Succinate-Based Dietary Supplement for Menopausal Symptoms: A Pooled Analysis of Two Identical Randomized, Double-Blind, Placebo-Controlled Clinical Trials

Abstract

Background To evaluate the efficacy of a succinate-based dietary supplement (SBDS; Amberen) in symptomatic menopausal women using a larger sample size derived by pooling data from two identical trials. Methods Raw data were pooled from two identical randomized, multicenter, double-blinded, placebo-controlled, 90-day clinical trials. Women aged 42–60 years with mild to moderate vasomotor and psychosomatic menopausal symptoms were included (114 in the treatment group and 113 in the placebo group). Symptoms were assessed by the Greene Climacteric Scale and State-Trait Anxiety Inventory. Changes in body mass index, body weight, waist and hip circumferences, and plasma levels of follicle stimulating hormone, luteinizing hormone, estradiol, leptin, and apolipoproteins A1 and B were also evaluated. Results SBDS use resulted in significant improvements in several endpoints including alleviation of 16 of 21 menopausal symptoms (p ≤ 0.05, Greene Scale) and a decrease in anxiety (p < 0.0001, State-Trait Anxiety Inventory) when compared to placebo. Significant reductions were observed in weight, body mass index, and waist and hip circumferences in the supplement cohort. Evaluation of physiological parameters showed a significant increase in serum estradiol levels compared to baseline (p < 0.0001) among users of the SBDS. Levels of follicle stimulating hormone and luteinizing hormone decreased slightly in both groups, without significant differences between the groups. Leptin levels decreased with statistical significance in the SBDS cohort compared to placebo (p=0.027). For those with initial leptin concentrations above the reference range, leptin decreased significantly in the SBDS group compared to the baseline (p < 0.0001) and to placebo (p=0.027). Conclusions The pooled analysis reaffirms the outcomes from the individual trials. A nonhormonal, succinate-based dietary supplement is shown to relieve menopausal symptoms when compared to a placebo regimen in a randomized, double-blinded clinical trial.

The 2023 nonhormone therapy position statement of The North American Menopause Society

“…An ammonium succinate-based supplement (Amberen) was studied for the management of menopause symptoms in a manufacturer-sponsored clinical trial, with an initial study published in 2016, 143 and later a pooled analysis including this study and a second additional study was published in 2019. 144 The studies were identical multicenter, double-blind, 90-day RCTs including women aged 42 to 60 years with mild to moderate menopause symptoms (n = 227). Both studies showed improvement in menopause symptoms such as sleep, fatigue, loss of interest in sex, joint and muscle pain, VMS, and a decrease in anxiety compared with the placebo group.…”

Paternal Zn-deficiency abolishes metabolic effects in offspring induced by diet type

“…Further, reduction of liver α-ketoglutaric acid and lactate, two critical intermediates for glycolysis, also suggested paternal ZnD altered the balance of glycolysis and affected TCA cycle. It is reported that succinate could provide an energy supply and catecholamine-like influence on the hypothalamus and increase the organ's sensitivity to input signals from peripheral endocrine glands, therefore elevating succinate in the liver, which may in turn affect the TCA cycle ( Radzinsky et al., 2019 ). Nevertheless, a lesser effect of paternal ZnD on glycolysis was found.…”

The role of diet in managing menopausal symptoms: A narrative review

“…A pooled analysis of two RCTs by Radzinsky et al (2019) found a significant benefit following 3 months of a multi‐nutrient intervention. However, the RCTs were conducted by the same research group and so corroborative evidence from other groups would be useful (Ataei‐Almanghadim et al., 2020; Radzinsky et al, 2019).…”