Vitamin D3 prevents side effects in breast cancer patients -multiple studies confirm a reduction in side effects of aromatase inhibitors
The most recent of the four studies was presented at the 2012 American Society of Clinical Oncologists (1). This was a phase III randomized, placebo-controlled, double-blind (VITAL) study which demonstrated that supplementation of traditional treatment with Vitamin D3 reduced the side effects of musculoskeletal pain and fatigue occurring in patients taking aromatase inhibitor therapy for the treatment of breast cancer. Fifty percent of women taking aromatase inhibitors reported musculoskeletal pain, and up to 30% reported fatigue. The results were presented by lead investigator Qamar J. Khan, MD, University of Kansas Medical Center.
In this study, 147 women with stage I to III breast cancer were enrolled to receive letrozole (Femara) therapy and a standard dose of Vitamin D3 (600IU) plus calcium (1,200mg) daily. Patients were then randomly assigned to receive an additional 30,000IU/week of Vitamin D3 or placebo. Patients were assessed for Vitamin D3 levels at the onset of treatment and at weeks 12 and 24. Three patients, all in the placebo arm, discontinued therapy early due to musculoskeletal pain. In the Vitamin D arm, blood levels increased from 22ng/mL at baseline to 53ng/mL at week 12 and 57ng/mL at week 24. In the placebo arm, blood levels of Vitamin D3 increased from 25ng/mL at baseline to 32ng/mL at week 12 and 31ng/mL at week 24.
When evaluated with the Simple Descriptive Pain Intensity Scale, 51% of the women in the placebo arm experienced a protocol-defined musculoskeletal event, compared with only 37% in the group treated with 30,000IU/week of Vitamin D3. Using the quantitative Brief Pain Inventory, 61% of patients in the placebo arm and 38% in the vitamin D arm reported a musculoskeletal event (P=0.008).
In addition, the investigators also evaluated the incidence of an adverse quality-of-life event. A significantly higher percentage of women in the placebo arm (72%) reported a musculoskeletal event and fatigue, compared with only 42 percent in the Vitamin D3 arm (P<0.001).
Two previous studies in breast cancer patients have shown similar effects. The first of these studies was presented at the San Antonio Breast Cancer Symposium in 2009, and demonstrated that Vitamin D3 led to significant improvements in pain and mobility (2).
This study included postmenopausal women with hormone receptor-positive breast cancer who
a) had received at least eight weeks of anastrozole (Arimidex) therapy prior to enrollment
b) had marginal 25-OH vitamin D levels (10 to 29 ng/mL) and
c) a history of generalized musculoskeletal pain that began or worsened since starting treatment with the aromatase inhibitor.
The study involved 60 patients, 30 assigned to each treatment group. All patients received 1,000 mg calcium and 400 IU vitamin D3 daily and were randomized to receive either Vitamin D3 supplementation with 50,000 IU/week for eight or 16 weeks, depending on baseline 25-OH Vitamin D levels and then switched to monthly Vitamin D3 doses of 50,000 IU or a matching placebo supplementation.
At two months, patients randomized to Vitamin D3 had significant improvement in pain compared with the placebo group, as assessed by scores on the Brief Pain Index (P=0.009) and the Fibromyalgia Impact Questionnaire (P=0.01). Patients in the Vitamin D group also had significantly better scores on an assessment of walking and climbing stairs (P=0.04).
The second study set out to establish the optimal concentration of 25(OH)D that would prevent or minimizes arthralgia(3). The study involved a prospective cohort of 290 women starting on aromatase inhibitors, who had baseline Vitamin D levels measured. All patients received daily Vitamin D3 (800 IU) with calcium. Women with a baseline 25(OH)D concentration <30 ng/ml also received 16,000 IU of D3 orally every 2 weeks.
The primary outcome was worsening joint pain
derived from baseline and 3-month visual analogic scale (VAS) for joint pain. Ninty percent of women had a VitaminD3 levels <30 ng/ml at baseline. After supplementation (daily 800 IU and additional 16,000 IU every two weeks), 50% of them still failed to reach adequate concentrations at three months.
In the whole cohort, there was an increase in joint pain (mean 1.16 points SD 2.66; P < 0.001) and the increase was significantly (P = 0.02) reduced in those who reached concentrations of 25(OH)D of ≥40 ng/ml. The investigators concluded that a target concentration of 40 ng/ml 25OHD would prevent development of arthralgia but higher doses than 16,000IU every two weeks are required to attain adequate levels in women with deficiency at baseline.
Finally, Vitamin D3 supplementation has been shown to reduce the rate of bone loss and fractures occurring in breast cancer patients treated with aromatase inhibitors (4). See our previous news letter June 2011.