGF‑binding protein 3 in the ferret model of lung cancer. Int J Cancer. 2007, 120, 1847–1854.

Liu C., Russell R.M., Wang X.D.: Low dose β‑carotene supplementation of ferrets attenuates smoke‑induced lung phosphorylation of JNK, p38, MAPK, and p53 proteins. J Nutr. 2004, 134, 2705–2710.

Deeb K.K., Trumpo D.L., Johnson C.S.: Vitamin D signaling pathways in cancer: poten‑tial for anticancer therapeutics. Nat Rev Cancer. 2007, 7, 684–700.

Hansdottir S., Monick M.M., Hinde S.L., Lovan N., Look D.C., Hunninghake G.W.: Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol. 2008, 181, 7090–7099.

Menezes R.J., Cheney R.T., Husain A., Tretiakova M., Loewen G., Johnson C.S. et al.: Vitamin D receptor expression in normal, premalignant, and malignant human lung tissue. Cancer Epidemiol Biomarkers Prev. 2008, 17 (5), 1104–1110.

Turner A.M., McGowan L., Millen A., Rajesh P., Webster C., Langman G. et al.: Circulating DBP level and prognosis in operated lung cancer: an exploration of pathophysiology. Eur Respir J. 2013, 41 (2), 410–416.

Herbst R.S., Heymach J.V., Lippman S.M.: Lung cancer. N Engl J Med. 2008, 25, 359 (13), 1367–1380.

Cheng T.Y., Neuhouser M.L.: Serum 25‑hydroxyvitamin D, vitamin A, and lung cancer mortality in the US population: a potential nutrient‑nutrient interaction. Cancer Causes Control. 2012, 23 (9), 1557–1565.

Bao Y., Ng K., Wolpin B.M., Michaud D.S., Giovannucci E., Fuchs C.S.: Predicted vitamin D status and pancreatic cancer risk in two prospective cohort studies. Br J Cancer. 2010, 102 (9), 1422–1427.

Kilkkinen A., Knekt P., Heliövaara M., Rissanen H., Marniemi J., Hakulinen T. et al.: Vitamin D status and the risk of lung cancer: a cohort study in Finland. Cancer Epidemiol Biomarkers Prev. 2008, 17 (11), 3274–3278.

Freedman D.M., Looker A.C., Abnet C.C., Linet M.S., Graubard B.I.: Serum 25‑hydroxyvitamin D and cancer mortality in the NHANES III study (1988–2006). Cancer Res. 2010, 70 (21), 8587–8597.

Oh K., Willett W.C., Wu K., Fuchs C.S., Giovannucci E.L.: Calcium and vitamin D intakes in relation to risk of distal colorectal adenoma in women. Am J Epidemiol. 2007, 165 (10), 1178–1186.

Wolpin B.M., Ng K., Bao Y., Kraft P., Stampfer M.J., Michaud D.S. et al.: Plasma 25‑hydroxyvitamin D and risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2012, 21 (1), 82–91.

Chen P., Hu P., Xie D., Qin Y., Wang F., Wang H.: Meta‑analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res Treat. 2010, 121 (2), 469–477.

Van Poppel H., Tombal B.: Chemoprevention of prostate cancer with nutrients and supplements. Cancer Manag Res. 2011, 3, 91–100.

Ling M.T., Luk S.U., Al‑Ejeh F., Khanna K.K.: Tocotrienol as a potential anticancer agent. Carcinogenesis. 2012, 33 (2), 233–239.

Lee I.M., Cook N.R., Gaziano J.M., Gordon D., Ridker P.M., Manson J.E. et al.: Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women Health Study: a randomized controlled trial. JAMA. 2005, 294, 56–65.

Wada S., Satomi Y., Murakoshi M., Noguchi N., Yoshikawa T., Nishino H.: Tumor suppressive effects of tocotrienol in vivo and in vitro. Cancer Lett. 2005, 229, 181–191.

Yang C.S., Suh N.: Cancer prevention by different forms of tocopherols. Top Curr Chem. 2013, 329, 21–34.

Barve A., Khor T.O., Reuhl K., Reddy B., Newmark H., Kong A.N.: Mixed tocotrienols inhibit prostate carcinogenesis in TRAMP mice. Nutr Cancer. 2010, 62, 789–794.

Barve A., Khor T.O., Nair S., Reuhl K., Suh N., Reddy B. et al.: Gamma‑tocopherol‑enriched mixed tocopherol diet inhibits prostate carcinogenesis in TRAMP mice. Int J Cancer. 2009, 124, 1693–1699.

Budin S.B., Othman F., Louis S.J., Bakar M.A., Das S., Mohamed J.: The effects of palm oil tocotrienol‑rich fraction supplementation on biochemical parameters, oxidative stress and the vascular wall of streptozotocin‑induced diabetic rats. Clinics. 2009, 64, 235–244.

Taridi N.M., Yahaya M.F., Teoh S.L., Latiff A.A., Ngah W.Z., Das S. et al.: Tocotrienol rich fraction (TRF) supplementation protects against oxidative DNA damage and improves cognitive functions in Wistar rats. Clin Ter. 2011, 162, 93–98.

Chin S.F., Hamid N.A., Latiff A.A., Zakaria Z., Mazlan M., Yusof Y.A. et al.: Reduction of DNA damage in older healthy adults by Tri E Tocotrienol supplementation. Nutrition. 2008, 24 (1), 1–10.

Ren Z., Pae M., Dao M.C., Smith D., Meydani S.N., Wu D.: Dietary supplementation with tocotrienols enhances immune function in C57BL/6 mice. J Nutr. 2010, 140, 1335–1341.

Ren Z., Pae M., Dao M.C., Smith D., Meydani S.N., Wu D.: Gamma‑tocotrienol as an effective agent in targeting prostate cancer stem cell‑like population. Int J Cancer. 2010, 128, 2182–2191.

Liu H.K., Wang Q., Li Y., Sun W.G., Liu J.R., Yang Y.M. et al.: Inhibitory effects of gamma‑tocotrienol on invasion and metastasis of human gastric adenocarcinoma SGC‑7901 cells. J Nutr Biochem. 2010, 21, 206–213.

Yap W.N., Chang P.N., Han H.Y., Lee D.T., Ling M.T., Wong Y.C. et al.: Gamma‑tocotrienol suppresses prostate cancer cell proliferation and invasion through multiple‑signalling pathways. Br J Cancer. 2008, 99, 1832–1841.

Chang P.N., Yap W.N., Lee D.T., Ling M.T., Wong Y.C., Yap Y.L.: Evidence of gamma‑tocotrienol as an apoptosis‑inducing, invasion‑suppressing, and chemotherapy drug‑sensitizing agent in human melanoma cells. Nutr Cancer. 2009, 61 (3), 357–366.

Mayland C.R., Bennett M.I., Allan K.: Vitamin C deficiency in cancer patients. Palliat Med. 2005, 19, 17–20.

Frömberg A., Gutsch D., Schulze D., Vollbracht C., Weiss G., Czubayko F. et al.: Ascorbate exerts anti‑proliferative effects through cell cycle inhibition and sensitizes tumor cells towards cytostatic drugs. Cancer Chemother Pharmacol. 2011, 67, 1157–1166.

Heaney M.L., Gardner J.R., Karasavvas N., Golde D.W., Scheinberg D.A., Smith E.A. et al.: Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res. 2008, 68, 8031–8038.

Deubzer B., Mayer F., Kuçi Z., Niewisch M., Merkel G., Handgretinger R. et al.: H2O2‑mediated cytotoxicity of pharmacologic ascorbate concentrations to neuroblastoma cells: potential role of lactate and ferritin. Cell Physiol Biochem. 2010, 25 (6), 767–774.

Gilloteaux J., Jamison J.M., Neal D.R., Loukas M., Doberzstyn T., Summers J.L.: Cell damage and death by autoschizis in human bladder (RT4) carcinoma cells resulting from treatment with ascorbate and menadione. Ultrastruct Pathol. 2010, 34 (3), 140–160.

Cullen J.J.: Ascorbate induces autophagy in pancreatic cancer. Autophagy. 2010, 6 (3), 421–422.

Verrax J., Pedrosa R.C., Beck R., Dejeans N., Taper H., Calderon P.B.: In situ modulation of oxidative stress: a novel and efficient strategy to kill cancer cells. Curr Med Chem. 2009, 16, 1821–1830.

Ichim T.E., Minev B., Braciak T., Luna B., Hunninghake R., Mikirova N.A. et al.: Intravenous ascorbic acid to prevent and treat cancer‑associated sepsis? J Transl Med. 2011, 9, 25.

Yeom C.H., Lee G., Park J.H., Yu J., Park S., Yi S.Y. et al.: High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis. J Transl Med. 2009, 7, 1–9.

Tan P.H., Sagoo P., Chan C., Yates J.B., Campbell J., Beutelspacher S.C. et al.: Inhibition of NF‑kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells. J Immunol. 2005, 174, 7633–7644.

Banim P.J., Luben R., McTaggart A., Welch A., Wareham N., Khaw K.T. et al.: Dietary antioxidants and the aetiology of pancreatic cancer: a cohort study using data from food diaries and biomarkers. Gut. 2012, 62 (10), 1489–1496.

Bravi F., Polesel J., Bosetti C., Talamini R., Negri E., Dal Maso L. et al.: Dietary intake of selected micronutrients and the risk of pancreatic cancer: an Italian case‑control study. Ann Oncol. 2011, 22, 202–206.

Heinen M.M., Verhage B.A., Goldbohm R.A., van den Brandt P.A.: Intake of vegetables, fruits, carotenoids and vitamins C and E and pancreatic cancer risk in The Netherlands Cohort Study. Int J Cancer. 2012, 130, 147–158.

Steevens J., Schouten L.J., Goldbohm R.A., van den Brandt P.A.: Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study. Int J Cancer. 2011, 129, 2681–2693.

Murphy S.J., Anderson L.A., Ferguson H.R., Johnston B.T., Watson P.R., McGuigan J. et al.: Dietary antioxidant and mineral intake in humans is associated with reduced risk of esophageal adenocarcinoma but not reflux esophagitis or Barrett’s esophagus. J Nutr. 2010, 140, 1757–1763.


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