vitamin
Vitamin B12
Also known as Cobalamin, B12Modeled ingredients
No ingredient relationship is modeled in this pilot.
Modeled forms
No form relationship is modeled in this pilot.
Evidence-grounded comparison · non-production preview
Review two canonical supplement records topic by topic, with evidence availability, source boundaries, and limitations kept explicit—without rankings or recommendations.
This comparison organizes two separately sourced supplement records. It describes evidence structure and availability without ranking supplements or recommending use.
Reference counts are descriptive. More references do not necessarily mean better or stronger evidence.
Identity boundaries
vitamin
No ingredient relationship is modeled in this pilot.
No form relationship is modeled in this pilot.
vitamin
Source boundaries
Vitamin B12 — Fact Sheet for Health Professionals
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Vitamin D — Fact Sheet for Health Professionals
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Structural orientation
26 structural observations are available. Topic states remain visible in the aligned comparison below.
Topic-by-topic evidence
Evidence topic
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
No explicit limitation phrase was identified in these imported source blocks.
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B(6), Folate, Vitamin B(12), Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press; 1998.
Government reference · Population basis: unknown · Directness: not assessedCarmel R. Cobalamin (vitamin B12). In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2014:369-89.
Study type could not be determined · Population basis: unknown · Directness: not assessedAllen LH. Vitamin B12. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. London and New York: Informa Healthcare; 2010:812-20.
Study type could not be determined · Population basis: unknown · Directness: not assessedAllen LH. Vitamin B-12. Adv Nutr 2012;3:54-5. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedStabler SP. Vitamin B12. In: Marriott BP, Birt DF, Stallings VA, Yates AA, eds. Present Knowledge in Nutrition. 11th ed. Washington, DC: Elsevier; 2020:257-71.
Study type could not be determined · Population basis: unknown · Directness: not assessedVitamin B12 is a water-soluble vitamin that is naturally present in some foods, added to others, and available as a dietary supplement and a prescription medication. Because vitamin B12 contains the mineral cobalt, compounds with vitamin B12 activity are collectively called cobalamins [1]. Methylcobalamin and 5-deoxyadenosylcobalamin are the metabolically active forms of vitamin B12. However, two others forms, hydroxycobalamin and cyanocobalamin, become biologically active after they are converted to methylcobalamin or 5-deoxyadenosylcobalamin [1-3].
Vitamin B12 is required for the development, myelination, and function of the central nervous system; healthy red blood cell formation; and DNA synthesis [1,4,5]. Vitamin B12 functions as a cofactor for two enzymes, methionine synthase and L-methylmalonyl-CoA mutase [1-3,5]. Methionine synthase catalyzes the conversion of homocysteine to the essential amino acid methionine [1,2]. Methionine is required for the formation of S-adenosylmethionine, a universal methyl donor for almost 100 different substrates, including DNA, RNA, proteins, and lipids [3,5]. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA in the metabolism of propionate, a short-chain fatty acid [2].
Vitamin B12 is bound to protein in food and must be released before it is absorbed [5]. The process starts in the mouth when food is mixed with saliva. The freed vitamin B12 then binds with haptocorrin, a cobalamin-binding protein in the saliva. More vitamin B12 is released from its food matrix by the activity of hydrochloric acid and gastric protease in the stomach, where it then binds to haptocorrin [1]. In the duodenum, digestive enzymes free the vitamin B12 from haptocorrin, and this freed vitamin B12 combines with intrinsic factor, a transport and delivery binding protein secreted by the stomach’s parietal cells. The resulting complex is absorbed in the distal ileum by receptor-mediated endocytosis [1,5]. If vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and therefore does not require the separation step.
Vitamin B12 — Fact Sheet for Health Professionals
NIH Office of Dietary Supplements. Government health-professional reference material imported without MEDucated medical review.
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
No explicit limitation phrase was identified in these imported source blocks.
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.
Government reference · Population basis: unknown · Directness: not assessedNorman AW, Henry HH. Vitamin D. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition, 10th ed. Washington DC: Wiley-Blackwell, 2012.
Study type could not be determined · Population basis: unknown · Directness: not assessedJones G. Vitamin D. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease, 11th ed. Philadelphia: Lippincott Williams & Wilkins, 2014.
Study type could not be determined · Population basis: unknown · Directness: not assessedSilva MC, Furlanetto TW. Intestinal absorption of vitamin D: A systematic review. Nutr Rev 2018;76:60-76. [PubMed abstract]
Systematic review · Population basis: unknown · Directness: not assessedVitamin D (also referred to as calciferol) is a fat-soluble vitamin that is naturally present in a few foods, added to others, and available as a dietary supplement. It is also produced endogenously when ultraviolet (UV) rays from sunlight strike the skin and trigger vitamin D synthesis.
Vitamin D obtained from sun exposure, foods, and supplements is biologically inert and must undergo two hydroxylations in the body for activation. The first hydroxylation, which occurs in the liver, converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. The second hydroxylation occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol [1].
Vitamin D promotes calcium absorption in the gut and maintains adequate serum calcium and phosphate concentrations to enable normal bone mineralization and to prevent hypocalcemic tetany (involuntary contraction of muscles, leading to cramps and spasms). It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts [1-3]. Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Vitamin D sufficiency prevents rickets in children and osteomalacia in adults. Together with calcium, vitamin D also helps protect older adults from osteoporosis.
Vitamin D has other roles in the body, including reduction of inflammation as well as modulation of such processes as cell growth, neuromuscular and immune function, and glucose metabolism [1-3]. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D. Many tissues have vitamin D receptors, and some convert 25(OH)D to 1,25(OH)2D.
In foods and dietary supplements, vitamin D has two main forms, D2 (ergocalciferol) and D3 (cholecalciferol), that differ chemically only in their side-chain structures. Both forms are well absorbed in the small intestine. Absorption occurs by simple passive diffusion and by a mechanism that involves intestinal membrane carrier proteins [4]. The concurrent presence of fat in the gut enhances vitamin D absorption, but some vitamin D is absorbed even without dietary fat. Neither aging nor obesity alters vitamin D absorption from the gut [4].
Vitamin D — Fact Sheet for Health Professionals
NIH Office of Dietary Supplements. Government health-professional reference material imported without MEDucated medical review.
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Evidence topic
No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.Evidence topic
No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.Evidence topic
No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.Evidence topic
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
No explicit limitation phrase was identified in these imported source blocks.
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B(6), Folate, Vitamin B(12), Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press; 1998.
Government reference · Population basis: unknown · Directness: not assessedVitamin B12 does not have a tolerable upper intake level because it is generally considered to be safe, even at high doses.
The FNB did not establish a UL for vitamin B12 because of its low potential for toxicity [1]. Even at large doses, vitamin B12 is generally considered to be safe because the body does not store excess amounts.
Vitamin B12 — Fact Sheet for Health Professionals
NIH Office of Dietary Supplements. Government health-professional reference material imported without MEDucated medical review.
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
No explicit limitation phrase was identified in these imported source blocks.
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.
Government reference · Population basis: unknown · Directness: not assessedGalior K, Grebe S, Singh R. Development of vitamin D toxicity from overcorrection of vitamin D deficiency: A review of case reports. Nutrients 2018, 10, 953. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedAuguste BL, Avila-Casado C, Bargman JM. Use of vitamin D drops leading to kidney failure in a 54-year-old man. CMAJ 2019;191:E390-4. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedVogiatzi MG, Jacobson-Dickman E, DeBoer MD. Vitamin D supplementation and risk of toxicity in pediatrics: A review of current literature. J Clin Endocrinol Metab 2014;99:1132-41. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedSingh P, Trivedi N. Tanning beds and hypervitaminosis D: A case report. Ann Intern Med 2014;160:810-1. [PubMed abstract]
Case report · Population basis: unknown · Directness: not assessedLaurent MR, Gielen E, Pauwels S, Vanderschueren D, Bouillon R. Hypervitaminosis D associated with tanning bed use: A case report. Ann Intern Med 2017;166:155-6. [PubMed abstract]
Case report · Population basis: unknown · Directness: not assessedPerez-Castrillon JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, Duenas A. Effects of atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Am J Cardiol 2007;99:903-5. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedJackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354:669-82. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedMalihi Z, Lawes CMM, Wu Z, Huang Y, Waayer D, Toop L, et al. Monthly high-dose vitamin D supplementation does not increase kidney stone risk or serum calcium: Results from a randomized controlled trial. Am J Clin Nutr 2019;109:1578-87. [PubMed abstract]
Randomized controlled trial · Population basis: unknown · Directness: not assessedMalihi Z, Wu Z, Stewart AW, Lawes CMM, Scragg R. Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: A systematic review and meta-analysis. Am J Clin Nutr 2016;104:1039-51. [PubMed abstract]
Meta-analysis · Population basis: unknown · Directness: not assessedVitamin D toxicity can cause hypercalcemia, hypercalciuria, and high serum 25(OH)D concentrations; in extreme cases, it may lead to renal failure, calcification of soft tissues, cardiac arrhythmias, and death. Vitamin D toxicity is almost always a result of excessive intakes of vitamin D through supplements. Taking calcium supplements in combination with vitamin D supplements may increase the risk of certain adverse effects. The Tolerable Upper Intake Level for vitamin D ranges from 25 to 100 mcg (1,000–4,000 IU), depending on age.
Excess amounts of vitamin D are toxic. Because vitamin D increases calcium absorption in the gastrointestinal tract, vitamin D toxicity results in marked hypercalcemia (total calcium greater than 11.1 mg/dL, beyond the normal range of 8.4–10.2 mg/dL), hypercalciuria, and high serum 25(OH)D levels (typically >375 nmol/l [150 ng/mL]) [158]. Hypercalcemia, in turn, can lead to nausea, vomiting, muscle weakness, neuropsychiatric disturbances, pain, loss of appetite, dehydration, polyuria, excessive thirst, and kidney stones.
In extreme cases, vitamin D toxicity causes renal failure, calcification of soft tissues throughout the body (including in coronary vessels and heart valves), cardiac arrhythmias, and even death. Vitamin D toxicity has been caused by consumption of dietary supplements that contained excessive vitamin D amounts because of manufacturing errors, that were taken inappropriately or in excessive amounts, or that were incorrectly prescribed by physicians, [158-160].
Experts do not believe that excessive sun exposure results in vitamin D toxicity because thermal activation of previtamin D3 in the skin gives rise to various non-vitamin D forms that limit formation of vitamin D3. Some vitamin D3 is also converted to nonactive forms [1]. However, frequent use of tanning beds, which provide artificial UV radiation, can lead to 25(OH)D levels well above 375 to 500 nmol/L (150–200 ng/mL) [161-163].
The combination of high intakes of calcium (about 2,100 mg/day from food and supplements) with moderate amounts of vitamin D (about 19 mcg [765 IU]/day from food and supplements) increased the risk of kidney stones by 17% over 7 years among 36,282 postmenopausal women who were randomly assigned to take 1,000 mg/day calcium and 10 mcg (400 IU)/day vitamin D or a placebo [164]. However, other, shorter (from 24 weeks to 5 years) clinical trials of vitamin D supplementation alone or with calcium in adults found greater risks of hypercalcemia and hypercalciuria, but not of kidney stones [165,166].
The FNB established ULs for vitamin D in 2010 (Table 4) [1]. While acknowledging that signs and symptoms of toxicity are unlikely at daily intakes below 250 mcg (10,000 IU), the FNB noted that even vitamin D intakes lower than the ULs might have adverse health effects over time. The FNB recommended avoiding serum 25(OH)D levels above approximately 125 to 150 nmol/L (50–60 ng/mL), and it found that even lower serum levels (approximately 75–120 nmol/L [30–48 ng/mL]) are associated with increases in rates of all-cause mortality, risk of cancer at some sites (e.g., pancreas), risk of cardiovascular events, and number of falls and fractures among older adults.
| Age | Male | Female | Pregnancy | Lactation |
|---|---|---|---|---|
| 0–6 months | 25 mcg (1,000 IU) | 25 mcg (1,000 IU) | ||
| 7–12 months | 38 mcg (1,500 IU) | 38 mcg (1,500 IU) | ||
| 1–3 years | 63 mcg (2,500 IU) | 63 mcg (2,500 IU) | ||
| 4–8 years | 75 mcg (3,000 IU) | 75 mcg (3,000 IU) | ||
| 9–13 years | 100 mcg (4,000 IU) | 100 mcg (4,000 IU) | ||
| 14–18 years | 100 mcg (4,000 IU) | 100 mcg (4,000 IU) | 100 mcg (4,000 IU) | 100 mcg (4,000 IU) |
| 19–50 years | 100 mcg (4,000 IU) | 100 mcg (4,000 IU) | 100 mcg (4,000 IU) | 100 mcg (4,000 IU) |
| 51–70 years | 100 mcg (4,000 IU) | 100 mcg (4,000 IU) | ||
| >70 years | 100 mcg (4,000 IU) | 100 mcg (4,000 IU) |
Vitamin D — Fact Sheet for Health Professionals
NIH Office of Dietary Supplements. Government health-professional reference material imported without MEDucated medical review.
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Evidence topic
No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.Evidence topic
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
No explicit limitation phrase was identified in these imported source blocks.
Jung SB, Nagaraja V, Kapur A, Eslick GD. Association between vitamin B12 deficiency and long-term use of acid-lowering agents: A systematic review and meta-analysis. Intern Med J 2015;45:409-16. [PubMed abstract]
Meta-analysis · Population basis: unknown · Directness: not assessedLam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA 2013;310:2435-42. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedMiller JW. Proton pump inhibitors, H2-receptor antagonists, metformin, and vitamin B-12 deficiency: Clinical implications. Adv Nutr 2018;9:511S-8S. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedVitamin B12 supplements may interact with medications, and some medications, including gastric acid inhibitors and metformin, may affect vitamin B12 levels.
Vitamin B12 supplements have the potential to interact with certain medications. In addition, several types of medications might adversely affect vitamin B12 levels. A few examples are provided below. Individuals taking these and other medications on a regular basis should discuss their vitamin B12 status with their health care providers.
Gastric acid inhibitors include proton pump inhibitors, such as omeprazole (Prilosec) and lansoprazole (Prevacid), and histamine 2-receptor antagonists, such as cimetidine (Tagamet) and ranitidine (Zantac). These drugs are used to treat gastroesophageal reflux disease and peptic ulcer disease. They can interfere with vitamin B12 absorption from food by slowing the release of gastric acid into the stomach and thereby lead to vitamin B12 deficiency [101-103].
Metformin, an antihyperglycemic agent used as first-line treatment for prediabetes and diabetes, might reduce the absorption of vitamin B12 and significantly reduce serum vitamin B12 concentrations [103].
Vitamin B12 — Fact Sheet for Health Professionals
NIH Office of Dietary Supplements. Government health-professional reference material imported without MEDucated medical review.
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
No explicit limitation phrase was identified in these imported source blocks.
Gotfredsen A, Westergren Hendel H, Andersen T. Influence of orlistat on bone turnover and body composition. Int J Obes Relat Metab Disord 2001;25:1154-60. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedJames WP, Avenell A, Broom J, Whitehead J. A one-year trial to assess the value of orlistat in the management of obesity. Int J Obes Relat Metab Disord 1997;21:S24-30. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedMcDuffie JR, Calis KA, Booth SL, Uwaifo GI, Yanovski JA. Effects of orlistat on fat-soluble vitamins in obese adolescents. Pharmacotherapy 2002;22:814-22. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedRobien K, Oppeneer SJ, Kelly JA, Hamilton-Reeves JM. Drug-vitamin D interactions: A systematic review of the literature. Nutr Clin Pract 2013;28:194-208. [PubMed abstract]
Systematic review · Population basis: unknown · Directness: not assessedSchwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: A new drug interaction with an unexpected consequence. Clin Pharmacol Ther 2009;85:198-203. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedPerez-Castrillon JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, Duenas A. Effects of atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Am J Cardiol 2007;99:903-5. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedAloia JF, Li-Ng M, Pollack S. Statins and vitamin D. Am J Cardiol 2007;100:1329. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedBuckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1996;125:961-8. [PubMed abstract]
Randomized controlled trial · Population basis: human · Directness: not assessedde Sevaux RGL, Hoitsma AJ, Corstens FHM, Wetzels JFM. Treatment with vitamin D and calcium reduces bone loss after renal transplantation: a randomized study. J Am Soc Nephrol 2002;13:1608-14. [PubMed abstract]
Randomized controlled trial · Population basis: unknown · Directness: not assessedLukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med 1990;112:352-64. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedSkversky AL, Kumar J, Abramowitz MK, Kaskel FJ, Melamed ML. Association of glucocorticoid use and low 25-hydroxyvitamin D levels: Results from the National Health and Nutrition Examination Survey (NHANES): 2001-2006. J Clin Endocrinol Metab 2011;96:3838-45. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedDrinka PJ, Nolten WE. Hazards of treating osteoporosis and hypertension concurrently with calcium, vitamin D, and distal diuretics. J Am Geriatr Soc 1984;32:405-7. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedCrowe M, Wollner L, Griffiths RA. Hypercalcaemia following vitamin D and thiazide therapy in the elderly. Practitioner 1984;228:312-3. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedVitamin D supplements may interact with medications, and some medications may affect vitamin D levels. These medications include orlistat, statins, steroids, and thiazide diuretics.
Vitamin D supplements may interact with several types of medications. A few examples are provided below. Individuals taking these and other medications on a regular basis should discuss their vitamin D intakes and status with their health care providers.
The weight-loss drug orlistat (Xenical and alli), together with a reduced-fat diet, can reduce the absorption of vitamin D from food and supplements, leading to lower 25(OH)D levels [167-170].
Statin medications reduce cholesterol synthesis. Because endogenous vitamin D is derived from cholesterol, statins may also reduce vitamin D synthesis [170]. In addition, high intakes of vitamin D, especially from supplements, might reduce the potency of atorvastatin (Lipitor), lovastatin (Altoprev and Mevacor), and simvastatin (FloLipid and Zocor), because these statins and vitamin D appear to compete for the same metabolizing enzyme [170-173].
Corticosteroid medications, such as prednisone (Deltasone, Rayos, and Sterapred), are often prescribed to reduce inflammation. These medications can reduce calcium absorption and impair vitamin D metabolism [174-176]. In the NHANES 2001–2006 survey, 25(OH)D deficiency (less than 25 nmol/L [10 ng/mL]) was more than twice as common among children and adults who reported oral steroid use (11%) than in nonusers (5%) [177].
Thiazide diuretics (e.g., Hygroton, Lozol, and Microzide) decrease urinary calcium excretion. The combination of these diuretics with vitamin D supplements (which increase intestinal calcium absorption) might lead to hypercalcemia, especially among older adults and individuals with compromised renal function or hyperparathyroidism [170,178,179].
Vitamin D — Fact Sheet for Health Professionals
NIH Office of Dietary Supplements. Government health-professional reference material imported without MEDucated medical review.
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Evidence topic
No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.Evidence topic
No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.Evidence topic
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
No explicit limitation phrase was identified in these imported source blocks.
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B(6), Folate, Vitamin B(12), Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press; 1998.
Government reference · Population basis: unknown · Directness: not assessedAllen LH. Vitamin B12. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. London and New York: Informa Healthcare; 2010:812-20.
Study type could not be determined · Population basis: unknown · Directness: not assessedOffice of Dietary Supplements, National Institutes of Health. Dietary Supplement Label Database. 2021.
Study type could not be determined · Population basis: unknown · Directness: not assessedPaul C, Brady DM. Comparative bioavailability and utilization of particular forms of B(12) Supplements with potential to mitigate B(12)-related genetic polymorphisms. Integr Med 2017;16:42-9. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedCarmel R. How I treat cobalamin (vitamin B12) deficiency. Blood 2008;112:2214-21. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedYazaki Y, Chow G, Mattie M. A single-center, double-blinded, randomized controlled study to evaluate the relative efficacy of sublingual and oral vitamin B-complex administration in reducing total serum homocysteine levels. J Altern Complement Med 2006;12:881-5. [PubMed abstract]
Randomized controlled trial · Population basis: unknown · Directness: not assessedSharabi A, Cohen E, Sulkes J, Garty M. Replacement therapy for vitamin B12 deficiency: Comparison between the sublingual and oral route. Br J Clin Pharmacol 2003;56:635-8. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedVitamin B12 is present in many dietary supplements, often as cyanocobalamin, but other forms may also be used. Supplements that only contain vitamin B12 typically have the highest doses of the vitamin, while multivitamin/mineral supplements and supplements that combine vitamin B12 with other B-complex vitamins usually contain lower doses.
Vitamin B12 is available in multivitamin/mineral supplements, in supplements containing other B-complex vitamins, and in supplements containing only vitamin B12. Multivitamin/mineral supplements typically contain vitamin B12 at doses ranging from 5 to 25 mcg [23]. Vitamin B12 levels are higher, generally 50 to 500 mcg, in supplements containing vitamin B12 with other B-complex vitamins and even higher, typically 500 to 1,000 mcg, in supplements containing only vitamin B12.
The most common form of vitamin B12 in dietary supplements is cyanocobalamin [1,3,23,24]. Other forms of vitamin B12 in supplements are adenosylcobalamin, methylcobalamin, and hydroxycobalamin [23].
No evidence indicates that absorption rates of vitamin B12 in supplements vary by form of the vitamin. These rates are about 50% at doses (less than 1–2 mcg) that do not exceed the cobalamin-binding capacity of intrinsic factor and are substantially lower at doses well above 1 to 2 mcg [24,25]. For example, absorption is only about 2% at doses of 500 mcg and 1.3% at doses of 1,000 mcg [25].
In addition to oral dietary supplements, vitamin B12 is available in sublingual preparations as tablets or lozenges [23]. Evidence suggests no difference in efficacy between oral and sublingual forms [26,27].
Vitamin B12 — Fact Sheet for Health Professionals
NIH Office of Dietary Supplements. Government health-professional reference material imported without MEDucated medical review.
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
No explicit limitation phrase was identified in these imported source blocks.
Silva MC, Furlanetto TW. Intestinal absorption of vitamin D: A systematic review. Nutr Rev 2018;76:60-76. [PubMed abstract]
Systematic review · Population basis: unknown · Directness: not assessedHolick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedHirsch AL. Industrial Aspects of Vitamin D. In: Feldman D, Pike JW, Adams JS, eds. Vitamin D. 3rd ed. Academic Press; 2011:73-93.
Study type could not be determined · Population basis: unknown · Directness: not assessedNational Institutes of Health. Dietary Supplement Label Database. 2020.
Study type could not be determined · Population basis: unknown · Directness: not assessedTripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: A systematic review and meta-analysis. Am J Clin Nutr 2012;95:1357-64. [PubMed abstract]
Meta-analysis · Population basis: unknown · Directness: not assessedLehmann U, Hirche F, Stangl GI, Hinz K, Westphal S, Dierkes J. Bioavailability of vitamin D2 and D3 in healthy volunteers, a randomised placebo-controlled trial. J Clin Endocrin Metab 2013;98:4339-45. [PubMed abstract]
Randomized controlled trial · Population basis: human · Directness: not assessedLogan VF, Gray AR, Peddie MC, Harper MJ, Houghton LA. Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months. Br J Nutr 2013;109:1082-8. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedTripkovic L, Wilson LR, Hart K, Johnsen S, de Lusignan S, Smith CP, et al. Daily supplementation with 15 µg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: A 12-wk randomized, placebo-controlled food-fortification trial. Am J Clin Nutr 2017;106:481-90. [PubMed abstract]
Randomized controlled trial · Population basis: human · Directness: not assessedGraeff-Armas LA, Bendik I, Kunz I, Schoop R, Hull S, Beck M. Supplemental 25-hydroxycholecalciferol is more effective than cholecalciferol in raising serum 25-hydroxyvitamin D concentrations in older adults. J Nutr 2020;150:73-81. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedQuesada-Gomez JM, Bouillon R. Is calcifediol better than cholecalciferol for vitamin D supplementation? Osteoporos Int 2018;29:1697-1711. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedVitamin D is present in dietary supplements as either vitamin D2 or vitamin D3. Both can raise the serum level of 25(OH)D. However, research shows that vitamin D3 increases serum 25(OH)D levels to a greater extent than vitamin D2 and can maintain those higher levels for longer periods of time.
Dietary supplements can contain vitamins D2 or D3. Vitamin D2 is manufactured using UV irradiation of ergosterol in yeast, and vitamin D3 is typically produced with irradiation of 7-dehydrocholesterol from lanolin obtained from the wool of sheep [13,31]. An animal-free version of vitamin D3 sourced from lichen is also available [32]. People who avoid all animal-sourced products can contact dietary supplement manufacturers to ask about their sourcing and processing techniques.
Both vitamins D2 and D3 raise serum 25(OH)D levels, and they seem to have equivalent ability to cure rickets [4]. In addition, most steps in the metabolism and actions of vitamins D2 and D3 are identical. However, most evidence indicates that vitamin D3 increases serum 25(OH)D levels to a greater extent and maintains these higher levels longer than vitamin D2, even though both forms are well absorbed in the gut [33-36].
Some studies have used dietary supplements containing the 25(OH)D3 form of vitamin D. Per equivalent microgram dose, 25(OH)D3 is three to five times as potent as vitamin D3 [37,38]. However, no 25(OH)D3 dietary supplements appear to be available to consumers on the U.S. market at this time [32].
Vitamin D — Fact Sheet for Health Professionals
NIH Office of Dietary Supplements. Government health-professional reference material imported without MEDucated medical review.
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Evidence topic
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
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Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B(6), Folate, Vitamin B(12), Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press; 1998.
Government reference · Population basis: unknown · Directness: not assessedThe Food and Nutrition Board at the National Academies of Sciences, Engineering, and Medicine has established Recommended Dietary Allowances and Adequate Intakes for vitamin B12. These values range from 2.4 to 2.8 mcg for adults and from 0.4 to 2.8 mcg for infants, children, and adolescents, depending on age.
Intake recommendations for vitamin B12 and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the National Academies of Sciences, Engineering, and Medicine [1]. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and sex, include the following:
Table 1 lists the current RDAs for vitamin B12 [1]. For adults, the main criterion that the FNB used to establish the RDAs was the amount needed to maintain a healthy hematological status and serum vitamin B12 levels. For infants age 0 to 12 months, the FNB established an AI that is equivalent to the mean intake of vitamin B12 in healthy, breastfed infants.
| Age | Male | Female | Pregnancy | Lactation |
|---|---|---|---|---|
| Birth to 6 months* | 0.4 mcg | 0.4 mcg | ||
| 7–12 months* | 0.5 mcg | 0.5 mcg | ||
| 1–3 years | 0.9 mcg | 0.9 mcg | ||
| 4–8 years | 1.2 mcg | 1.2 mcg | ||
| 9–13 years | 1.8 mcg | 1.8 mcg | ||
| 14–18 years | 2.4 mcg | 2.4 mcg | 2.6 mcg | 2.8 mcg |
| 19+ years | 2.4 mcg | 2.4 mcg | 2.6 mcg | 2.8 mcg |
| * Adequate Intake (AI) |
Vitamin B12 — Fact Sheet for Health Professionals
NIH Office of Dietary Supplements. Government health-professional reference material imported without MEDucated medical review.
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
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Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.
Government reference · Population basis: unknown · Directness: not assessedSempos CT, Binkley N. 25-hydroxyvitamin D assay standardisation and vitamin D guidelines paralysis. Public Health Nutrition 2020;23:1153-64. [PubMed abstract]
Clinical guideline · Population basis: unknown · Directness: not assessedDemay MB, Pittas AG, Bikle DD, Diab DL, Kiely ME, et al. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2024 Jul 12;109(8):1907-1947. [PubMed abstract]
Clinical guideline · Population basis: unknown · Directness: not assessedShah VP, Nayfeh T, Alsawaf Y, Saadi S, Farah M, et al. A Systematic Review Supporting the Endocrine Society Clinical Practice Guidelines on Vitamin D. J Clin Endocrinol Metab. 2024 Jul 12;109(8):1961-1974. [PubMed abstract]
Systematic review · Population basis: unknown · Directness: not assessedBouillon R. Comparative analysis of nutritional guidelines for vitamin D. Nat Rev Endocrinol 2017;13:466-79. [PubMed abstract]
Clinical guideline · Population basis: unknown · Directness: not assessedScientific Advisory Committee on Nutrition. Vitamin D and Health. 2016.
Study type could not be determined · Population basis: unknown · Directness: not assessedThe Food and Nutrition Board at the National Academies of Sciences, Engineering, and Medicine has established Recommended Dietary Allowances and Adequate Intakes for vitamin D. These values range from 15 to 20 mcg (600–800 IU) for adults and from 10 to 15 mcg (400–600 IU) for infants, children, and adolescents, depending on age.
Intake recommendations for vitamin D and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by expert committees of NASEM [1]. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values include the following:
The FNB established RDAs for vitamin D to indicate daily intakes sufficient to maintain bone health and normal calcium metabolism in healthy people. RDAs for vitamin D are listed in both micrograms (mcg) and International Units (IU); 1 mcg vitamin D is equal to 40 IU (Table 2). Even though sunlight is a major source of vitamin D for some people, the FNB based the vitamin D RDAs on the assumption that people receive minimal sun exposure [1]. For infants from birth to 12 months, the FNB developed AIs based on the amount of vitamin D that maintains serum 25(OH)D levels above 20 ng/mL (50 nmol/L) and supports bone development.
| Age | Male | Female | Pregnancy | Lactation |
|---|---|---|---|---|
| 0–6 months* | 10 mcg (400 IU)* | 10 mcg (400 IU)* | ||
| 7–12 months* | 10 mcg (400 IU)* | 10 mcg (400 IU)* | ||
| 1–3 years | 15 mcg (600 IU) | 15 mcg (600 IU) | ||
| 4–8 years | 15 mcg (600 IU) | 15 mcg (600 IU) | ||
| 9–13 years | 15 mcg (600 IU) | 15 mcg (600 IU) | ||
| 14–18 years | 15 mcg (600 IU) | 15 mcg (600 IU) | 15 mcg (600 IU) | 15 mcg (600 IU) |
| 19–50 years | 15 mcg (600 IU) | 15 mcg (600 IU) | 15 mcg (600 IU) | 15 mcg (600 IU) |
| 51–70 years | 15 mcg (600 IU) | 15 mcg (600 IU) | ||
| >70 years | 20 mcg (800 IU) | 20 mcg (800 IU) | ||
| *Adequate Intake (AI) |
Many other countries around the world and some professional societies have somewhat different guidelines for vitamin D intakes [15]. These differences are a result of an incomplete understanding of the biology and clinical implications of vitamin D, different purposes for the guidelines (e.g., for public health in a healthy population or for clinical practice), and/or the use in some guidelines of observational studies in addition to randomized clinical trials to establish recommendations [9,15]. For example, the United Kingdom Scientific Advisory Committee on Nutrition recommends intakes of 10 mcg (400 IU)/day for individuals age 4 years and older [16]. The Endocrine Society recommends routine vitamin D supplementation for children and teens age 1 to 18 years, pregnant women, adults with pre-diabetes, and adults age 75 years and older, but not for healthy adults age 19 to 74 [11,12]. The Endocrine Society does not recommend specific doses but notes that all individuals should adhere to the RDA.
Vitamin D — Fact Sheet for Health Professionals
NIH Office of Dietary Supplements. Government health-professional reference material imported without MEDucated medical review.
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Evidence topic
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
No explicit limitation phrase was identified in these imported source blocks.
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B(6), Folate, Vitamin B(12), Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press; 1998.
Government reference · Population basis: unknown · Directness: not assessedCarmel R. Cobalamin (vitamin B12). In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2014:369-89.
Study type could not be determined · Population basis: unknown · Directness: not assessedAllen LH. Vitamin B12. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. London and New York: Informa Healthcare; 2010:812-20.
Study type could not be determined · Population basis: unknown · Directness: not assessedAllen LH, Miller JW, de Groot L, Rosenberg IH, Smith AD, Refsum H, et al. Biomarkers of Nutrition for Development (BOND): Vitamin B-12 Review. J Nutr 2018;148:1995S-2027S. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedGreen R, Allen LH, Bjorke-Monsen AL, Brito A, Gueant JL, Miller JW, et al. Vitamin B12 deficiency. Nat Rev Dis Primers 2017;3:17040. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedWong CW. Vitamin B12 deficiency in the elderly: Is it worth screening? Hong Kong Med J 2015;21:155-64. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedPfisterer KJ, Sharratt MT, Heckman GG, Keller HH. Vitamin B12 status in older adults living in Ontario long-term care homes: prevalence and incidence of deficiency with supplementation as a protective factor. Appl Physiol Nutr Metab 2016;41:219-22. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedCavalcoli F, Zilli A, Conte D, Massironi S. Micronutrient deficiencies in patients with chronic atrophic autoimmune gastritis: A review. World J Gastroenterol 2017;23:563-72. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedWeck MN, Stegmaier C, Rothenbacher D, Brenner H. Epidemiology of chronic atrophic gastritis: Population-based study among 9444 older adults from Germany. Aliment Pharmacol Ther 2007;26:879-87. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedKalkan Ç, Karakaya F, Tüzün A, Gençtürk ZB, Soykan I. Factors related to low serum vitamin B12 levels in elderly patients with non-atrophic gastritis in contrast to patients with normal vitamin B12 levels. Geriatr Gerontol Int 2016;16:686-92. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedRojas Hernandez CM, Oo TH. Advances in mechanisms, diagnosis, and treatment of pernicious anemia. Discov Med 2015;19:159-68. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedAo M, Tsuji H, Shide K, Kosaka Y, Noda A, Inagaki N, et al. High prevalence of vitamin B-12 insufficiency in patients with Crohn's disease. Asia Pac J Clin Nutr 2017;26:1076-81. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedBledsoe AC, King KS, Larson JJ, Snyder M, Absah I, Choung RS, et al. Micronutrient deficiencies Are common in contemporary celiac disease despite lack of overt malabsorption symptoms. Mayo Clin Proc 2019;94:1253-60. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedWard MG, Kariyawasam VC, Mogan SB, Patel KV, Pantelidou M, Sobczyńska-Malefora A, et al. Prevalence and risk factors for functional vitamin B12 deficiency in patients with Crohn's disease. Inflamm Bowel Dis 2015;21:2839-47. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedPan Y, Liu Y, Guo H, Jabir MS, Liu X, Cui W, et al. Associations between folate and vitamin B12 levels and inflammatory bowel disease: A meta-analysis. Nutrients 2017;9:382. [PubMed abstract]
Meta-analysis · Population basis: unknown · Directness: not assessedGomollón F, Gargallo CJ, Muñoz JF, Vicente R, Lue A, Mir A, et al. Oral cyanocobalamin is effective in the treatment of vitamin B12 deficiency in Crohn's disease. Nutrients 2017;9:308. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedDogan K, Aarts EO, Koehestanie P, Betzel B, Ploeger N, de Boer H, et al. Optimization of vitamin suppletion after Roux-en-Y gastric bypass surgery can lower postoperative deficiencies: a randomized controlled trial. Medicine (Baltimore) 2014;93:e169. [PubMed abstract]
Randomized controlled trial · Population basis: unknown · Directness: not assessedKornerup LS, Hvas CL, Abild CB, Richelsen B, Nexo E. Early changes in vitamin B12 uptake and biomarker status following Roux-en-Y gastric bypass and sleeve gastrectomy. Clin Nutr 2019;38:906-11. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedPawlak R, Lester SE, Babatunde T. The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: A review of literature. Eur J Clin Nutr 2014;68:541-8. [PubMed abstract]
Narrative review · Population basis: unknown · Directness: not assessedDror DK, Allen LH. Vitamin B-12 in human milk: A systematic review. Adv Nutr 2018;9:358s-66s. [PubMed abstract]
Systematic review · Population basis: human · Directness: not assessedPiccoli GB, Clari R, Vigotti FN, Leone F, Attini R, Cabiddu G, et al. Vegan-vegetarian diets in pregnancy: Danger or panacea? A systematic narrative review. Bjog 2015;122:623-33. [PubMed abstract]
Narrative review · Population basis: unknown · Directness: not assessedCertain groups of people are more likely than others to be vitamin B12 deficient. These include older adults, people with pernicious anemia or gastrointestinal disorders, and those who have had gastrointestinal surgery. Other groups that are at risk of vitamin B12 deficiency include people who follow vegetarian diets and the infants of women who follow vegan diets.
The following groups are among those most likely to be vitamin B12 deficient.
Depending on the definition used, between 3% and 43% of community-dwelling older adults, especially those with atrophic gastritis, have vitamin B12 deficiency based on serum vitamin B12 levels [43,44]. The deficiency rate at a cutoff of less than 211 pg/mL (156 pmol/L) at admission to a long-term care facility, according to one study, was 14%, and 38% of these older adults had levels lower than 407 pg/mL (300 pmol/L) [44].
Conditions associated with vitamin B12 inadequacy include pernicious anemia, present in about 15% to 25% of older adults with vitamin B12 deficiency [45]. Atrophic gastritis, an autoimmune condition affecting 2% of the general population but 8% to 9% of adults age 65 and older, decreases production of intrinsic factor and secretion of hydrochloric acid in the stomach and thus decreases absorption of vitamin B12 [45,46]. A third condition associated with vitamin B12 deficiency in older adults is Helicobacter pylori infection, possibly because this bacterium causes inflammation that leads to malabsorption of vitamin B12 from food [47].
Pernicious anemia is an irreversible autoimmune disease that affects the gastric mucosa and results in gastric atrophy [1,48]. This disease leads to attacks on parietal cells in the stomach, resulting in failure to produce intrinsic factor and malabsorption of dietary vitamin B12, recycled biliary vitamin B12, and free vitamin B12 [1,6,11].Therefore, without treatment, pernicious anemia causes vitamin B12 deficiency, even in the presence of adequate vitamin B12 intakes.
Pernicious anemia is the most common cause of clinically evident vitamin B12 deficiency around the world [11,48]. The incidence of pernicious anemia in the United States is an estimated 151 per 100,000, and this condition is more common in women and in people of European ancestry [48].
Individuals with stomach and small intestine disorders, such as celiac disease and Crohn’s disease, may be unable to absorb enough vitamin B12 from food to maintain healthy body stores [2,3,49]. However, although rates of vitamin B12 deficiency are higher in people with celiac disease than other people [50], the evidence for whether rates of vitamin B12 deficiency are higher in people with Crohn’s disease is mixed [49,51,52]. Vitamin B12 deficiency in people with Crohn’s disease is typically treated with intramuscular cobalamin injections, but high doses of oral cyanocobalamin therapy (e.g., 1,000 mcg/day) might be equally effective [53].
Surgical procedures in the gastrointestinal tract, such as for weight loss or to remove all or part of the stomach, can cause a complete or partial loss of cells that secrete hydrochloric acid and cells that secrete intrinsic factor [54,55]. Thus, these procedures reduce the amount of vitamin B12, particularly food-bound vitamin B12, that the body absorbs [54,55]. High doses (1,000 mcg/day) of oral methylcobalamin supplements appear to be as effective as hydroxycobalamin injections in normalizing vitamin B12 values in patients who have undergone Roux-en-Y gastric bypass surgery [55].
Vegans who consume no animal products and vegetarians who consume some animal products (e.g., dairy products, eggs, or both) but not meat have a higher risk of developing vitamin B12 deficiency because natural food sources of vitamin B12 are limited to animal foods [3,57]. Consumption of foods fortified with vitamin B12 (such as fortified nutritional yeasts) as well as vitamin B12 supplements can substantially reduce the risk of deficiency [57].
Exclusively breastfed infants of women who consume no animal products might have very limited reserves of vitamin B12 and can develop vitamin B12 deficiency, sometimes very early in life [58]. The infant’s deficiency can be severe, especially if the mother’s deficiency is severe or caused by pernicious anemia; sometimes, the mother’s own deficiency is clinically mild and not recognized. Undetected and untreated vitamin B12 deficiency in infants can result in neurological damage, failure to thrive, developmental delays, and anemia [2,58,59]. The reasons include the small amounts of vitamin B12 in the breast milk of vegan mothers as well as the limited amounts of vitamin B12 crossing the placenta in these women during fetal development.
Vitamin B12 — Fact Sheet for Health Professionals
NIH Office of Dietary Supplements. Government health-professional reference material imported without MEDucated medical review.
Source attribution does not imply NIH or ODS endorsement of MEDucated.
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
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Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.
Government reference · Population basis: unknown · Directness: not assessedSilva MC, Furlanetto TW. Intestinal absorption of vitamin D: A systematic review. Nutr Rev 2018;76:60-76. [PubMed abstract]
Systematic review · Population basis: unknown · Directness: not assessedBrown LL, Cohen B, Tabor D, Zappala G, Maruvada P, Coates PM. The vitamin D paradox in Black Americans: A systems-based approach to investigating clinical practice, research, and public health—expert panel meeting report. BMC Proceedings, 2018;12(Suppl 6):6. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedPicciano MF. Nutrient composition of human milk. Pediatr Clin North Am 2001;48:53-67. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedWagner CL, Greer FR, American Academy of Pediatrics Section on Breastfeeding, American Academy of Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics 2008;122:1142-52. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedDawodu A, Tsang RC. Maternal vitamin D status: Effect on milk vitamin D content and vitamin D status of breastfeeding infants. Adv Nutr 2012;3:353-61. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedDavis CD, Dwyer JT. The 'sunshine vitamin': benefits beyond bone? J Natl Cancer Inst 2007;99:1563-5. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedSimon AE, Ahrens KA. Adherence to vitamin D intake guidelines in the United States. Pediatrics 2020;145:e20193574. [PubMed abstract]
Clinical guideline · Population basis: unknown · Directness: not assessedChalcraft JR, Cardinal LM, Wechsler PJ, Hollis BW, Gerow KG, Alexander BM, et al. Vitamin D synthesis following a single bout of sun exposure in older and younger men and women. Nutrients 2020; 12, 2237; doi:10.3390/nu12082237. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedSowah D, Fan X, Dennett L, Hagtvedt R, Straube S. Vitamin D levels and deficiency with different occupations: A systematic review. BMC Public Health 2017;17:519. [PubMed abstract]
Systematic review · Population basis: unknown · Directness: not assessedPappa HM, Bern E, Kamin D, Grand RJ. Vitamin D status in gastrointestinal and liver disease. Curr Opin Gastroenterol 2008;24:176-83. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedDrincic A, Fuller E, Heaney RP, Armas LAG. 25-hydroxyvitamin D response to graded vitamin D3 supplementation among obese adults. J Clin Endocrinol Metab 2013;98:4845-51. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedEkwaru JP, Zwicker JD, Holick MF, Giovannucci E, Veugelers PJ. The importance of body weight for the dose response relationship of oral vitamin D supplementation and serum 25-hydroxyvitamin D in healthy volunteers. PLOS ONE 2014;9:e111265. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedChakhtoura M, Rahme M, Fuleihan E-H. Vitamin D metabolism in bariatric surgery. Endocrinol Metab Clin North Am 2017;46:947-82. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedPeterson L, Zeng X, Caufield-Noll CP, Schweitzer MA, Magnuson TH, Steele KE. Vitamin D status and supplementation before and after bariatric surgery: A comprehensive literature review. Surg Obes Relat Dis 2016;12:693-702. [PubMed abstract]
Narrative review · Population basis: unknown · Directness: not assessedChakhtoura MT, Nakhoul N, Akl EA, Mantzoros CS, El Hajj Guleihan GA. Guidelines on vitamin D replacement in bariatric surgery? Identification and systematic appraisal. Metabolism 2016;65:586-97. [PubMed abstract]
Clinical guideline · Population basis: unknown · Directness: not assessedCertain groups of people are more likely than others to have inadequate vitamin D status. These include breastfed infants, older adults, people with limited sun exposure, people with dark skin, people with conditions that limit fat absorption, and people with obesity or those who have undergone gastric bypass surgery.
Obtaining sufficient vitamin D from natural (nonfortified) food sources alone is difficult. For many people, consuming vitamin D-fortified foods and exposing themselves to some sunlight are essential for maintaining a healthy vitamin D status. However, some groups might need dietary supplements to meet their vitamin D requirements. The following groups are among those most likely to have inadequate vitamin D status.
Consumption of human milk alone does not ordinarily enable infants to meet vitamin D requirements, because it provides less than 0.6 to 2.0 mcg/L (25 to 78 IU/L) [1,56,57]. The vitamin D content of human milk is related to the mother’s vitamin D status; studies suggest that the breastmilk of mothers who take daily supplements containing at least 50 mcg (2,000 IU) vitamin D3 have higher levels of the nutrient [57,58].
Although UVB exposure can produce vitamin D in infants, the American Academy of Pediatrics (AAP) advises parents to keep infants younger than 6 months out of direct sunlight, dress them in protective clothing and hats, and apply sunscreen on small areas of exposed skin when sun exposure is unavoidable [59]. The AAP recommends 10 mcg (400 IU)/day vitamin D supplements for exclusively and partially breastfed infants starting shortly after birth and lasting until they are weaned and consume at least 1,000 mL/day vitamin D-fortified formula or whole milk [57]. The AAP also recommends 10 mcg (400 IU)/day supplemental vitamin D for all infants who are not breastfed and ingest less than 1,000 mL/day vitamin D-fortified formula or milk. An analysis of NHANES 2009–2016 data found that only 20.5% of breastfed infants and 31.1% of infants who were not breastfed ingested these recommended amounts of supplements [60].
Older adults are at increased risk of developing vitamin D insufficiency, partly because the skin's ability to synthesize vitamin D declines with age [1,61]. In addition, older adults are likely to spend more time than younger people indoors, and they might have inadequate dietary intakes of the vitamin [1].
Homebound individuals; people who wear long robes, dresses, or head coverings for religious reasons; and people with occupations that limit sun exposure are among the groups that are unlikely to obtain adequate amounts of vitamin D from sunlight [62]. The use of sunscreen also limits vitamin D synthesis from sunlight. However, because the extent and frequency of sunscreen use are unknown, the role that sunscreen may play in reducing vitamin D synthesis is unclear [1].
Greater amounts of the pigment melanin in the epidermal layer of the skin result in darker skin and reduce the skin’s ability to produce vitamin D from sunlight [1]. Black Americans, for example, typically have lower serum 25(OH)D levels than White Americans. However, whether these lower levels in persons with dark skin have significant health consequences is not clear [14]. Those of African American ancestry, for example, have lower rates of bone fracture and osteoporosis than do Whites (see the section below on bone health and osteoporosis).
Because vitamin D is fat soluble, its absorption depends on the gut’s ability to absorb dietary fat [4]. Fat malabsorption is associated with medical conditions that include some forms of liver disease, cystic fibrosis, celiac disease, Crohn’s disease, and ulcerative colitis [1,63]. In addition to having an increased risk of vitamin D deficiency, people with these conditions might not eat certain foods, such as dairy products (many of which are fortified with vitamin D), or eat only small amounts of these foods. Individuals who have difficulty absorbing dietary fat might therefore require vitamin D supplementation [63].
Individuals with a body mass index (BMI) of 30 or more have lower serum 25(OH)D levels than individuals without obesity. Obesity does not affect the skin’s capacity to synthesize vitamin D. However, greater amounts of subcutaneous fat sequester more of the vitamin [1]. People with obesity might need greater intakes of vitamin D to achieve 25(OH)D levels similar to those of people with normal weight [1,64,65].
Individuals with obesity who have undergone gastric bypass surgery can also become vitamin D deficient. In this procedure, part of the upper small intestine, where vitamin D is absorbed, is bypassed, and vitamin D that is mobilized into the bloodstream from fat stores might not raise 25(OH)D to adequate levels over time [66,67]. Various expert groups—including the American Association of Metabolic and Bariatric Surgery, The Obesity Society, and the British Obesity and Metabolic Surgery Society—have developed guidelines on vitamin D screening, monitoring, and replacement before and after bariatric surgery [66,68]
Vitamin D — Fact Sheet for Health Professionals
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Evidence topic
No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.No source-backed evidence is currently available for this topic in MEDucated.
The attached ODS revision does not provide an imported source section for this topic.Evidence topic
Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
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Carmel R. Cobalamin (vitamin B12). In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2014:369-89.
Study type could not be determined · Population basis: unknown · Directness: not assessedAllen LH, Miller JW, de Groot L, Rosenberg IH, Smith AD, Refsum H, et al. Biomarkers of Nutrition for Development (BOND): Vitamin B-12 Review. J Nutr 2018;148:1995S-2027S. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedLangan RC, Goodbred AJ. Vitamin B12 deficiency: Recognition and management. Am Fam Physician 2017;96:384-9. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedMaruvada P, Stover PJ, Mason JB, Bailey RL, Davis CD, Field MS, et al. Knowledge gaps in understanding the metabolic and clinical effects of excess folates/folic acid: A summary, and perspectives, from an NIH workshop. Am J Clin Nutr 2020;112:1390-403 [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedHannibal L, Lysne V, Bjørke-Monsen A-L, Behringer S, Grünert SC, Spiekerkoetter U, et al. Biomarkers and algorithms for the diagnosis of vitamin B12 deficiency. Front Mol Biosci 2016;3:27. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedMineva EM, Sternberg MR, Zhang M, Aoki Y, Storandt R, Bailey RL, et al. Age-specific reference ranges are needed to interpret serum methylmalonic acid concentrations in the US population. Am J Clin Nutr 2019;110:158-68. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedGreen R, Allen LH, Bjorke-Monsen AL, Brito A, Gueant JL, Miller JW, et al. Vitamin B12 deficiency. Nat Rev Dis Primers 2017;3:17040. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedSerum or plasma vitamin B12 levels are typically used to assess a person’s vitamin B12 status, with values lower than 200 or 250 pg/mL generally being considered subnormal. The most sensitive marker of vitamin B12 status is a vitamin B12-associated metabolite called methylmalonic acid, and serum levels of this metabolite can be used to confirm a diagnosis of vitamin B12 deficiency if a patient’s serum vitamin B12 level is between 150 and 399 pg/mL.
Vitamin B12 status is typically assessed by measurements of serum or plasma vitamin B12 levels. The cutoff between normal vitamin B12 levels and deficiency varies by method and laboratory, but most laboratories define subnormal serum or plasma values as those lower than 200 or 250 picograms per milliliter (pg/mL) (148 or 185 picomols per liter [pmol/L]) [2]. Levels of serum methylmalonic acid (MMA), a vitamin B12-associated metabolite, are the most sensitive markers of vitamin B12 status, and an MMA level greater than 0.271 micromol/L suggests vitamin B12 deficiency [6-8]. However, MMA levels also rise with renal insufficiency and tend to be higher in older adults [6,9,10]. Another marker is total plasma homocysteine levels, which rise quickly as vitamin B12 status declines; a serum homocysteine level higher than 15 micromol/L, for example, suggests vitamin B12 deficiency [11]. However, this indicator has poor specificity because it is influenced by other factors, such as low folate levels and, especially, by declines in kidney function [6]. Experts suggest that if a patient’s serum vitamin B12 level is between 150 to 399 pg/mL (111 to 294 pmol/L), the patient’s serum MMA levels should be checked to help confirm a diagnosis of vitamin B12 deficiency [7,9].
Vitamin B12 — Fact Sheet for Health Professionals
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Imported NIH ODS source content is available for this topic. MEDucated has preserved the source wording and has not converted it into personalized guidance.
Structural characterization
Reference counts describe frozen source associations; a larger count does not establish stronger evidence.
No explicit limitation phrase was identified in these imported source blocks.
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.
Government reference · Population basis: unknown · Directness: not assessedNorman AW, Henry HH. Vitamin D. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition, 10th ed. Washington DC: Wiley-Blackwell, 2012.
Study type could not be determined · Population basis: unknown · Directness: not assessedJones G. Vitamin D. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease, 11th ed. Philadelphia: Lippincott Williams & Wilkins, 2014.
Study type could not be determined · Population basis: unknown · Directness: not assessedSempos CT, Heijboer AC, Bikle DD, Bollerslev J, Bouillon R, Brannon PM, et al. Vitamin D assays and the definition of hypovitaminosis D. Results from the First International Conference on Controversies in Vitamin D. Br J Clin Pharmacol 2018;84:2194-207. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedLeFevre ML. Screening for vitamin deficiency in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2015;162:133-40. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessedBrooks SPJ, Sempos CT. The importance of 25-hydroxyvitamin D assay standardization and the Vitamin D Standardization Program. Journal of AOAC International 2017;100:1223-4.
Study type could not be determined · Population basis: unknown · Directness: not assessedTaylor CL, Sempos CT, Davis CD, Brannon PM. Vitamin D: moving forward to address emerging science. Nutrients 2017, 9, 1308; doi:10.3390/mu9121308. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedSempos CT, Binkley N. 25-hydroxyvitamin D assay standardisation and vitamin D guidelines paralysis. Public Health Nutrition 2020;23:1153-64. [PubMed abstract]
Clinical guideline · Population basis: unknown · Directness: not assessedOffice of Dietary Supplements, National Institutes of Health. Vitamin D Standardization Program (VDSP).
Study type could not be determined · Population basis: unknown · Directness: not assessedDemay MB, Pittas AG, Bikle DD, Diab DL, Kiely ME, et al. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2024 Jul 12;109(8):1907-1947. [PubMed abstract]
Clinical guideline · Population basis: unknown · Directness: not assessedShah VP, Nayfeh T, Alsawaf Y, Saadi S, Farah M, et al. A Systematic Review Supporting the Endocrine Society Clinical Practice Guidelines on Vitamin D. J Clin Endocrinol Metab. 2024 Jul 12;109(8):1961-1974. [PubMed abstract]
Systematic review · Population basis: unknown · Directness: not assessedHolick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedBrown LL, Cohen B, Tabor D, Zappala G, Maruvada P, Coates PM. The vitamin D paradox in Black Americans: A systems-based approach to investigating clinical practice, research, and public health—expert panel meeting report. BMC Proceedings, 2018;12(Suppl 6):6. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessedSerum concentration of 25(OH)D is the main indicator of vitamin D status. However, the serum concentrations of 25(OH)D that are associated with vitamin D deficiency have not been definitively identified. The Food and Nutrition Board at the National Academies of Sciences, Engineering, and Medicine states that levels of 50 nmol/L (20 ng/mL) or more are sufficient for most people, and that the risk of deficiency increases at serum concentrations of less than 30 nmol/L (12 ng/mL).
Serum concentration of 25(OH)D is currently the main indicator of vitamin D status. It reflects vitamin D produced endogenously and that obtained from foods and supplements [1]. In serum, 25(OH)D has a fairly long circulating half-life of 15 days [1]. Serum concentrations of 25(OH)D are reported in both nanomoles per liter (nmol/L) and nanograms per milliliter (ng/mL). One nmol/L is equal to 0.4 ng/mL, and 1 ng/mL is equal to 2.5 nmol/L.
Assessing vitamin D status by measuring serum 25(OH)D concentrations is complicated by the considerable variability of the available assays (the two most common ones involve antibodies or chromatography) used by laboratories that conduct the analyses [5,6]. As a result, a finding can be falsely low or falsely high, depending on the assay used and the laboratory. The international Vitamin D Standardization Program has developed procedures for standardizing the laboratory measurement of 25(OH)D to improve clinical and public health practice [5,7-10].
In contrast to 25(OH)D, circulating 1,25(OH)2D is generally not a good indicator of vitamin D status because it has a short half-life measured in hours, and serum levels are tightly regulated by parathyroid hormone, calcium, and phosphate [1]. Levels of 1,25(OH)2D do not typically decrease until vitamin D deficiency is severe [2].
Although 25(OH)D functions as a biomarker of exposure, the extent to which 25(OH)D levels also serve as a biomarker of effect on the body (i.e., relating to health status or outcomes) is not clear [1,3].
Researchers have not definitively identified serum concentrations of 25(OH)D associated with deficiency (e.g., rickets), adequacy for bone health, and overall health. After reviewing data on vitamin D needs, an expert committee of the Food and Nutrition Board (FNB) at the National Academies of Sciences, Engineering, and Medicine (NASEM) concluded that people are at risk of vitamin D deficiency at serum 25(OH)D concentrations less than 30 nmol/L (12 ng/mL; see Table 1 for definitions of deficiency and inadequacy) [1]. Some people are potentially at risk of inadequacy at 30 to 50 nmol/L (12–20 ng/mL). Levels of 50 nmol/L (20 ng/mL) or more are sufficient for most people. The FNB also noted that serum concentrations greater than 125 nmol/L (50 ng/mL) can be associated with adverse effects [1] (Table 1). The Endocrine Society has not identified 25(OH)D concentrations associated with vitamin D sufficiency, insufficiency, and deficiency and does not recommend routine testing of 25(OH)D concentrations in healthy individuals [11,12].
| nmol/L* | ng/mL* | Health status |
|---|---|---|
| <30 | <12 | Associated with vitamin D deficiency, which can lead to rickets in infants and children and osteomalacia in adults |
| 30 to <50 | 12 to <20 | Generally considered inadequate for bone and overall health in healthy individuals |
| ≥50 | ≥20 | Generally considered adequate for bone and overall health in healthy individuals |
| >125 | >50 | Linked to potential adverse effects, particularly at >150 nmol/L (>60 ng/mL) |
| *Serum concentrations of 25(OH)D are reported in both nanomoles per liter (nmol/L) and nanograms per milliliter (ng/mL). One nmol/L = 0.4 ng/mL, and 1 ng/mL = 2.5 nmol/L. |
Optimal serum concentrations of 25(OH)D for bone and general health have not been established because they are likely to vary by stage of life, by race and ethnicity, and with each physiological measure used [1,13,14]. In addition, although 25(OH)D levels rise in response to increased vitamin D intake, the relationship is nonlinear [1]. The amount of increase varies, for example, by baseline serum levels and duration of supplementation.
Vitamin D — Fact Sheet for Health Professionals
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Source attribution does not imply NIH or ODS endorsement of MEDucated.
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The attached ODS revision does not provide an imported source section for this topic.No source-backed evidence is currently available for this topic in MEDucated.
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