Tony Clark, CSO (Author) and Steve Fratini, PhD (Editor)
August 20, 2025
Histidine is a fundamental building block of proteins and enzymes essential for a wide range of biological functions. Histidine intake is critical during periods of rapid growth, such as childhood, or in the presence of certain health conditions. Its unique role as a precursor to histamine and its involvement in a variety of metabolic processes make it vital for overall health. Histidine’s antioxidant properties can help to reduce oxidative stress—the result of an imbalance of free radicals and antioxidants—which plays a role in cancer, dementia, heart disease, and kidney disease. Emerging research suggests that histidine plays a crucial role in regulating inflammatory processes that contribute to many chronic diseases.
Histidine’s versatile structure allows it to perform crucial roles in the body, from maintaining the integrity of nerve cells to supporting a healthy immune system. Key benefits include:
Protein and Enzyme Synthesis: Histidine is incorporated into numerous proteins and enzymes that are critical for growth and tissue repair. Its presence is vital for the proper function of key proteins like hemoglobin, which carries oxygen in the blood.
Myelin Sheath Protection: Histidine is essential for maintaining the myelin sheath, a protective layer that insulates nerve cells. This function is vital for proper brain and nervous system communication, as a healthy myelin sheath ensures efficient nerve signal transmission.
Immune Response and Inflammation: The body converts histidine into histamine, a compound that plays a central role in the immune system. Histamine is involved in local immune responses, regulating physiological functions in the gut, and acting as a neurotransmitter.
Antioxidant and Anti-inflammatory Properties: Histidine and its related compounds, such as carnosine, act as potent antioxidants, helping to neutralize harmful free radicals that can cause oxidative stress. Studies suggest that histidine has anti-inflammatory properties, with some research linking lower histidine levels to inflammation in obese individuals.
Metabolic and Liver Health: Emerging research has shown a link between low histidine levels and conditions like non-alcoholic fatty liver disease (NAFLD). Studies have indicated that histidine supplementation can help reduce fat accumulation in the liver, suggesting it may be a valuable therapeutic target for improving metabolic and liver health.
Histidine's anti-inflammatory properties are multifaceted, stemming from its direct antioxidant actions and its role as a precursor to key anti-inflammatory compounds.
A significant part of histidine's anti-inflammatory effect is mediated by carnosine; a powerful dipeptide histidine forms with beta-alanine. Carnosine is concentrated in muscle and brain tissues and is a crucial antioxidant. It works as follows:
Scavenging Free Radicals: Carnosine effectively neutralizes reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are unstable molecules that can cause cellular damage and trigger inflammation.
Chelating Metals: It can bind to divalent metal ions like copper and iron, preventing them from participating in reactions that generate harmful free radicals.
Inhibiting Glycation: Carnosine also helps to prevent the formation of advanced glycation end products (AGEs), which are inflammatory compounds that accumulate in the body as part of the aging process and in conditions like diabetes.
Because the body's ability to create carnosine is dependent on the availability of histidine, maintaining adequate histidine levels is critical for leveraging these protective benefits.
Research suggests that histidine itself can directly influence specific inflammatory pathways. Studies have shown that histidine supplementation can help alleviate inflammation in the adipose (fat) tissue of obese individuals. This is thought to occur through mechanisms that involve the NF-κB pathway, a protein complex that controls the expression of genes responsible for producing pro-inflammatory cytokines and other inflammatory mediators. By modulating this pathway, histidine helps to suppress the body's inflammatory response.
Low levels of plasma histidine are often observed in people with chronic inflammatory conditions, such as chronic kidney disease (CKD) and rheumatoid arthritis. This association has led researchers to investigate whether histidine supplementation can serve as a therapeutic strategy.
In patients with CKD, low histidine levels are associated with increased inflammation, oxidative stress, and even higher mortality rates.
In obese women with metabolic syndrome, histidine supplementation has been shown to improve insulin resistance and reduce markers of systemic inflammation, such as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α).
Animal studies have also demonstrated that histidine can reduce lung inflammation by inhibiting the activation of the NLRP3 inflammasome, a key component of the innate immune system involved in inflammatory responses.
While more research is needed to fully understand the clinical applications, the evidence suggests that histidine plays a vital role in regulating the inflammatory processes that contribute to many chronic diseases.
To ensure adequate intake, histidine can be obtained from a variety of protein-rich foods. Higher quality protein sources of histidine include the following foods.
Animal Sources:
Beef
Pork
Lamb
Chicken
Fish
Milk
Eggs
Plant Sources:
Tofu and soybeans
Lentils and beans (e.g., navy beans, kidney beans, chick peas)
Nuts and seeds (e.g., chia seeds, pumpkin seeds, sesame seeds)
While histidine is generally considered safe, especially when consumed through diet, it is important to consult a healthcare professional before taking supplements or increasing the consumption of histidine rich foods. Research on dietary and supplement efficacy and potential side effects is ongoing.
Holeček, M. (2020). Histidine in Health and Disease: Metabolism, Physiological Importance, and Use as a Supplement. Nutrients, 12(3), 847. doi:10.3390/nu12030847
Du, S., et al. (2017). Effects of Histidine Supplementation on Global Serum and Urine ¹H NMR-based Metabolomics and Serum Amino Acid Profiles in Obese Women from a Randomized Controlled Study. Journal of Proteome Research, 16(5), 1851–1861. doi:10.1021/acs.jproteome.7b00030
Quesada-Vazquez, S., et al. (2023). Potential therapeutic implications of histidine catabolism by the gut microbiota in NAFLD patients with morbid obesity. Cell Reports Medicine, 4(12), 101341. doi:10.1016/j.xcrm.2023.101341
Niu, Y. C., et al. (2012). Histidine and arginine are associated with inflammation and oxidative stress in obese women. British Journal of Nutrition, 108(1), 164-171. doi:10.1017/S000711451100516X
University of Rochester Medical Center. (n.d.). Histidine. Retrieved from https://www.urmc.rochester.edu/encyclopedia/content?contenttypeid=19&contentid=Histidine, August 18, 2025.
Cleveland Clinic (2024). Oxidative Stress. Retrieved from https://my.clevelandclinic.org/health/articles/oxidative-stress, August 19, 2025.
DiNicolantonio, J.J., et al. (2018). Role of dietary histidine in the prevention of obesity and metabolic syndrome. Open Heart 2018;5:e000676.
Wantanabe, M., et al. (2008). Consequences of low plasma histidine in chronic kidney disease patients: associations with inflammation, oxidative stress, and mortality. Am J Clin Nutr. 2008;87(6):1860-6. doi: 10.1093/ajcn/87.6.1860.
Tian, Q., et al. (2021). Histidine ameliorates elastase- and lipopolysaccharide-induced lung inflammation by inhibiting the activation of the NLRP3 inflammasome. Acta Biochimica et Biophysica Sinica, 2021; Volume 53, Issue 8, Pages 1055–1064, https://doi.org/10.1093/abbs/gmab072.
Clark, T. and Fratini, S. (2024). Adjusted Dietary Reference Intakes (ADRI) for Indispensable Amino Acids. Indispensable Guide to Amino Acids. Retrieved from https://www.indispensableguidetoaminoacids.page/articles/iaa-adri-original-research, August 19, 2025.
Clark, T. and Fratini, S. (2023). Protein Quality (Part 2). Indispensable Guide to Amino Acids. Retrieved from https://www.indispensableguidetoaminoacids.page/articles/protein-quality-part-2, August 19, 2025.