Mag Me? Magnesium for Hot Flashes

Abstract & Commentary

By Russell H. Greenfield, MD

Synopsis: In a small 5-week pilot trial examining the use of magnesium for the treatment of hot flashes, women with a history of breast cancer experienced improvements in hot flash frequency and severity, but no significant impact on overall quality of life.

Source: Park H, et al. A pilot phase II trial of magnesium supplements to reduce menopausal hot flashes in breast cancer patients. Support Care Cancer 2011;19:859-863.

Based on clinical observation in two patients that was reported in 20091 and further uncontrolled observations, the authors of this small pilot trial sought to explore the potential benefits of magnesium supplementation in women with a history of breast cancer who were experiencing hot flashes.

A total of 31 subjects with bothersome hot flashes (defined as occurring 14 or more times a week for at least a month, and being of sufficient severity that treatment was desired) after breast cancer treatment were enrolled. All subjects had normal renal function, no recent change in dose of tamoxifen, raloxifene, or aromatase inhibitors, and were rated to have good performance status.

Baseline data were collected during the first week of the trial when magnesium was not administered. Over the following 2 weeks participants were provided with magnesium oxide 400 mg (250 mg elemental magnesium per tablet) to be taken at bedtime; if symptoms decreased adequately, they were instructed to remain on the same dose throughout the remainder of the trial (2 more weeks). If, however, bothersome symptoms persisted, subjects were permitted to double the dose to 400 mg twice daily (500 mg of elemental magnesium). A pill count was completed at the end of the study.

Subjects were asked to maintain a prospective hot flash diary over the 5-week period and to complete a number of questionnaires designed to 1) assess severity and frequency of hot flashes, and 2) assess change in measures of quality of life. The primary question to be resolved was whether oral magnesium supplementation would decrease the frequency and severity of hot flashes (the hot flash score) by 50%, a level deemed clinically significant by the researchers. Secondary outcomes of interest were the effects of magnesium on quality of life and side effects or toxicities.

Only 29/31 subjects actually received the magnesium supplements (average age 54 years, 24 postmenopausal [15 reported duration of hot flashes for > 18 months], 6 African Americans; 8 on tamoxifen, 9 on aromatase inhibitors, 14 on antidepressants), and 25/29 completed the full study. One subject was lost to follow-up and three others discontinued treatment (two due to possible side effects) before any assessments of impact on hot flashes had been performed. All survey forms were completed and returned. Compliance was reportedly very high, with all but three subjects taking all their pills (the three took 70% of their magnesium supplements). A total of 17 participants increased the dose of magnesium to 800 mg daily after 2 weeks.

Results were promising — both hot flash frequency and score were significantly reduced, with 56% experiencing a > 50% reduction in hot flash score and 76% a > 25% reduction at the end of 4 weeks compared with baseline. Average weekly hot flash frequency decreased by 41% (P = 0.009) by week 5, and average weekly hot flash score decreased by 50% (P = 0.02). However, magnesium supplementation had no significant effect on overall quality of life or degree of sleep disturbance, but significant improvements in fatigue, perceived distress level due to hot flashes, and severity of abnormal sweating was noted.

The authors conclude that oral magnesium supplementation is effective in reducing the severity and frequency of hot flashes in women after treatment for breast cancer.

Commentary

Hot flashes can be one of the most troubling symptoms experienced by women during perimenopause. Such vasomotor symptoms also can complicate breast cancer treatment with agents such as tamoxifen and aromatase inhibitors, and not uncommonly occur during hormone therapy for the treatment of prostate cancer. In light of safety concerns associated with estrogen replacement therapy, conventional medical treatment has emphasized the use of SSRIs, SNRIs, and clonidine, all of which appear to offer benefit but at the cost of potential for significant side effects. A variety of complementary and alternative medicine therapies show promise for the treatment of hot flashes, including acupuncture and Chinese medicinal herbs, mind/body therapies such as visualization and yoga, and select supplements and Western botanicals, yet the search for safe, effective, and inexpensive interventions to relieve hot flashes continues — which is why the positive results from the present study might offer a breath of fresh, cold air to hot flash sufferers.

Magnesium is commonly administered in a variety of clinical settings, including for prevention of cardiovascular disease, and treatment of asthma and eclampsia, and has been shown to be safe in people with normal kidney function. With respect to hot flashes the mechanism of possible beneficial action is unknown, but it is acknowledged that magnesium has effects on both blood vessels and nerves, and that it may also impact serotonin levels. In general, magnesium supplementation is quite safe except in the setting of significant renal impairment. In the current study, side effects occurred in two participants — one subject experienced a migraine (which is interesting, since the mineral can be used as a preventive treatment against migraines) and one had nausea. Two subjects also developed what was termed "grade 1 diarrhea." Glycinate and gluconate forms of magnesium seem less likely to cause this disturbance in bowel habits. Supplemental magnesium is affordable (the magnesium oxide used in this trial cost $0.02 per day), and food sources of magnesium are plentiful and include leafy greens, nuts, beans, whole grains, and avocados.

It's enticing to jump on the magnesium bandwagon right away to try to help our patients with hot flashes, but it is important to keep in mind that this study focused on women with a history of breast cancer, that it was a small pilot trial with no placebo group, and that results were not parsed to determine the impact of antidepressant use. It is reasonable to assume that a beneficial impact on hot flashes also might occur in other settings, but it will be helpful to have corroborative data (the authors are planning a Phase 3 trial). That stated, there seems no harm in exploring a trial of magnesium therapy for people experiencing hot flashes provided kidney function is normal.

Reference

1. Smith TJ. Magnesium supplements for menopausal hot flashes. J Clin Oncol 2009;27:1151-1152.