Exploring how biological sex, reproductive hormones, mitochondrial function, fat distribution, and evolutionary adaptations influence the way our bodies store and use energy—and why personalized nutrition should account for these differences.
Why might two individuals with similar body weights, dietary habits, and physical activity levels respond differently to the same nutritional intervention?
Why do men and women often demonstrate different patterns of fat storage?
Why does the body sometimes prioritize preserving energy over maintaining reproductive function?
And why can the hormonal changes associated with menopause alter metabolic health even when lifestyle habits remain relatively consistent?
These questions reveal an important limitation of conventional nutritional advice: human metabolism is not identical across individuals, and biological sex is one important source of that variation.
Metabolism is frequently discussed as though everyone operates according to the same biological processes, with differences determined primarily by caloric intake and physical activity.
Although energy balance remains fundamental to human physiology, the mechanisms governing energy storage, fuel utilization, appetite, insulin sensitivity, and reproductive function are considerably more complex.
In 2024, endocrinologist Franck Mauvais-Jarvis published Sex Differences in Energy Metabolism: Natural Selection, Mechanisms and Consequences in Nature Reviews Nephrology.
The review investigated how evolutionary pressures, genetic factors, reproductive hormones, and tissue-specific metabolic processes contribute to differences between male and female energy regulation.
The author proposed that several characteristic features of female metabolism—including greater subcutaneous fat storage and increased reliance on lipid oxidation during prolonged exercise—may reflect adaptations that historically supported survival and reproduction during periods of limited food availability.
More recent research published in Nature Reviews Endocrinology, Nature Aging, Nature Metabolism, and Nature Medicine has expanded this framework.
These investigations reveal how sex-related differences influence skeletal muscle metabolism, insulin signaling, mitochondrial function, adipose tissue biology, and metabolic changes across the lifespan.
Together, they support a more individualized approach to nutrition and exercise.
However, they also require an important distinction.
Population-level biological differences do not establish that every man or woman has the same metabolism or requires a particular diet.
Individual responses remain influenced by genetics, age, reproductive status, physical conditioning, medications, health conditions, and environmental circumstances.
Understanding these interactions is central to precision nutrition.
1. Energy Metabolism: More Than Calories Consumed and Expended
Human metabolism involves a collection of biochemical processes responsible for obtaining, storing, distributing, and utilizing energy.
Food provides substrates that can be converted into ATP, stored for future use, or incorporated into cellular structures.
Carbohydrates can provide glucose for immediate use or storage as glycogen.
Fats can be oxidized for energy or stored as triglycerides.
Proteins supply amino acids necessary for tissue maintenance and other biological functions, although amino acids can also contribute to energy metabolism.
These processes occur throughout the body.
Skeletal muscle, liver, adipose tissue, pancreas, gastrointestinal tract, and brain all participate in regulating energy availability.
The relative contribution of different fuels depends on several factors.
These include whether a person is fasting or recently fed, the intensity of physical activity, hormonal signaling, and the body's immediate physiological demands.
Sex-related biological differences can influence these processes.
However, energy balance and fuel selection should not be confused.
A person can oxidize a greater proportion of fat during exercise without necessarily losing more body fat over time.
Similarly, a dietary intervention can change fuel utilization without producing equivalent improvements in cardiometabolic health.
The distinction between fuel use, energy storage, and long-term health outcomes is essential.
2. Why Evolutionary Biology Matters to Metabolism
The central argument of the Mauvais-Jarvis review is that reproductive demands may have contributed to the evolution of different metabolic strategies in male and female mammals.
Pregnancy and lactation require substantial energy and nutrient availability.
Successful reproduction depends partly on maintaining sufficient resources to support maternal physiology and developing offspring.
The review proposes that these demands may have favored mechanisms enabling females to preserve energy stores and essential body proteins during periods of scarcity.
One potential adaptation involves greater storage of energy in subcutaneous adipose tissue.
Another involves increased reliance on fat oxidation during prolonged physical activity.
These mechanisms may help preserve glucose availability and reduce reliance on protein breakdown.
The author contrasts these features with the generally greater skeletal muscle mass and carbohydrate utilization observed in men under certain conditions.
However, evolutionary explanations must be interpreted carefully.
The proposed historical selection pressures cannot be directly tested in modern human populations.
Many supporting mechanisms come from animal research, comparative physiology, and observations of contemporary humans.
The review therefore provides a useful explanatory model rather than definitive proof that every sex-related metabolic characteristic evolved for one specific reproductive purpose.
Its strongest contribution is showing how energy regulation and reproductive biology are interconnected.
3. Why Women Typically Store More Body Fat
One of the most consistently observed sex differences in human body composition involves the relative amounts and distribution of adipose tissue.
Women generally have a higher percentage of body fat than men, including among physically active individuals.
However, the significance of adipose tissue depends on more than its total quantity.
Adipose tissue is a metabolically active organ that stores energy and produces signaling molecules.
Its biological effects vary according to location, cellular characteristics, and metabolic state.
The 2024 review emphasizes that women generally possess larger subcutaneous fat depots, particularly around the hips and thighs.
Men, on average, demonstrate a greater tendency toward visceral and abdominal fat accumulation.
These patterns reflect interactions among sex hormones, genetics, developmental influences, and lifestyle.
They are not universal rules.
Nevertheless, the differences have important metabolic implications.
4. Subcutaneous Versus Visceral Fat: Why Location Matters
Subcutaneous adipose tissue is located beneath the skin.
Visceral adipose tissue is found within the abdominal cavity surrounding internal organs.
Both tissues perform important physiological functions.
However, excessive visceral adiposity is more consistently associated with several cardiometabolic risk factors.
These include insulin resistance, dyslipidemia, and increased cardiovascular risk.
The Mauvais-Jarvis review describes how estrogen signaling may promote the preferential storage of energy in subcutaneous rather than visceral adipose tissue.
In contrast, changes in sex hormone signaling can influence the distribution of fat toward more central depots.
This helps explain why body composition cannot be evaluated exclusively through total weight or body mass index.
Two individuals with identical BMI values may demonstrate different metabolic characteristics because of differences in fat distribution, muscle mass, and physical fitness.
The clinical implication is not that everyone should pursue the lowest possible body-fat percentage.
It is that healthy adipose tissue function and appropriate metabolic regulation matter more than appearance alone.
5. Estrogen Is a Metabolic Hormone, Not Just a Reproductive Hormone
Estrogen is most commonly discussed in relation to menstrual cycles, fertility, pregnancy, and menopause.
However, its physiological roles extend far beyond reproduction.
Estrogen receptors are expressed in several metabolically important tissues.
These include skeletal muscle, liver, adipose tissue, pancreas, and parts of the nervous system.
Through these receptors, estrogen signaling influences processes involved in glucose metabolism, lipid handling, cellular function, and energy regulation.
A 2025 Nature Metabolism review, Metabolic Messengers: Oestradiol, examines estradiol's contributions to systemic metabolic health in both women and men.
The authors emphasize the importance of estrogen receptor-alpha and its tissue-specific biological effects.
This reinforces an important distinction.
Estrogen is not exclusively relevant to female metabolism.
Men also produce estrogen, in part through the conversion of testosterone by aromatase.
Its biological effects depend on tissue-specific receptor expression, local metabolism, and circulating concentrations.
Consequently, the metabolic roles of estrogen cannot be understood solely through a simple comparison of male and female hormone levels.
6. Sex Differences in Fuel Utilization During Exercise
One of the most interesting findings reviewed by Mauvais-Jarvis involves differences in the relative use of carbohydrates and fats during prolonged exercise.
Several studies have reported that women oxidize a greater proportion of fat relative to carbohydrates than men during comparable endurance exercise.
Men, on average, may demonstrate greater relative reliance on carbohydrate metabolism under certain exercise conditions.
These differences are frequently investigated using indirect calorimetry.
Researchers measure oxygen consumption and carbon dioxide production to estimate the contribution of different energy substrates.
The review discusses estrogen-related mechanisms that may contribute to increased fat utilization during prolonged activity.
However, the relationship depends heavily on exercise intensity, training status, nutritional conditions, and how participants are matched.
For example, comparing athletes based solely on absolute running speed may create misleading conclusions if their aerobic capacities differ.
Researchers must account for differences in training history and relative exercise intensity.
The practical implication is that average fuel-selection patterns may differ by sex, but individual exercise prescription should not rely solely on those averages.
7. Does Greater Fat Oxidation Mean Women Should Eat More Fat?
Not necessarily.
This is one of the most important distinctions for patient education.
The observation that women may oxidize a greater proportion of fat during some endurance activities does not establish that women universally benefit from high-fat or ketogenic diets.
Fuel utilization is only one aspect of metabolic health.
Dietary recommendations must also consider nutrient adequacy, cardiovascular risk, glucose regulation, gastrointestinal function, physical activity, reproductive status, and personal preferences.
Furthermore, a person's ability to oxidize fat during exercise does not determine which dietary pattern is most appropriate.
The strongest evidence for many dietary interventions comes from studies evaluating clinical outcomes rather than individual substrate measurements.
For example, dietary patterns rich in fiber-containing plant foods, adequate protein, and appropriate sources of unsaturated fats have established benefits across several cardiometabolic outcomes.
The relative proportion of dietary fat and carbohydrate can be individualized according to medical needs and activity demands.
However, the 2024 review does not justify prescribing fundamentally different macronutrient ratios to every man and woman.
Understanding biological differences should improve personalization—not replace one universal dietary rule with two new ones.
8. Why Muscle Mass Matters to Metabolic Health
Skeletal muscle is a major site of glucose disposal and energy utilization.
It also contributes to physical capacity and the maintenance of metabolic health across the lifespan.
Men generally possess greater absolute and relative skeletal muscle mass than women.
However, this difference does not mean that men are automatically more metabolically healthy.
The Mauvais-Jarvis review notes that healthy women can demonstrate equal or greater insulin sensitivity despite having less muscle mass.
This apparent contradiction illustrates the importance of tissue-specific regulation.
Insulin sensitivity depends on much more than the quantity of muscle.
It also reflects cellular signaling, lipid metabolism, adipose tissue function, hormonal status, and physical conditioning.
A 2025 Nature Reviews Endocrinology review, Sex Differences in Skeletal Muscle Metabolism in Exercise and Type 2 Diabetes Mellitus, expands this discussion.
The authors emphasize that women remain underrepresented in skeletal muscle research despite increasing recognition of sex-related physiological differences.
They also highlight how exercise training provides important metabolic benefits in both men and women.
This reinforces the importance of individualized fitness assessment rather than assuming that one sex inherently responds better to exercise.
9. Mitochondria and Sex-Related Metabolic Differences
Mitochondria participate in oxidative ATP production and numerous aspects of cellular regulation.
Their function is particularly important in metabolically active tissues, including skeletal muscle.
The Mauvais-Jarvis review summarizes research indicating sex-related differences in mitochondrial characteristics.
Some experimental studies have identified greater mitochondrial respiratory capacity or resistance to oxidative stress in female tissues.
Estrogen signaling is one potential contributor.
However, these findings vary according to species, organ, hormonal status, and experimental methods.
It would therefore be misleading to conclude that all women possess universally superior mitochondria.
The review also discusses maternal inheritance of mitochondrial DNA.
In typical human inheritance, mitochondrial DNA is transmitted through the maternal lineage.
The author considers whether evolutionary pressures may have influenced the preservation of mitochondrial function through maternal transmission.
However, the broader evolutionary interpretation remains a hypothesis.
For practical healthcare, mitochondrial function is better supported through established interventions such as appropriate physical activity and treatment of relevant medical conditions than through assumptions based solely on biological sex.
10. Insulin Sensitivity: Why the Same Glucose Reading May Not Tell the Whole Story
Insulin helps coordinate glucose uptake and metabolism in several tissues.
Insulin resistance occurs when cells demonstrate a reduced response to insulin under particular physiological conditions.
However, glucose regulation is determined by the interaction of multiple processes.
These include insulin secretion, insulin sensitivity, hepatic glucose production, gastrointestinal absorption, and counterregulatory hormones.
The Mauvais-Jarvis review describes sex differences in several aspects of glucose homeostasis.
Some research suggests that women generally demonstrate greater skeletal muscle insulin sensitivity before menopause.
However, fasting glucose and glucose tolerance can differ in ways that are not captured by one measurement.
For example, impaired fasting glucose and impaired glucose tolerance do not have identical physiological characteristics.
Their prevalence can also differ between men and women.
Consequently, evaluating metabolic health may require examining several related measurements rather than relying on fasting glucose alone.
Clinical interpretation should follow validated diagnostic criteria, taking into account the patient's medical history and relevant risk factors.
11. Why Diabetes May Develop Differently in Women and Men
The progression from normal glucose regulation to type 2 diabetes can involve changes in insulin sensitivity, pancreatic beta-cell function, adiposity, and other metabolic processes.
The 2024 review discusses evidence suggesting that women may experience a greater deterioration in certain cardiometabolic risk factors before developing type 2 diabetes.
These changes can include increased adiposity, adverse lipid profiles, and other metabolic abnormalities.
The author proposes that differences in baseline metabolic characteristics may contribute.
However, sex-related differences in diabetes risk and progression are influenced by numerous factors.
Age, menopause, ethnicity, genetics, healthcare access, and lifestyle all matter.
The clinical significance is that risk assessment should not assume identical metabolic trajectories across every population.
Early identification and management of established cardiometabolic risk factors remain important for everyone.
12. Menopause: A Major Transition in Metabolic Regulation
Menopause represents an important physiological transition involving substantial changes in ovarian hormone production.
These changes can influence adipose tissue distribution, insulin sensitivity, lipid metabolism, bone health, and other physiological processes.
A 2024 review in Nature Aging, Exploring the Effects of Estrogen Deficiency and Aging on Organismal Homeostasis During Menopause, examines the relationship between declining estrogen signaling and metabolic regulation.
The authors emphasize that menopause involves changes across multiple organ systems rather than one isolated hormonal event.
However, it can be difficult to separate the consequences of menopause from those of aging.
Changes in physical activity, sleep, body composition, and other health factors may occur over the same period.
The practical lesson is that nutritional and exercise requirements may change across the lifespan.
A strategy that was appropriate at age 25 may need adjustment later.
However, menopause does not automatically require hormone therapy or a particular dietary protocol.
Individual decisions should reflect medical history, symptoms, risks, preferences, and established clinical guidance.
13. The Menstrual Cycle and Metabolic Regulation
Hormonal regulation is not static during the reproductive years.
Estradiol, progesterone, and other hormones fluctuate throughout the menstrual cycle.
These changes can influence several aspects of physiology.
In April 2026, researchers published Plasma Proteomic Signature of the Human Menstrual Cycle in Nature Medicine.
The study analyzed nearly 3,000 circulating proteins among 2,760 women.
Researchers identified 198 proteins that varied across the menstrual cycle.
The findings demonstrate that cyclic reproductive physiology is associated with measurable changes extending beyond conventional reproductive hormone measurements.
However, identifying these changes does not establish that every person needs a different nutrition or training program during each menstrual phase.
A separate 2026 npj Digital Medicine study examining wearable data identified variation in sleep and physiological measurements across menstrual cycles.
The findings highlight the potential value of individual longitudinal observations.
Nevertheless, menstrual-cycle responses vary, and current evidence does not support rigid universal prescriptions assigning specific workouts or macronutrient ratios to each phase.
14. Energy Availability and Reproductive Function
One of the strongest connections between nutrition, exercise, and reproductive physiology concerns energy availability.
Energy availability refers to the dietary energy remaining for normal physiological processes after accounting for exercise-related energy expenditure.
When energy availability becomes insufficient, the body may alter several physiological functions.
These can include reproductive hormone signaling, bone metabolism, and other processes.
This relationship is particularly relevant to athletes and highly active individuals.
Relative Energy Deficiency in Sport, commonly known as RED-S, describes a syndrome associated with problematic low energy availability.
It can affect individuals of any sex.
In women, menstrual disturbances may provide one indication of insufficient energy availability.
However, normal menstruation does not guarantee adequate fueling, and menstrual irregularities have many potential causes.
Low energy availability can also affect men through endocrine and other physiological changes.
The clinical lesson is not that women should avoid demanding exercise.
It is that training demands and nutritional intake must be appropriately matched.
Adequate fueling is essential for health, recovery, and performance.
15. Why Fat Loss and Metabolic Health Are Not Identical Goals
Weight management is often framed as a simple equation involving calorie intake and expenditure.
Although energy balance is essential to changes in body energy stores, long-term outcomes are influenced by numerous biological and behavioral factors.
These include appetite, food environment, hormonal signaling, physical activity, sleep, medications, and individual metabolic characteristics.
Sex-related differences can contribute to variation in body composition and energy regulation.
However, these differences do not invalidate the principles of energy balance.
They help explain why identical interventions may produce different experiences and outcomes.
Importantly, body weight alone is an incomplete measure of health.
An individual may improve insulin sensitivity, cardiovascular fitness, muscular strength, or blood pressure without achieving substantial weight loss.
Another may lose weight while experiencing inadequate nutrition or reductions in physical capacity.
The objective of comprehensive metabolic care should therefore extend beyond changes on a scale.
16. Why Men and Women Should Both Prioritize Resistance Training
Despite biological differences in muscle mass and hormonal regulation, resistance training offers meaningful benefits to both men and women.
These include improvements in strength, muscle function, physical capacity, and several aspects of metabolic health.
Resistance exercise becomes especially relevant during aging.
Maintaining muscular strength contributes to mobility and functional independence.
For women, resistance training may also be important during and after menopause as changes in hormones, body composition, and bone health occur.
For men, maintaining muscle function remains similarly important during aging and periods of reduced physical activity.
However, exercise programs should not be prescribed solely on the basis of biological sex.
Prior training, current strength, medical conditions, recovery capacity, and goals are often more informative for determining an appropriate starting point.
Sex-related physiology can help refine programming, but it should not override the individual's actual performance and response.
17. What About Cardiovascular and Endurance Training?
Aerobic exercise contributes to cardiovascular health, mitochondrial adaptation, and metabolic regulation.
The previously discussed sex differences in substrate utilization may influence some aspects of endurance physiology.
However, they do not establish that one sex should perform predominantly low-intensity exercise while the other should emphasize high-intensity training.
Both moderate-intensity aerobic activity and appropriately prescribed higher-intensity training can produce useful adaptations.
The optimal combination depends on fitness, health status, goals, and recovery.
For example, someone preparing for an endurance event may require a substantial volume of aerobic training.
An individual primarily seeking general health may benefit from a more balanced program involving aerobic exercise, resistance training, and other forms of physical activity.
The most important consideration is providing the appropriate training stimulus for the individual.
18. The Future of Precision Nutrition: Biology Without Stereotypes
Precision nutrition seeks to understand why individuals respond differently to dietary interventions.
A 2025 Nature Medicine review, Precision Nutrition for Cardiometabolic Diseases, describes how advances in digital health, metabolomics, and other technologies are expanding opportunities for individualized dietary research.
However, the authors also emphasize major challenges involving reproducibility, clinical validation, and equitable implementation.
Biological sex is one variable that may improve personalization.
But it is not sufficient by itself.
Two women may differ substantially in metabolic health because of age, menstrual status, medications, physical conditioning, dietary habits, and medical conditions.
Likewise, two men may have very different nutritional needs because of differences in body composition, activity, and metabolic risk.
A scientifically useful precision-nutrition approach therefore considers the individual's actual characteristics rather than relying exclusively on population averages.
Biological sex can inform personalized care, but it should never substitute for understanding the individual.
19. Why Better Sex-Balanced Research Is Essential
The 2025 Nature Reviews Endocrinology review on skeletal muscle metabolism identifies an important limitation in exercise and metabolic research.
Historically, women have been underrepresented in many physiological studies.
This has limited researchers' ability to characterize sex-related differences with adequate confidence.
The problem extends beyond the number of participants.
Studies may also fail to report relevant information about reproductive status, hormonal medications, training history, or other characteristics.
Without these details, meaningful comparisons become difficult.
The authors argue that improving sex-balanced research and reporting is essential for precision medicine.
This is an important lesson for healthcare more broadly.
The goal should not be to assume that male and female biology differ in every meaningful respect.
It should be to investigate when differences matter, when they do not, and how those findings can improve patient outcomes.
20. How This Research Informs Eat Well & Move Well
We recognize that nutritional needs and metabolic responses vary among individuals.
The science of sex-related energy metabolism reinforces the importance of considering biological, hormonal, behavioral, and environmental factors together.
Within Eat Well, our approach emphasizes comprehensive nutrition education and individualized dietary strategies.
Depending on the individual's circumstances, relevant considerations may include energy intake, macronutrient distribution, micronutrient adequacy, dietary patterns, metabolic health, activity levels, and reproductive life stage.
For some individuals, the primary goal may involve improving glucose regulation or addressing nutritional deficiencies.
Others may need strategies supporting athletic performance, healthy body composition, or recovery from physical activity.
Individuals experiencing pregnancy, postpartum changes, menopause, or other reproductive transitions may have additional nutritional considerations requiring appropriate professional guidance.
We also recognize that eating patterns cannot be evaluated independently of movement, sleep, stress, and medical conditions.
For example, an individual's energy needs may change substantially when training volume increases.
Persistent sleep disruption can complicate metabolic and behavioral regulation.
Medication effects and endocrine disorders may also influence weight or glucose metabolism.
Our objective is not to prescribe separate universal diets for men and women.
Instead, we aim to use relevant biological information to make recommendations more appropriate to the individual.
When clinically indicated, validated assessments and collaboration with qualified healthcare professionals may help investigate medical conditions affecting nutritional health.
This approach connects Eat Well with Move Well through the relationship between nutrition, exercise, recovery, and metabolic adaptation.
Conclusion: Metabolism Is Shared Biology Expressed Through Individual Differences
Human metabolism depends on fundamental processes common to everyone.
We obtain energy from nutrients, store reserves, regulate blood glucose, and adjust fuel utilization according to physiological demands.
However, these shared processes are influenced by biological sex, hormonal status, genetics, developmental history, and environmental conditions.
The 2024 review by Mauvais-Jarvis provides a compelling framework for understanding how sex-related differences in reproductive biology may have shaped energy storage and fuel utilization.
More recent research has expanded this perspective through investigations of skeletal muscle metabolism, estrogen signaling, menopause, and precision nutrition.
Together, these findings demonstrate that metabolic health cannot always be fully understood through uniform recommendations.
Yet they also caution against oversimplification.
Not all men metabolize nutrients identically.
Not all women require the same dietary strategies.
And individual differences often overlap considerably between sexes.
The goal of precision nutrition is not to create rigid nutritional rules based on sex. It is to understand which biological differences meaningfully influence health—and use that knowledge to make better decisions for each individual.
We believe this approach reflects a more comprehensive understanding of nutrition.
Food provides the substrates necessary for life, but its effects emerge through a biological system shaped by hormones, tissues, activity, development, and environment.
Understanding these relationships helps us move beyond generalized dietary advice toward a more informed and personalized approach to metabolic health.
Research References
Mauvais-Jarvis F. Sex differences in energy metabolism: natural selection, mechanisms and consequences. Nature Reviews Nephrology. 2024;20:56–69. https://doi.org/10.1038/s41581-023-00781-2
MacGregor K, Ellefsen S, Pillon NJ, Hammarström D, Krook A. Sex differences in skeletal muscle metabolism in exercise and type 2 diabetes mellitus. Nature Reviews Endocrinology. 2025;21:166–179. https://doi.org/10.1038/s41574-024-01058-9
Camon C, Garratt M, Correa SM. Exploring the effects of estrogen deficiency and aging on organismal homeostasis during menopause. Nature Aging. 2024;4:1731–1744. https://doi.org/10.1038/s43587-024-00767-0
Hevener AL, Correa SM. Metabolic messengers: oestradiol. Nature Metabolism. 2025;7:1114–1122. https://doi.org/10.1038/s42255-025-01317-7
Precision nutrition for cardiometabolic diseases. Nature Medicine. 2025;31:1444–1453. https://doi.org/10.1038/s41591-025-03669-9
Riishede I, Rode L, Lundegaard PR, et al. Plasma proteomic signature of the human menstrual cycle. Nature Medicine. 2026;32:2311–2318. https://doi.org/10.1038/s41591-026-04326-5
Gonzalez A, O'Day JJ, Johnson SC, et al. The menstrual cycle through the lens of a wearable device: insights into physiology, sleep, and cycle variability. npj Digital Medicine. 2026;9:633. https://doi.org/10.1038/s41746-026-02799-9
Fritzen AM, Lundsgaard AM, Kiens B. Tuning fatty acid oxidation in skeletal muscle with dietary fat and exercise. Nature Reviews Endocrinology. 2020;16:683–696. https://doi.org/10.1038/s41574-020-0405-1