Aubra 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).

Impacted through 2 nutrients: Vitamin B6, Vitamin B12.

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.

Vitamin C deficiency weakens collagen in capillary and vascular walls, so severe scurvy can present with ocular hemorrhages in the conjunctiva and retina that threaten vision if not treated. Case reports and small series describe retinal hemorrhages, flame‑shaped hemorrhages, and even retrobulbar bleeding compressing the optic nerve, which can lead to optic neuropathy and visual loss in advanced cases. The encouraging point is that, when vitamin C deficiency is recognized early and promptly repleted, many ocular hemorrhages and visual symptoms can partially or fully resolve, making it critical to consider vitamin C status in patients with otherwise unexplained ocular bleeding and visual complaints.

Research: Errera MH, Dupas B, Man H, Gualino V, Gaudric A, Massin P. Une cause inhabituelle d'anomalies rétiniennes, hémorragies rétiniennes révélatrices de scorbut [Unusual retinal abnormality: retinal hemorrhages related to scurvy]. J Fr Ophtalmol. 2011 Mar;34(3):186.e1-3. Masuda Y, Saigusa K, Norisue Y. A Case of Scurvy Associated With Intracerebral Hemorrhage in a Patient With Alcohol Use Disorder. Cureus. 2024 Feb 23;16(2):e54777. Andrew Go Lee, et al. Ocular Manifestations of Vitamin C Deficiency. American Academy of Opthamology. November 2025. A. Martel, et al. Spontaneous eyelid and subconjunctival socket bleeding related to vitamin C deficiency: First case reportHémorragie palpébrale et sous conjonctivale spontanée sur cavité anophtalme secondaire à un déficit en vitamine C : premier cas rapporté. Journal Français d'Ophtalmologie. Volume 43, Issue 9, November 2020.

Low zinc status has been linked to a higher risk and faster progression of age-related macular degeneration (AMD), in part because zinc is concentrated in the retina and supports antioxidant defenses there. In the landmark AREDS trial, a supplement formula containing zinc (80 mg as zinc oxide), along with antioxidants, reduced the risk of progression to advanced AMD by about 25% in people with intermediate disease or advanced disease in one eye over roughly 5 years. Other research has shown that inadequate zinc intake is more common in older adults with AMD, reinforcing the idea that maintaining healthy zinc levels may be an important, and often overlooked, strategy for preserving macular health with age.

Research: Smailhodzic D, van Asten F, Blom AM, Mohlin FC, den Hollander AI, van de Ven JPH, et al. (2014) Zinc Supplementation Inhibits Complement Activation in Age-Related Macular Degeneration. PLoS ONE 9(11): e112682. Lengyel D, Török B. Erworbene vorübergehende Nachtblindheit bei Vitamin-A- und Zinkmangel bei Anorexia nervosa neun Jahre nach Nierentransplantation [Acquired temporary night blindness in vitamin A and zinc deficiency in anorexia nervosa nine years after kidney transplantation]. Klin Monbl Augenheilkd. 2006 May;223(5):453-5. German.Blasiak J, Pawlowska E, Chojnacki J, Szczepanska J, Chojnacki C, Kaarniranta K. Zinc and Autophagy in Age-Related Macular Degeneration. Int J Mol Sci. 2020 Jul 15;21(14):4994. Benjamin P. Nicholson, et al. Chapter 37 - Zinc Deficiency and the Eye. Handbook of Nutrition, Diet and the Eye 2014, Pages 371-376.

Low or deficient vitamin B12 status elevates homocysteine levels by impairing its conversion to methionine, a process that requires B12 as a cofactor. This hyperhomocysteinemia is linked to increased cardiovascular risks, including atherosclerosis, heart disease, and stroke, through vascular inflammation and endothelial damage. Additionally, low B12 contributes to metabolic disturbances like insulin resistance and type 2 diabetes risk, compounding heart health concerns in susceptible individuals.

Research: Sucharita S, Thomas T, Antony B, Vaz M. Vitamin B12 supplementation improves heart rate variability in healthy elderly Indian subjects. Auton Neurosci. 2012 May 21;168(1-2):66-71. Al-Daghri NM, Rahman S, Sabico S, Yakout S, Wani K, Al-Attas OS, Saravanan P, Tripathi G, McTernan PG, Alokail MS. Association of Vitamin B12 with Pro-Inflammatory Cytokines and Biochemical Markers Related to Cardiometabolic Risk in Saudi Subjects. Nutrients. 2016 Sep 6;8(9):460. Eken, Y.; Tekin, N.; Şahin, F.; Tay, İ.; Yıldırım Saral, N.; Serteser, M.; Baykal, A.T. Vitamin B12 Status and Cardiovascular Risk: Novel Insights from NMR-Based Lipoprotein Profiling in 20,665 Adults. J. Clin. Med. 2026. Liu Y, Geng T, Wan Z, Lu Q, Zhang X, Qiu Z, Li L, Zhu K, Liu L, Pan A, Liu G. Associations of Serum Folate and Vitamin B12 Levels With Cardiovascular Disease Mortality Among Patients With Type 2 Diabetes. JAMA Netw Open. 2022 Jan 4;5(1):e2146124.

Low or depleted vitamin B12 status is linked to reduced bone mineral density (BMD), increasing osteoporosis risk in both men and women. Individuals with low B12 show significantly lower BMD at key sites like the hip and spine compared to those with adequate levels. Routine serum B12 monitoring, alongside periodic bone density scans and supplementation for at-risk groups, helps preserve bone health and mitigate fracture risks.

Research: Stone KL, Bauer DC, Sellmeyer D, Cummings SR. Low serum vitamin B-12 levels are associated with increased hip bone loss in older women: a prospective study. J Clin Endocrinol Metab. 2004 Mar;89(3):1217-21. Clements M, Heffernan M, Ward M, Hoey L, Doherty LC, Hack Mendes R, Clarke MM, Hughes CF, Love I, Murphy S, McDermott E, Grehan J, McCann A, McAnena LB, Strain JJ, Brennan L, McNulty H. A 2-Year Randomized Controlled Trial With Low-Dose B-Vitamin Supplementation Shows Benefits on Bone Mineral Density in Adults With Lower B12 Status. J Bone Miner Res. 2022 Dec;37(12):2443-2455. Tucker KL, Hannan MT, Qiao N, Jacques PF, Selhub J, Cupples LA, Kiel DP. Low plasma vitamin B12 is associated with lower BMD: the Framingham Osteoporosis Study. J Bone Miner Res. 2005 Jan;20(1):152-8.

In both children and adults, vitamin E deficiency can contribute to retinopathy and visual impairment because α‑tocopherol serves as a key fat‑soluble antioxidant that protects photoreceptor cells and retinal membranes from cumulative oxidative damage. Clinical reports describe patients with prolonged low vitamin E status developing pigmentary retinopathy, reduced visual acuity, and abnormal electroretinograms, sometimes alongside peripheral neuropathy, which can improve partially when deficiency is identified and corrected. These neurosensory changes appear more frequently in settings of fat malabsorption or genetic disorders affecting vitamin E transport, highlighting the importance of monitoring vitamin E status in at‑risk groups with otherwise unexplained visual decline.

Research: Runge P, Muller DP, McAllister J, Calver D, Lloyd JK, Taylor D. Oral vitamin E supplements can prevent the retinopathy of abetalipoproteinaemia. Br J Ophthalmol. 1986 Mar;70(3):166-73. Pang J, Kiyosawa M, Seko Y, Yokota T, Harino S, Suzuki J. Clinicopathological report of retinitis pigmentosa with vitamin E deficiency caused by mutation of the alpha-tocopherol transfer protein gene. Jpn J Ophthalmol. 2001 Nov-Dec;45(6):672-6. Edwards G, Olson CG, Euritt CP, Koulen P. Molecular Mechanisms Underlying the Therapeutic Role of Vitamin E in Age-Related Macular Degeneration. Front Neurosci. 2022 May 4;16:890021. Ng EY, Chiew Y, Phang SCW, Ng YT, Tan GCJ, et al. (2021) The Effects of Vitamin E on Non-proliferative Diabetic Retinopathy in Type 2 Diabetes Mellitus. Int J Diabetes Clin Res 8:142.

When vitamin C runs low, its impact isn’t just skin‑deep, it can also affect the heart and lungs, sometimes contributing to shortness of breath, fatigue, and fluid retention. Severe vitamin C deficiency has been reported as a reversible cause of pulmonary hypertension and right‑sided heart failure, with pressures in the lung circulation and cardiac strain improving after vitamin C is replaced. Broader cardiovascular research also links low vitamin C with higher blood pressure and stiffer arteries, while short‑term supplementation in some hypertensive or diabetic patients has lowered systolic blood pressure and improved arterial stiffness, suggesting that adequate vitamin C helps support healthier vascular tone and cardiac workload.

Research: Kurnick A, Zaveri S, Tadayoni A, Chandrakumar HP, John S. Reversible severe pulmonary hypertension and right heart failure with cardiogenic shock due to scurvy: a case report. Eur Heart J Case Rep. 2023 Aug 17;7(8):ytad404. Duvall MG, Pikman Y, Kantor DB, Ariagno K, Summers L, Sectish TC, Mullen MP. Pulmonary hypertension associated with scurvy and vitamin deficiencies in an autistic child. Pediatrics. 2013 Dec;132(6):e1699-703. Abe K, Kibe R, David K, Reddy V, Allard B, Fakaosita M. Reversible right-sided heart failure and pulmonary hypertension caused by scurvy in a 7-year-old boy with autism spectrum disorder and a review of the literature. Paediatr Int Child Health. 2023 Nov;43(4):95-99. Conte L, Louden J, Weber LA. Multivalve dysfunction and cardiogenic shock linked to scurvy: A case report. Anatol J Cardiol. 2021 May;25(5):355-359.

Impacted through 2 nutrients: Zinc, Vitamin B12.

Closely linked to reproductive and hormonal problems in both men and women, zinc deficiency can contribute to hypogonadism, low testosterone, reduced sperm count, and menstrual irregularities. In men, low zinc status has been associated with decreased serum testosterone, reduced sperm density and motility, and poorer overall semen quality, while zinc repletion in deficient individuals has been shown to improve some of these parameters. In women, inadequate zinc intake is tied to more frequent cycle disturbances, dysmenorrhea, and potential impacts on ovulation and fertility, underscoring zinc’s important role in healthy hormonal balance and reproductive function.

Research: Zhao J, Dong X, Hu X, Long Z, Wang L, Liu Q, Sun B, Wang Q, Wu Q, Li L. Zinc levels in seminal plasma and their correlation with male infertility: A systematic review and meta-analysis. Sci Rep. 2016 Mar 2;6:22386. Mohan H, Verma J, Singh I, Mohan P, Marwah S, Singh P. Inter-relationship of zinc levels in serum and semen in oligospermic infertile patients and fertile males. Indian J Pathol Microbiol. 1997 Oct;40(4):451-5. PMID: 9444854. Zečević N, Veselinović A, Perović M, Stojsavljević A. Association Between Zinc Levels and the Impact of Its Deficiency on Idiopathic Male Infertility: An Up-to-Date Review. Antioxidants (Basel). 2025 Jan 29;14(2):165. Dhar S, Yadav R, Tomar A. Serum Zinc Levels in Women with Polycystic Ovarian Syndrome are Lower as Compared to Those without Polycystic Ovarian Syndrome: A Cohort Study. J Hum Reprod Sci. 2024 Jan-Mar;17(1):25-32.

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

Impacted through 3 nutrients: Vitamin C, Zinc, Vitamin E.

Zinc deficiency during childhood and adolescence is strongly linked to impaired linear growth and delayed sexual maturation, and is a recognized contributor to stunting in many low‑ and middle‑income countries. In some population studies, zinc deficiency has been present in over 30–40% of children, and zinc supplementation programs have been associated with modest but meaningful improvements in height gain over time. Clinically, even marginal zinc deficiency can quietly slow growth velocity and pubertal progression, making adequate zinc intake an important, often overlooked pillar of healthy growth and development.

Research: Abdollahi M, Ajami M, Abdollahi Z, Kalantari N, Houshiarrad A, Fozouni F, Fallahrokni A, Mazandarani FS. Zinc supplementation is an effective and feasible strategy to prevent growth retardation in 6 to 24 month children: A pragmatic double blind, randomized trial. Heliyon. 2019 Nov 1;5(11):e02581. Walravens PA, Krebs NF, Hambidge KM. Linear growth of low income preschool children receiving a zinc supplement. Am J Clin Nutr. 1983 Aug;38(2):195-201. Rerksuppaphol S, Rerksuppaphol L. Zinc supplementation enhances linear growth in school-aged children: A randomized controlled trial. Pediatr Rep. 2018 Jan 4;9(4):7294. Zinc deficiency as risk factor for stunting among children aged 2-5 years. (2017). Universa Medicina, 36(1), 11-18.

Vitamin E deficiency can drive a progressive neurologic syndrome, including ataxia, sensory neuropathy, and myelopathy, because α‑tocopherol is a critical fat‑soluble antioxidant that protects neuronal membranes and prevents peroxidation of polyunsaturated fatty acids under oxidative stress. In both children with chronic cholestatic liver disease and adults without obvious fat malabsorption, low vitamin E status has been linked to characteristic large‑fiber sensory axonopathy and other degenerative changes, illustrating that unrecognized deficiency can present with strikingly “neurologic‑first” symptoms. When vitamin E deficiency is identified early, appropriately dosed, bioavailable α‑tocopherol supplementation can stabilize or partially reverse neurologic findings in some patients, underscoring the importance of screening at‑risk groups and not dismissing isolated ataxia or neuropathy as purely genetic or idiopathic.

Research: Sokol RJ, Butler-Simon N, Conner C, Heubi JE, Sinatra FR, Suchy FJ, Heyman MB, Perrault J, Rothbaum RJ, Levy J, et al. Multicenter trial of d-alpha-tocopheryl polyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis. Gastroenterology. 1993 Jun;104(6):1727-35. Bonello M, Ray P. A Case of Ataxia with Isolated Vitamin E Deficiency Initially Diagnosed as Friedreich's Ataxia. Case Rep Neurol Med. 2016;2016:8342653. Agarwal A, Garg D, Srivastava AK. Ataxia with Vitamin E Deficiency: A Never to be Missed Treatable Ataxia. Ann Indian Acad Neurol. 2023 Nov-Dec;26(6):1011-1012. Chan KH, O'Sullivan M, Farouji I, Are G, Slim J. Sensory Axonopathy Associated With Vitamin E Deficiency. Cureus. 2021 Feb 17;13(2):e13389.

Vitamin E deficiency can present as a predominantly neuromuscular picture, in which slowly progressive peripheral neuropathy (often large‑fiber, length‑dependent, and sensory‑predominant) coexists with proximal muscle weakness and myopathy due to ongoing oxidative damage to peripheral nerves and muscle cell membranes. In reported series, patients have developed areflexia, gait instability, distal numbness, and reduced vibration sense along with elevated creatine kinase or myopathic changes on EMG, sometimes after years of unrecognized low vitamin E status rather than an obvious malabsorption syndrome. When deficiency is documented and α‑tocopherol is repleted with an adequately absorbed preparation, some individuals show meaningful improvements in strength, sensory symptoms, and electrophysiologic measures, highlighting that peripheral neuropathy and myopathy attributed to “idiopathic” or purely degenerative causes may in fact be partially reversible when vitamin E deficiency is identified and treated.

Research: Puri, V., Chaudhry, N., Tatke, M. and Prakash, V. (2005), Isolated vitamin E deficiency with demyelinating neuropathy. Muscle Nerve, 32: 230-235. Martinello F, Fardin P, Ottina M, Ricchieri GL, Koenig M, Cavalier L, Trevisan CP. Supplemental therapy in isolated vitamin E deficiency improves the peripheral neuropathy and prevents the progression of ataxia. J Neurol Sci. 1998 Apr 1;156(2):177-9. Hegele RA, Angel A. Arrest of neuropathy and myopathy in abetalipoproteinemia with high-dose vitamin E therapy. Can Med Assoc J. 1985 Jan 1;132(1):41-4. Sokol RJ, Butler-Simon N, Heubi JE, Iannaccone ST, McClung HJ, Accurso F, Hammond K, Heyman M, Sinatra F, Riely C, et al. Vitamin E deficiency neuropathy in children with fat malabsorption. Studies in cystic fibrosis and chronic cholestasis. Ann N Y Acad Sci. 1989;570:156-69.

In high‑risk settings such as prematurity or chronic fat malabsorption, vitamin E deficiency can contribute to hemolytic anemia because α‑tocopherol is a fat‑soluble antioxidant that keeps red blood cell membranes more stable under everyday oxidative stress. By helping prevent damage to the polyunsaturated fatty acids in these membranes, vitamin E lowers the chance that red blood cells will break apart too early, which can otherwise show up as fatigue, pallor, jaundice, and lab evidence of anemia. In very low birth‑weight infants and in people with long‑standing fat‑absorption problems, spotting low vitamin E levels early and using a well‑absorbed natural Vitamin E supplement can meaningfully reduce hemolysis risk and support healthier hemoglobin levels over time.

Research: Jilani T, Iqbal MP. Does vitamin E have a role in treatment and prevention of anemia? Pak J Pharm Sci. 2011 Apr;24(2):237-42. Gomez-Pomar E, Hatfield E, Garlitz K, Westgate PM, Bada HS. Vitamin E in the Preterm Infant: A Forgotten Cause of Hemolytic Anemia. Am J Perinatol. 2018 Feb;35(3):305-310. Gross, S., Landaw, S. & Oski, F. The effects of vitamin E on hemolysis in premature infants during the first week of life. Pediatr Res 11, 472 (1977).Jilani T, Iqbal MP. Vitamin E deficiency in South Asian population and the therapeutic use of alpha-tocopherol (Vitamin E) for correction of anemia. Pak J Med Sci. 2018 Nov-Dec;34(6):1571-1575.

In both inherited and acquired deficiency states, vitamin E deficiency can contribute to cerebellar dysfunction and central cognitive effects because α‑tocopherol protects vulnerable neurons, including cerebellar Purkinje cells, from ongoing oxidative damage across the lifespan. In AVED, where an α‑TTP defect prevents normal vitamin E transport, deficiency is associated with spinocerebellar ataxia, Purkinje cell loss, degeneration of sensory neurons, and a characteristic “dying back” neuropathy, yet long‑term α‑tocopherol supplementation over many years can slow or even prevent further neurologic progression when started early. Experimental and clinical data also show that even brief interruptions in vitamin E supplementation can measurably lower plasma total radical‑trapping antioxidant capacity before obvious symptom worsening, highlighting renewed oxidative vulnerability of nervous tissue and reinforcing the importance of consistent repletion to support normal neurogenesis and central nervous system function.

Research: Thapa S, Shah S, Chand S, Sah SK, Gyawali P, Paudel S, Khanal P. Ataxia due to vitamin E deficiency: A case report and updated review. Clin Case Rep. 2022 Sep 6;10(9):e6303. Schuelke M, Finckh B, Sistermans EA, Ausems MG, Hübner C, von Moers A. Ataxia with vitamin E deficiency: biochemical effects of malcompliance with vitamin E therapy. Neurology. 2000 Nov 28;55(10):1584-6. N. Stojiljkovic, S. Redko, F. Gupta, S. Kathiresu Nageshwaran, W. Tse. Cerebellar ataxia due to vitamin E deficiency [abstract]. Mov Disord. 2023; 38 (suppl 1). Traber MG. Vitamin E: necessary nutrient for neural development and cognitive function. Proc Nutr Soc. 2021 Aug;80(3):319-326.

Impacted through 2 nutrients: Vitamin B6, Vitamin B12.

Low or deficient vitamin C status can matter more than people realize because it can show up as everyday problems they already have, like bleeding gums when they brush or cuts and scrapes that seem slow to heal. Low vitamin C weakens collagen formation, making blood vessels in the gums and skin more fragile and increasing the risk of bleeding gums, easy bruising, and rough, dry skin. Clinical periodontal studies also show that ascorbic acid used alongside standard care can improve bleeding on probing, plaque and gingival indices, clinical attachment level, pocket depth, and gum aesthetics, supporting its role in healthier gums and more efficient healing of both oral tissues and skin.

Research: Murererehe J, Uwitonze AM, Nikuze P, Patel J and Razzaque MS (2022) Beneficial Effects of Vitamin C in Maintaining Optimal Oral Health. Front. Nutr. 8:805809. Ruzijevaite G, Acaite E, Jagelaviciene E. Therapeutic Impact of Ascorbic Acid on Oral and Periodontal Tissues: A Systematic Literature Review. Medicina (Kaunas). 2024 Dec 11;60(12):2041. Al-Niaimi F, Chiang NYZ. Topical Vitamin C and the Skin: Mechanisms of Action and Clinical Applications. J Clin Aesthet Dermatol. 2017 Jul;10(7):14-17. Epub 2017 Jul 1. Fitzpatrick, R.E. and Rostan, E.F. (2002), Double-Blind, Half-Face Study Comparing Topical Vitamin C and Vehicle for Rejuvenation of Photodamage. Dermatologic Surgery, 28: 231-236. Lassig AAD, Wilson AC, Jungbauer WN, Joseph AM, Lindgren B, Odland R. The Effects of Supplemental Vitamin C in Mandibular Fracture Patients: A Randomized Clinical Trial. Recent Progress in Nutrition 2023. Tajari F, Toloue Ghamari B, Jafari Kafiabadi M, Shariatzade H, Biglari F, Mahmoudi Nasab O, Salavati Mohammadi N, Najd Mazhar F. Effect of Vitamin C Injection on Flexor Tendon Healing in Zone II: A Randomized Controlled Trial. Cureus. 2026 Jan 22;18(1):e102075.

When vitamin C intake is too low for too long, it can start to show up in the muscles and joints as deep, aching pain and stiffness rather than just “simple” fatigue. Vitamin C is essential for building and maintaining healthy collagen in cartilage, tendons, and bone, so deficiency can cause bone tenderness, joint pain, and, in children, impaired growth and skeletal deformities similar to rickets or scurvy. In more advanced cases, people may notice difficulty walking, painful swelling around joints, and slower recovery from everyday strains or minor injuries because the connective tissues simply cannot repair and mineralize properly without adequate vitamin C.

Research: Mangano KM, Noel SE, Dawson-Hughes B, Tucker KL. Sufficient Plasma Vitamin C Is Related to Greater Bone Mineral Density among Postmenopausal Women from the Boston Puerto Rican Health Study. J Nutr. 2021 Dec 3;151(12):3764-3772. Kim YA, Kim KM, Lim S, Choi SH, Moon JH, Kim JH, Kim SW, Jang HC, Shin CS. Favorable effect of dietary vitamin C on bone mineral density in postmenopausal women (KNHANES IV, 2009): discrepancies regarding skeletal sites, age, and vitamin D status. Osteoporos Int. 2015 Sep;26(9):2329-37. Ratajczak AE, Szymczak-Tomczak A, Skrzypczak-Zielińska M, Rychter AM, Zawada A, Dobrowolska A, Krela-Kaźmierczak I. Vitamin C Deficiency and the Risk of Osteoporosis in Patients with an Inflammatory Bowel Disease. Nutrients. 2020 Jul 29;12(8):2263. Souza M, Moraes SAS, de Paula DR, Maciel AA, Batista EJO, Silva DGF, Bahia CP, Oliveira KRHM, Herculano AM. Local treatment with ascorbic acid accelerates recovery of post-sutured Achilles tendon in male Wistar rats. Braz J Med Biol Res. 2019;52(9):e8290.

Zinc deficiency often first shows up on the skin, with acrodermatitis‑like eruptions around the mouth, perineum, and distal extremities, accompanied by alopecia and sometimes nail changes. Characteristic lesions can be erythematous, scaly, or pustular, and both congenital and acquired zinc deficiency states have been reported to improve dramatically within days to weeks of adequate zinc repletion. Clinically, zinc is also crucial for normal collagen synthesis and immune function in the skin, so deficiency is linked to delayed wound healing and weaker scars, whereas restoring zinc status can enhance re‑epithelialization and reduce wound complications.

Research: Kelly S, Stelzer JW, Esplin N, Farooq A, Karasik O. Acquired Acrodermatitis Enteropathica: A Case Study. Cureus. 2017 Sep 8;9(9):e1667. Alwadany MM, Al Wadani AF, Almarri FH, Alyami HS, Al-Subaie MA. Acrodermatitis Enteropathica: A Rare Case With Lifelong Implications. Cureus. 2023 Apr 18;15(4):e37783. Al-Khafaji Z, Brito S, Bin BH. Zinc and Zinc Transporters in Dermatology. Int J Mol Sci. 2022 Dec 18;23(24):16165. Ogawa Y, Kinoshita M, Shimada S, Kawamura T. Zinc and Skin Disorders. Nutrients. 2018 Feb 11;10(2):199.

Low or depleted vitamin B12 status appears more common in people with obesity, contributing to weight gain through impaired metabolic reactions and reduced insulin sensitivity. Obesity itself exerts about a 1.6-fold decreasing effect on vitamin B12 levels, underscoring the importance of monitoring BMI and B12 across the lifespan for multisystem health, including neuronal migration. Large population data further confirm that higher serum B12 levels are inversely associated with obesity, highlighting the need to optimize B12 to mitigate these interconnected risks.

Research: Sun Y, Sun M, Liu B, Du Y, Rong S, Xu G, Snetselaar LG, Bao W. Inverse Association Between Serum Vitamin B12 Concentration and Obesity Among Adults in the United States. Front Endocrinol (Lausanne). 2019 Jun 27;10:414. Boachie J, Adaikalakoteswari A, Samavat J, Saravanan P. Low Vitamin B12 and Lipid Metabolism: Evidence from Pre-Clinical and Clinical Studies. Nutrients. 2020 Jun 29;12(7):1925. Demirtas MS, Kilicaslan C, Erdal H. Evaluation of vitamin B12 levels among severe obese and obese adolescents. J Investig Med. 2024 Apr;72(4):319-325. Samavat, Jinous (2019) The role of vitamin B12 deficiency on obesity, adipocytes and inflammation. PhD thesis, University of Warwick. Neal ES, Kumar V, Borges K, Cuffe JSM. Vitamin B12 deficiency induces glucose intolerance, delays peak insulin levels and promotes ketogenesis in female rats. J Endocrinol. 2023 Jan 19;256(2):e220158.

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.

Even a modest shortfall in vitamin C can quietly weaken collagen, which makes blood vessels and skin more fragile and sets the stage for easy bruising and rough, bumpy skin. Clinical descriptions of scurvy consistently report extensive bruising and the classic “follicular hyperkeratosis” pattern—dry, rough skin with hard plugs around hair follicles and tiny perifollicular hemorrhages—that clear rapidly once vitamin C is replaced. For someone who bruises at the slightest bump or notices persistent, goose‑bump–like roughness on the thighs or legs, it can be eye‑opening to learn that a simple vitamin C gap in their diet may be contributing—and that correcting it often leads to visible skin changes within weeks.

Research: Pasquali M, Still MJ, Vales T, Rosen RI, Evinger JD, Dembure PP, Longo N, Elsas LJ. Abnormal formation of collagen cross-links in skin fibroblasts cultured from patients with Ehlers-Danlos syndrome type VI. Proc Assoc Am Physicians. 1997 Jan;109(1):33-41. PMID: 9010914. Fitzpatrick RE, Rostan EF. Double-blind, half-face study comparing topical vitamin C and vehicle for rejuvenation of photodamage. Dermatol Surg. 2002 Mar;28(3):231-6. Fraser IM, Dean M. Extensive bruising secondary to vitamin C deficiency. BMJ Case Rep. Humbert P, Fanian F, Lihoreau T, Jeudy A, Pierard GE. Bateman purpura (dermatoporosis): a localized scurvy treated by topical vitamin C - double-blind randomized placebo-controlled clinical trial. J Eur Acad Dermatol Venereol. 2018 Feb;32(2):323-328. 2009;2009:bcr08.2008.0750.

Vitamin C shortfalls can matter more than people realize because they can quietly undermine iron status and contribute to microcytic, iron‑deficiency–type anemia. Vitamin C is one of the few nutrients that significantly boosts non‑heme iron absorption, helping convert dietary iron into a form the gut can take up more easily and counteracting common inhibitors found in grains, legumes, tea, and coffee. In people whose diets are low in both iron and vitamin C, this combination can show up as persistent fatigue, pallor, and microcytic red blood cells on lab work, with studies in iron‑depleted women showing that added ascorbic acid improved iron absorption and anemia markers over just a few weeks.

Research: Alhatem A, Cai D. Behind the Skin: A Rare Case of Scurvy-Associated Megaloblastic Anemia. Clin Med Insights Case Rep. 2019 May 10;12:1179547619849036. Ricaurte FR, Kewan T, Daw H. Scurvy: A Rare Cause of Anemia. Cureus. 2019 Sep 18;11(9):e5694.Golding PH. Experimental folate deficiency in human subjects: what is the influence of vitamin C status on time taken to develop megaloblastic anaemia? BMC Hematol. 2018 Jun 19;18:13. Kim YL. Vitamin C and functional iron deficiency anemia in hemodialysis. Kidney Res Clin Pract. 2012 Mar;31(1):1-3.

In many patients, inadequate zinc status affects the gastrointestinal tract, contributing to chronic or recurrent diarrhea, anorexia, and characteristic changes in taste (hypogeusia) and smell (hyposmia) that further suppress intake. Clinical studies in children with acute and persistent diarrhea have shown that zinc supplementation shortens illness duration and reduces subsequent diarrheal episodes, underscoring how low zinc status both results from and perpetuates gut losses. The practical implication is that, when patients present with otherwise unexplained diarrhea, poor appetite, and altered taste or smell, especially in the setting of malabsorption, restrictive diets, or chronic illness, evaluating and correcting zinc deficiency can be an important step in breaking this cycle and restoring nutritional and gastrointestinal health.

Research: Mozaffar B, Ardavani A, Muzafar H, Idris I. The Effectiveness of Zinc Supplementation in Taste Disorder Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Nutr Metab. 2023 Mar 8;2023:6711071. Heckmann SM, Hujoel P, Habiger S, Friess W, Wichmann M, Heckmann JG, Hummel T. Zinc gluconate in the treatment of dysgeusia--a randomized clinical trial. J Dent Res. 2005 Jan;84(1):35-8. Mahajan SK, Prasad AS, Lambujon J, Abbasi AA, Briggs WA, McDonald FD. Improvement of uremic hypogeusia by zinc: a double-blind study. Am J Clin Nutr. 1980 Jul;33(7):1517-21. Aliani M, Udenigwe CC, Girgih AT, Pownall TL, Bugera JL, Eskin MN. Zinc deficiency and taste perception in the elderly. Crit Rev Food Sci Nutr. 2013;53(3):245-50. Tanaka H, Mori E, Yonezawa N, Sekine R, Nagai M, Tei M, Otori N. Efficacy of Normalising Serum Zinc Level for Patients with Olfactory Dysfunction and Zinc Deficiency. ORL J Otorhinolaryngol Relat Spec. 2024;86(2):73-81.

Low or depleted vitamin B12 status can worsen gastrointestinal problems by impairing mucosal repair and driving malabsorption in conditions such as Crohn’s disease, celiac disease, and small intestinal bacterial overgrowth, where inflammation, resections, and dysbiosis limit B12 uptake. Reduced B12 also weakens white blood cell production and immune defenses, increasing susceptibility to bacterial, viral, and fungal infections that further destabilize gut balance and make it even harder to restore adequate B12 levels.

Research: Akbulut S. An assessment of serum vitamin B12 and folate in patients with Crohn's disease. Medicine (Baltimore). 2022 Dec 16;101(50):e31892. Trimarchi H, Forrester M, Schropp J, Pereyra H, Freixas EA. Low initial vitamin B12 levels in Helicobacter pylori--positive patients on chronic hemodialysis. Nephron Clin Pract. 2004;96(1):c28-32. www.jcimcr.org Page 2 Citation: Andrès E, Lorenzo-Villalba N. Maldigestion and malabsorption of cobalamins (Vitamin B12): Mechanisms, clinical spectrum, at-risk populations, and therapeutic approaches. J Clin Images Med Case Rep. 2025; 6(11): 3841.

In fat‑malabsorption states and cholestatic liver disease, vitamin E deficiency can amplify oxidative injury because α‑tocopherol is normally carried on circulating lipoproteins and helps shield both cell membranes and lipids from ongoing free‑radical damage. In severe genetic fat‑malabsorption such as abetalipoproteinemia, very low plasma vitamin E levels have been linked to progressive ophthalmopathy and neuropathy, and even with aggressive supplementation, HDL particles can remain severely oxidized, signaling persistent lipid peroxidation and oxidative modification of lipoproteins. Together, these observations support the idea that vitamin E deficiency layered on top of structurally abnormal or depleted lipoproteins creates a “perfect storm” for heightened oxidative stress in tissues, underscoring the need for early detection, carefully absorbed α‑tocopherol formulations, and close monitoring of at‑risk patients with chronic cholestasis or malabsorption.

Research: Burnett JR, Hooper AJ. Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia. Free Radic Biol Med. 2015 Nov;88(Pt A):59-62. Siener R, Machaka I, Alteheld B, Bitterlich N, Metzner C. Effect of Fat-Soluble Vitamins A, D, E and K on Vitamin Status and Metabolic Profile in Patients with Fat Malabsorption with and without Urolithiasis. Nutrients. 2020 Oct 12;12(10):3110. Margareth L. G. SaronI, et al. Nutritional status of patients with biliary atresia and autoimmune hepatitis related to serum levels of vitamins A, D and E. Department of Pediatrics. UNICAMP, Campinas, SP, Brazil 2008. Granot E, Kohen R. Oxidative stress in abetalipoproteinemia patients receiving long-term vitamin E and vitamin A supplementation. Am J Clin Nutr. 2004 Feb;79(2):226-30.