Barton, D.L., Loprinzi, C.L., Quella, S.K., Sloan, J.A., Veeder, M.H., Egner, J.R., … Novotny, P. (1998). Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. Journal of Clinical Oncology, 16, 495–500.

The purpose of the study was to examine the effect of vitamin E in breast cancer survivors.

Participants received an eight-week supply of study medication (400 IU of vitamin E succinate or placebo twice daily) labeled with the days and weeks for dosing.

One hundred twenty-five (125) women aged  33–67were randomized; 5 participants on the placebo-arm withdrew before starting study medication, which resulted in 120 patients assessable for toxicity. One hundred five (105) participants completed five weeks of study; 104 finished all nine weeks.  

• Inclusion criteria:
  • Older than age 18 with a history of breast cancer
  • Must have had hot flashes for at least one month with a frequency of at least 14 times per week.
  • Life expectancy of six months or more and an ECOG performance status of 0 or 1 
  • Tamoxifen use allowed
• Exclusion criteria:
  • Current or planned therapy with chemotherapy, androgens, estrogens, progestational agents, corticosteroids, or other agents used for treating hot flashes not allowed
  • Women who took more than two multivitamin tablets per day or more than 60 IU of vitamin E daily  
  • Pregnant or lactating women, those with a history of bleeding, immune deficiencies, or thrombophlebitis

In this placebo-controlled, randomized, crossover trial, women were stratified by age (18 to 49 years and 50 years and older), current tamoxifen use (yes or no), duration of hot flashes (less than 9 months versus 9 months or more), average frequency of flashes (2–3 per day, 4–9 per day, or 10 or more per day), and current multivitamin use (yes or no).

Baseline hot-flash counts for each woman were obtained for the first seven days. Starting the second week and for the remaining seven weeks, study medication was taken, and the women continued to keep a daily diary of hot flash severity and frequency.

Treatment efficacy was measured using three variables: mean daily hot-flash frequency, mean daily hot-flash severity (grades 1 to 4 to representing mild, moderate, severe, and very severe), and mean daily hot flash score (frequency times average severity). All factors were measured during the last week of each treatment and compared with baseline week. The 105 participants who finished the first treatment period showed a similar reduction in hot flash frequencies for the two study arms. (25% versus 22%; p = .90). This effect represents an average decrease of roughly 1.6 hot flashes per day to a level of 4.7 hot flashes per day. The hot flash score decreased by 28% with vitamin E and 20% with placebo (p = .68). A crossover analysis, however, showed that vitamin E was associated with a minimal decrease in hot flashes (one less hot flash per day than was seen with a placebo) (p ≤ .05). At the study end, participants did not prefer vitamin E over the placebo. No toxicity was demonstrated.

Although this trial was able to show a hot flash reduction with vitamin E compared to a placebo, the clinical magnitude of this reduction was marginal