Loestrin 24 Fe can affect this through 3 different nutrient pathways: Vitamin B12, Folic Acid, Vitamin B6. This medication is commonly used for Contraception.
Each nutrient below contributes to this impact through a different mechanism.
Low or deficient vitamin B12 status is a leading cause of megaloblastic anemia, where impaired DNA synthesis disrupts red blood cell division and produces large, fragile megaloblasts instead of healthy cells. Clinically, vitamin B12–deficiency anemia is relatively common, with some population studies suggesting that up to 10–15% of older adults have biochemical B12 deficiency and a subset of these develop overt megaloblastic changes and anemia. In addition to fatigue and pallor from reduced oxygen‑carrying capacity, patients may show macrocytosis on CBC, elevated methylmalonic acid and homocysteine, and, if unrecognized, can progress to severe anemia that coexists with potentially irreversible neurologic complications
Habeb B, Khair S, Reid A (July 14, 2025) Unmasking Pernicious Anemia: A Reversible Cause of Pancytopenia Due to Severe Vitamin B12 Deficiency. Cureus 17(7): e87911. Lee YP, Loh CH, Hwang MJ, Lin CP. Vitamin B12 deficiency and anemia in 140 Taiwanese female lacto-vegetarians. J Formos Med Assoc. 2021 Nov;120(11):2003-2009. Ankar A, Kumar A. Vitamin B12 Deficiency. 2024 Sep 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. PMID: 28722952. Wong CW. Vitamin B12 deficiency in the elderly: is it worth screening? Hong Kong Med J. 2015 Apr;21(2):155-64.
Folate (folic acid) deficiency impairs DNA synthesis in rapidly dividing cells, which leads to megaloblastic anemia characterized by enlarged red blood cells, fatigue, pallor, and sometimes shortness of breath. Population studies have shown that folate deficiency and macrocytosis can be present for months before overt symptoms appear, and in some cohorts, up to roughly one quarter of anemic adults had an underlying folate or B12 deficiency rather than iron deficiency alone. The encouraging clinical point is that, once identified, folate‑responsive megaloblastic anemia often improves within weeks of adequate folic acid repletion, with reticulocyte counts rising in about 5–7 days and hemoglobin recovering more gradually over several weeks.
Koury MJ, Price JO, Hicks GG. Apoptosis in megaloblastic anemia occurs during DNA synthesis by a p53-independent, nucleoside-reversible mechanism. Blood. 2000 Nov 1;96(9):3249-55. Daniel S. Socha, MD, Sherwin I. DeSouza, MD, Aron Flagg, MD, Mikkael Sekeres, MD, MS and Heesun J. Rogers, MD, PhD. Severe megaloblastic anemia: Vitamin deficiency and other causes. Cleveland Clinic Journal of Medicine March 2020, 87 (3) 153-164. H.B. Castellanos-Sinco, et al. Megaloblastic anaemia: Folic acid and vitamin B12 metabolism. Revista Médica del Hospital General de México. Vol. 78. Issue 3. Pages 105-150 (July - September 2015). Anis Hariz, et al. Megaloblastic Anemia. StatPearls April 3, 2023.
Because vitamin B6 is a required cofactor for the first step of heme synthesis, deficiency can impair hemoglobin production and lead to anemia that is sometimes microcytic or shows sideroblastic features on bone‑marrow exam. Case reports and series describe patients with otherwise unexplained microcytic, hypochromic or sideroblastic anemia, including ringed sideroblasts, who were ultimately found to have B6 deficiency and experienced normalization of hemoglobin after pyridoxine supplementation. The practical point is that vitamin B6 deficiency is an important, often overlooked, reversible cause of anemia in adults, so it is worth checking B6 status when the anemia pattern does not line up with iron, folate, or B12 results, or when those levels are normal but the anemia persists.
Allain JS, Belhomme N, Henriot B, Haas M, Le Gall-Godard M, Pastoret C, Jego P. Une anémie microcytaire sidéroblastique carentielle traitée efficacement par de la vitamine B6 [A microcytic sideroblastic anemia successfully treated with B6 vitamin]. Rev Med Interne. 2019 Jul;40(7):462-465. French. Murakami R, Takumi T, Gouji J, Nakamura H, Kondou M. Sideroblastic anemia showing unique response to pyridoxine. Am J Pediatr Hematol Oncol. 1991 Fall;13(3):345-50. Kudo, K., Ito, M., Horibe, K., Iwase, K., & Kojima, S. (1999). An infant case of sideroblastic anemia that responded to oral pyridoxine. [Rinshō ketsueki] The Japanese journal of clinical hematology, 40(8), 667-672. John N. Bickers, et al. Pyridoxine Responsive Anemia. Blood (1962) 19 (3): 304–312.
Some side effects may be linked to nutrient depletion caused by this medication.
Studies suggest that women using oral contraceptives might have lower levels of vitamin C within their white blood cells (leukocytes) and platelets. This depletion could be linked to reduced activity of antioxidant enzymes like glutathione peroxidase (GPx) and glutathione reductase (GR) in the blood. These enzymes play a role in protecting cells from damage. Research also shows that supplementing with vitamin C, alongside vitamin E, can significantly increase the activity of these antioxidant enzymes in women taking OCs. This suggests that vitamin C supplementation might be beneficial for women on birth control pills.
Studies suggest a potential for mild thiamine (vitamin B1) deficiency with long-term use of Oral Contraceptives (OCs). One finding showed that red blood cell activity of an enzyme dependent on thiamine (transketolase) decreased during OC treatment. This decrease indicates that the cells might not have enough thiamine to function optimally, suggesting a mild thiamine deficiency induced by the contraceptives. Supplementation with thiamine (vitamin B1) should be considered for women using OCs.
Research suggests a potential decrease in magnesium levels in women using Oral Contraceptives (OCs). Studies have shown that women taking OCs have significantly lower serum magnesium compared to those not using them. Interestingly, the type of pill or duration of use doesn't seem to influence the degree of magnesium depletion. The observed decrease in magnesium with OC use might be associated with an increased risk of blood clots. Supplementation with magnesium should be considered during oral contraceptives use.
Oral contraceptives (OCs) have been linked to a decrease in Vitamin B12 levels. Studies have shown a significant reduction in serum B12, the vitamin circulating in the blood, in women taking OCs for extended periods. One US study found a 40% decrease in B12 levels after five years of OC use. This decrease is concerning because vitamin B12 plays a crucial role in converting a form of folate (N-methyltetrahydrofolic acid) into its active form (tetrahydrofolic acid). This active folate is essential for healthy red blood cell production and other bodily functions. Due to the vital role of vitamin B12, supplementation when using OCs long-term should be considered.
Women using oral contraceptives (OCs) for extended periods may experience a decrease in their folate levels. Studies suggest that OC use might lower blood folate levels by up to 40%. This depletion can be a concern because folate plays a crucial role in red blood cell production. One research finding highlights a case where a patient developed anemia and nerve problems (polyneuropathy) after stopping vitamin B12 therapy, suggesting that folate deficiency might have been the main underlying issue. Supplementation of folate should be considered during oral contraceptive use.
Research suggests that oral contraceptives (OCs) may play a role in vitamin B6 deficiency. A deficiency is concerning because vitamin B6 plays a crucial role in mood regulation and blood sugar control. Some women using OCs experience symptoms like depression and impaired glucose tolerance, which could potentially be linked to this vitamin B6 deficiency. Low vitamin B6 levels are independently associated with an increased risk of blood clots in both arteries and veins (venous and arterial thromboembolism, or TE). This association suggests that the B6 deficiency caused by OCs might partly explain the higher risk of TE observed in women using birth control pills. This highlights the importance of ensuring adequate vitamin B6 intake for women on OCs and therefore supplementation should be considered.
Studies suggest that oral contraceptives (OCs) may contribute to zinc deficiency. Research has shown a significant decrease in serum zinc levels, the zinc circulating in the blood, in women taking OCs. This decrease is thought to be due to potential changes in how the body absorbs, excretes, or utilizes zinc within tissues. Due to its vital role in many bodily functions, ensuring sufficient zinc intake through supplementation should be considered for women on birth control pills.
When using oral contraceptives (OCs), the body might experience increased oxidative stress due to hormonal changes. Vitamin E, a potent antioxidant, could potentially help counteract this stress and promote cellular health. Research shows that combining vitamin E with vitamin C supplementation might be even more beneficial. Studies like one where Group C received both vitamins showed a significant increase in the activity of enzymes (GPx and GR) crucial for antioxidant defense, along with a reduction in markers of oxidative damage (plasma MDA levels). This suggests that a combined approach with vitamins E and C might offer enhanced protection against cellular stress for women using OCs.
Women using oral contraceptives (OCs) may experience mood changes, including depression. Research suggests a potential link between these emotional shifts and a decrease in brain levels of the neurotransmitter norepinephrine (noradrenaline). This decrease could be related to reduced availability of its precursor molecule, tyrosine, in the brain. Studies have shown a significant decline in tyrosine levels in women on OCs. One study found that the area under the curve (AUC) in plasma for tyrosine in OC users were 43% of control levels. Tyrosine supplementation could potentially help regulate mood and improve emotional well-being while taking OCs.
Women using Oral Contraceptives (OCs) may benefit from including vitamin B2 (riboflavin) in their regimen. Vitamin B2 plays a critical role in activating other B vitamins, like folic acid and B6, which are essential for various bodily functions. Studies have shown that women on OCs have lower levels of active vitamin B2, as measured by the activity of an enzyme dependent on it (glutathione reductase). These reduced levels might be linked to migraines, a frequent side effect of OCs that can sometimes lead women to discontinue the medication. By ensuring adequate B2 intake, women on OCs may potentially experience reduced migraine frequency and benefit from the proper activation of other B vitamins.