Fiorinal Side Effects & Health Impacts

Low folate status contributes to elevated homocysteine, a metabolite that has been associated with endothelial dysfunction, arterial stiffness, and a higher risk of stroke and coronary heart disease. Large observational studies consistently show that individuals with higher homocysteine levels have greater rates of cardiovascular events, and folate intake is one of the key nutritional determinants of homocysteine. Clinically, folic acid supplementation (often combined with vitamins B6 and B12) can lower homocysteine and appears to modestly reduce stroke risk in some populations, making the identification and correction of folate deficiency an important part of broader cardiovascular risk reduction.

Research: Yanping Li, et al. Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta‐Analysis of Randomized Controlled Trials. Journal of the American Heart Association. Volume 5, Number 8. August 15 2016.Yi X, Zhou Y, Jiang D, Li X, Guo Y, Jiang X. Efficacy of folic acid supplementation on endothelial function and plasma homocysteine concentration in coronary artery disease: A meta-analysis of randomized controlled trials. Exp Ther Med. 2014 May;7(5):1100-1110. Kaye AD, Jeha GM, Pham AD, Fuller MC, Lerner ZI, Sibley GT, Cornett EM, Urits I, Viswanath O, Kevil CG. Folic Acid Supplementation in Patients with Elevated Homocysteine Levels. Adv Ther. 2020 Oct;37(10):4149-4164. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr; Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006 Apr 13;354(15):1567-77. Wald DS, Bishop L, Wald NJ, et al. Randomized Trial of Folic Acid Supplementation and Serum Homocysteine Levels. Arch Intern Med. 2001;161(5):695–700.

Folate deficiency in the periconceptional period significantly increases the risk of neural tube defects (NTDs) such as spina bifida and anencephaly, because adequate folate is required for proper closure of the embryonic neural tube in the first month of pregnancy. Large observational datasets and randomized trials have shown that appropriate folic acid supplementation before conception and in early pregnancy can reduce NTD risk by roughly 50–70% in the general population, with even greater risk reduction in women with a prior NTD‑affected pregnancy. The practical implication is that all women of childbearing potential, not just those actively planning pregnancy, are typically advised to maintain adequate daily folic acid intake so that red‑cell folate stores are sufficient well before conception occurs.

Research: Viswanathan M, Urrutia RP, Hudson KN, Middleton JC, Kahwati LC. Folic Acid Supplementation to Prevent Neural Tube Defects: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2023;330(5):460–466. Wald NJ. Folic acid and neural tube defects: Discovery, debate and the need for policy change. J Med Screen. 2022 Sep;29(3):138-146. Mathieu d'Argent E, Ravel C, Rousseau A, Morcel K, Massin N, Sussfeld J, Simon T, Antoine JM, Mandelbaume J, Daraï E, Kolanska K. High-Dose Supplementation of Folic Acid in Infertile Men Improves IVF-ICSI Outcomes: A Randomized Controlled Trial (FOLFIV Trial). J Clin Med. 2021 Apr 26;10(9):1876. Jadhav, S. N., & Pitale, D. L. (2020). Effectiveness of folic acid in unexplained infertility. International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 9(9), 3780–3783.

Vitamin B12 deficiency is strongly associated with cognitive impairment, including problems with memory, attention, and executive function, and is considered a reversible cause of dementia when caught early. Low or borderline B12 levels are more common in older adults, particularly those with atrophic gastritis, long-term use of acid-suppressing medications, or vegetarian/vegan diets, and studies show that deficient individuals often perform worse on cognitive tests than those with adequate status. Clinically, correcting B12 deficiency can lead to measurable improvements in cognition and mood in some patients, which is why B12 levels are routinely checked in the evaluation of cognitive decline and suspected dementia.

Research: Jatoi S, Hafeez A, Riaz SU, Ali A, Ghauri MI, Zehra M. Low Vitamin B12 Levels: An Underestimated Cause Of Minimal Cognitive Impairment And Dementia. Cureus. 2020 Feb 13;12(2):e6976. Ueno A, Hamano T, Nagata M, Yamaguchi T, Endo Y, Enomoto S, Kimura H, Ikawa M, Yamamura O, Yamanaka D, Kimura Y, Nakamoto Y, Nishiyama Y. Association of vitamin B12 deficiency in a dementia cohort with hippocampal atrophy on MRI. J Prev Alzheimers Dis. 2025 Sep;12(8):100265. Issac TG, Soundarya S, Christopher R, Chandra SR. Vitamin B12 deficiency: an important reversible co-morbidity in neuropsychiatric manifestations. Indian J Psychol Med. 2015 Jan-Mar;37(1):26-9. Moore E, Mander A, Ames D, Carne R, Sanders K, Watters D. Cognitive impairment and vitamin B12: a review. Int Psychogeriatr. 2012 Apr;24(4):541-56.

In older adults, low folate status has been associated with a higher risk of mild cognitive impairment (MCI) and faster cognitive decline over time, likely through effects on one‑carbon metabolism and homocysteine. Several longitudinal cohort studies have found that individuals with lower serum or red‑cell folate and higher homocysteine show steeper declines on memory and global cognition tests, and in some cohorts have a significantly higher incidence of MCI or dementia over follow‑up. The clinically important takeaway is that, when folate deficiency is detected and corrected (usually along with ensuring adequate vitamin B12), some patients demonstrate stabilization or modest improvement in cognitive performance, particularly when interventions are combined with aggressive management of vascular risk factors such as hypertension and diabetes.

Research: Ma, F., Wu, T., Zhao, J. et al. Folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines in elderly Chinese subjects with MCI. Sci Rep 6, 37486 (2016). Wang M, Fang M, Zang W. Effects of folic acid supplementation on cognitive function and inflammation in elderly patients with mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials. Arch Gerontol Geriatr. 2024 Nov;126:105540. O’Connor, D.M.A., Scarlett, S., De Looze, C. et al. Low folate predicts accelerated cognitive decline: 8-year follow-up of 3140 older adults in Ireland. Eur J Clin Nutr 76, 950–957 (2022).Putu Eka Widyadharma. Folic acid supplementation improves cognitive function: A systematic review. December 2020 Romanian Journal of Neurology 19(4):219-223.

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.

Impacted through 3 nutrients: Folic Acid, Zinc, Vitamin B12.

In pregnancy, inadequate folate status not only increases neural tube defect risk but is also associated with maternal megaloblastic anemia, which can worsen fatigue, reduce exercise tolerance, and increase the likelihood of transfusion around delivery. Observational studies have linked low folate and elevated homocysteine with a higher risk of miscarriage, placental complications, and low birth weight, and some data suggest that suboptimal folate status may contribute to certain infertility contexts, particularly when combined with other nutritional or metabolic stressors. The clinical takeaway is that maintaining sufficient folate intake before conception and throughout pregnancy is a key strategy to reduce anemia and support healthier fertility and pregnancy outcomes beyond neural tube defect prevention.

Research: Murto, T. et al. Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility. Dey M, Dhume P, Sharma SK, Goel S, Chawla S, Shah A, Madhumidha G, Rawal R. Folic acid: The key to a healthy pregnancy - A prospective study on fetomaternal outcome. Tzu Chi Med J. 2023 Oct 31;36(1):98-102. Hariz A, Bhattacharya PT. Megaloblastic Anemia. [Updated 2023 Apr 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan. Lazar VMA, Rahman S, Chowdhury NH, Hasan T, Akter S, Islam MS, Ahmed S, Baqui AH, Khanam R. Folate deficiency in pregnancy and the risk of preterm birth: A nested case-control study. J Glob Health. 2024 Jul 12;14:04120. Zheng J-S, Guan Y, Zhao Y, et al. Pre-conceptional intake of folic acid supplements is inversely associated with risk of preterm birth and small-for-gestational-age birth: a prospective cohort study. British Journal of Nutrition. 2016;115(3):509-516. Reproductive BioMedicine Online, Volume 28, Issue 6, 766 - 772

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.

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.

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.

Research: 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.

Impacted through 2 nutrients: Vitamin C, Zinc.

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.

Impacted through 2 nutrients: Folic Acid, 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.

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.