Monocytes: Diagnostic Significance and Clinical Insights

Authors: Payal Bhandari M.D., Madison Granados 

Contributors: Emilia Feria, Vivi Chador, Hailey Chin  

Monocytes

Monocytes are made in the bone marrow. They transform into macrophage or dendritic cells and attack invaders, ingest foreign material, remove dead cells, and facilitate healing and repair. An abnormally low monocyte count indicates that the immune system is compromised and there’s a higher risk of infections. An abnormally high monocyte count is often associated with chronic infection, chronic inflammation and cancer.

Typical Adult Range

Ranges and thresholds can vary due to: 

(1) Lab-specific equipment, techniques, and chemicals, and 

(2) Patient demographics, including age, sex, and ethnicity.

Key Insights

 

Blood contains red blood cells (RBCs), white blood cells (WBCs), and platelets. RBCs transport oxygen via hemoglobin, WBCs defend against infections and maintain immune balance, and platelets prevent blood loss by forming clots and aiding tissue repair.

Figure 1: Blood is divided into three parts: 55% is plasma, which comprises of water (93%), salts, proteins, lipids, and glucose; 45% are red blood cells; and 1% are WBCs and platelets. 

A WBC differential measures neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Monocytes eliminate pathogens and provide key diagnostic insights into inflammatory conditions like infections, autoimmune disorders, and cancer. Lifestyle factors like diet, stress, and exercise influence monocyte levels and overall health.

What Are Monocytes?

 

Monocytes are innate immune cells that protect against pathogens and abnormal cells, mediate tissue repair, and clear toxic byproducts like free hemoglobin and beta-amyloid. They are crucial for maintaining tissue health, responding to infections, inflammation, and cancer, and are involved in autoimmune diseases, atherosclerosis, cancers, and infections.

            

Figure 2: Monocytes and their derivatives aid wound repair, clear debris, support muscle regeneration, reduce fibrosis, and remove beta-amyloid plaques in the brain.

Monocyte Formation and Regulation

 

All blood cells originate from hematopoietic stem cells (HSCs), which differentiate into platelets, RBCs, and WBCs. Immature WBCs form myeloid or lymphoid progenitors, with monocyte development regulated by proinflammatory proteins like PU.1, C/EBPα, and IRF8 during inflammation64. Environmental signals guide monocyte development and adaptability to physiological needs.

          

Figure 3: Hematopoietic stem cells in bone marrow differentiate into red blood cells, platelets, and white blood cells, including monocytes, lymphocytes, eosinophils, neutrophils, and basophils5. Most WBCs are produced in the marrow, with the rest formed in the thymus, spleen, liver, and lymph nodes.

Mature monocytes enter circulation as classical, intermediate, or non-classical types. Classical monocytes dominate, transforming into non-classical monocytes that patrol vessels and clear debris. Inflammatory signals recruit classical monocytes to tissues, where they become macrophages or dendritic cells, performing roles like debris clearance, antigen presentation, and cytokine release.

           

Figure 4: Monocytes vary in function, with classical monocytes transforming into non-classical types or dendritic cells for tissue repair and inflammation. Non-classical monocytes patrol vessels, inhibiting infections and cancer via natural killer cell activity.

 

Clinical Significance of a High Monocyte Count (Monocytosis)

 

Monocytosis, a high monocyte count (over 8% of WBCs), is stimulated by CD115 and linked to chronic infections, allergies, stress, autoimmune disorders, and cancers like leukemia and lymphomas.

 

Monocytosis reflects the body’s response to inflammation, infection, or cancer, often driven by hypoxia-induced vascular injury (atherosclerosis). Atherosclerosis involves oxidized LDL cholesterol embedding in vessel walls, triggering reactive oxygen species (ROS) that activate the reticuloendothelial system to clear debris and repair wounds. . Macrophages ingest cholesterol, forming foam cells, while platelets and smooth muscle cells create a fibrous cap and new vessels. Excess ROS and proinflammatory proteins damage healthy cells, mutate genes, and impair metabolic regulation and cell division. This sets the stage for: 

  • autoimmune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type 1 diabetes , 

  • excess fat storage in the inner lining of blood vessels, adipose tissue, the liver, and various organs with reduced capacity to harvest energy [i.e., type 2 diabetes, fatty liver disease, cardiovascular diseases (CVD), and obesity], 

  • hormonal imbalances like thyroid dysfunction, excess synthesis of certain types of steroids and stress hormones, 

  • various infections, 

  • mutated/abnormally functioning/cancer cell growth  

  • multiorgan depletion.

 

Figure 5: Atherosclerosis thickens vessel walls with fat and scar tissue, forming clots to prevent bleeding. It restricts arterial blood flow, raises blood pressure, and redirects venous flow, potentially damaging organ structure and function .

Monocytosis is linked to dehydration and vasoconstriction, reducing blood flow to organs like the digestive tract 14 .This lowers stomach acid production, disrupts gut microbiota, and impairs nutrient absorption, leading to undigested food particles that increase blood viscosity and cause hypoxia. Hypoxia reduces cellular function and increases ROS production.

 

 

Figure 6: Healthy gut microbiota support digestion, nutrient absorption, and waste excretion, maintaining metabolic balance. Dysbiosis disrupts this balance, impairing metabolism and increasing harmful pathogens that affect immune responses. 

Persistent atherosclerosis-induced inflammation over activates monocytes and WBCs, diverting focus from pathogen destruction to wound repair. Over time, they attack healthy tissue, while overactive platelets and endothelial cells increase fibrosis, clotting, angiogenesis, and chronic inflammation, impairing blood flow and raising blood pressure.

 

Figure 7: Chronic inflammation increases ROS, proinflammatory proteins, and oxidized cholesterol, activating leukocytes and platelets, leading to tissue damage, clots, and restricted blood flow.

 

Atherosclerosis-induced vascular diseases, the leading global cause of death, 14 are linked to dysregulated energy use, worsening dysbiosis, and activation of dormant viruses. Viruses, parasitic agents needing host cells to replicate, release toxins like hemolysin under stress, damaging cell membranes and accelerating cell destruction for replication.

Figure 8: Viruses infect cells by binding to surface receptors, injecting genetic material, or entering via endocytosis. Inside, they hijack host functions to replicate and produce new particles, spreading the infection to neighboring cells 22. 

Monocytes play a key role in responding to viral infections,  which are linked to atherosclerosis-induced inflammation activating viruses like herpes virus, CMV, EBV, and HSV . These viruses can spread via bodily fluids, close contact, or insects, altering brain and organ function, and contributing to mood disorders, cognitive decline, and autoimmune diseases like SLE and RA26 4. Monocytosis is associated with increased antibodies against self-tissues, proinflammatory proteins, and tissue destruction.

Clinical Significance of Low Monocyte Count (Monocytopenia)

 

Monocytopenia, a low monocyte count (<2-8% of WBCs),weakens immune defense, worsening infections, cancer, autoimmune disorders, and atherosclerosis.  It also signals compromised microbiota and a reticuloendothelial system failing to filter blood, regulate immune cells, and clear waste. Impaired monocyte production is commonly seen in conditions such as:

  1. Chronic dysbiosis redirects the immune system to tissue repair, aiding atherosclerosis while reducing defense against pathogens and abnormal cells. Dormant viruses like HIV activate, infect host cells, replicate, and spread, causing recurrent and chronic infections. 

  2. Overactivation of the reticuloendothelial system affects key organs:

    1. Spleen: Dysbiosis and nutrient deficiencies impair hemoglobin synthesis and oxygen delivery, forcing the spleen to clear toxins and regulate WBC production.

    2. Liver: Hypoxia triggers ROS, increasing glucose synthesis, fat storage, and muscle breakdown while reducing fat metabolism and protein synthesis. Monocytes infiltrate injury sites, lowering their circulation levels.

    3. Bone Marrow: ROS damage stem cells, disrupting blood cell production and causing disorders like anemia, leukemia, and lymphoma. Treatments like chemotherapy and radiation worsen monocytopenia.

3. Atherosclerosis-induced vasoconstriction reduces blood flow, disrupting fluid balance, nutrient absorption, protein synthesis, and waste excretion .  Undigested food particles trigger inflammation, overstimulating the reticuloendothelial system and worsening systemic issues.

4. Autoimmune disorders: Chronic atherosclerosis and dysbiosis impair immune cell differentiation, causing monocytes to attack healthy tissue, infiltrate injury sites, and lower circulating levels.

Monocytopenia often precedes type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), and atherosclerosis-related diseases by years14 . Over 90% of the 415 million adults with diabetes in 2015 had T2DM, with 55% also having NAFLD, the leading cause of chronic liver disease globally 14  . Both T2DM and NAFLD involve chronic inflammation, reducing monocyte levels and exacerbating liver damage through immune cell infiltration. Shared pathways of oxidative stress and inflammation link these conditions to increased cardiovascular disease risk.

Monocytopenia is linked to autoimmune diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), affecting 3-5% of the U.S. population.14 In 2020, 17.6 million people globally had RA, with a female-to-male ratio of 2.45 and a prevalence rate of 208.8 cases per 100,000. Despite a 23.8% decline in RA-related mortality since 1990, its prevalence and burden are rising, with cases expected to reach 31.7 million by 2050. RA accounted for 3.06 million disability-adjusted life years (DALYs) in 2020, 76.4% from years lived with disability (YLDs), and 7.1% linked to smoking.

 

Over 90% of people worldwide are infected with viruses like Epstein–Barr virus (EBV), often asymptomatic in childhood. EBV reactivates under stress, causing infectious mononucleosis (IM) and conditions like autoimmune disorders and cancers, including Hodgkin’s lymphoma and gastric carcinoma. EBV, the first known human cancer-causing virus, highlights that about 10% of cancers stem from chronic viral infections such as HIV, HSV, and HHV. 

          

Figure 9: Excess oxidized cholesterol, proinflammatory proteins, and reactive oxygen species cause tissue damage, gene mutations, and impaired cell division. Nitric oxide, vital for blood vessel integrity, is reduced, while macrophages and neutrophils shield tumor cells, aiding their survival. Tumor cells activate platelets, promoting clotting, angiogenesis, and cancer cell migration via proinflammatory proteins.

 

Clinical Manifestation of an Abnormal Monocyte Count

Abnormal monocyte counts rarely cause direct symptoms but often result from underlying conditions. Treatments for cancers and autoimmune diseases like lupus and IBD may further elevate monocyte levels and impair organ function.

                

Figure 10: Chronic abnormal monocyte activity, driven by excess proinflammatory proteins and ROS, triggers inflammation that damages organ systems. This overactivation impairs cell division, gene function, antioxidant activity (e.g., glutathione and vitamin D metabolism), and leads to premature cell death, contributing to cardiovascular, digestive, and neurological conditions.

Conclusion

Monocyte count is a key indicator of immune health, reflecting risks for inflammation, organ dysfunction, and diseases like atherosclerosis, autoimmune disorders, infections, and cancers. High monocyte counts increase tissue damage, while low counts hinder organ function and raise disease risk. Factors like poor nutrition, stress, and sleep disturbances disrupt blood flow, microbiota, digestion, and hormonal balance. Managing monocyte levels involves lifestyle changes, such as diet, exercise, hydration, and stress reduction, often reducing the need for medications that may complicate immune function. A multidisciplinary approach is essential to restore balance and prevent serious health conditions.

 

Source References and Supplemental Research:

  1.  Young B, Lowe jo, Stevens A, Heath JW (2006). Wheater’s Functional Histology (5th ed.). Elsevier Limited. ISBN 978-0-443-06850-8.

  2. Dean L. Blood Groups and Red Cell Antigens [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2005. Chapter 1, Blood and the cells it contains. Available from: [PubMed] 

  3.  LaRosa D, Orange J. 1. lymphocytes. J Allergy Clin Immunol Pract. 2008;121(2). doi:10.1016/j.jaci.2007.06.016 [Crosslink]

  4.  Hirose S, Lin Q, Ohtsuji M, Nishimura H, Verbeek JS. Monocyte subsets involved in the development of systemic lupus erythematosus and rheumatoid arthritis. Int Immunol. 2019;31(11):687-696. doi:10.1093/intimm/dxz036 [PubMed] [PMC Full Text] [Crosslink]

  5.  Grinenko T, Eugster A, Thielecke L, et al. Hematopoietic stem cells can differentiate into restricted myeloid progenitors before cell division in mice. Nat Commun. 2018;9(1):1898. Published 2018 May 15. doi:10.1038/s41467-018-04188-7 [PMC Full Text] [PubMed] [Crosslink] 

  6.  Robinson A, Han CZ, Glass CK, Pollard JW. Monocyte regulation in homeostasis and malignancy. Trends in Immunology. 2021;42(2):104-119. doi:10.1016/j.it.2020.12.001 [PubMed] [PMC Full Text] [Crosslink]

  7.  Auffray, C., Fogg, D., Garfa, M. et al.  2007. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317:666. [Google Scholar] [Crossref] [PubMed]

  8.  Karlmark KR, Tacke F, Dunay IR. Monocytes in health and disease – Minireview. Eur J Microbiol Immunol (Bp). 2012;2(2):97-102. doi:10.1556/EuJMI.2.2012.2.1 [PubMed] [PMC Full Text] [Crosslink]

  9.   Shi, C. and Pamer, E. G. 2011. Monocyte recruitment during infection and inflammation. Nat. Rev. Immunol.11:762. [Google Scholar] [Crossref] [PubMed]

  10.  Tahir N. Neutrophilia. [StatPearls]. April 27, 2023. Accessed July 9, 2024. https://www.ncbi.nlm.nih.gov/books/NBK570571/.

  11.   Auffray, C., Sieweke, M. H. and Geissmann, F. 2009. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu. Rev. Immunol.27:669. [Google Scholar] [PubMed]

  12.  Woollard, K. J. and Geissmann, F. 2010. Monocytes in atherosclerosis: subsets and functions. Nat. Rev. Cardiol.7:77.[Google Scholar] [Crossref] [PubMed]

  13.  Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12:204–12. [PubMed] [Crosslink]. 

  14.  Herrero-Cervera, A., Soehnlein, O. & Kenne, E. Neutrophils in chronic inflammatory diseases. Cell Mol Immunol. 2022;19(2):177-191. doi:10.1038/s41423-021-00832-3 [PubMed] [PMC Full Text] [Crosslink]

  15.  Mikołajczyk, T. P., Osmenda, G., Batko, B. et al.  2016. Heterogeneity of peripheral blood monocytes, endothelial dysfunction and subclinical atherosclerosis in patients with systemic lupus erythematosus. Lupus25:18.[Google Scholar] [Crossref] [PubMed]

  16.  Winchester, R., Giles, J. T., Nativ, S. et al.  2016. Association of elevations of specific T cell and monocyte subpopulations in rheumatoid arthritis with subclinical coronary artery atherosclerosis. Arthritis Rheumatol.68:92.[Google Scholar][Crossref] [PubMed]

  17.  Nordestgaard, B. G., & Varbo, A. (2014). Triglycerides and cardiovascular disease. The Lancet, 384(9943), 626–635. https://doi.org/10.1016/s0140-6736(14)61177-6 [Science Direct] [Scopus] [Google Scholar] 

  18.  Varbo, A., Benn, M., Tybjærg-Hansen, A., & Nordestgaard, B. G. (2013). Elevated remnant cholesterol causes both Low-Grade inflammation and ischemic heart disease, whereas elevated Low-Density lipoprotein cholesterol causes ischemic heart disease without inflammation. Circulation, 128(12), 1298–1309. https://doi.org/10.1161/circulationaha.113.003008 [Scopus] [Google Scholar]

  19.  Soehnlein O, Libby P. Targeting inflammation in atherosclerosis — from experimental insights to the clinic. Nat Rev Drug Discov. 2021;20:589–610. [PubMed]. 

  20.  What Is Gut Dysbiosis? Cleveland Clinic. [Cleveland Clinic] 

  21.  Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: update From the GBD 2019 study. J Am Coll Cardiol. 2020;76:2982–3021. [PubMed] [PMC Full Text] [Crosslink]. 

  22. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Cell Biology of Infection. [PubMed]

  23.  Vandenesch, F, Lina G, Henry T. Staphylococcus aureus hemolysins, bi-component leukocidins, and cytolytic peptides: a redundant arsenal of membrane-damaging virulence factors? Front. Cell. Infect. Microbiol., 15 February 2012. Sec. Bacteria and Host. Volume 2 – 2012. https://doi.org/10.3389/fcimb.2012.00012. [Frontiers]

  24.  Fol M, Karpik W, Zablotni A, Kulesza J, Kulesza E, Godkowicz M, Druszczynska M. Innate Lymphoid Cells and Their Role in the Immune Response to Infections. Cells. 2024; 13(4):335. https://doi.org/10.3390/cells13040335. [MDPI]

  25.  Tugizov S, Herrera R, Veluppillai P, Greenspan J, Greenspan D, Palefsky JM. Epstein-Barr virus (EBV)-infected monocytes facilitate dissemination of EBV within the oral mucosal epithelium. J Virol. 2007;81(11):5484-5496. doi:10.1128/JVI.00171-07 [PubMed] [PMC Full Text] [Crosslink]

  26.  Kabat GC, Kim MY, Manson JE, et al. White Blood Cell Count and Total and Cause-Specific Mortality in the Women’s Health Initiative. Am J Epidemiol. 2017;186(1):63-72. doi:10.1093/aje/kww226. [PubMed] 

  27.  Hilgers A, Frank J. Chronic Fatigue Syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardiac changes. Wien Med Wochenschr. 1994;144(16):399-406. [Pubmed]

  28.  Wang Y, Ding L, Zhu Q, Shu M, Cai Q. Common Infections May Lead to Alzheimer’s Disease. Virol Sin. 2018;33(5):456-458. doi:10.1007/s12250-018-0049-7 [Pubmed] [Springer]

  29.  Pyzik A, Grywalska E, Matyjaszek-Matuszek B, et al. Does the Epstein-Barr Virus Play a Role in the Pathogenesis of Graves’ Disease?. Int J Mol Sci. 2019;20(13):3145. Published 2019 Jun 27. doi:10.3390/ijms20133145 [Pubmed] [MDPI] [PMC]

  30. Cleveland Clinic. Monocytes: A Type of White Blood Cell — What Are Normal Ranges? Cleveland clinic. Published 2021. [Cleveland Clinic] 

  31.  Sebastian, S., Lucey, B.C. (2008). Reticuloendothelium Malignancy: Current Role of Imaging. In: Blake, M.A., Kalra, M.K. (eds) Imaging in Oncology. Cancer Treatment and Research, vol 143. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-75587-8_17. [SpringerLink]

  32.  Godkin A, Smith KA. Chronic infections with viruses or parasites: breaking bad to make good. Immunology. 2017;150(4):389-396. doi:10.1111/imm.12703 [Pubmed] [Crossref]

  33.  Dasagrandhi, D., Muthuswamy, A. & Swaminathan, J.K. Atherosclerosis: nexus of vascular dynamics and cellular cross talks. Mol Cell Biochem 477, 571–584 (2022). https://doi.org/10.1007/s11010-021-04307-x. [SpringerLink]

  34.  Mandy O J Grootaert, Martin R Bennett, Vascular smooth muscle cells in atherosclerosis: time for a re-assessment, Cardiovascular Research, Volume 117, Issue 11, 1 October 2021, Pages 2326–2339, https://doi.org/10.1093/cvr/cvab046. [Oxford Academic]

  35.  Poznyak A, Grechko AV, Poggio P, Myasoedova VA, Alfieri V, Orekhov AN. The diabetes mellitus–atherosclerosis connection: the role of lipid and glucose metabolism and chronic inflammation. Int J Mol Sci. 2020;21:1835. [PMC Full Text] [Crosslink]. 

  36.  Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 2018;24:908–22. [PubMed] [PMC Full Text] [Crosslink]. 

  37.  Alkhouri, N., Tamimi, T.AR., Yerian, L. et al. The Inflamed Liver and Atherosclerosis: A Link Between Histologic Severity of Nonalcoholic Fatty Liver Disease and Increased Cardiovascular Risk. Dig Dis Sci 55, 2644–2650 (2010). https://doi.org/10.1007/s10620-009-1075-y. [SpringerLink]

  38.  Wang L, Wang FS, Gershwin ME. Human autoimmune diseases: a comprehensive update. J Intern Med. 2015;278:369–95. [PubMed] [Crosslink]. 

  39.  GBD 2021 Rheumatoid Arthritis Collaborators. Global, regional, and national burden of rheumatoid arthritis, 1990-2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023;5(10):e594-e610. Published 2023 Sep 25. doi:10.1016/S2665-9913(23)00211-4 [PubMed] [PMC Full Text] [Crosslink]

  40.  Smatti MK, Al-Sadeq DW, Ali NH, Pintus G, Abou-Saleh H, Nasrallah GK. Epstein-Barr Virus Epidemiology, Serology, and Genetic Variability of LMP-1 Oncogene Among Healthy Population: An Update. Front Oncol. 2018;8:211. Published 2018 Jun 13. doi:10.3389/fonc.2018.00211 [PubMed] [PMC Full Text] [Crosslink]

  41.  Yu H, Robertson ES. Epstein-Barr Virus History and Pathogenesis. Viruses. 2023;15(3):714. Published 2023 Mar 9. doi:10.3390/v15030714 [PubMed] [PMC Full Text] [Crosslink]

  42.  Alizon S, Bravo IG, Farrell PJ, Roberts S. Towards a multi-level and a multi-disciplinary approach to DNA oncovirus virulence. Philos Trans R Soc Lond B Biol Sci. 2019;374(1773):20190041. doi:10.1098/rstb.2019.0041 [Pubmed] [The Royal Society] [PMC]

  43.  Yen Jean MC, Hsu CC, Hung WC, et al. Association between lifestyle and hematological parameters: A study of Chinese male steelworkers. J Clin Lab Anal. 2019;33(7):e22946. doi:10.1002/jcla.22946 [PubMed] [PMC Full Text] [Crosslink]

  44.  Wirth MD, Sevoyan M, Hofseth L, Shivappa N, Hurley TG, Hébert JR. The Dietary Inflammatory Index is associated with elevated white blood cell counts in the National Health and Nutrition Examination Survey. Brain Behav Immun. 2018;69:296-303. doi:10.1016/j.bbi.2017.12.003 [PubMed] [PMC Full Text] [Crosslink]

  45.  Cedars-Sinai Staff. Are animal proteins better for you than plant proteins? Cedars Sinai. January 16, 2019. Accessed September 2, 2024. [Website] 

  46.  Koenig G, Seneff S. Gamma-glutamyltransferase: A predictive biomarker of cellular antioxidant inadequacy and disease risk. Dis Markers. 2015:2015:818570. PMID: 26543300. doi: 10.1155/2015/818570. [PubMed] [Wiley] [PubMed]

  47.  De Chiara, F., Checcllo, C. U., & Azcón, J. R. (2019). High protein diet and metabolic plasticity in Non-Alcoholic Fatty liver Disease: Myths and Truths. Nutrients, 11(12), 2985. https://doi.org/10.3390/nu11122985 [PubMed] 

  48.  Balkaransingh PD, Wheeler D, Ning Y, Helou MA, Massey G. Dietary determinants of the White Blood Cell Count. Blood. 2013;122(21):1705-1705. doi:10.1182/blood.v122.21.1705.1705 [Crosslink] [Full Text]

  49.  Guoyao Wu; Yun-Zhong Fang; Sheng Yang; Joanne R. Lupton; Nancy D. Turner (2004). “Glutathione Metabolism and its Implications for Health”. Journal of Nutrition. 134 (3): 489–492. doi:10.1093/jn/134.3.489. PMID 14988435 [PubMed] [Crosslink] 

  50.  Ho, P.I.; Ortiz, D.; Rogers, E.; Shea, T.B. Multiple aspects of homocysteine neurotoxicity: Glutamate excitotoxicity, kinase hyperactivation and DNA damage. J. Neurosci. Res. 2002, 70, 694–702. [Google Scholar] [CrossRef] [PubMed]

  51.  Menni C, Louca P, Berry SE, et al. High intake of vegetables is linked to lower white blood cell profile and the effect is mediated by the gut microbiome. BMC Med. 2021;19(1):37. Published 2021 Feb 11. doi:10.1186/s12916-021-01913-w [PubMed] [PMC Full Text] [Crosslink]

  52.  Hernáez Á, Lassale C, Castro-Barquero S, Babio N, Ros E, Castañer O, Tresserra-Rimbau A, Pintó X, Martínez-González MÁ, Corella D, et al. Mediterranean Diet and White Blood Cell Count—A Randomized Controlled Trial. Foods. 2021; 10(6):1268. https://doi.org/10.3390/foods10061268. [MDPII]

  53.  Moll S, Varga EA. Homocysteine and MTHFR Mutations. Circulation. 2015;132(1). doi:https://doi.org/10.1161/circulationaha.114.013311 [AHA Journals] [Crosslink] 

  54.  Esse, R.; Barroso, M.; Almeida, I.; Castro, R. The contribution of homocysteine metabolism disruption to endothelial dysfunction: State-of-the-art. Int. J. Mol. Sci. 2019, 20, 867. [Google Scholar] [CrossRef] [Green Version]. 

  55.  Kruman, I.I.; Culmsee, C.; Chan, S.L.; Kruman, Y.; Guo, Z.; Penix, L.; Mattson, M.P. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J. Neurosci. 2000, 20, 6920–6926. [PubMed]

  56.  Ho, P.I.; Ashline, D.; Dhitavat, S.; Ortiz, D.; Collins, S.C.; Shea, T.B.; Rogers, E. Folate deprivation induces neurodegeneration: Roles of oxidative stress and increased homocysteine. Neurobiol. Dis. 2003, 14, 32–42. [PubMed]

  57.  Piskin E, Cianciosi D,  Gulec S, Tomas M, Capanoglu E. Iron Absorption: Factors, Limitations, and Improvement Methods. ACS Omega. 2022 Jun 21; 7(24): 20441–20456. doi: 10.1021/acsomega.2c01833 [PMC] [Crosslink] 

  58.  Boldt D. H. New Perspectives on Iron: An Introduction. Am. J. Med. Sci. 1999, 318 (4), 207. 10.1097/00000441-199910000-00001. [PubMed]

  59.  Smirnoff N. Ascorbic Acid Metabolism and Functions: A Comparison of Plants and Mammals. Free Radic. Biol. Med. 2018, 122, 116–129. 10.1016/j.freeradbiomed.2018.03.033. [PubMed]

  60.  Benkhedda K.; L’abbé M. R.; Cockell K. A. Effect of Calcium on Iron Absorption in Women with Marginal Iron Status. Br. J. Nutr. 2010, 103 (5), 742–748. 10.1017/S0007114509992418. [PubMed] [Cambridge Core]

  61.  Ziegler E.E. Consumption of cow’s milk as a cause of iron deficiency in infants and toddlers. Nutr. Rev. 2011;69:37–42. doi: 10.1111/j.1753-4887.2011.00431.x. [PubMed] [Oxford Academic]

  62.  Cory H, Passarelli S, Szeto J, Tamez M, Mattei J. The Role of Polyphenols in Human Health and Food Systems: A Mini-Review. Front Nutr. 2018;5:87. Published 2018 Sep 21. doi:10.3389/fnut.2018.00087 [PubMed]

  63. Zhang H, Tsao R. Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Curr Opin Food Sci. (2016) 8:33–42. 10.1016/j.cofs.2016.02.002 [CrossRef] [Google Scholar]

  64.  Sandberg A-S, Scheers N. Phytic Acid: Properties, Uses, and Determinations. In: ; :365-368. Accessed September 2, 2024. [ScienceDirect] 

  65.  Hart J. J.; Tako E.; Kochian L. V.; Glahn R. P. Identification of Black Bean (Phaseolus Vulgaris L.) Polyphenols That Inhibit and Promote Iron Uptake by Caco-2 Cells. J. Agric. Food Chem. 2015, 63 (25), 5950–5956. 10.1021/acs.jafc.5b00531. [PubMed]

  66.  Naghedi-Baghdar, H., Nematy, M., Kooshyar, M. M., Taghipour, A., Sajadi Tabassi, S. A., Shokri, S., Javan, R., & Nazari, S. M. (2018). Effect of a functional food (vegetable soup) on blood rheology in patients with polycythemia. Avicenna journal of phytomedicine, 8(5), 389–398. [PubMed]

  67. Watso, J. C., & Farquhar, W. B. (2019). Hydration Status and Cardiovascular Function. Nutrients, 11(8), 1866. https://doi.org/10.3390/nu11081866 [PubMed]

  68. Popkin BM, D’Anci KE, Rosenberg IH. Water, hydration, and health. Nutr Rev. 2010;68(8):439-458. doi:10.1111/j.1753-4887.2010.00304.x [PubMed]

  69. Billett HH. Hemoglobin and Hematocrit. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 151. Available from: [PubMed] 

  70. Kennedy M. How much water you’re actually supposed to drink each day – and why 8 cups isn’t right for everyone. Business Insider. December 14, 2021. [Website] 

  71.  Pałka T, Koteja PM, Tota Ł, et al. The Influence of Various Hydration Strategies (Isotonic, Water, and No Hydration) on Hematological Indices, Plasma Volume, and Lactate Concentration in Young Men during Prolonged Cycling in Elevated Ambient Temperatures. Biology (Basel). 2023;12(5):687. Published 2023 May 7. doi:10.3390/biology12050687 [PubMed] [PMC Full Text] [Crosslink]

  72.  Ballard H. S. (1997). The hematological complications of alcoholism. Alcohol health and research world, 21(1), 42–52. [PubMed]

  73.  Bradley CS, Erickson BA, Messersmith EE, et al. Evidence of the Impact of Diet, Fluid Intake, Caffeine, Alcohol and Tobacco on Lower Urinary Tract Symptoms: A Systematic Review. J Urol. 2017;198(5):1010-1020. doi:10.1016/j.juro.2017.04.097 [PubMed] [PMC Full Text] [Full Text]

  74.  Polhuis KCMM, Wijnen AHC, Sierksma A, Calame W, Tieland M. The Diuretic Action of Weak and Strong Alcoholic Beverages in Elderly Men: A Randomized Diet-Controlled Crossover Trial. Nutrients. 2017;9(7):660. Published 2017 Jun 28. doi:10.3390/nu9070660 [PubMed]

  75.  Chung PS, Tsai KZ, Lin YP, Lin YK, Lin GM. Association between Leukocyte Counts and Physical Fitness in Male Military Members: The CHIEF Study. Sci Rep. 2020;10(1):6082. Published 2020 Apr 8. doi:10.1038/s41598-020-63147-9 [PubMed] [PMC Full Text] [Crosslink]

  76.  Johannsen NM, Swift DL, Johnson WD, et al. Effect of different doses of aerobic exercise on total white blood cell (WBC) and WBC subfraction number in postmenopausal women: results from DREW. PLoS One. 2012;7(2):e31319. doi:10.1371/journal.pone.0031319 [PubMed] [PMC Full Text] [Crosslink]

  77.  El-Sayed M. S. (1998). Effects of exercise and training on blood rheology. Sports medicine (Auckland, N.Z.), 26(5), 281–292. https://doi.org/10.2165/00007256-199826050-00001 [PubMed] [Springer]

  78.  Kilic-Toprak, E., Ardic, F., Erken, G., Unver-Kocak, F., Kucukatay, V., & Bor-Kucukatay, M. (2012). Hemorheological responses to progressive resistance exercise training in healthy young males. Medical science monitor : international medical journal of experimental and clinical research, 18(6), CR351–CR360. https://doi.org/10.12659/msm.882878 [PubMed] [ISI] [PubMed]

  79.  Kamal A, Malik RN. Hematological Evidence of Occupational Exposure to Chemicals and Other Factors among Auto-Repair Workers in Rawalpindi, Pakistan. Osong Public Health Res Perspect. 2012;3(4):229-238. doi:10.1016/j.phrp.2012.10.003 [PubMed]

  80.  Premont RT, Reynolds JD, Zhang R, Stamler JS. Role of Nitric Oxide Carried by Hemoglobin in Cardiovascular Physiology: Developments on a Three-Gas Respiratory Cycle. Circ Res. 2020;126(1):129-158. doi:10.1161/CIRCRESAHA.119.315626 [PubMed] [PMC Full Text] [Circulation Research]

  81.  Pedersen KM, Çolak Y, Ellervik C, Hasselbalch HC, Bojesen SE, Nordestgaard BG. Smoking and Increased White and Red Blood Cells. Arterioscler Thromb Vasc Biol. 2019;39(5):965-977. doi:10.1161/ATVBAHA.118.312338 [PubMed] [Crosslink]

  82.  Carel RS, Eviatar J. Factors affecting leukocyte count in healthy adults. Prev Med. 1985;14(5):607-619. doi:10.1016/0091-7435(85)90081-7 [PubMed] [Crosslink] 

  83.  Pillai AA, Fazal S, Mukkamalla SKR, Babiker HM. Polycythemia. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 20, 2023. [PubMed]

  84.  Lewandowska AM, Rudzki M, Rudzki S, Lewandowski T, Laskowska B. Environmental risk factors for cancer – review paper. Ann Agric Environ Med. 2019;26(1):1-7. doi:10.26444/aaem/94299 [PubMed] [Full Text]