Women Are the Largest Supplement Consumers—But Most Research Excludes Them
Seventy-seven percent of women use at least one dietary supplement. Despite this, the representation of women in exercise and nutrition research is severely lacking. The problem isn't just that women are excluded—it's that physiological differences between men and women mean recommendations based on male-only research may not apply.
A comprehensive review published in Sports Medicine examined the physiological underpinnings of sex-based differences and their implications for nutritional strategies in active women. The findings reveal both what works and how much we still don't know.
Sex-Based Differences Start With Muscle Fiber Type
Important physiological differences between men and women exist that influence metabolism, fatigability, vasodilation, and body composition. Most men have a greater quantity of skeletal muscle than women, which translates to greater absolute strength. But when examining the physiological properties of skeletal muscle, women demonstrate characteristics that may confer metabolic advantages.
Women tend to have 7-23% greater proportion of type I muscle fibers compared to men. Type I fibers oxidize more fat but less amino acids and carbohydrates, potentially demonstrating increased exercise capacity and reduced skeletal muscle fatigability. While trained men display greater glycolytic capacity, trained women exhibit faster oxygen uptake kinetics during moderate-intensity exercise and smaller decreases in ATP levels after all-out exercise.
When comparing skeletal muscle mitochondrial oxidative function between trained men and women, women demonstrated about one-third greater mitochondrial intrinsic respiratory rates. This suggests female skeletal muscle may be more suited to resynthesize ATP from oxidative phosphorylation during exercise, with implications for decreased fatigability and increased exercise recovery.
Women demonstrate greater vasodilatory responses of the arteries, providing more blood flow to exercising skeletal muscle and possibly increasing oxygen delivery to and metabolite removal from working muscle. Data from muscle biopsies revealed higher density of capillaries per unit of skeletal muscle in the vastus lateralis among women compared to men.
Given these foundational differences, dietary supplements that target anaerobic energy production or ingredients optimized when higher threshold motor units are activated—such as muscle buffers like beta-alanine—may be particularly helpful for active women.
Hormonal Fluctuations Create Metabolic Shifts
Between approximately ages 12 and 51, women experience predictable fluctuations in ovarian hormones estrogen and progesterone. A regular menstrual cycle ranges from 23 to 38 days and consists of three main phases: the follicular phase, ovulation, and the luteal phase. These hormonal fluctuations facilitate varying modulations in energy expenditure and macronutrient metabolism.
The impact of low estrogen in the early follicular phase is observed by lower muscle glycogen levels as a result of increased glucose production, glucose uptake, and carbohydrate oxidation. The increased carbohydrate oxidation results in upregulation of creatine kinase and interleukin-6, which may be attenuated with increased carbohydrate consumption during this phase. The reduced capacity for glycogen storage in the early follicular phase has been found to be negated with a carbohydrate-loading protocol of greater than 8 g per kilogram per day in moderately trained endurance athletes.
The luteal phase is represented by high progesterone. The increased presence of progesterone promotes the shuttling of glucose into the liver as well as upregulating glucose transporter translocation to enhance glycogen storage in the endometrial tissue. As a result, glycogen supercompensation may be more difficult to attain in the luteal phase without higher routine daily carbohydrate levels owing to changes in insulin sensitivity.
Globally, energy expenditure is larger in the luteal phase owing to increased demands of cell growth with development of the endometrial lining. As progesterone upregulates to meet increased cell growth demands, protein biosynthesis requisite for endometrial thickening depletes amino acid levels. Early evidence suggests consuming more than 1.5 g per kilogram per day, or 0.3-0.5 g per kilogram per meal, may be beneficial to attenuate the increased amino acid oxidation and could have better implications for recovery.
Oral Contraceptives Create a Third Hormonal Profile
More than 60% of adult women in the United States and 57% of American collegiate women athletes utilize some form of hormonal contraception. Oral contraceptive pills are the most common type. Despite this prevalence, the effects of oral contraceptives on exercise performance and metabolism are poorly understood.
Exogenous estrogens and progestins in oral contraceptives significantly reduce endogenous levels of estrogen and progesterone via chronic down-regulation of the hypothalamic-pituitary-ovarian axis. Evidence shows oral contraceptives with higher dosage amounts can decrease glucose tolerance, augmenting insulin resistance. An increased C-reactive protein response was observed in Olympic women athletes taking oral contraceptives, illustrating an upregulated inflammatory response possibly indicating increased muscle damage or insufficient recovery.
Early data demonstrate significantly higher oxidative stress in women athletes using oral contraceptives than their non-user counterparts irrespective of lifestyle habits. Based on existing physiological data, dietary supplements may help modulate the inflammatory response, reduce muscle damage, and possibly lower oxidative stress among those utilizing oral contraceptives, though research in this area is severely lacking.
Body Composition Changes Accelerate During Menopause Transition
Sex-dependent differences in body composition begin at puberty primarily due to estrogen's role in body composition regulation. Estrogen levels remain consistent from puberty into adulthood. However, in the years preceding menopause, known as peri-menopause with an average age of 45, estrogen levels begin to dramatically decrease until the final menstrual period at an average age of 51.
When resting energy expenditure was measured in pre-menopausal women during different menstrual phases and after estrogen suppression, changes in resting energy expenditure paralleled changes in estrogen. Resting energy expenditure was highest in the mid-luteal phase, lower by 29 kcal per day in the early follicular phase, and further reduced by 42 kcal per day after estrogen suppression.
As women transition from peri-menopause to post-menopause, the loss of estrogen may decrease energy expenditure. In a 1-year longitudinal study, 24-hour energy expenditure decreased significantly with age and fat oxidation decreased by 32% in women who became post-menopausal compared with pre-menopausal women.
Data from the longitudinal Study of Women's Health Across the Nation cohort demonstrated the rate of fat gain in pre-menopausal women was an average of 0.25 kg per year, but over the approximately 3.5-year menopause transition, adverse changes in body composition began to accelerate. The rate of fat gain doubled to 0.45 kg per year leading to a 6% total gain in fat mass, an average absolute gain of 1.6 kg, and an average 0.5% loss in lean mass.
These unfavorable alterations in body composition indicate peri-menopause may be a key time period for exercise and nutritional interventions, particularly in regard to maintenance of lean mass, mitigating fat mass gain, and alterations in energy expenditure.
Anabolic Resistance Develops With Age
In the transition from pre-menopause to peri-menopause, preliminary data indicate a pronounced decrease in skeletal muscle protein balance. Menopausal-related hormonal changes and losses in muscle mass may be a direct result of skeletal muscle dysregulation owing to development of anabolic resistance to nutrient intake, particularly to the precursor essential amino acids.
The reduced capacity for protein anabolism leads to a decrease in protein turnover and eventually a loss of muscle size and quality, particularly in post-menopause. The process of protein turnover, particularly protein synthesis, is energetically expensive, indicating the rate of protein turnover may be a primary determinant of total daily energy expenditure.
Decreases in protein turnover can significantly influence energy balance. Additionally, because the energy required for protein turnover is primarily derived from fatty acid oxidation, a reduction in protein turnover corresponds with a reduction in fatty acid oxidation and potential subsequent accumulation in fat mass.
Protein Requirements for Active Women
In women athletes specifically, very limited research has been conducted on protein requirements, but existing data suggest active women should consume a minimum of 1.6 g per kilogram per day of protein. Higher protein diets, greater than 2.0 g per kilogram per day, have been shown to be important for maintaining lean mass and resting energy expenditure under periods of intentional and unintentional caloric restriction, which may be more prevalent among active women.
The loss of lean mass is a common characteristic of age, and women appear to experience greater loss compared with men. This blunted sensitivity to protein appears to be overcome when larger amounts of essential amino acids including leucine are ingested, suggesting an essential amino acid supplement may be an important intervention to mitigate lean mass loss with age.
A study in older women demonstrated that bolus whey protein (20 g) versus low-dose leucine-enriched essential amino acids (3 g) equally stimulated muscle protein synthesis. When paired with exercise, muscle protein synthesis increased and remained elevated for both. These results suggest supplemental intake of essential amino acids may be equally beneficial compared with whey protein for middle-aged and older women, with the lower dose being more feasible for consumption.
When considering the distribution of macronutrients, the carbohydrate-to-protein ratio has been shown to be important for supporting optimal body composition and fat loss in women. The consumption of a ratio of 2:1 carbohydrate to protein has demonstrated significant losses in percent body fat while supporting a gain in lean mass.
Research on timing of nutrients around exercise in active women has highlighted the importance of amino acid availability in regulating muscle protein synthesis, metabolism, and adaptations to exercise. Data indicate consuming protein either before or after exercise is a key factor in muscle protein synthesis in active women, and the timing of protein may be even more critical for women compared with men.
Supplement Considerations Across the Lifespan
Evidence supports specific supplementation strategies for active women, though research in many areas remains limited. Beta-alanine may be particularly effective for women who have lower baseline muscle carnosine levels, with middle-aged women showing significant strength improvements following 28 days of supplementation. The ingredient may also have antioxidant properties relevant during the follicular phase when inflammation is elevated.
Creatine supplementation shows benefits for women related to strength, hypertrophy, performance, and cognitive outcomes. Women demonstrate 70-80% lower endogenous creatine stores than men, and creatine kinase levels fluctuate with the menstrual cycle. The supplement may be particularly effective post-partum and during the menopause transition. A common misconception is undesirable weight gain, but initial gains with loading doses are cellular hydration, not fat gain.
Caffeine elimination fluctuates over the menstrual cycle with slower elimination during the luteal phase and with oral contraceptive use. The accumulation during high-estrogen phases may magnify premenstrual symptoms and intensify sympathetic effects. Women show greater plasma caffeine levels at the same dose as men, suggesting dose adjustments may be necessary based on menstrual phase or contraceptive use.
Nitrate supplementation may be more effective in women, who have higher baseline nitric oxide levels and greater ability to reduce nitrates to nitric oxide compared with men. The effects appear more pronounced in early post-menopausal women for blood pressure support.
Essential fatty acids, particularly omega-3, have demonstrated improved inflammatory environments, which may be beneficial during the follicular phase when systemic inflammation is elevated. Omega-3 may also support muscle protein synthesis and reduce symptoms of depression and anxiety, which are reported at higher rates in women.
Vitamin D levels decrease as women age, with the highest deficiency rate in post-menopausal women. For active women, vitamin D affects muscle strength, performance, recovery, and bone health. Magnesium requirements may change with oral contraceptive use, pregnancy, and menopause. Supplementation may improve premenstrual syndrome symptoms and provide cardioprotective benefits as women age.
Probiotics may be particularly relevant for women, who have lower intestinal permeability and higher microbial diversity but greater sensitivity to perturbation. Supplementation has shown improved intestinal function, reduced inflammation, improved iron absorption, and reduced urinary tract infection recurrence.
The Research Gap Remains the Biggest Problem
Women have unique and changeable hormone profiles that influence their physiology and nutritional needs. Understanding the menstrual cycle, oral contraceptive use, and the evolving hormonal landscape as women age is essential to support health and well-being.
Evidence supports use of specific ingredients to optimize body composition, delay fatigue, and improve mental and physical health. But the most striking finding in this comprehensive review is not what works—it's how little we know. The representation of women in exercise and nutrition research is severely lacking. Most supplement recommendations are extrapolated from research in men or from populations that don't match the specific hormonal profile of active women.
Major research gaps include effects of supplements across menstrual cycle phases, long-term metabolic effects of oral contraceptives on training adaptations, optimal nutrition during the peri-menopause transition, and sex-specific supplement responses. Future research and product development must include women across the lifespan.
Until that happens, active women must make nutritional decisions based on incomplete evidence, understanding that their physiological needs differ from men at every stage of life.
Study: Smith-Ryan, A. E., Cabre, H. E., & Moore, S. R. (2022). Active women across the lifespan: Nutritional ingredients to support health and wellness. Sports Medicine, 52(Suppl 1), S101-S117
