Hair loss evolving into a lifestyle and metabolic phenotype: A hypothesis exploring oxidative stress and acquired androgen sensitivity through reactive oxygen species

Lifestyle factors in hair loss

Lifestyle factors leading to hair loss and the scientific studies elaborating the mechanisms of these causes are listed in Tables 1 and 2. Stress and anxiety cause hair loss through the release of cortisol, adrenocorticotropic hormone (ACTH), and ROS-mediated action of substance P.^[5,6] Diet modifications affect hair loss through calorie restriction^[7], crash dieting^[8], specific low nutrient content of vegetarian and vegan diets are proven to cause deficiencies of vitamin B12, vitamin D, calcium, iron, iodine, zinc, and omega-3, which are essential for hair growth^[9,10]. According to the theory of Triage, nutritional deficiencies in the body are compensated for by depriving the hair follicles of essential nutrients and redirecting them to maintain optimum function of the vital organs^[11], which inflicts loss of energy and nutritional support for the hair follicles, resulting in arrest of anagen and/or telogen extension (AATE), presenting as miniaturization, identified clinically as AGA. The Triage redistribution restricts the availability of nutrients for growth, repair of cell organelles, DNA damage, metabolic dysfunction, causing accumulation of ROS, cellular degeneration, premature aging, senile, inactive cells, resulting in AATE without any role of DHT.^[11] Extreme diets are harmful to hair. A high-protein diet causes calcinuria, leading to hair loss.^[12] The keto diet induces biotin deficiency.^[13] High sugar, animal foods, and trans fats promote inflammation, leading to hair loss.^[14,15]

Lifestyle and habits influence hair loss. Lack of sleep due to late-night socializing, net surfing, and deadlines at work is associated with hair loss.^[16] Modern social life, with the rising acceptance of alcohol and smoking, has been linked to AGA.^[17,18] Studies have identified sedentary lifestyle, fatigue, exhaustion, and lack of exercise to be associated with hair loss.^[19,20,21] Loss of circadian rhythm^[22] from night shifts, frequent flying across time zones, and seasonal variation^[23] leads to metabolic dysregulation resulting in hair loss. Prolonged exposure to electromagnetic radiation^[24] and UV rays^[25] causes hair loss through the generation of ROS and DNA damage. Pollution promotes hair loss through ROS, metabolic dysfunction, inflammation, and altered immunity.^[26] Hair loss is also caused by pesticides, fertilizers, and endocrine-disrupting chemical contaminants in food.^[27,28]

It was observed that heredity may not be solely contributing to early hair loss. All patients in the study, including those with a family history, had a positive correlation with three or more lifestyle factors linked to hair loss, most commonly stress, alcohol, smoking, sleep, and diet [Tables 1 and 2]. The causes worked in tandem; there was never a single cause or genetic predisposition detected alone. All the lifestyle, environmental, and nutritional factors share primary or secondary ROS-mediated mechanisms that affect the basic biological cellular functions, leading to AATE and hair loss [Table 1].^[5-29] The lifestyle, metabolic, and nutritional factors build an unhealthy epigenome, inducing hair loss through epigenetic changes.^[26,29] Environmental pollution with suspended particle matter can obstruct the quality of UV-B light reaching the skin, hampering the generation of vitamin D.^[26] Modified diets,^[9-11] and depletion of nutrients from the soil are responsible for the low nutritive value of foods,^[30,31], depriving the natural resources upon which cellular function and repair depend, leading to progressive damage and hair loss.^[7,11] Scientific studies have provided the understanding, explored the mechanisms, and indicated the role of lifestyle, environment, and nutritional factors in hair loss, acting through anagen arrest or telogen extension without a direct involvement of DHT or genetics.

Metabolic factors

Metabolic disorders associated with hair loss include thyroid function, gut dysbiosis, hypertension, cardiovascular disorders, diabetes, insulin resistance, obesity, dyslipidemias, metabolic syndrome, and premature aging or senescence, as listed in Table 4.^[32-43] It is noteworthy that all these conditions are referred to as lifestyle-induced metabolic disorders.

Thyroid function influences hair growth and is affected by environmental pollution, electromagnetic radiation, nutritional deficiencies, and epigenetics.^[24,26-29] Responses from the gut-brain axis influence hair growth. Addressing gut issues with probiotics has proven beneficial in AGA.^[33] Early hair loss is a biomarker for cardiovascular disorders, as identified by Sharma et al. 2013, while Triantafyllidi et al. 2017 explored the correlation of AGA with hypertension.^[34,35] Hair loss reflects the changes in glucose metabolism. Matilainen et al. 2000 identified AGA as a biomarker of insulin resistance, while Miranda et al. 2016 defined the hair follicle characteristics as early markers of diabetes.^[36,37] Adipose cells and fat metabolism are related to hair growth. Obesity influences the regulation of hair follicle stem cells.^[38] Kim et al. 2017 analyzed the role of lipid profile and dyslipidemia in AGA,^[39] and Palmar et al. 2020 elaborated the effects of cholesterol homeostasis on hair growth,^[40] [Table 3]. Genome-wide association studies (GWAS) by Shen et al. 2024 have identified raised VLDL as a biomarker of AGA.^[41] Qiu et al. 2022 established the association of AGA with metabolic syndrome.^[42] Modern lifestyle factors are silently contributing to the generation of ROS, oxidative stress, derangement of cellular metabolism, loss of homeostasis, release of inflammatory cytokines, impaired immune response, overexpression of androgens, and cellular aging.^[3-5,42] Thus, sowing the seeds for hair loss and also for the development of multiple lifestyle-induced metabolic disorders. Each of these causes, genetic predisposition, action of androgens, nutrient deficiencies, cellular dysfunction, and oxidative stress or ROS, can disrupt the hair cycles^[45], leading to arrest of AATE.

Genomics and stem cell studies indicate the role of nutrients and cellular metabolism

GWAS on environmental factors by Qian et al. 2025 and evaluation of PITX2 polymorphism by Murgan et al. 2025 have indicated the interaction of genes with environmental and lifestyle factors in the development of AGA.^[46,47] Multiomic Mendelian randomization analysis of lifestyle and oxidative stress-related genes by Zhu et al. 2025 has confirmed through genetic mechanisms that oxidative stress generated by ROS contributes primarily to the pathogenesis of hair loss through follicular cytokines, lipid peroxidation, suppressing dermal papilla cell proliferation, cell migration, and inducing senescence.^[48] Stem cell studies by Chen et al. 2020 demonstrated that macrophages capacitate the hair follicle stem cell (HFSC) niche to sense systemic nutritional status and relay adipocytes to modulate HFSC programming according to the nutrient availability.^[49] Flores et al. 2017 and Kim et al. 2020 have confirmed the role of lactic dehydrogenase and glutamine in the regulation of follicular stem cell activity.^[50,51] Genomic data and stem cell studies have confirmed the role of lifestyle, environment, and oxidative stress in hair loss, postulating the need for directing our attention away from the conventional focus on genetics and DHT.

Studies identify impaired nutrient metabolism and cellular pathways

Ji Li et al. 2023 compared the metabolomics of 48 AGA patients with 52 matched controls, identifying impaired metabolism of arginine and proline as biomarkers of AGA.^[52] Kubota et al. 2024 defined the role of methionine, while Zhang et al. 2024 defined the role of homocysteine in AGA. Homocysteine is a risk factor involved in atherosclerosis, cardiovascular disorders, vascular disease, and endothelial damage, contributing to the etiopathology of vitiligo, psoriasis, and alopecia areata in addition to AGA.^[53,54] Dermal papilla cell cultures by Duan et al. 2025 reported that arginine deficiency accelerates ROS accumulation, inhibits mTOR signaling, suppresses dermal papilla cell proliferation, and arrests hair growth. The effects were reversed clinically with arginine supplementation.^[55] Vanichvongvan et al. 2025 explained the role of the citrate cycle in pattern hair loss and its interaction with glycolysis, gluconeogenesis, carbon metabolism, biosynthesis of amino acids, pentose phosphate pathway, fructose, and mannose metabolism, which are crucial for hair follicle survival and growth.^[56] Metabolomics and cell cultures have confirmed impaired utilization of nutrients and cellular pathways in hair loss.

Balding follicles display ROS-mediated aging or senescence

Researchers conducting studies on cell cultures of AGA follicles have reported signs of aging, including ROS induced oxidative stress, slow metabolism, damage to the DNA, cellular proteins, lipids, cell organelles, loss of regulation of cellular functions, errors of transcription, cell signaling, increased latency between growth cycles, overexpression of androgens and induction of apoptosis, which together constitute a senescence associated secretory phenotype (SASP).^[43,57,58] Scalp biopsies from senescent alopecia in men older than 60 years studied by Price et al. 2001 were indistinguishable from those of young men presenting with male pattern hair loss.^[59] In a comparative study of balding and non-balding dermal papilla cells by Chew et al. 2022, the AGA cells displayed mitochondrial metabolic dysfunction, oxidative stress, and reduced generation of ATP, along with ROS-mediated altered gene expression, similar to aging. The changes promptly responded to the use of antioxidants.^[60] Various studies have demonstrated that hair loss due to pollution, epigenetic changes, and stress-induced hair loss through substance ‘P’ are all mediated by ROS and respond clinically to the use of antioxidants and nutrients, achieving hair growth without the use of DHT blockers or finasteride.^{[24,26,45,61]} A broader understanding of hair loss may include additional genetic influences, non-androgenic lifestyle, metabolic and nutritional factors, with possibilities for benefit from adjunct therapies, especially in the absence of a genetic history and with normal androgen levels.