Dolishale can affect this through 2 different nutrient pathways: Vitamin B6, Folic Acid. This medication is commonly used for Contraception.
Each nutrient below contributes to this impact through a different mechanism.
In the brain, vitamin B6 (pyridoxine) is a cofactor for enzymes that make key neurotransmitters such as serotonin, dopamine, and GABA, so low B6 status can contribute to depressive symptoms, irritability, and increased stress sensitivity. Epidemiologic studies in older adults and other populations have found that low plasma pyridoxal‑5‑phosphate (the active B6 form) or lower dietary B6 intake is associated with higher depression scores and roughly doubled odds of having clinically significant depressive symptomatology. The encouraging finding from emerging trials is that, in people with low or marginal B6 status, supplementation can modestly improve measures of anxiety and depressed mood, especially when used as part of a broader treatment plan that also addresses sleep, stress, and other nutrient deficiencies.
Lu J, Mao H, Tan Y, Luo G. Associations of Dietary Intake of Vitamin B6 and Plasma Pyridoxal 5'-Phosphate Level With Depression in US Adults: Findings From NHANES 2005-2010. Brain Behav. 2024 Nov;14(11):e70128.Arévalo SP, Scott TM, Falcón LM, Tucker KL. Vitamin B-6 and depressive symptomatology, over time, in older Latino adults. Nutr Neurosci. 2019 Sep;22(9):625-636. Durrani D, Idrees R, Idrees H, Ellahi A. Vitamin B6: A new approach to lowering anxiety, and depression? Ann Med Surg (Lond). 2022 Sep 15;82:104663. Ryan KM, Allers KA, Harkin A, McLoughlin DM. Blood plasma B vitamins in depression and the therapeutic response to electroconvulsive therapy. Brain Behav Immun Health. 2020 Mar 28;4:100063.
Folate deficiency has been associated with a higher risk of depressive symptoms, irritability, and other mood disturbances, likely through its role in one‑carbon metabolism, monoamine neurotransmitter synthesis, and methylation processes in the brain. Clinical and epidemiologic studies have found that people with low folate or elevated homocysteine are more likely to experience major depression, and lower folate status has been linked to poorer response to certain antidepressant medications. The encouraging clinical point is that, in folate‑deficient individuals, correcting folate status (often with folic acid or methylfolate, and alongside vitamin B12 when indicated) may improve mood symptoms and, in some cases, enhance antidepressant treatment response, especially when combined with comprehensive psychiatric and lifestyle interventions.
David Mischoulon, Maurizio Fava. Folate in Depression: Efficacy, Safety, Differences in Formulations, and Clinical Issues. The Journal of Clinical Psychiatry. 2009. Gao S, Khalid A, Amini-Salehi E, Radkhah N, Jamilian P, Badpeyma M, Zarezadeh M. Folate supplementation as a beneficial add-on treatment in relieving depressive symptoms: A meta-analysis of meta-analyses. Food Sci Nutr. 2024 Mar 8;12(6):3806-3818. Reynolds EH, Crellin R, Bottiglieri T, Laundy M, Toone BK, et al. Methylfolate as Monotherapy in Depression. A Pilot Randomised Controlled Trial. J Neurol Psychol. 2015;3(1): 5. Reynolds EH. Folic acid, ageing, depression, and dementia. BMJ. 2002 Jun 22;324(7352):1512-5. Gilbody S, Lightfoot T, Sheldon T. Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity. J Epidemiol Community Health. 2007 Jul;61(7):631-7.
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.
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.
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.
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.
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.
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.
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.
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.
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.