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Prostate Cancer, Nutrition, and Dietary Supplements (PDQ®)

Calcium

Overview

This section contains the following key information:

  • Calcium is required for certain metabolic functions such as vascular contraction and vasodilation, muscle function, nerve transmission, intracellular signaling, and hormonal secretion.
  • Major sources of calcium in the United States are food and dietary supplements.
  • Studies of the association between calcium and prostate cancer have been limited to nutritional sources of calcium, such as dairy products.
  • Some studies suggest that high total calcium intake may be associated with increased risk of advanced and metastatic prostate cancer, compared with lower intake of calcium.
  • Additional research is needed to clarify the effects of calcium and/or dairy products on prostate cancer risk.

General Information and History

Calcium, the most abundant mineral in the body, is found in some foods, added to others, available as a dietary supplement, and present in some medicines (such as antacids). Calcium is required for vascular contraction and vasodilation, muscle function, nerve transmission, intracellular signaling, and hormonal secretion, although less than 1% of total body calcium is needed to support these critical metabolic functions.[1] Serum calcium is very tightly regulated and does not fluctuate with changes in dietary intake; the body uses bone tissue as a reservoir for, and source of calcium to maintain constant concentrations of calcium in blood, muscle, and intercellular fluids.[1]

The major sources of calcium in the U.S. population are food and dietary supplements.[2] According to recent National Health and Nutrition Examination Survey data, U.S. adults obtain 38% of their dietary calcium from milk and milk products, such as yogurt and cheese.[3] Nondairy sources include vegetables, such as Chinese cabbage, kale, and broccoli. Spinach provides calcium, but its bioavailability is poor. Most grains do not have high amounts of calcium unless they are fortified; however, they contribute calcium to the diet because they contain small amounts of calcium, and people consume them frequently. Foods fortified with calcium include many fruit juices and drinks, tofu, and cereals. In the United States, dietary supplements, including calcium supplements, are commonly used to prevent chronic diseases, including cancer.[1] Mean dietary calcium intakes for males aged 1 year and older ranged from 871 to 1,266 mg/day depending on life stage group (i.e., infant, adolescent, or adult). About 43% of the U.S. population uses dietary supplements containing calcium, which increases calcium intake by about 330 mg/day among supplement users.[1,2]

To evaluate the association between calcium intake and prostate cancer mortality and morbidity, it may be important to assess objective, biological markers of calcium, include data that account for nutritional and supplemental calcium intake, and control for other confounding factors. However, studies of association between calcium and prostate cancer have been limited to nutritional sources of calcium, such as dairy products. Although more than half of the U.S. population uses vitamin and mineral supplements (at an annual cost of over 11 billion dollars), few studies include supplement use in the association of disease risk, including prostate cancer or mortality rates.[1,2] (Refer to the PDQ summary on Prostate Cancer Prevention for more information.)

Preclinical/Animal Studies

In vitro studies

Prostate cancer cells were treated with bovine milk, almond milk, soy milk, casein, or lactose in a 2011 study. Treatment with bovine milk resulted in growth stimulation of LNCaP prostate cancer cells. Growth of prostate cancer cells was not affected by treatment with soy milk, and treatment with almond milk resulted in growth inhibition.[4]

In vivo studies

One study investigated the effects of dietary calcium on prostate tumor progression in LPB-Tag transgenic mice. The animals consumed low (0.2%) or high (2.0%) calcium diets and were sacrificed at age 5, 7, or 9 weeks. Tumor weight and progression were similar in mice that were fed low- and high-calcium diets.[5]

A 2012 study examined the impact of dietary vitamin D and calcium on prostate cancer growth in athymic mice. The mice were injected with human prostate cancer cells and were randomly assigned to receive specific diets (e.g., high calcium/vitamin D or normal calcium/no vitamin D). The mice that received the normal calcium/vitamin D-deficient diet exhibited significantly greater (P < .05) tumor volumes than did mice that received the other diets.[6]

Human Studies

Epidemiologic studies

Several epidemiological studies have found an association between high intakes of calcium, dairy foods, or both, and an increased risk of developing prostate cancer.[7-9] However, others have found only a weak relationship, no relationship, or a negative association between calcium intake and prostate cancer risk.[10-13] On the basis of these studies, interpretation of the evidence is complicated by the difficulty of separating the effects of dairy products from the effects of calcium. Additionally, earlier epidemiological studies had several limitations. The association of calcium intake with prostate cancer was limited to evidence from self-reported food frequency questionnaires of nutritional sources of calcium, with a focus on dairy foods.[14,15] Competing risk factors, such as other major nutrients in dairy (i.e., fats) and concomitant and confounding factors (i.e., age, body mass index, steroid hormones, and other metabolic events in the causal pathway) were not accounted for. Additionally, no objective markers of calcium, such as serum calcium, were obtained from these cohorts. Observational studies overall, however, suggest that high total calcium intake may be associated with increased risk of advanced and metastatic prostate cancer, compared with lower intake of calcium.[11,12,16-18] Additional research is needed to clarify the effects of calcium and/or dairy products on prostate cancer risk and elucidate potential biological mechanisms.

Intervention studies

In a randomized clinical trial published in 2005, 672 men received either 3 g of calcium carbonate (1,200 mg calcium) or placebo daily for 4 years and were followed up for 12 years. During the first 6 years of the study, there were significantly fewer prostate cancer cases in the calcium group compared with the placebo group. However, this difference was no longer statistically significant at the 10-year evaluation.[19]

Meta-analyses

A meta-analysis published in 2005 reported that there may be an association between increased risk of prostate cancer and greater consumption of dairy products and calcium.[20]

A 2008 meta-analysis reviewed 45 observational studies and found no evidence of a link between dairy products and risk of prostate cancer.[21] A meta-analysis of cohort studies published between 1996 and 2006 found a positive association between milk and dairy product consumption and risk of prostate cancer.[22]

In a recent review, the U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews, conducted meta-analyses using Mantel-Haenszel fixed effects models for overall cancer incidence, cardiovascular disease incidence, and all-cause mortality. Vitamin D and/or calcium supplementation showed no overall effect on cancer incidence and mortality, including prostate cancer.[3] In another meta-analysis of the association of calcium without the coadministration of vitamin D, a reduced risk of prostate cancer was observed, although there were only a few events.[23]

Current clinical trials

Check NCI’s list of cancer clinical trials for CAM clinical trials on calcium carbonate and calcium citrate that are actively enrolling patients.

General information about clinical trials is also available from the NCI Web site.

References

  1. Ross AC, Taylor CL, Yaktine AL, et al., eds.: Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press, 2011. Also available online. Last accessed February 5, 2015.
  2. Lampe JW: Dairy products and cancer. J Am Coll Nutr 30 (5 Suppl 1): 464S-70S, 2011. [PUBMED Abstract]
  3. Fortmann SP, Burda BU, Senger CA, et al.: Vitamin, Mineral, and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality, 2013. Available online. Last accessed February 5, 2015.
  4. Tate PL, Bibb R, Larcom LL: Milk stimulates growth of prostate cancer cells in culture. Nutr Cancer 63 (8): 1361-6, 2011. [PUBMED Abstract]
  5. Mordan-McCombs S, Brown T, Zinser G, et al.: Dietary calcium does not affect prostate tumor progression in LPB-Tag transgenic mice. J Steroid Biochem Mol Biol 103 (3-5): 747-51, 2007. [PUBMED Abstract]
  6. Ray R, Banks M, Abuzahra H, et al.: Effect of dietary vitamin D and calcium on the growth of androgen-insensitive human prostate tumor in a murine model. Anticancer Res 32 (3): 727-31, 2012. [PUBMED Abstract]
  7. Butler LM, Wong AS, Koh WP, et al.: Calcium intake increases risk of prostate cancer among Singapore Chinese. Cancer Res 70 (12): 4941-8, 2010. [PUBMED Abstract]
  8. Kurahashi N, Inoue M, Iwasaki M, et al.: Dairy product, saturated fatty acid, and calcium intake and prostate cancer in a prospective cohort of Japanese men. Cancer Epidemiol Biomarkers Prev 17 (4): 930-7, 2008. [PUBMED Abstract]
  9. Raimondi S, Mabrouk JB, Shatenstein B, et al.: Diet and prostate cancer risk with specific focus on dairy products and dietary calcium: a case-control study. Prostate 70 (10): 1054-65, 2010. [PUBMED Abstract]
  10. Park Y, Mitrou PN, Kipnis V, et al.: Calcium, dairy foods, and risk of incident and fatal prostate cancer: the NIH-AARP Diet and Health Study. Am J Epidemiol 166 (11): 1270-9, 2007. [PUBMED Abstract]
  11. Giovannucci E, Liu Y, Stampfer MJ, et al.: A prospective study of calcium intake and incident and fatal prostate cancer. Cancer Epidemiol Biomarkers Prev 15 (2): 203-10, 2006. [PUBMED Abstract]
  12. Koh KA, Sesso HD, Paffenbarger RS Jr, et al.: Dairy products, calcium and prostate cancer risk. Br J Cancer 95 (11): 1582-5, 2006. [PUBMED Abstract]
  13. Ahn J, Albanes D, Peters U, et al.: Dairy products, calcium intake, and risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 16 (12): 2623-30, 2007. [PUBMED Abstract]
  14. Park SY, Murphy SP, Wilkens LR, et al.: Calcium, vitamin D, and dairy product intake and prostate cancer risk: the Multiethnic Cohort Study. Am J Epidemiol 166 (11): 1259-69, 2007. [PUBMED Abstract]
  15. Pettersson A, Kasperzyk JL, Kenfield SA, et al.: Milk and dairy consumption among men with prostate cancer and risk of metastases and prostate cancer death. Cancer Epidemiol Biomarkers Prev 21 (3): 428-36, 2012. [PUBMED Abstract]
  16. Mitrou PN, Albanes D, Weinstein SJ, et al.: A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland). Int J Cancer 120 (11): 2466-73, 2007. [PUBMED Abstract]
  17. Kesse E, Bertrais S, Astorg P, et al.: Dairy products, calcium and phosphorus intake, and the risk of prostate cancer: results of the French prospective SU.VI.MAX (Supplémentation en Vitamines et Minéraux Antioxydants) study. Br J Nutr 95 (3): 539-45, 2006. [PUBMED Abstract]
  18. Rohrmann S, Platz EA, Kavanaugh CJ, et al.: Meat and dairy consumption and subsequent risk of prostate cancer in a US cohort study. Cancer Causes Control 18 (1): 41-50, 2007. [PUBMED Abstract]
  19. Baron JA, Beach M, Wallace K, et al.: Risk of prostate cancer in a randomized clinical trial of calcium supplementation. Cancer Epidemiol Biomarkers Prev 14 (3): 586-9, 2005. [PUBMED Abstract]
  20. Gao X, LaValley MP, Tucker KL: Prospective studies of dairy product and calcium intakes and prostate cancer risk: a meta-analysis. J Natl Cancer Inst 97 (23): 1768-77, 2005. [PUBMED Abstract]
  21. Huncharek M, Muscat J, Kupelnick B: Dairy products, dietary calcium and vitamin D intake as risk factors for prostate cancer: a meta-analysis of 26,769 cases from 45 observational studies. Nutr Cancer 60 (4): 421-41, 2008. [PUBMED Abstract]
  22. Qin LQ, Xu JY, Wang PY, et al.: Milk consumption is a risk factor for prostate cancer in Western countries: evidence from cohort studies. Asia Pac J Clin Nutr 16 (3): 467-76, 2007. [PUBMED Abstract]
  23. Bristow SM, Bolland MJ, MacLennan GS, et al.: Calcium supplements and cancer risk: a meta-analysis of randomised controlled trials. Br J Nutr 110 (8): 1384-93, 2013. [PUBMED Abstract]
  • Updated: March 3, 2015