Intake of vitamin B12 in relation to vitamin B12 status in groups susceptible to deficiency: a systematic review

  • Linnea Bärebring Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
  • Christel Lamberg-Allardt Department of Food and Nutrition, University of Helsinki, Finland
  • Birna Thorisdottir Faculty of Sociology, Anthropology and Folkloristics and Health Science Institute, University of Iceland, Iceland
  • Alfons Ramel Faculty of Food Science and Nutrition, University of Iceland, Iceland
  • Fredrik Söderlund Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, the Karolinska Institute, Sweden
  • Erik Kristoffer Arnesen Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway
  • Bright I. Nwaru Krefting Research Centre, Institute of Medicine, University of Gothenburg, Sweden
  • Jutta Dierkes Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Norway; and Department of Laboratory Medicine and Pathology, Haukeland University Hospital, Norway
  • Agneta Åkesson Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, the Karolinska Institute, Sweden
Keywords: cobalamin, vitamin B12, holotranscobalamin, ; methylmalonic acid, homocysteine, dietary guidelines


Objective: To systematically review the evidence for whether habitual or different levels of experimental intake of vitamin B12 from diet and supplements is sufficient to ensure adequate B12 status in groups most susceptible to vitamin B12 deficiency.

Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to 21 May 2021, for intervention studies, prospective cohort studies and case-control studies assessing B12 intake from diet and/or supplements in relation to B12 status (s/p-B12, holotranscobalamin, methylmalonic acid, homocysteine or breastmilk B12). Cross-sectional studies were eligible for studies conducted during pregnancy and lactation. Included populations were children (0–18 years), young adults (18–35 years), pregnant or lactating women, older adults (≥65 years) and vegans or vegetarians. Study selection, data extraction and risk of bias assessment were conducted by two assessors independently. The evidence was synthesized qualitatively and classified according to the World Cancer Research Fund.

Results: The searches yielded 4855 articles of which 89 were assessed in full text and 18 included. Three studies were conducted during pregnancy and three during lactation or infancy – all observational. Eight studies were conducted among older adults; most were interventions among B12-deficient participants. Four studies were eligible for vegetarian and vegans, all interventions. The strength of evidence that habitual B12 intake or an intake in line with the current Nordic recommended intake (RI) is sufficient to ensure adequate status was considered Limited – no conclusion for all included populations.

Conclusion: Evidence is insufficient to assess if or which level of B12 intake is sufficient to maintain adequate status for all included populations. Population-based cohort studies and low-to-moderate dose interventions that address this question are highly warranted.


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Lyon P, Strippoli V, Fang B, Cimmino L. B Vitamins and One-Carbon metabolism: implications in human health and disease. Nutrients 2020; 12(9): 2867. doi: 10.3390/nu12092867

Mohamed M, Thio J, Thomas RS, Phillips J. Pernicious anaemia. Br Med J 2020; 369: m1319. doi: 10.1136/bmj.m1319

Sobczyńska-Malefora A, Delvin E, McCaddon A, Ahmadi KR, Harrington DJ. Vitamin B(12) status in health and disease: a critical review. Diagnosis of deficiency and insufficiency – clinical and laboratory pitfalls. Crit Rev Clin Lab Sci 2021; 58(6): 399–429. doi: 10.1080/10408363.2021.1885339

Green R, Allen LH, Bjørke-Monsen AL, Brito A, Guéant JL, Miller JW, et al. Vitamin B(12) deficiency. Nat Rev Dis Primers 2017; 3: 17040. doi: 10.1038/nrdp.2017.40

Rizzo G, Laganà AS, Rapisarda AM, La Ferrera GM, Buscema M, Rossetti P, et al. Vitamin B12 among vegetarians: status, assessment and supplementation. Nutrients 2016; 8(12): 767. doi: 10.3390/nu8120767

Schürmann S, Kersting M, Alexy U. Vegetarian diets in children: a systematic review. Eur J Nutr 2017; 56(5): 1797–817. doi: 10.1007/s00394-017-1416-0

Allen LH. How common is vitamin B-12 deficiency? Am J Clin Nutr 2009; 89(2): 693S–6S. doi: 10.3945/ajcn.2008.26947A

Nordic Council of Ministers. Nordic Nutrition Recommendations 2012: Integrating nutrition and physical activity. 5th ed. Copenhagen, Denmark; 2014.

Dror DK, Allen LH. Vitamin B-12 in Human milk: a systematic review. Adv Nutr. 2018; 9(suppl_1): 358S–66S. doi: 10.1093/advances/nmx019

Arnesen EK, Christensen JJ, Andersen R, Eneroth H, Erkkola M, Høyer A, et al. The Nordic nutrition recommendations 2022 – structure and rationale of qualified systematic reviews. Food Nutr Res 2020; 64: 4403. doi: 10.29219/fnr.v64.4403

Arnesen EK, Christensen JJ, Andersen R, Eneroth H, Erkkola M, Høyer A, et al. The Nordic nutrition recommendations 2022 – handbook for qualified systematic reviews. Food Nutr Res 2020; 64: 4404. doi: 10.29219/fnr.v64.4404

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Br Med J 2021; 372: n71. doi: 10.1136/bmj.n71

Christensen JJ, Arnesen EK, Andersen R, Eneroth H, Erkkola M, Høyer A, et al. The Nordic nutrition recommendations 2022 – principles and methodologies. Food Nutr Res 2020; 64. doi: 10.29219/fnr.v64.4402

Mourad Ouzzani, Hossam Hammady, Zbys Fedorowicz, Ahmed Elmagarmid. Rayyan – a web and mobile app for systematic reviews. Syst Rev 2016; 5: 210. doi: 10.1186/s13643-016-0384-4

Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. Br Med J 2019; 366: l4898. doi: 10.1136/bmj.l4898

Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. Br Med J 2016; 355: i4919. doi: 10.1136/bmj.i4919

Nutrition Evidence Systematic Review. Risk of Bias for Nutrition Observational Studies (RoB-NObs) Tool 2019. Available from: [cited 11 October 2021].

The National Heart, Lung and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies [2021-10-19]. Available from: [cited 11 October 2021].

McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): an R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods 2020; 12(1): 55–61. doi: 10.1002/jrsm.1411

Koebnick C, Hoffmann I, Dagnelie PC, Heins UA, Wickramasinghe SN, Ratnayaka ID, et al. Long-term ovo-lacto vegetarian diet impairs vitamin B-12 status in pregnant women. J Nutr 2004; 134(12): 3319–26. doi: 10.1093/jn/134.12.3319

Visentin CE, Masih SP, Plumptre L, Schroder TH, Sohn KJ, Ly A, et al. Low serum vitamin B-12 concentrations are prevalent in a cohort of pregnant Canadian women. J Nutr. 2016; 146(5): 1035–42. doi: 10.3945/jn.115.226845

Denissen KFM, Heil SG, Eussen S, Heeskens JPJ, Thijs C, Mommers M, et al. Intakes of Vitamin B-12 from dairy food, meat, and fish and shellfish are idependently and positively associated with Vitamin B-12 biomarker status in pregnant Dutch Women. J Nutr. 2019; 149(1): 131–8. doi: 10.1093/jn/nxy233

Greibe E, Lildballe DL, Streym S, Vestergaard P, Rejnmark L, Mosekilde L, et al. Cobalamin and haptocorrin in human milk and cobalamin-related variables in mother and child: a 9-mo longitudinal study. Am J Clin Nutr 2013; 98(2): 389–95. doi: 10.3945/ajcn.113.058479

Henjum S, Manger M, Hampel D, Brantsaeter AL, Shahab-Ferdows S, Bastani NE, et al. Vitamin B12 concentrations in milk from Norwegian women during the six first months of lactation. Eur J Clin Nutr 2020; 74(5): 749–56. doi: 10.1038/s41430-020-0567-x

Hay G, Johnston C, Whitelaw A, Trygg K, Refsum H. Folate and cobalamin status in relation to breastfeeding and weaning in healthy infants. Am J Clin Nutr 2008; 88(1):105–14. doi: 10.1093/ajcn/88.1.105

Seal EC, Metz J, Flicker L, Melny J. A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. J Am Geriatr Soc 2002; 50(1): 146–51. doi: 10.1046/j.1532-5415.2002.50020.x

Eussen SJ, De Groot LC, Clarke R, Schneede J, Ueland PM, Hoefnagels WH, et al. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Arch Intern Med. 2005 2005;165(10):1167–72. doi: 10.1001/archinte.165.10.1167

Dhonukshe-Rutten RA, Van Zutphen M, De Groot LC, Eussen SJ, Blom HJ, Van Staveren WA. Effect of supplementation with cobalamin carried either by a milk product or a capsule in mildly cobalamin-deficient elderly Dutch persons. Am J Clin Nutr 2005; 82(3): 568–74. doi: 10.1093/ajcn.82.3.568

Favrat B, Vaucher P, Herzig L, Burnand B, Ali G, Boulat O, et al. Oral vitamin B12 for patients suspected of subtle cobalamin deficiency: a multicentre pragmatic randomised controlled trial. BMC Fam Pract 2011; 12: 2. doi: 10.1186/1471-2296-12-2

Hill MH, Flatley JE, Barker ME, Garner CM, Manning NJ, Olpin SE, et al. A vitamin B-12 supplement of 500 mug/d for eight weeks does not normalize urinary methylmalonic acid or other biomarkers of vitamin B-12 status in elderly people with moderately poor vitamin B-12 status. J Nutr 2013; 143(2): 142–7. doi: 10.3945/jn.112.169193

Rajan S, Wallace JI, Brodkin KI, Beresford SA, Allen RH, Stabler SP. Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. J Am Geriatr Soc 2002;50(11):1789–95. doi: 10.1046/j.1532-5415.2002.50506.x

Stabler SP, Allen RH, Dolce ET, Johnson MA. Elevated serum S-adenosylhomocysteine in cobalamin-deficient elderly and response to treatment. Am J Clin Nutr 2006; 84(6): 1422–9. doi: 10.1093/ajcn/84.6.1422

Jungert A, Zenke-Philippi C, Neuhauser-Berthold M. Dynamics and interactions of cobalamin and folate status during advanced aging – a longitudinal study in a community-dwelling cohort with multiple follow-ups. Nutr J 2020; 19(1): 64. doi: 10.1186/s12937-020-00576-2

Kwok T, Chook P, Qiao M, Tam L, Poon YK, Ahuja AT, et al. Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status. J Nutrition Health Aging 2012; 16(6): 569–73. doi: 10.1007/s12603-012-0036-x

Obersby D, Chappell D, Dunnett A, Tsiami A. Efficacy of methylcobalamin to normalise elevated homocysteine of vitamin B12 deficient vegetarians: a double blind placebo control study. Curr Res Nutr Food Sci 2015; 3(3): 187–96. doi: 10.12944/CRNFSJ.3.3.02

Lederer AK, Hannibal L, Hettich M, Behringer S, Spiekerkoetter U, Steinborn C, et al. Vitamin B12 status upon short-term intervention with a Vegan Diet – a randomized controlled trial in healthy participants. Nutrients 2019; 11(11): 18. doi: 10.3390/nu11112815

Del Bo C, Riso P, Gardana C, Brusamolino A, Battezzati A, Ciappellano S. Effect of two different sublingual dosages of vitamin B12 on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency: a randomized controlled trial. Clin Nutr 2019; 38(2): 575–83. doi: 10.1016/j.clnu.2018.02.008

Crozier SR, Inskip HM, Godfrey KM, Cooper C, Robinson SM. Nausea and vomiting in early pregnancy: effects on food intake and diet quality. Matern Child Nutr 2017; 13(4): e12389. doi: 10.1111/mcn.12389

Hacker NF, Gambone JC, Hobel CJ. Hacker and Moore’s essentials of obstetrics and Gynecology. 5th ed. Philadelphia: Saunders Elsevier; 2010.

Obbagy JE, English LK, Psota TL, Wong YP, Butte NF, Dewey KG, et al. Complementary feeding and micronutrient status: a systematic review. Am J Clin Nutr 2019; 109(Suppl_7): 852S–71S. doi: 10.1093/ajcn/nqy266

Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B(6), Folate, Vitamin B(12), Pantothenic Acid, Biotin, and Choline. Washington DC: National Academy of Sciences; 1998.

Wong CW. Vitamin B12 deficiency in the elderly: is it worth screening? Hong Kong Med J 2015; 21(2): 155–64. doi: 10.12809/hkmj144383

Bakaloudi DR, Halloran A, Rippin HL, Oikonomidou AC, Dardavesis TI, Williams J, et al. Intake and adequacy of the vegan diet. A systematic review of the evidence. Clin Nutr 2021; 40(5): 3503–21. doi: 10.1016/j.clnu.2020.11.035
How to Cite
Bärebring L., Lamberg-Allardt C., Thorisdottir B., Ramel A., Söderlund F., Arnesen E. K., Nwaru B. I., Dierkes J., & Åkesson A. (2023). Intake of vitamin B12 in relation to vitamin B12 status in groups susceptible to deficiency: a systematic review. Food & Nutrition Research, 67.
Nordic Nutrition Recommendations 2022

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