Aspirin Side Effects & Health Impacts

Folate depletion impairs one-carbon metabolism, leading to elevated homocysteine, endothelial dysfunction and potential promotion of atherothrombotic events.

Meta-analyses of randomized trials show that folic acid supplementation lowers homocysteine and modestly reduces stroke and overall cardiovascular disease risk in some populations, especially where baseline folate status is low, highlighting the adverse vascular profile of folate deficiency.

Li Y et al. Folic acid supplementation and the risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. J Am Heart Assoc. 2016;5(8):e003768.; Wang Y et al. The effect of folic acid in patients with cardiovascular disease: a meta-analysis. Medicine (Baltimore). 2019;98(38):e17106.; Miller ER et al. Meta-analysis of folic acid supplementation trials on risk of cardiovascular disease. Am J Cardiol. 2010;106(4):517-527.

Folate deficiency impairs DNA synthesis, resulting in ineffective erythropoiesis, macrocytosis and megaloblastic anemia, often accompanied by glossitis, mucosal changes and fatigue.

Hematology and nutrition reviews describe folate deficiency as a classic cause of megaloblastic anemia and mucosal abnormalities, frequently exacerbated by medications that antagonize folate metabolism.

O’Leary F, Samman S. Vitamin B12 in health and disease. Nutrients. 2010;2(3):299-316. (discussion of folate and B12 in megaloblastic anemia); Lešić S et al. The impact of vitamin deficiencies on oral manifestations. Dent J (Basel). 2024;12(4):109.

Zinc depletion compromises innate and adaptive immune responses, leading to lymphopenia, reduced T-cell function and higher susceptibility to infections.

Classic dermatology and immunology literature shows that zinc deficiency causes lymphopenia and reduced immune capacity; more recent work links marginal deficiency to impaired inflammatory and anti-microbial responses.

Fraker PJ et al. The dynamic link between the integrity of the immune system and zinc status. JAMA Dermatol. 1987;123(2):169-174.; Lopez EA et al. Systematic review and meta-analysis of the effect of zinc on wound healing. Nutr Clin Pract. 2025;40(2):123-135.

Low zinc disrupts keratinocyte proliferation, collagen synthesis and epithelial repair, resulting in delayed wound healing, dermatitis and poor tissue regeneration.

Experimental and clinical studies demonstrate that zinc deficiency is associated with skin lesions, delayed wound closure and abnormal inflammatory responses, while zinc repletion can improve healing outcomes in selected populations.

Lin PH, Sermersheim M et al. Zinc in wound healing modulation. Nutrients. 2017;9(1):16.; News-Medical. The role of zinc in immune health and wound healing. 2024.; Lopez EA et al. Systematic review and meta-analysis of the effect of zinc on wound healing. Nutr Clin Pract. 2025;40(2):123-135.

Severe vitamin C depletion disrupts collagen hydroxylation, leading to fragile blood vessels, bleeding gums, easy bruising, corkscrew hairs, poor wound healing, anemia and, in advanced cases, scurvy.

Modern case reports and re-analyses of classic scurvy trials show that vitamin C deficiency causes defective collagen and capillary integrity, with slow recovery of scar strength even after repletion if deficiency is prolonged.

Gandhi M et al. Scurvy: rediscovering a forgotten disease. Clin Case Rep. 2023;11(6):e10296835.; Hujoel PP, Hujoel MLA. Vitamin C and scar strength: analysis of a historical trial. Am J Cardiol. 2022;129(1):106-112.; Vissers MCM, Das AB. Re-opening old wounds—vitamin C and wound healing. Am J Clin Nutr. 2022;115(4):795-796.

Moderate vitamin C depletion reduces collagen deposition and antioxidant capacity, which can manifest as slower wound healing, arthralgia and fatigue even before overt scurvy develops.

Systematic reviews report improved healing of chronic wounds with vitamin C supplementation in deficient or high-need states, supporting the clinical impact of inadequate ascorbate on tissue repair.

Bechara N et al. The role of vitamin C in tissue repair and wound healing: a systematic review. Int Wound J. 2022;19(5):1143-1160.; Pope M et al. Scurvy: an elusive diagnosis. Clin Case Rep. 2023;11(4):e7418.

B12 depletion impairs DNA synthesis in rapidly dividing cells, leading to macrocytic (megaloblastic) anemia, fatigue, pallor and, in severe cases, pancytopenia.

Clinical reviews identify vitamin B12 deficiency as a common cause of megaloblastic anemia; hematologic abnormalities often improve with replacement, underscoring the hematopoietic consequences of depletion.

Langan RC, Zawistoski KJ. Update on vitamin B12 deficiency. Am Fam Physician. 2017;96(6):384-389.; Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017;129(19):2603-2611.