By Stephanie-Anne Girard, PhD | Director, Scientific Affairs at SGS Nutrasource
Diversity and inclusion have emerged as pivotal elements shaping the landscape of clinical research. This shift towards inclusivity ensures the relevance, accuracy, and applicability of research outcomes. Sex and gender influence various aspects of human health and disease making the representation of women crucial in understanding the complexities of nutritional science (1).
Women, constituting approximately half of the global population, bring unique perspectives, experiences, and biological variables. From physiological variances to societal roles, these factors intricately shape dietary habits, nutritional requirements, and health outcomes (1). Yet, despite their significance, women have historically been underrepresented in randomized controlled trials (RCTs), skewing data, compromising the validity and applicability of study findings (2).
One important gap lies in sex or gender-specific medicine whereby gender-specific differences and their influence on diagnostic, pathogenesis, disease progression and therapeutic outcomes have been underestimated (3). In the gastroenterology field, incidence and therapeutic outcome are greatly impacted by gender. Gall-stone disease and gall bladder cancer occur predominantly in women. Irritable Bowel Syndrome (IBS), one of the most common functional gastrointestinal disorders, has been shown to have sex and gender-associated differences in the prevalence and the effectiveness of treatment. Women are not only more likely to suffer from IBS than men (4) but they also report being more fatigued, anxious, depressed with a lower quality of life (3). Additionally, women often have limited access to preventative care leading to delayed diagnosis and poorer health outcomes (5). These disparities between gender can detrimentally impact women’s prognosis. Another area where male dominance has long prevailed is sports nutrition research. This skewed representation not only obscures women’s specific nutritional needs for optimal performance and recovery but also perpetuates the misconception that findings in men can be universally extrapolated (6). The repercussions of this imbalance ripple through various life stages, from onset of menarche, reproductive years, mid-life to menopause and aging, where women’s nutritional challenges remain inadequately addressed. Throughout the menstrual cycle, levels of serum zinc and magnesium decrease and supplementation with iron may be required to compensate for blood loss (7). Conversely, during menopause, iron stores in the body can accumulate rapidly, leading to inflammation and worsening menopausal symptoms (8). Menopause, a significant transition in a woman’s life, introduces a myriad of hormonal changes that impact nutrient metabolism and overall health (9). Despite its profound implications, menopause-related nutritional research has often been understudied, leaving an unmet need of understanding and addressing women’s unique requirements during this life cycle stage.
Beyond physiological considerations, societal pressures and expectations surrounding beauty standards have fueled the rise of the “beauty-from-within” movement. This trend, popularized in certain regions of Asia, emphasizes the role of dietary supplements in enhancing skin, hair, and nail health (10). Emerging research underscores the potential of nutritional interventions, highlighting the need for further exploration in this area. In fact, dietary supplements such as prebiotics, probiotics and synbiotics have gained attention for their potential benefits in promoting overall health, including skin health (11, 12). Due to the stereotype that skincare is primarily a women’s concern, nutricosmetics have targeted women but, by doing so, significant advancements have been made understanding dermatological concerns. Additionally, mounting evidence suggests that the gut microbiome influences overall health and exhibits sex-specific differences in composition (13). Considering women are disproportionately affected by conditions such as IBS, osteoarthritis, depression and anxiety, investigation of the effect of pre/pro/synbiotics supplementation on the gut microbiome should be closely examined (14). Certain researchers recommend that interventional clinical trials with probiotic(s) should separate their results into gender-specific outcomes (15).
Another overlooked aspect of women’s health research lies in elements included in the vaginal microbiome clinical studies. Emerging evidence suggests that diet and specific probiotics, may influence the composition of the vaginal microbiome, crucial for maintaining vaginal health, preventing infections (16) and ultimately opening new avenues for research into nutritional interventions that promote women’s reproductive health (18).
Early-stage research studies, important for understanding nutrient metabolism and drug interactions, have also fallen short in their inclusion of women. Historically, male-centric pharmacokinetic studies have neglected the influence of hormonal fluctuations and biological differences, leading to inaccuracies in dosage recommendations and potential adverse effects for women (19, 20).
Recognizing these disparities, regulatory bodies like the FDA, Health Canada and NIH have implemented policies mandating the inclusion of women and minorities in clinical trials. These initiatives underscore the importance of diverse representation in research, not only for ethical reasons but also for ensuring the safety and efficacy of nutritional products for all demographics (21, 22). Additionally, the EMA is regularly assessing the need for updated and separate guideline on gender, specifically whether there is a need for a specific guideline for the clinical investigation of medicinal products in women (23).
Beyond regulatory mandates, the scientific community must proactively address the underrepresentation of women in nutritional research. Historically, this gender bias stems from pre-clinical animal studies conducted on males due to absence of hormonal fluctuation and a more “straightforward” interpretation of study results (20). By embracing inclusivity in clinical study design, conducting sex-specific analyses, and accounting for hormonal variations, researchers can unlock a deeper understanding of women’s unique nutritional needs. While there have been advances toward increased representation of women in clinical research, due in part to these regulatory changes and consumer demand, this progress must continue. When planning and designing clinical trials involving pro/pre/synbiotics, we should consider variables such as absorption and metabolism, which may be influenced by the biotics themselves, the gut microbiome of the study population, along with the potential impact of the participant’s sex/gender. In fact, sex/gender-based subgroup analysis as well as including sex/gender as a covariate in statistical modeling should be applied. By closing the gender gap, we pave the way for a more comprehensive understanding of nutritional science, ultimately enhancing health outcomes for all consumers.
About the Author
Stephanie-Anne Girard, Director, Scientific Affairs brings 15+ years of expertise designing and overseeing natural health product / dietary supplement, and pharmaceutical clinical research. Her extensive knowledge spans diverse therapeutic areas, including gastrointestinal health, women’s health, gut-brain axis, metabolic syndrome/cardiovascular health, immunity, vaccines, and oncology. She published numerous scientific articles in peer-reviewed journals and has presented at many international conferences and scientific meetings. Dr. Girard holds a PhD in Nutritional Sciences from the University of Florida, a Masters’ degree in Pharmacology from the University of Montreal and a BSc in Microbiology and Immunology from McGill University.
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