Phenelzine Side Effects & Health Impacts

Low vitamin B6 status can promote accumulation of homocysteine, a sulfur‑containing amino acid that can damage the endothelium, increase oxidative stress, and promote clot formation, all of which are relevant to cardiovascular disease and stroke. Large observational studies and cross‑sectional analyses have shown that people with lower plasma pyridoxal‑5‑phosphate (active B6) levels have higher rates of stroke and other vascular events, and in some cohorts low B6 was a stronger predictor of stroke or transient ischemic attack than homocysteine itself. The encouraging finding from meta‑analyses and clinical trials is that B‑vitamin combinations including B6 can lower homocysteine and modestly reduce the combined risk of stroke, myocardial infarction, and vascular death in high‑risk patients, suggesting that maintaining adequate B6 is one useful piece of broader cardiovascular prevention

Research: Vanuzzo D, Pilotto L, Lombardi R, Lazzerini G, Carluccio M, Diviacco S, Quadrifoglio F, Danek G, Gregori D, Fioretti P, Cattaneo M, De Caterina R. Both vitamin B6 and total homocysteine plasma levels predict long-term atherothrombotic events in healthy subjects. Eur Heart J. 2007 Feb;28(4):484-91. Zhang M, Zhong J, Peng Y, Hao L, Xiao B. Pyridoxal 5'-phosphate and risk of stroke: triangulation of evidence from a nationally representative cohort and bidirectional Mendelian randomization analysis. EPMA J. 2024 Dec 18;16(1):95-111. Wei J, Ji JS. Modification of vitamin B6 on the associations of blood lead levels and cardiovascular diseases in the US adults. BMJ Nutrition, Prevention & Health. 2020;:bmjnph-2020-000088. Li, B., Hu, M., Ma, Y. et al. Association between Vitamin E, Vitamin B6, and Vitamin B12 with coronary heart disease. Sci Rep 14, 19960 (2024).

In the brain, vitamin B6 (pyridoxine) is needed to produce neurotransmitters and to keep homocysteine in check, so low B6 status has been linked to both depressed mood and subtle cognitive problems such as slower processing and poorer attention in some adults. Observational work in older populations suggests that lower blood levels or intakes of B6 tend to track with worse performance on memory, executive‑function, and psychomotor‑speed tests, raising concern that marginal B6 status may contribute to age‑related cognitive decline. Clinically, when B6 deficiency coexists with depression, correcting it is viewed as one modifiable factor that may help support clearer thinking and better cognitive function alongside standard psychiatric and lifestyle treatments.

Research: Palacios N, Scott T, Sahasrabudhe N, Gao X, Tucker KL. Lower Plasma Vitamin B-6 is Associated with 2-Year Cognitive Decline in the Boston Puerto Rican Health Study. J Nutr. 2019 Apr 1;149(4):635-641. Hughes CF, Ward M, Tracey F, Hoey L, Molloy AM, Pentieva K, McNulty H. B-Vitamin Intake and Biomarker Status in Relation to Cognitive Decline in Healthy Older Adults in a 4-Year Follow-Up Study. Nutrients. 2017 Jan 10;9(1):53. Kim H, Kim G, Jang W, Kim SY, Chang N. Association between intake of B vitamins and cognitive function in elderly Koreans with cognitive impairment. Nutr J. 2014 Dec 17;13(1):118. Zhao L, Guan L, Sun J, Li X. Serum levels of folate, vitamin B6, and vitamin B12 are associated with cognitive impairments in depression patients. Acta Neuropsychiatrica. 2024;36(1):44-50

In the nervous system, vitamin B6 is essential for making the inhibitory neurotransmitter GABA, so significant deficiency can lower seizure threshold and lead to seizures or encephalopathy, particularly in infants but occasionally in adults. Classic pyridoxine‑dependent or B6‑responsive seizure syndromes in infants often present with refractory seizures that improve dramatically after B6 or pyridoxal‑5‑phosphate is given, highlighting how crucial this pathway is for brain stability. Clinically, this means that in patients, especially infants, with otherwise unexplained or treatment‑resistant seizures or encephalopathy, assessing and correcting B6 status is a low‑risk, potentially lifesaving step that should be considered early.

Research: Sousou JM, Griffith EM, Marsalisi C, Reddy P. Pyridoxine Deficiency and Neurologic Dysfunction: An Unlikely Association. Cureus. 2023 Oct 25;15(10):e47647. Gerlach, A.T., Thomas, S., Stawicki, S.P., Whitmill, M.L., Steinberg, S.M., & Cook, C.H. (2011). Vitamin B6 deficiency: a potential cause of refractory seizures in adults. JPEN. Journal of parenteral and enteral nutrition, 35 2, 272-5 . Lee, D., Lee, Y., Shin, H., Kang, K., Park, J., Kim, B., Kwon, O., & Lee, J. (2015). Seizures Related to Vitamin B6 Deficiency in Adults. Journal of Epilepsy Research, 5, 23 - 24. Murty VS, Kishore MS, Patel MR. A Rare Case of Pyridoxine-dependent Seizures in Infancy. J Clin Neonatol. 2013 Jan;2(1):39-41.

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.

Research: 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.

In some adults, vitamin B6 deficiency can manifest as a distal, symmetric peripheral neuropathy that is predominantly sensory rather than motor, with numbness, tingling, or burning pain starting in the feet and hands. Clinical descriptions note that this large‑fiber neuropathy often produces loss of vibration and position sense with relatively preserved pain and temperature sensation, which can lead to sensory ataxia and gait unsteadiness in more advanced cases. The practical point is that, because both B6 deficiency and excess can cause peripheral neuropathy, it is important to assess B6 status in patients with otherwise unexplained distal sensory symptoms and to correct deficiencies.

Research: Miguel Chuquilin Arista, et al. Pyridoxine Deficiency in Patients with Peripheral Neuropathy Symptoms. Neurology Journals. A Case Series (P01.137). February 12, 2013 issue 80 (7_supplement) P01.137. Sawhney A, Singhal S, Patel R (July 10, 2022) Isolated Pyridoxine Deficiency Presenting as Peripheral Neuropathy Post-chemotherapy. Cureus 14(7): e26725. Renting L, Zwart NRK, Ueland PM, McCann A, Ulvik A, van Halteren HK, et al. Vitamin B6 status and chronic chemotherapy-induced peripheral neuropathy: a prospective cohort study among patients with non-metastatic colorectal cancer receiving oxaliplatin-based chemotherapy. BMJ Oncology. 2024;3:e000462

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.

Research: 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.

On the skin and mucous membranes, vitamin B6 deficiency can cause a seborrheic dermatitis‑like rash with redness, scaling, and itching on the face, scalp, neck, or upper chest, along with fissuring at the lips. Clinical descriptions note that B6‑related mucosal changes can include cheilitis, stomatitis, and glossitis, and some field studies in children have linked low pyridoxine status with a higher prevalence of angular stomatitis and tongue inflammation that improve with B‑complex supplementation. The practical implication is that, when patients present with persistent seborrheic dermatitis‑like eruptions plus mouth sores or tongue soreness, particularly in the setting of poor diet, alcoholism, or malabsorption, assessing vitamin B6 (and other B‑vitamin) status can be an important step toward resolving these dermatologic and mucosal lesions.

Research: Fabrizio Galimberti, et al. Skin findings associated with nutritional deficiencies. Cleveland Clinic Journal of Medicine Volume 83. Number 10 October 2016. Kseniya Perminova. Lesions of the mucous membrane due to hypovitaminosis. 30 January 2024. Mary J. Brown; Sharon F. Daley; Kevin Beier. Vitamin B6 Deficiency. StatPearls. August 8, 2023. Sousou JM, Griffith EM, Marsalisi C, Reddy P. Pyridoxine Deficiency and Neurologic Dysfunction: An Unlikely Association. Cureus. 2023 Oct 25;15(10):e47647.