G6PD deficiency disrupts NADPH, glutathione, and nitric oxide metabolism, leading to oxidative stress and red blood cell hemolysis. Low levels are associated with vitamin D deficiency, infection, autoimmunity, and cardiometabolic disease.
The G6PD enzyme is found in every cell in the body. It is involved in the first and most important step of the pentose phosphate pathway that generates NADPH, a critical compound that fights free radicals and oxidative stress and maintains glutathione in its reduced form (Richardson 2022). The NADPH molecule is also used as a cofactor in nitric oxide (NO) synthesis. A G6PD deficiency not only impairs synthesis of NO, but also causes hyperglycemia which can increase advanced glycosylated end products which further impair nitric oxide activity and related vasodilation (Gaskin 2001).
NADPH is also an important factor in the synthesis of fatty acids, cholesterol, steroids, and DNA. NADPH can be generated by enzymes other than G6PD in most cells but not in RBCs which are more susceptible to a deficiency of G6PD (Luzzatto 2016).
A deficiency of G6PD can negatively affect many cells and tissues, especially red blood cells, and can contribute to hemolytic anemia, fibrosis, autoimmune disorders, vitamin D deficiency, hypertension, and cardiovascular disease. Low levels of G6PD may be due to an inherited enzyme deficiency or may be associated with metabolic disorders including diabetes, metabolic syndrome, and obesity. Elevations in aldosterone that are associated with stress can decrease G6PD activity and contribute to insulin resistance, hyperglycemia, and dyslipidemia (Jain 2020).
Severity of G6PD deficiency ranges from mild to severe though most individuals are asymptomatic. However, laboratory abnormalities in those with hemolysis may include anemia, elevated Heinz bodies, decreased haptoglobin, and elevated indirect bilirubin (Frank 2005).
Other lab abnormalities in G6PD deficiency depend on existing comorbidities and associated biomarkers of glucose dysregulation, dyslipidemia, nutrient insufficiencies, and oxidative stress.
One 24-year-old individual with an undiagnosed deficiency of G6PD deficiency (3.8 U/g Hb vs. lab range of 8.6-18 U/g Hb) presented with severe rhabdomyolysis, metabolic acidosis, and significantly elevated bilirubin, AST, ALT, CRP, and ferritin (Eziokwu 2018). Persistent unresolved anemia in G6PD deficiency should be evaluated for deficiencies of folate, B2, B6, B12, or iron (Northrop-Clewes 2013).
Those with G6PD deficiency should avoid fava beans, synthetic dyes (Lee 2017), sulfites, quinine (Noland 2020), high-dose vitamin C (Quinn 2017), and certain medications that may promote hemolysis in these individuals. Other foods, including falafel, chickpeas, and broad beans may also trigger hemolysis in those with G6PD deficiency (Hagag 2018).
A 2017 systematic review of 32 publications comprising 10 herbal and dietary supplements found no or insufficient evidence of increased risk of hemolysis with vitamins C, E, and K, Gingko biloba, or alpha lipoic acid in those with G6PD deficiency. However, an increased risk was observed for henna. Researchers note that green tea and its extracts have been reported to trigger hemolysis in G6PD deficient individuals. They also note that high doses of vitamin C, e.g., 20-40 grams per day, may also trigger hemolysis in these individuals. Ingestion of the herbal supplements Acalypha indica and Coptis chinensis may also cause adverse reactions with G6PD deficiency (Lee 2017 Adverse Effects).
Please note: We cannot provide clinical guidance on specific cases or conditions.
References
Chen, Yicong et al. “Association between aspirin-induced hemoglobin decline and outcome after acute ischemic stroke in G6PD-deficient patients.” CNS neuroscience & therapeutics vol. 27,10 (2021): 1206-1213. doi:10.1111/cns.13711
Eziokwu, Akaolisa S, and Dana Angelini. “New Diagnosis of G6PD Deficiency Presenting as Severe Rhabdomyolysis.” Cureus vol. 10,3 e2387. 28 Mar. 2018, doi:10.7759/cureus.2387
Gaskin, R S et al. “G6PD deficiency: its role in the high prevalence of hypertension and diabetes mellitus.” Ethnicity & disease vol. 11,4 (2001): 749-54.
Hagag, Adel A et al. “Study of Glucose-6-Phosphate Dehydrogenase Deficiency: 5 Years Retrospective Egyptian Study.” Endocrine, metabolic & immune disorders drug targets vol. 18,2 (2018): 155-162. doi:10.2174/1871530317666171003160350
Jain, Sushil K et al. “The potential link between inherited G6PD deficiency, oxidative stress, and vitamin D deficiency and the racial inequities in mortality associated with COVID-19.” Free radical biology & medicine vol. 161 (2020): 84-91. doi:10.1016/j.freeradbiomed.2020.10.002
Frank, Jennifer E. “Diagnosis and management of G6PD deficiency.” American family physician vol. 72,7 (2005): 1277-82.
Lee, Shaun Wen Huey et al. “What G6PD-deficient individuals should really avoid.” British journal of clinical pharmacology vol. 83,1 (2017): 211-212. doi:10.1111/bcp.13091
Lee, Shaun Wen Huey et al. “Adverse effects of herbal or dietary supplements in G6PD deficiency: a systematic review.” British journal of clinical pharmacology vol. 83,1 (2017): 172-179. doi:10.1111/bcp.12976
Luzzatto, Lucio et al. “Glucose-6-Phosphate Dehydrogenase Deficiency.” Hematology/oncology clinics of North America vol. 30,2 (2016): 373-93. doi:10.1016/j.hoc.2015.11.006
Noland, Diana, Jeanne A. Drisko, and Leigh Wagner, eds. Integrative and functional medical nutrition therapy: principles and practices. Springer Nature, 2020.
Northrop-Clewes, Christine A, and David I Thurnham. “Biomarkers for the differentiation of anemia and their clinical usefulness.” Journal of blood medicine vol. 4 11-22. 20 Mar. 2013, doi:10.2147/JBM.S29212
Quinn, Joseph et al. “Effect of High-Dose Vitamin C Infusion in a Glucose-6-Phosphate Dehydrogenase-Deficient Patient.” Case reports in medicine vol. 2017 (2017): 5202606. doi:10.1155/2017/5202606
Richardson, S. Russ. and Gerald F. O'Malley. “Glucose 6 Phosphate Dehydrogenase Deficiency.” StatPearls, StatPearls Publishing, 21 June 2022.