Menopause is clinically defined as the end of the reproductive period and diagnosed after 12 months from the last menstrual period. Women typically reach menopause between 45 and 55; however, there is not a set age or duration of menopause. Levels of estrogens and progesterone begin to fluctuate already before menopause during the menopausal transition, also referred to as perimenopause, which lasts on average 4.5 years (1). Menopausal discomforts including, but not limited to, hot flashes, night sweats, insomnia, changes in mood such as irritability, and vitality occur in perimenopause, menopause and post-menopause. The menopausal phase is unique to each woman, and the discomforts can vary from mild to severe, be non-existent or persist for years.

Hot flashes as well as nocturnal hot flashes, referred to as night sweats, are experienced by approximately 75-80 % of women during menopause in Western populations (2). The discomfort caused by hot flashes and night sweats are perceived as most troublesome and frequent influences of the overall quality of life and even women’s social life (2, 3).

Hormone replacement therapy (HRT) in various forms is often prescribed to relieve symptoms caused by the hormonal imbalance. However recent insights indicate that many women seek natural and safe dietary supplements targeted for relief of menopausal discomforts. In the UK, 86% of women seek alternative and complementary solutions (including supplements) to manage their menopause better (3). In addition, women are expecting “Science and Trust” when shopping for menopause products, with 96% who say they would purchase a product that has been scientifically proven to be effective and 94% who mention that trust in a brand or product is important when shopping for menopause products (3).

Dietary supplements, formulated with clinically studied ingredients and assessed by menopausal women represent a great opportunity to empower peri- and menopausal women and to address their needs. Specifically combining probiotics with botanical ingredients offers potential to target several menopausal discomforts. Based on internal focus group research and in-depth market insights, IFF Health Sciences’ innovation team created The Mystic, a proprietary blend of probiotic and botanicals designed to help support some of the most prevalent and bothersome discomforts related to menopause.

The Mystic contains a unique probiotic strain, Lacticaseibacillus paracasei Lpc-37, at a 1.7x10¹⁰ CFU daily dose selected for its documented clinically studied stress-modulating properties (4), IFF’s proprietary soy isoflavone extract SoyLife (150 mg of 40% extract, equivalent to 60 mg of isoflavones), and a herbal extract of lemon balm (350 mg of Melissa officinalis L. extract) traditionally used for relaxation and sleep (5).

Each ingredient was carefully selected based on the clinical data available and their potential to support menopausal women.

Soy isoflavones, particularly daidzein from soy germ, are often categorized as phytoestrogens due to their structural similarity to estrogen and their ability to be metabolized by intestinal microbiota into equol. Equol is a non-steroidal compound with a higher affinity for estrogen receptor beta (ER-β) than its precursor or other isoflavones like genistein (6). The mechanisms of action of soy isoflavonoids are well-characterized in the scientific literature, including European Food Safety Authority's comprehensive safety assessment confirms that daily intake of up to 150 mg of isolated isoflavones in food supplements poses no adverse effects in peri- and post-menopausal women (7).

SoyLife is a unique soy germ extract, with daidzein comprising over 50% of its total isoflavone content. The selective interaction of equol with ER-β may be relevant in menopausal physiology, where estrogen levels decline and ER-β-mediated gene transcription can become dysregulated. Through this pathway, in some women, equol may help support balance in estrogen-responsive tissues, contributing to the alleviation of menopausal discomforts without exerting strong estrogenic effects (8). Clinical efficacy of the isoflavone-rich soy germ product SoyLife has been evaluated in menopausal populations (9; 10). Nahas et al. (9) conducted a randomized, double-blind, placebo-controlled trial in 50 postmenopausal women with contraindications for HRT. Participants received 60 mg/day of soy germ isoflavones (as glycosides) from SoyLifefor six months. The study demonstrated a statistically significant reduction in hot flashes starting at month four, with 44% of women reporting complete disappearance of symptoms versus 12% in the placebo group. Additionally, LDL cholesterol decreased by 11.8%, HDL increased by 27.3%, and estradiol levels rose modestly without affecting FSH, LH, or vaginal cytology. Ye et al. (2012) evaluated SoyLife^® in a single-blind, placebo-controlled trial involving 87 early postmenopausal women. Subjects received either 84 mg or 126 mg/day of isoflavones (as aglycones) for 24 weeks. Both doses significantly reduced hot flash frequency and overall menopausal symptoms, as measured by the Kupperman index.

Probiotics, on the other hand, may affect wellbeing during the menopausal phase of life via the gastrointestinal tract. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (11). Menopause is thought to affect the gut microbiota in an age-independent manner indicated by an association with serum estradiol levels and specific bacterial species in the gut (12, 13), reduced diversity, microbiome compositional shifts towards age-matched male subjects and the reduced abundance of short-chain fatty acid producers (14). Thus, there is growing interest to study if probiotics could address menopausal related changes in the gut microbiome, but high-quality placebo-controlled RCTs are still largely missing.

While direct effects of probiotics on menopausal women remain less studied, the role of probiotics on mental wellbeing via gut-brain axis communication has been extensively investigated in recent years (15). Emerging evidence has built on the use of targeted probiotics, psychobiotics, for mental wellbeing (16, 17). This data maybe be applicable to menopause since this transition is frequently accompanied by impacts on mental wellbeing including heightened psychological stress, sleep disturbances, and mood fluctuation

In a randomized, double-blind, placebo-controlled trial by (4), 120 healthy adults were evaluated for the effect of the probiotic L. paracasei Lpc-37 on psychological and physiological indicators of stress. Participants received 1.7x10¹⁰ CFU/day of Lpc-37 for five weeks. Notably, the female subgroup (n=57) exhibited a statistically significant reduction in perceived stress scores (PSS) compared to placebo (p=0.049), with a 4.6% decrease versus an 11.2% increase in the control group. Furthermore, the expected rise in blood pressure as a result of an administered acute stress test was significantly lower in the Lpc-37female subgroup compared to placebo (p=0.031).

In addition, a standardized extract of lemon balm (350 mg), traditionally used to promote calmness and well-being (5), was included in the Mystic formulation. The extract was obtained using a method consistent with that employed in traditional use referred to in the monograph.

To complement the clinical data supporting the ingredients, the Mystic formulation has been assessed in a consumer perception study, to understand how menopausal women would perceive its benefits and investigate if the formulation was meeting their expectations.

Self-reported questionnaires on perceived discomforts and wellbeing are commonly used as a simple, cost- and time-effective, non-invasive means to assess and monitor menopausal discomforts affecting the quality of life of menopausal women in real-world setting (18) and were selected for use in this study.

The Mystic lifestyle study was conducted as an open-label, single-arm human consumer perception study in France on 100 women to evaluate the perceived effects of a dietary supplement targeting discomforts related to menopausal phase of life. Eligible participants were women aged 45–65 years experiencing perimenopausal/menopausal related discomfort and seeking a solution for those. HRT and other long-term medications were exclusion criteria. The study duration was 60 days, during which participants consumed the investigational product (IP) daily by taking two capsules in the morning. Compliance was very good with all participants cpmpleting the study, and 81 following the supplementation as instructed, 4 forgetting to take the daily dose once, 14 twice and 1 more often. Participants also completed self-reported questionnaires on the perceived discomforts and quality of life at baseline, 15 days, 30 days, and endpoint (60 days). The frequency and severity of discomforts perceived were evaluated according to a line scale from 1-10. In addition, questions related to product satisfaction and willingness to buy were asked with Likert scale, and diaries were used to gather information on the IP compliance. The analysis focused on both average score reductions and shifts in the proportion of participants reporting high severity of the perceived discomfort (scores 8-10). The IP was manufactured by IFF (Danisco USA Inc, Madison, WI, US) per Good Manufacturing Practices.

Primary outcomes included changes in perceived discomforts in both frequency and severity of hot flashes and night sweats, sleep quality, mental and physical fatigue, irritability, and quality of life. Consumer satisfaction ratings including willingness to buy or to recommend the formulation were also asked. Data were analyzed using descriptive statistics and paired t-tests to assess changes. The main results of summary statistics are included in the Table 1.

There were no short or long-term risks expected in consumption of the Mystic, and no adverse events with potential association to the supplemented product were observed in the study.

Figure 1a. Experienced average intensity of hot flashes

Figure 1b. Experienced average intensity of night sweats

Table 1. Key statistics including the percentage of women who reported decrease in their perceived discomforts, average scores of discomfort intensity at each time point, and percentage of women reporting top scores at baseline and in the end of study for each followed variable

Vasomotor Discomforts (Hot flashes and night sweats)

Hot flashes (see Figure 1a) and night sweats (Figure 1b) showed substantial perceived improvement. For hot flashes, the average score decreased from 6.94 at baseline to 4.36 at Day 60, representing a 37% average reduction in the perceived intensity. Notably, the proportion of participants reporting high severity (scores 8–10) dropped from 43% to 11%. Similarly, night sweats declined from 6.48 to 3.91 (−40%), with the high severity subgroup decreasing from 44% to 8%. These reductions suggest a statistically meaningful shift in perceived discomforts (p<0.001), supported by 78% and 80% of participants respectively reporting improvement at Day 60 both hot flashes and night sweats.

Fatigue and sleep

Perceived mental and physical fatigue were among the most clearly improved domains (p<0.001). Mental fatigue scores dropped from 7.47 to 4.21 (−44%), and physical fatigue from 7.37 to 4.42 (−40%). The proportion of participants in the high severity subgroup (scores 8–10) fell from 55% to 11% for both discomforts. These results indicate a strong perceived benefit, with 86% of participants reporting improvement in each category. In addition, 72% of women reported an improvement in the quality of their sleep at Day 60.

Irritability

Perceived irritability also showed marked improvement. The average score decreased from 6.52 to 3.65 (−44%), and the proportion of participants reporting high severity dropped from 39% to just 3%. With 83% of participants reporting improvement, this domain demonstrated one of the most dramatic shifts in perceived discomforts.

Vitality and Well-being (Inverted Scales)

Well-being and vitality, assessed using an inverted scale (higher scores indicating better outcomes), improved from 5.11 to 6.10 (+19%). The proportion of participants in the lowest scoring subgroup (8–10 on inverted scale) increased from 15% to 29%, indicating enhanced vitality. General well-being also improved, with scores rising from 5.22 to 6.60 (+26%) and the low scoring subgroup increasing from 7% to 27%. These findings suggest a positive shift in overall quality of life, with 59% and 63% of participants respectively reporting improvement.

Perceived results at 15 days

After just 15 days of supplementation, 68% of women reported a perceived reduction in hot flashes (-24% average change), 64% in night sweats (with -25% reduction reported on average) and 75% in mental fatigue (-30% reduction reported). As the supplementation continued, perceived benefits further increased across all measured domains. 71% of women reported Mystic met their expectations within two weeks of supplementation.

After 60 days of supplementation, the average reported number of menopausal discomforts decreased from five at baseline to two, and the frequency and intensity of the remaining discomforts was perceived as lower. Not surprisingly, the decrease in perceived discomforts was reflected in the overall quality of life. Overall, 79%of women reported an improvement in their quality of life. Results are summarized in Table 1.

The consumer perception study demonstrates promising results in supporting wellbeing during menopause with a product combining clinically studied probiotic and botanical ingredients. The Mystic supplementation was associated with substantial perceived improvements in discomforts related to hot flashes and night sweats, physical and mental fatigue, and irritability. The rapid onset of effects, visible by Day 15, suggests early consumer-perceived benefits. Improvements in vitality and general well-being further support The Mystic’s potential role in enhancing quality of life during menopause. It can be concluded that across all measured domains, The Mystic supplementation was associated with meaningful improvements in perceived menopause-related discomforts, noticed already at the two-week time point.

The formulation was well-received by the menopausal women, with over 84% of participants funding the product effective after 60 days of use. Eight out of ten women said they would purchase the product after trying it and would recommend it to others seeking relief from menopause-related discomforts.

Beyond showing benefits for the target population, the use of dietary/food supplements emerged as a highly valued feature among menopausal women when choosing supplements. These insights underscore the Mystic’s potential to enhance quality of life during menopause.