BACKGROUND AND PURPOSE:

• Folic acid reduces noradrenaline secretion and increases serotonin activity
• Ewies et al. (BJOG, 2021) assessed whether folic acid supplementation ameliorated hot flushes

METHODS:

• Phase III double-blind, placebo-controlled randomized trial
  • FOlic Acid supplementation in the management of Menopausal symptoms (FOAM Trial)
• Participants
  • 40 to 70 years
  • Postmenopausal
  • Normal baseline serum folate level (3.1-20.0µg/L)
  • ≥50 hot flushes weekly
• Interventions
  • Folic acid 5 mg daily for 12 weeks
  • Placebo
• Study design
  • Frequency and severity of hot flushes: Recorded daily by participants (Sloan Diary)
  • Quality of life: Greene Climacteric and Utian Quality of Life (UQoL) Scales
  • All outcomes measured at 4, 8 and 12 weeks
• Sample size
  • Target: Detect 3.4 point mean difference in the change in Hot Flush Score with folic acid vs placebo
  • 80% power | Two-sided type 1 error alpha=0.05
  • 70 patients required per arm | Plan for 162 women to account for a 15% rate loss to follow-up rate
• Primary outcome
  • Change in daily Hot Flush Score at week 12, based on Sloan Diary Composite Score
• Secondary outcomes
  • Hot flush frequency and severity as calculated
  • Reduction in Hot Flush Score
  • Other menopausal symptoms
  • Longitudinal QoL data as measured by the Utian QoL Scale

RESULTS:

• 143 women
• Mean (SD) change in Hot Flush Score at week 12
  • Folic acid group: -6.98 (10.30)
  • Placebo: -4.57 (9.46)
• No significant difference in mean change in Hot Flush Score between the two groups
  • Mean change: -2.41 (95% CI, -5.68 to 0.87); P=0.149
  • Adjusted mean change: -2.61 (95% CI, -5.72 to 0.49); P=0.098
• Only benefit in secondary outcomes for folic acid group was seen in changes in total and emotional UQoL scores at week 8
  • Mean change for total score: 5.22 (95% CI, 1.16 to 9.28)
  • Mean change for emotional score: 1.88 (95% CI, 0.23 to 3.52)
  • Difference was not present at 12 weeks

CONCLUSION:

• Compared to placebo, folic acid did not have a significant benefit in reducing hot flush scores over 12 weeks in postmenopausal women
• The authors note that the lack of difference between the two groups

…may be due to higher than expected response to placebo

Definitive evidence of benefit would however require a larger study

Learn More – Primary Sources:

Folic Acid Supplementation in Postmenopausal Women with Hot Flushes: Phase III Randomised Double-Blind Placebo-Controlled Trial

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