Vitamin E

Vitamin E

PEP Topic 
Hot Flashes
Description 

Vitamin E is a fat-soluble vitamin found in seeds, nuts, leafy vegetables, and vegetable oils. It is a type of antioxidant and helps prevent cell damage caused by free radicals (highly reactive chemicals). It is being studied in the prevention and treatment of some types of cancer. Vitamin E has been used as an oral or parenteral supplement and as a solution for topical application. Vitamin E has been examined in management of diarrhea, mucositis, peripheral neuropathy, skin effects, cognitive impairment, and hot flashes.

Effectiveness Not Established

Research Evidence Summaries

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.

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Study Purpose:

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

Intervention Characteristics/Basic Study Process:

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.

Sample Characteristics:

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

Study Design:

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).

Measurement Instruments/Methods:

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.

Results:

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.

Conclusions:

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

Biglia, N., Sgandurra, P., Peano, E., Marenco, D., Moggio, G., Bounous, V., … Sismondi, P. (2009). Non-hormonal treatment of hot flushes in breast cancer survivors: Gabapentin vs. vitamin E. Climacteric, 12, 310–318. 

doi:10.1080/13697130902736921
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Study Purpose:

The study assessed the efficacy and the tolerability of gabapentin 900 mg/day compared to vitamin E for the control of vasomotor symptoms in women with breast cancer.

Intervention Characteristics/Basic Study Process:

Vitamin E was chosen as a placebo-equivalent on the basis of previous experience  showing only minimal effect on hot flushes in breast cancer participants, and no toxicity or side-effects. Participants were randomly allocated to one of two treatment groups: vitamin E 800 IU/day or gabapentin 900 mg/day by oral route (Neurontin 300 mg capsules) for a period of 12 weeks.

Sample Characteristics:

The sample was comprised of 115 postmenopausal women with a median age of 50 years. 

  • Inclusion criteria:
    • Breast cancer surgically treated at least one year prior; no evidence of systemic disease 
    • Eight or more hot flushes per day 
    • Postmenopausal status (amenorrhea for more than 12 months or amenorrhea for 6–12 months with a serum FSH level greater than 40 mIU/ml and estradiol less than 20 pg/ml or bilateral oophorectomy or ovarian suppression by GnRH analogs) 
    • Adjuvant therapy with tamoxifen, aromatase inhibitors or GnRH analogs, provided that it was started at least two months before
  • Exclusion criteria:
    • Use of any antidepressant treatment, progestagens, or any other medication to treat hot flushes within the previous three months 
    • Concomitant chemotherap
    •  Uncontrolled hypertension 
    • Impaired renal or hepatic function
    • Diabetes

Study Design:

This was a randomized, non-placebo-controlled, nonblinded study.

Measurement Instruments/Methods:

Each participant completed a one-week self-report diary on hot flushes at study entry and daily during the 12 weeks of study. In order to assess the duration of treatment efficacy, participants filled out the hot flush diary for three months after treatment discontinuation.

Results:

Treatment efficacy was assessed by two measures: frequency (total number of hot flushes) and severity score, calculated by assigning scores of 1, 2, 3 and 4, respectively, to mild, moderate, severe, and very severe hot flushes. This hot flush diary had previously been validated. Each value was obtained by averaging data collected over 1 week. Differences and percentage changes from baseline to weeks 4, 8, and 12 were calculated. Among the women allocated to vitamin E, 16.36% never started therapy, and 34.78% dropped out because of inefficacy. Hot flush frequency and score decreased by 57.05% and 66.87%, respectively (p = 50.05) in the gabapentin group. The effect of vitamin E was fairly small: hot flush frequency and severity score were reduced by 10.02% and 7.28%, respectively (p > 0.05).

Conclusions:

Gabapentin 900 mg/day is effective for relieving hot flushes in participants previously treated for breast cancer. Vitamin E has only marginal effect on vasomotor symptoms.

Limitations:

Study limitations were small sample size and high dropout rate.

Systematic Review/Meta-Analysis

Rada, G., Capurro, D., Pantoja, T., Corbalán, J., Moreno, G., Letelier, L. M., & Vera, C. (2010). Non-hormonal interventions for hot flushes in women with a history of breast cancer. Cochrane Database of Systematic Reviews, (9) CD004923.

doi: 10.1002/14651858.CD004923.pub2
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Purpose:

To assess the efficacy of non-hormonal interventions for the treatment of hot flushes in women with a history of breast cancer

TYPE OF STUDY Combined systematic review and meta analysis

Search Strategy:

  • DATABASES: CENTRAL, CINAHL, PsycINFO, LILACS, MEDLINE, EMBASE, WHO clinical trials registry combined with hand search of reference lists of reviews, included articles, conference proceedings and contacts with experts.
  • KEYWORDS:  Detailed key words by database listed in appendix - all included randomized controlled trials of therapies for vasomotor symptoms (hot flashes, night sweats) in women with breast cancer
  • INCLUSION CRITERIA: Randomized controlled clinical trials of non-hormonal interventions pertaining to women of any age experiencing hot flashes and with or without a history of breast cancer.  Studies that included women without a history of breast cancer were accepted if data on these cases was presented separately or if these women constituted <20% of the study population  
  • EXCLUSION CRITERIA: Studies of hormonal interventions and hormone-like interventions including plant phytoestrogens, black cohosh, and tibolone
  • METHOD OF STUDY EVALUATION: Evaluated studies according to the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2; Two persons evaluated each study and extracted information about the studies onto forms; Bias in studies was assessed and noted.
     

Literature Evaluated:

TOTAL REFERENCES RETRIEVED : N =1012


 

Sample Characteristics:

  • FINAL NUMBER OF STUDIES INCLUDED: N = 16    
  • KEY SAMPLE CHARACTERISTICS: All women with breast cancer and reporting vasomotor symptoms. There were inconsistencies in inclusion criteria related to number or severity of hot flashes required for inclusion.

Phase of Care and Clinical Applications:

APPLICATIONS Late Effects and Survivorship

Results:

  • Outcomes inconsistently reported across studies 
  • Outcomes included hot flash frequency, severity, bother, interference, hot flash composite scores (frequency x severity). 
  • Secondary outcomes were also inconsistently reported and included side effects, recurrence risk, and health-related quality of life

Conclusions:

  • Clonidine is effective but may have intolerable side effects.
  • Gabapentin and SSRIs/SNRIs may be effective but must be weighed against side effects, cost, dosing, and absolute benefit.
  • Vitamin E should not be recommended as it was not effective.
  • Evidence for other non-pharmacological therapies is limited.

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