Bladder Cancer Supplement Recommendations

Multiple nutritional supplements have been associated with reduced cancer incidence and/or cancer progression. The list below contains those with the greatest evidence-base and benefit, though it is not necessary that they all be included.

Vitamin D

  • Low vitamin D levels have been associated with a greater occurrence and risk of dying from bladder cancer.
  • Suggested dose is that sufficient to raise vitamin D blood levels to >40 ng/mL, which may require 5000 IU per day or more.[1]

Isothiocyanates

  • Isothiocyanates occur in many commonly consumed cruciferous vegetables (broccoli, cauliflower, kale, etc.) and exhibit significant anti-cancer activities. Available data suggest that they are particularly promising for bladder cancer prevention and/or treatment.[2]
  • Suggested dose: 600mcg isothiocyanates per day.

Green tea extract

  • Catechins, antioxidants found in green tea, particularly EGCG, have been shown to inhibit bladder cancer cell invasion and spreading (metastasis).[3][4]
  • Suggested dose: 1g EGCG and mixed catechins per day.

Vitamin E & mixed tocopherols

  • A small trial of vitamin E for patients with low grade bladder cancer significantly reduced cancer recurrence in both smokers and non-smokers.[5] A previous study found that long-term vitamin E supplementation was associated with a 40% reduction in bladder cancer mortality, and some evidence suggests it may enhance the effectiveness of some chemotherapy.[6][7]
  • Suggested dose: 400 IU of mixed tocopherols and tocotrienols per day.

N-acetylcysteine

  • This antioxidant has been shown to inhibit several processes in bladder cancer cells, including adhesion, invasion, and migration.[8]
  • Suggested dose: 600mg, 2-3 times per day.

Curcumin

  • Derived from the spice turmeric, curcumin has multiple mechanisms of anti-cancer action. Additionally, it may enhance the effects of Bacillus Calmette-Guerin (BCG), the most commonly used agent for bladder cancer.[9][10] Doses range depending on type of curcumin, Meriva® and Longvida® have been shown to be much more efficiently absorbed forms.[11][12]
  • Suggested dose: 1-2g of Meriva® or Longvida® curcumin per day.

Milk thistle

  • Silymarin and silibinin from milk thistle have anti-proliferative and anti-metastatic properties, and have increased apoptosis (programmed cell death) in bladder cancer cells.[13][14]
  • Suggested dose: at least 500mg silymarin per day.

Diindolylmethane (DIM)

  • Diindolylmethane (DIM), extracted from cruciferous vegetables, such as broccoli, cauliflower, cabbage, etc., has been shown to induce apoptosis (programmed cell death) and reduce the invasiveness of bladder cancer cells, and may improve chemotherapeutic effectiveness against more resistant cells.[15]
  • Suggested dose: 250mg per day.

Quercetin

  • The antioxidants in quercetin have been shown to inhibit the growth of cancer cells, and protect bladder cancer cells from carcinogenic toxins.[16][17]
  • Suggested dose: 200-400mg three times per day.

Melatonin

  • A hormone, supplemental melatonin intake has improved survival in a number of cancers, and may enhance conventional therapy effectiveness.[18]
  • Suggested dose: at least 3mg at night, preferably time-released.

Vitamin K2

  • Vitamin K-2 (MK-7) has the longest half-life, meaning it is the most stable, of all forms of vitamin K. Shown to improve bone and cardiovascular health, higher intakes of this form have also been associated with reduced cancer occurrence & fatality, and may improve effectiveness of other therapies.[19][20][21]
  • Suggested dose, 100 mcg vitamin K-2 (MK-7).

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[1] Garland CF, French CB, Baggerly LL, et al. Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Res. 2011 Feb;31(2):607-11.

[2] Geng F1, Tang L, Li Y, et al. Allyl isothiocyanate arrests cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via Bcl-2 protein phosphorylation. J Biol Chem. 2011 Sep 16;286(37):32259-67. doi: 10.1074/jbc.M111.278127.

[3] Qin J, Wang Y, Bai Y, et al. Epigallocatechin-3-gallate inhibits bladder cancer cell invasion via suppression of NF-κB mediated matrix metalloproteinase-9 expression. Mol Med Rep. 2012 Nov;6(5):1040-4.

[4] Rieger-Christ KM, Hanley R, et al. The green tea compound, (-)-epigallocatechin-3-gallate downregulates N-cadherin and suppresses migration of bladder carcinoma cells. J Cell Biochem. 2007 Oct 1;102(2):377-88.

[5] Mazdak H, Zia H. Vitamin e reduces superficial bladder cancer recurrence: a randomized controlled trial. Int J Prev Med. 2012 Feb;3(2):110-5.

[6] Jacobs EJ, Henion AK, Briggs PJ, et al. Vitamin C and vitamin E supplement use and bladder cancer mortality in a large cohort of US men and women. Am J Epidemiol. 2002 Dec 1;156(11):1002-10.

[7] Kanai K, Kikuchi E, et al. Vitamin E succinate induced apoptosis and enhanced chemosensitivity to paclitaxel in human bladder cancer cells in vitro and in vivo. Cancer Sci. 2010 Jan;101(1):216-23.

[8] Supabphol A, Muangman V, Chavasiri W, et al. N-acetylcysteine inhibits proliferation, adhesion, migration and invasion of human bladder cancer cells. J Med Assoc Thai. 2009 Sep;92(9):1171-

[9] Tian B, Wang Z, et al. Effects of curcumin on bladder cancer cells and development of urothelial tumors in a rat bladder carcinogenesis model. Cancer Lett. 2008 Jun 18;264(2):299-308.

[10] Kamat AM, Tharakan ST, et al. Curcumin potentiates the antitumor effects of Bacillus Calmette-Guerin against bladder cancer through the downregulation of NF-kappaB and upregulation of TRAIL receptors. Cancer Res. 2009 Dec 1;69(23):8958-66.

[11] Marczylo TH, Verschoyle RD, Cooke DN, et al. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer Chemother Pharmacol. 2007 Jul;60(2):171-7

[12] DiSilvestro RA1, Joseph E, Zhao S, Bomser J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012 Sep 26;11:79. doi: 10.1186/1475-2891-11-79.

[13] Vinh PQ, Sugie S, Tanaka T, et al. Chemopreventive effects of a flavonoid antioxidant silymarin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice. Jpn J Cancer Res. 2002 Jan;93(1):42-9.

[14] Tyagi AK, Agarwal C, et al. Silibinin down-regulates survivin protein and mRNA expression and causes caspases activation and apoptosis in human bladder transitional-cell papilloma RT4 cells. Biochem Biophys Res Commun. 2003 Dec 26;312(4):1178-84.

[15] Sun Y, Cheng MK, et al. Inhibition of STAT signalling in bladder cancer by diindolylmethane: relevance to cell adhesion, migration and proliferation. Curr Cancer Drug Targets. 2013 Jan;13(1):57-68.

[16] Sekeroğlu V, Aydin B, Sekeroğlu ZA. Viscum album L. extract and quercetin reduce cyclophosphamide-induced cardiotoxicity, urotoxicity and genotoxicity in mice. Asian Pac J Cancer Prev. 2011;12(11):2925-31

[17] Kim Y, Kim WJ, Cha EJ. Quercetin-induced Growth Inhibition in Human Bladder Cancer Cells Is Associated with an Increase in Ca-activated K Channels. Korean J Physiol Pharmacol. 2011 Oct;15(5):279-83.

[18] Cutando A, López-Valverde A, et al. Role of melatonin in cancer treatment. Anticancer Res. 2012 Jul;32(7):2747-53.

[19] Nimptsch K, Rohrmann S, Kaaks R, et al. Dietary vitamin K intake in relation to cancer incidence and mortality: results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr. 2010 May;91(5):1348-58.

[20] Nimptsch K, Rohrmann S, Linseisen J. Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr. 2008 Apr;87(4):985-92.

[21] Zhang H, Ozaki I, Hamajima H, et al. Vitamin K2 augments 5-fluorouracil-induced growth inhibition of human hepatocellular carcinoma cells by inhibiting NF-κB activation. Oncol Rep. 2011 Jan;25(1):159-66.

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