August 24, 2017

Magnesium and Cancer

Andrea S. Blevins Primeau, PhD, MBA

About 60% of Americans are deficient in magnesium, including up to 60% of patients who are critically ill.

Magnesium is a critical mineral that is involved in over 600 enzymatic reactions, including those
important for brain, heart, and skeletal muscle functions.1 Interestingly, about 60% of Americans
are deficient in magnesium, including up to 60% of patients who are critically ill.

In regard to cancer, magnesium intake has been associated with the incidence of some cancers
and has been studied as a protective agent against chemotherapy-induced nephrotoxicity and
neurotoxicity.

Cancer Risk

Colorectal Cancer

Several studies have demonstrated an association between high magnesium intake and reduced
risk of colorectal cancer (CRC).
An analysis of the prospective, Swedish Mammography Cohort, evaluated 61,433 women aged 40
to 75 without a history of cancer for a mean follow-up of 14.8 years. 2 The highest quintile of
magnesium intake was associated with a significantly lower risk of CRC compared with the lowest
quintile (multivariate rate ratio [RR], 0.59; 95% CI, 0.40-0.87). This benefit was observed for both
colon (RR, 0.66; 95% CI, 0.41-1.07) and rectal (RR, 0.45; 95% CI, 0.22-0.89) cancers.

A case-control study evaluated 2204 subjects from the Tennessee Colorectal Polyp Study, which
demonstrated that increasing total magnesium intake was significantly associated with decreasing
risk of CRC (highest tertile odds ratio [OR], 0.54; 95% CI, 0.36-0.82; P < .01).3 The highest tertile of
dietary magnesium intake (>298 mg/day) was significantly associated with reduced risk of CRC in
an age-adjusted model (OR, 0.75; 95% CI, 0.60-0.95; P = .02).

A study of 140,601 postmenopausal women from the Women’s Health Initiative with an mean
follow-up of 13 years demonstrated a significant reduction in CRC risk with the highest quintile of
total magnesium intake compared with the lowest quintile of magnesium intake (hazard ratio
[HR], 0.79; 95% CI, 0.67-0.94; P < .0001).4 The benefit was driven by colon cancer (HR, 0.80; 95%
CI, 0.66-0.97; P < .0001), with a trend for rectal cancer (HR, 0.76; 95% CI, 0.51-1.13; P < .001).

Another study, however, found no association between magnesium intake and incidence of CRC.

A study with a mean follow-up of 11 years of the Women’s Health Study cohort demonstrated no
association between total magnesium intake and CRC incidence, even when potentially
confounding factors such as body mass index, physical activity, or smoking status, were
considered.5

Pancreatic Cancer

A study of 66,806 subjects aged 50 to 76 at baseline from the Vitamins and Lifestyle cohort
evaluated magnesium intake and the incidence of pancreatic cancer during a mean follow-up of
6.8 years.6 Subjects with magnesium intake below the recommended dietary allowance were
more likely to develop pancreatic cancer, particularly in those whose intake was less than 75% of
the recommended dietary allowance (HR, 1.76; 95% CI, 1.04-2.96). In this study, a 100 mg/day
decrease in magnesium intake resulted in a 24% increase in risk of pancreatic cancer (HR, 1.24;
95% CI, 1.02-1.50; P = .03).

Nephrotoxicity

Several studies have demonstrated that magnesium administered during chemotherapy

treatment has a protective effect against nephrotoxicity.

A double-blind, placebo-controlled phase 2 study randomly assigned 40 patients with epithelial

ovarian cancer to receive magnesium sulphate (5 g) before each course of chemotherapy
(paclitaxel plus cisplatin) with magnesium subcarbonate (500 mg 3 times per day) administered
during treatment intervals.7 Magnesium supplementation was effective in increasing serum
magnesium levels, and resulted in a significantly lower decrease in glomerular filtration rate (GFR)
compared with placebo as indicated by serum creatinine (P = .0069), Cockroft-Gault
(CICG; P = .0077), and Modification Diet of Renal Disease (MDRD; P = .032).

A study of 85 patients with lung cancer receiving cisplatin-based chemotherapy received high or
low volume hydration with magnesium or high volume hydration without magnesium. 8 The group
that did not receive magnesium demonstrated a significant increase in serum creatinine and
significant decrease in creatinine clearance compared with baseline. There was no difference in
serum creatinine or creatinine clearance compared with baseline for patients who received high
volume hydration with magnesium, and a trend toward increased serum creatinine and decreased
creatinine clearance in the group that receive low volume hydration with magnesium.

A prospective cohort study evaluated magnesium (15 mEq) supplied as part of a prehydration
regimen to 28 patients with cervical cancer receiving treatment with cisplatin. 9 There was no
significant change in serum creatinine or estimated GFR in the magnesium group compared with
baseline. In the group that did not receive magnesium, however, there was a significant increase
in serum creatinine and a significant decrease in the estimated GFR compared with baseline. 

Another prospective cohort study of 74 patients receiving cisplatin-based therapy for gynecologic
cancer also demonstrated that prehydration with magnesium sulfate resulted in lower rates of
moderate renal dysfunction classified as “risk” compared with patients who received prehydration
without magnesium.10

Neurotoxicity

Several studies have evaluated the effect of calcium and magnesium infusions on oxaliplatin-
induced neuropathy, which were summarized in a systematic review published in 2016. 11

The systematic review included 694 evaluable patients from 5 different trials. Results from pooled
data demonstrated no significant difference in grade 2 or higher neuropathy between the patients
who received calcium magnesium or controls.

Conclusions

Epidemiologic studies suggest that total magnesium intake may reduce the risk of CRC and
pancreatic cancer.

Several studies, including a randomized controlled trial, suggest that prehydration with
magnesium or magnesium supplementation is protective against cisplatin-induced nephrotoxicity.
Magnesium in addition to calcium, however, does not appear to be protective against
chemotherapy-induced neurotoxicity.
References

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disease. Physiol Rev. 2015;95:1-46. doi: 10.1152/physrev.00012.2014.
2. Larsson SC, Bergkvist L, Wolk A. Magnesium intake in relation to risk of colorectal cancer in
women. JAMA. 2005;293:86-89.
3. Dai Q, Shrubsole MJ, Ness RM, et al. The relation of magnesium and calcium intakes and a
genetic polymorphism in the magnesium transporter to colorectal neoplasia risk. Am J Clin
Nutr. 2007;86:743-751.
4. Gorczyca AM, He K, Xun P, et al. Association between magnesium intake and risk of
colorectal cancer among postmenopausal women. Cancer Causes Control. 2015;26:1761-
1769. doi: 10.1007/s10552-015-0669-2.
5. Lin J, Cook NR, Lee IM, et al. Total magnesium intake and colorectal cancer incidence in
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9965.EPI-06-0454.
6. Dibaba D, Xun P, Yokota K, et al. Magnesium intake and incidence of pancreatic cancer: the
VITamins and Lifestyle study. Br J Cancer. 2015;113:1615-1621. doi: 10.1038/bjc.2015.382.
7. Bodnar L, Wcislo G, Gasowska-Bodnar A, et al. Renal protection with magnesium
subcarbonate and magnesium sulphate in patients with epithelial ovarian cancer after
cisplatin and paclitaxel chemotherapy: a randomized phase II study. Eur J Cancer.
2008;44:2608-2614. doi: 10.1016/j.ejca.2008.08.005.
8. Oka T, Kimura T, Suzumura T, et al. Magnesium supplementation and high volume
hydration reduce the renal toxicity caused by cisplatin-based chemotherapy in patients
with lung cancer: a toxicity study. BMC Pharmacol Toxicol. 2014;15:70-79.
9. Yamamoto Y, Watanabe K, Tsukiyama I, et al. Nephroprotective effects of hydration with
magnesium in patients with cervical cancer receiving cisplatin. Anticancer
Res. 2015;35:2199-2204.
10.Yamamoto Y, Watanabe K, Tsukiyama I, et al. Hydration with 15 mEq magnesium is
effective at reducing risk for cisplatin-induced nephrotoxicity in patients receiving cisplatin
(≥50 mg/m2) combination chemotherapy. Anticancer Res. 2016;36:1873-1877.
11.Jordan B, Jahn F, Beckmann J, et al. Calcium and magnesium infusions for the prevention of
oxaliplatin-induced peripheral neurotoxicity: a systematic review. Oncology. 2016;90:299-
306. doi: 10.1159/000445977.