Codeine + Aspirin Side Effects & Health Impacts

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.

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 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.

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.

Neurological symptoms like depression, cognitive impairment, and peripheral neuropathy often signal low or deficient vitamin B12 status, with tingling or numbness in extremities being particularly common. These effects stem from B12's vital role in myelin synthesis and nerve protection; without it, demyelination occurs, leading to neurotoxicity via oxidative stress and neuronal damage. Population studies show up to 20% of older adults with low B12 exhibit cognitive decline, underscoring the need for early monitoring to prevent irreversible neurological harm.

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. Boumenna T, Scott TM, Lee JS, Palacios N, Tucker KL. Folate, vitamin B-12, and cognitive function in the Boston Puerto Rican Health Study. Am J Clin Nutr. 2021 Jan 4;113(1):179-186. Nalder L, Zheng B, Chiandet G, Middleton LT, de Jager CA. Vitamin B12 and Folate Status in Cognitively Healthy Older Adults and Associations with Cognitive Performance. J Nutr Health Aging. 2021;25(3):287-294. Esnafoglu, E. and Ozturan, D.D. (2020), The relationship of severity of depression with homocysteine, folate, vitamin B12, and vitamin D levels in children and adolescents. Child Adolesc Ment Health, 25: 249-255. Khosravi M, Sotoudeh G, Amini M, Raisi F, Mansoori A, Hosseinzadeh M. The relationship between dietary patterns and depression mediated by serum levels of Folate and vitamin B12. BMC Psychiatry. 2020 Feb 13;20(1):63. Kim JM, Stewart R, Kim SW, Yang SJ, Shin IS, Yoon JS. Predictive value of folate, vitamin B12 and homocysteine levels in late-life depression. Br J Psychiatry. 2008 Apr;192(4):268-74.

Even a modest shortfall in vitamin C can leave the immune system less resilient, showing up as more frequent colds, flus, or lingering infections that are slow to clear. Vitamin C concentrates to very high levels inside neutrophils, where it helps fuel their oxidative burst, regulate antioxidant enzymes, and support normal cell survival, so low vitamin C can mean these “first‑responder” white blood cells do not work at full strength. Clinical trials are mixed but intriguing: in a substantial subset of studies, vitamin C supplementation improved neutrophil functions such as oxidative burst, antioxidant enzyme activity, and even reduced premature neutrophil cell death in very sick patients, suggesting that correcting low vitamin C may help the body respond more effectively when infections strike.

Research: Van Straten M, Josling P. Preventing the common cold with a vitamin C supplement: a double-blind, placebo-controlled survey. Adv Ther. 2002 May-Jun;19(3):151-9. Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017 Nov 3;9(11):1211. Moore A, Khanna D. The Role of Vitamin C in Human Immunity and Its Treatment Potential Against COVID-19: A Review Article. Cureus. 2023 Jan 13;15(1):e33740. Bhoot HR, Zamwar UM, Chakole S, Anjankar A. Dietary Sources, Bioavailability, and Functions of Ascorbic Acid (Vitamin C) and Its Role in the Common Cold, Tissue Healing, and Iron Metabolism. Cureus. 2023 Nov 23;15(11):e49308. Liugan M, Carr AC. Vitamin C and Neutrophil Function: Findings from Randomized Controlled Trials. Nutrients. 2019 Sep 4;11(9):2102.

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.

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.

Low or deficient vitamin B12 status is a leading cause of megaloblastic anemia, where impaired DNA synthesis disrupts red blood cell division and produces large, fragile megaloblasts instead of healthy cells. Clinically, vitamin B12–deficiency anemia is relatively common, with some population studies suggesting that up to 10–15% of older adults have biochemical B12 deficiency and a subset of these develop overt megaloblastic changes and anemia. In addition to fatigue and pallor from reduced oxygen‑carrying capacity, patients may show macrocytosis on CBC, elevated methylmalonic acid and homocysteine, and, if unrecognized, can progress to severe anemia that coexists with potentially irreversible neurologic complications

Research: Habeb B, Khair S, Reid A (July 14, 2025) Unmasking Pernicious Anemia: A Reversible Cause of Pancytopenia Due to Severe Vitamin B12 Deficiency. Cureus 17(7): e87911. Lee YP, Loh CH, Hwang MJ, Lin CP. Vitamin B12 deficiency and anemia in 140 Taiwanese female lacto-vegetarians. J Formos Med Assoc. 2021 Nov;120(11):2003-2009. Ankar A, Kumar A. Vitamin B12 Deficiency. 2024 Sep 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. PMID: 28722952. Wong CW. Vitamin B12 deficiency in the elderly: is it worth screening? Hong Kong Med J. 2015 Apr;21(2):155-64.

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.

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.