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Open Access

Peer-reviewed

Research Article

Skin melanin is associated with body temperature regulation in humans and mice

  • Kale S. Bongers,

    Roles Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Writing – original draft, Writing – review & editing

    Affiliations Division of Pulmonary, Critical Care, and Occupational Medicine, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America

    ⨯
  • Santiago Tovar,

    Roles Data curation, Investigation, Writing – review & editing

    Affiliation Department of Medicine, Emory University, Atlanta, GeorgiaUnited States of America

    ⨯
  • Zanthia Wiley,

    Roles Writing – review & editing

    Affiliation Department of Medicine, Emory University, Atlanta, GeorgiaUnited States of America

    ⨯
  • Michele Sumler,

    Roles Writing – review & editing

    Affiliation Department of Anesthesiology, Emory University, Atlanta, GeorgiaUnited States of America

    ⨯
  • Nina G. Jablonski,

    Roles Writing – review & editing

    Affiliation Department of Anthropology, Pennsylvania State University, University Park, Pennsylvania, United States of America

    ⨯
  • Adewole S. Adamson,

    Roles Writing – review & editing

    Affiliation Department of Internal Medicine, Dell Medical School, Austin, Texas, United States of America

    ⨯
  • Sivasubramanium V. Bhavani

    Roles Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Writing – original draft, Writing – review & editing

    sbhava2@emory.edu

    Affiliations Department of Medicine, Emory University, Atlanta, GeorgiaUnited States of America, Emory Critical Care Center, Emory University, Atlanta, GeorgiaUnited States of America

    ⨯

Abstract

Body temperature, a universally measured clinical indicator of physiological equilibrium, guides critical treatment decisions. Multiple studies have observed significant body temperature differences among racial subgroups, with Black patients consistently having higher temperatures than White patients. However, race is a social construct and not a biological category; thus, race alone cannot explain this temperature variability. We hypothesized that skin melanin, which often varies across racial categories, could explain body temperature differences. Here, using a prospectively enrolled human cohort study and a parallel mouse model, we demonstrate that skin melanin is associated with body temperature in humans and mice. In humans, colorimeter-measured melanin index was positively correlated with temperature. Likewise, we found that pigmented mice had higher temperatures than albino mice. Our results reveal that melanin could explain the consistent differences in body temperature observed across socially defined racial groups and suggest a potential role for melanin in thermoregulation.

Citation: Bongers KS, Tovar S, Wiley Z, Sumler M, Jablonski NG, Adamson AS, et al. (2025) Skin melanin is associated with body temperature regulation in humans and mice. PLoS One 20(11): e0334735. https://doi.org/10.1371/journal.pone.0334735

Editor: Ling Hou, Wenzhou Medical University, CHINA

Received: July 23, 2025; Accepted: October 1, 2025; Published: November 7, 2025

Copyright: © 2025 Bongers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Anonymized data is provided in the supplement.

Funding: This study is funded by the following grants: R01 R01HL175626 from National Heart, Lung, and Blood Institute (to SVB), K23GM144867 from the National Institute of General Medical Sciences (to SVB); K08AR083015 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (to KSD).

Competing interests: The authors have declared that no competing interests exist.

Introduction

Thermoregulation is a fundamental physiological process in health and disease. Over the past few decades, studies have noted significant differences in body temperature across racial subgroups in the U.S., with the consistent finding of higher oral temperatures in Black patients compared to White patients [1–5]. Race is a social construct and not a biological category [6]. Thus, racial designations do not explain these body temperature differences. However, skin melanin expression varies across populations and has been historically linked with socially defined racial categories [7,8]. Rather than the social construct of race, the biological variable of melanin may explain the observed differences in temperature.

To test whether melanin is associated with body temperature, we performed two distinct investigations: 1) in a prospective human clinical study, we evaluated the association between quantified skin melanin and oral temperature; 2) in mouse model studies, we compared the differences in temperature between albino mice (which produce no melanin) and pigmented mice (which produce melanin).

Methods

Human clinical study

Adult patients admitted to three medical ICUs at two different hospitals in Atlanta, GA, USA were eligible for enrollment during the period of 01/01/2024–31/12/2024. Demographic information including self-reported race as documented in the Electronic Health Record was noted. Geographic ancestry information was not available. Oral temperature was measured with a Welch Allyn thermometer. Skin tone was measured on the forehead using the Delfin colorimeter to obtain two metrics: 1) melanin index, and 2) Individual Typology Angle (ITA). Melanin index is a unitless measure of the reflectance ratio of the skin, with higher values for darker skin tone and ITA is a standardized metric calculated based on the L*a*b color space, with lower values for darker skin tone [9]. All measurements were taken between 11am to 5 pm. Covariates of interest that could affect body temperature were recorded including age, sex, requirement of vasopressors, mechanical ventilation, and continuous renal replacement therapy, and timing of temperature measurement. The agreement between melanin index and ITA was assessed using the intraclass correlation coefficient (ICC). The association between oral temperature and each of the two skin tone measures was evaluated using Pearson correlation coefficients. To further examine the relationship between oral temperature and melanin index, multivariable linear regression was performed, adjusting for age, sex, vasopressor use, mechanical ventilation, continuous renal replacement therapy, and timing of temperature measurement. The study was approved by the Institutional Review Board at Emory University (Study #5545), with a waiver of documentation of informed consent (i.e., signature). Verbal consent was obtained from participating subjects or their legally authorized representatives using the IRB-approved consent script, and the process was documented by the clinical research coordinator in the study records at the time of enrollment. Informed consent was not waived; only the requirement for a subject’s signature was waived, as approved by the IRB.

Mouse models

Seven-week-old female C57BL/6 and B6(Cg)-tyrc-2J mice were obtained from Jackson Laboratories (Bar Harbor, ME). As described previously [10], mice were housed at 21°C in colony cages with a 12:12-hour light-dark cycle with ad libitum access to water and standard chow (Envigo Teklad, Indianapolis, IN). Rectal temperatures were measured at the same time of day with a Fisherbrand™ Traceable™ thermometer with RET-3 mouse rectal probe (ThermoFisher Scientific, Waltham, MA). For non-mixing studies, mice were kept isolated by strain and left to equilibrate for 7 days prior to temperature measurement. For subsequent mixing studies, mice were mixed so that each cage contained mice from each strain for 14 days, at which time body temperatures were again measured. Importantly, prior studies demonstrate microbiome mixing by 7 days of co-housing [11,12]. All animal studies were approved by the Institutional Animal Care and Use Committees of the Universities of Michigan (PRO00009673) and Iowa (#4052592). Mice were euthanized via carbon dioxide asphyxiation followed by cervical dislocation for confirmation, as per AVMA guidelines. Additional anesthesia and analgesia methods were not used for rectal temperature measurement or euthanasia.

Results

Human clinical study

In the prospective study of 275 hospitalized patients, the median age was 62 years (IQR 47−73 years), 54% males, and 74% Black, 19% White, and 7% other race. Melanin and ITA were significantly correlated (r = −0.95, p < 0.001). Both melanin and ITA were significantly correlated with oral temperature (r=+0.17, p = 0.004 and r = −0.17, p = 0.004, respectively) (Fig 1). When adjusting for age, sex, presence of vasopressors, mechanical ventilation, or renal replacement therapy, and timing of measurement, melanin index and ITA remained significantly associated with oral temperature (p = 0.03 and p = 0.04, respectively). When excluding patients with a fever (temperature>38.3°C), melanin and ITA remained significant associated with oral temperature (p = 0.02 and p = 0.03, respectively). When the models were adjusted for race, neither melanin nor race were significantly associated with body temperature. To disentangle the role of melanin from the construct of race in association with temperature, we performed the following mouse model.

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Fig 1. Correlation between melanin and oral temperature.

Melanin index and Individual Typology Angle (ITA) are plotted against oral temperature in 275 hospitalized patients, and the regression fit with 95% confidence interval is shown. Melanin and ITA were both significantly correlated with oral temperature.

https://doi.org/10.1371/journal.pone.0334735.g001

Mouse model

To evaluate whether these associations were due to pigmentation or merely an epiphenomenon, we used a mouse model to minimize biological and environmental variability which might confound the human study. Utilizing C57BL/6 mice (which are pigmented) and B6(Cg)-tyrc-2J mice (which are on the C57BL/6 genetic background but are homozygous for a tyrosinase mutation rendering them albino [13]), we compared baseline body temperatures. Similar to the finding of higher body temperature in patients with higher melanin content, we found the pigmented C57BL/6 mice had a significantly higher body temperature than the otherwise genetically-matched albino B6(Cg)-tyrc-2J strain (38.6 ± 0.41°C versus 38.4 ± 0.42°C, P < 0.04) (Fig 2A). Since the gut microbiome can influence body temperature in mice [10], and gut microbiota can vary by mouse shipment [14,15], as an additional control we minimized microbiome effects via a two-week cage mixing study (a duration previously shown to equilibrate gut microbiota [11,12]), and again found that the pigmented C57BL/6 mice had a significantly higher body temperature than albino B6(Cg)-tyrc-2J mice (38.6 ± 0.33°C versus 38.3 ± 0.35°C, P < 0.0001) (Fig 2B).

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Fig 2. Skin pigmentation mediates body temperature in mice.

(A-C) Female C57BL/6 and B6(Cg)-tyrc-2J mice were obtained from Jackson Laboratories, and temperature was assessed with a rectal thermometer. Error bars denote SEM. (A) B6(Cg)-tyrc-2J have lower basal body temperature compared to C57BL/6 mice prior to microbiome mixing. n = 55-70 mice per treatment. P < 0.04. (B) After microbiome mixing, B6(Cg)-tyrc-2J continued to have lower basal body temperature compared to C57BL/6 mice. n = 55-70 mice per treatment. P < 0.0001.

https://doi.org/10.1371/journal.pone.0334735.g002

Discussion

This paper presents novel evidence of a relationship between melanin concentration and temperature through both human and mouse studies, in which we found that: 1) higher levels of melanin were associated with higher oral temperatures in humans; and 2) pigmented mice had higher rectal temperatures than albino mice on the same genetic background. Over several decades, studies have consistently noted higher oral temperatures in Black patients compared to White patients in the U.S [1–5]. Since race is a social construct and not a biological category [6], race by itself is unlikely to explain this difference in temperature measurement. However, in human clinical studies, race and skin tone are often closely intertwined, and it is difficult to disentangle the role of melanin in thermoregulation [7]. The mouse model provides evidence that melanin may play a role in thermoregulation.

While the temperature differences we found were relatively small in absolute terms, given the relatively narrow homeostatic range of body temperature (approximately 2°C), this is a potentially clinically relevant change. Additionally, given the typical “all or none” clinical response to fever, where a certain temperature threshold (38.3°C in ICU patients [16]) often triggers changes to treatment (such as empiric antibiotics or antipyretics), slight temperature differences may lead to outsized clinical effects at a healthcare-system level.

These findings have important implications for our understanding of body temperature regulation. Thermoregulation is complex and involves the neurological, cardiovascular, musculoskeletal, endocrine, and immune systems [17,18]. However, the role of epidermal melanin in thermoregulation remains poorly understood. Melanin is produced in melanocytes from the amino acid tyrosine through a process beginning with an oxidation step by the enzyme tyrosinase [19]. Melanin is then transported to keratinocytes in the skin, where it serves to absorb ultraviolet light and near-infrared radiation to protect the underlying tissue [19–21]. Through this role, melanin plays a direct part in heat transfer in endothermic species [22–24], and thus could be involved in thermoregulation. Other potential mechanisms are possible. For example, melanin is associated with a reduced capacity for Vitamin D synthesis, particularly under conditions of limited UVB exposure. Additionally, melanin helps protect bioactive folates from photodegradation, which may have downstream effects on physiological processes [25]. These molecules could potentially mediate thermoregulatory pathways. Furthermore, melanin’s precursor tyrosine is also a precursor to catecholamine synthesis [26,27]. Small human studies have shown that tyrosine supplementation reduces temperature drop during cold tolerance testing through increased cutaneous vasoconstriction [26,27], which could suggest a tradeoff between melanin and catecholamine production regulating body temperature. Further studies are needed to investigate these mechanistic hypotheses. In particular, evaluating potential body temperature changes in mice with genetically-inducible melanin would be useful.

Beyond melanin itself, other melanin-regulating pathways may also play a role in thermoregulation. First, melanocyte-stimulating hormone (MSH) stimulates melanogenesis in human melanocytes [28–30] and MSH administration can prevent fever in septic rabbits through effects on prostaglandin synthesis [31] and induce hypothermia in rats [32]; MSH receptor agonists have biphasic effects on body temperature [33]. Second, melanin-concentrating hormone (MCH) also plays an important role in skin pigmentation in some species of fish [34], while in mammals, antibodies blocking the MCH receptor appear to play a role in vitiligo pathogenesis [35]. Knockout of the genes encoding MCH [36] and the MCH receptor [37] increases basal body temperature, while exogenous MCH infusion reduces body temperature [38]. Third, the gene KIT Ligand (KITLG) is also known to be both involved in melanogenesis and a regulator of thermogenesis in brown adipose tissue [39]. Additional studies are needed to explore relationships between melanogenesis and thermogenesis, which may involve several of these interrelated pathways.

Our study has several limitations. First, oral temperatures may not reflect core body temperatures, and different sites of measurement may have different associations with melanin. Second, our human melanin quantification study took place in ICUs, and critically ill patients may have different thermoregulatory responses from the general population. Third, geographic ancestry of the patients was not ascertained, and while race is a social construct, ancestry is likely more closely linked to differences in melanin. Fourth, there may be unmeasured confounders associated with both race and melanin in our human study which could explain temperature differences. Fifth, confounders such as ambient temperature were not measured and adjusted for. Finally, our mouse models used rectal rather than oral temperature measurements, as oral temperature measurement is not a validated method in mice [40]. This difference in measurement sites (oral temperatures in humans, but rectal temperatures in mice) may affect comparability of the results. Future studies using human rectal temperature measurements and alternate methods of murine temperature measurement, particularly long-term surgically-implanted monitors [40], would be informative.

In conclusion, higher melanin levels are associated with higher oral temperature in humans and higher rectal temperature in mice, suggesting a potential role of melanin in thermoregulation.

Supporting information

S1 Table. De-identified patient-level information on melanin, ITA, and oral temperature.

https://doi.org/10.1371/journal.pone.0334735.s001

(CSV)

References

  1. 1. Mackowiak PA, Wasserman SS, Levine MM. A critical appraisal of 98.6 degrees F, the upper limit of the normal body temperature, and other legacies of Carl Reinhold August Wunderlich. JAMA. 1992;268(12):1578–80. pmid:1302471
  2. 2. McGann KP, Marion GS, Camp L, Spangler JG. The influence of gender and race on mean body temperature in a population of healthy older adults. Arch Fam Med. 1993;2(12):1265–7. pmid:8130908
  3. 3. Obermeyer Z, Samra JK, Mullainathan S. Individual differences in normal body temperature: longitudinal big data analysis of patient records. BMJ. 2017;359:j5468. pmid:29237616
  4. 4. Speaker SL, Pfoh ER, Pappas MA, Hu B, Rothberg MB. Oral Temperature of Noninfected Hospitalized Patients. JAMA. 2021;325(18):1899–901. pmid:33974027
  5. 5. Bhavani SV, Wiley Z, Verhoef PA, Coopersmith CM, Ofotokun I. Racial Differences in Detection of Fever Using Temporal vs Oral Temperature Measurements in Hospitalized Patients. JAMA. 2022;328(9):885–6. pmid:36066526
  6. 6. Witzig R. The medicalization of race: scientific legitimization of a flawed social construct. Ann Intern Med. 1996;125(8):675–9. pmid:8849153
  7. 7. Horsley V, Dadzie OE, Hall R, Jablonski NG. Disentangling Race from Skin Color in Modern Biology and Medicine. Journal of Investigative Dermatology. 2023.
  8. 8. Jablonski NG. Skin color and race. Am J Phys Anthropol. 2021;175(2):437–47. pmid:33372701
  9. 9. Hao S, Dempsey K, Matos J, Cox CE, Rotemberg V, Gichoya JW, et al. Utility of Skin Tone on Pulse Oximetry in Critically Ill Patients: A Prospective Cohort Study. Crit Care Explor. 2024;6(9):e1133. pmid:39268149
  10. 10. Bongers KS, Chanderraj R, Woods RJ, McDonald RA, Adame MD, Falkowski NR, et al. The Gut Microbiome Modulates Body Temperature Both in Sepsis and Health. Am J Respir Crit Care Med. 2023;207(8):1030–41. pmid:36378114
  11. 11. Caruso R, Ono M, Bunker ME, Núñez G, Inohara N. Dynamic and Asymmetric Changes of the Microbial Communities after Cohousing in Laboratory Mice. Cell Rep. 2019;27(11):3401–3412.e3. pmid:31189120
  12. 12. Runge S, von Zedtwitz S, Maucher AM, Bruno P, Osbelt L, Zhao B, et al. Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype. Nat Commun. 2025;16(1):5301. pmid:40506454
  13. 13. Beermann F, Orlow SJ, Lamoreux ML. The Tyr (albino) locus of the laboratory mouse. Mamm Genome. 2004;15(10):749–58. pmid:15520878
  14. 14. Bongers KS, Chanderraj R, Deng H, Song Y, Newstead MW, Metcalf JD, et al. Inflammatory Responses to Polymicrobial Intra-abdominal Sepsis are Highly Variable but Strongly Correlated to Enterobacteriaceae Outgrowth. Shock. 2024;62(2):275–85. pmid:38888452
  15. 15. Long LL, Svenson KL, Mourino AJ, Michaud M, Fahey JR, Waterman L, et al. Shared and distinctive features of the gut microbiome of C57BL/6 mice from different vendors and production sites, and in response to a new vivarium. Lab Anim (NY). 2021;50(7):185–95. pmid:34127866
  16. 16. O’Grady NP, Alexander E, Alhazzani W, Alshamsi F, Cuellar-Rodriguez J, Jefferson BK, et al. Society of Critical Care Medicine and the Infectious Diseases Society of America Guidelines for Evaluating New Fever in Adult Patients in the ICU. Crit Care Med. 2023;51(11):1570–86. pmid:37902340
  17. 17. Mota-Rojas D, Titto CG, Orihuela A, Martínez-Burnes J, Gómez-Prado J, Torres-Bernal F, et al. Physiological and Behavioral Mechanisms of Thermoregulation in Mammals. Animals (Basel). 2021;11(6):1733. pmid:34200650
  18. 18. Tansey EA, Johnson CD. Recent advances in thermoregulation. Adv Physiol Educ. 2015;39(3):139–48. pmid:26330029
  19. 19. Slominski A, Tobin DJ, Shibahara S, Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev. 2004;84(4):1155–228. pmid:15383650
  20. 20. D’Alba L, Shawkey MD. Melanosomes: Biogenesis, Properties, and Evolution of an Ancient Organelle. Physiol Rev. 2019;99(1):1–19. pmid:30255724
  21. 21. Brenner M, Hearing VJ. The protective role of melanin against UV damage in human skin. Photochem Photobiol. 2008;84(3):539–49. pmid:18435612
  22. 22. Margalida A, Negro JJ, Galván I. Melanin-based color variation in the Bearded Vulture suggests a thermoregulatory function. Comp Biochem Physiol A Mol Integr Physiol. 2008;149(1):87–91. pmid:18060818
  23. 23. Riley PA. Melanin. Int J Biochem Cell Biol. 1997;29(11):1235–9.
  24. 24. Roldan-Kalil J, Zueva L, Alves J, Tsytsarev V, Sanabria P, Inyushin M. Amount of Melanin Granules in Human Hair Defines the Absorption and Conversion to Heat of Light Energy in the Visible Spectrum. Photochem Photobiol. 2023;99(4):1092–6. pmid:36403200
  25. 25. Jablonski NG, Chaplin G. The evolution of human skin coloration. J Hum Evol. 2000;39(1):57–106. pmid:10896812
  26. 26. Lang JA, Krajek AC, Schwartz KS, Rand JE. Oral L-Tyrosine Supplementation Improves Core Temperature Maintenance in Older Adults. Med Sci Sports Exerc. 2020;52(4):928–34.
  27. 27. Lang JA, Smaller KA. Oral l-tyrosine supplementation augments the vasoconstriction response to whole-body cooling in older adults. Exp Physiol. 2017;102(7):835–44. pmid:28477375
  28. 28. Herraiz C, Martínez-Vicente I, Maresca V. The α-melanocyte-stimulating hormone/melanocortin-1 receptor interaction: A driver of pleiotropic effects beyond pigmentation. Pigment Cell Melanoma Res. 2021;34(4):748–61. pmid:33884776
  29. 29. Yardman-Frank JM, Fisher DE. Skin pigmentation and its control: From ultraviolet radiation to stem cells. Exp Dermatol. 2021;30(4):560–71. pmid:33320376
  30. 30. Carney BC, Travis TE, Moffatt LT, Johnson LS, McLawhorn MM, Simbulan-Rosenthal CM, et al. Hypopigmented burn hypertrophic scar contains melanocytes that can be signaled to re-pigment by synthetic alpha-melanocyte stimulating hormone in vitro. PLoS One. 2021;16(3):e0248985. pmid:33765043
  31. 31. Davidson J, Milton AS, Rotondo D. Alpha-melanocyte-stimulating hormone suppresses fever and increases in plasma levels of prostaglandin E2 in the rabbit. J Physiol. 1992;451:491–502. pmid:1403821
  32. 32. Yehuda S, Carasso RL, Mostofsky DI. The facilitative effects of alpha-MSH and melanin on learning, thermoregulation, and pain in neonatal MSG-treated rats. Peptides. 1991;12(3):465–9. pmid:1681521
  33. 33. Lute B, Jou W, Lateef DM, Goldgof M, Xiao C, Piñol RA, et al. Biphasic effect of melanocortin agonists on metabolic rate and body temperature. Cell Metab. 2014;20(2):333–45. pmid:24981835
  34. 34. Kawauchi H, Baker BI. Melanin-concentrating hormone signaling systems in fish. Peptides. 2004;25(10):1577–84. pmid:15476924
  35. 35. Kemp EH, Weetman AP. Melanin-concentrating hormone and melanin-concentrating hormone receptors in mammalian skin physiopathology. Peptides. 2009;30(11):2071–5. pmid:19442695
  36. 36. Segal-Lieberman G, Bradley RL, Kokkotou E, Carlson M, Trombly DJ, Wang X, et al. Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype. Proc Natl Acad Sci U S A. 2003;100(17):10085–90. pmid:12897241
  37. 37. Ahnaou A, Dautzenberg FM, Huysmans H, Steckler T, Drinkenburg WHIM. Contribution of melanin-concentrating hormone (MCH1) receptor to thermoregulation and sleep stabilization: evidence from MCH1 (-/-) mice. Behav Brain Res. 2011;218(1):42–50. pmid:21074567
  38. 38. Ito M, Gomori A, Ishihara A, Oda Z, Mashiko S, Matsushita H, et al. Characterization of MCH-mediated obesity in mice. Am J Physiol Endocrinol Metab. 2003;284(5):E940–5. pmid:12554598
  39. 39. Yang Z, Shi H, Ma P, Zhao S, Kong Q, Bian T, et al. Darwinian Positive Selection on the Pleiotropic Effects of KITLG Explain Skin Pigmentation and Winter Temperature Adaptation in Eurasians. Mol Biol Evol. 2018;35(9):2272–83. pmid:29961894
  40. 40. Meyer CW, Ootsuka Y, Romanovsky AA. Body Temperature Measurements for Metabolic Phenotyping in Mice. Front Physiol. 2017;8:520. pmid:28824441