Skip to main content
    • Aa
    • Aa

Intake and status of folate and related B-vitamins: considerations and challenges in achieving optimal status

  • Helene McNulty (a1) and John M. Scott (a2)

Folate and the metabolically related B-vitamins, vitamin B12 and riboflavin, have attracted much scientific and public health interest in recent years. Apart from a well established role in preventing neural tube defects (NTDs), evidence is emerging to support other potential roles for folate and/or related B-vitamins in protecting against cardiovascular disease (especially stroke), certain cancers, cognitive impairment and osteoporosis. However, typical folate intakes are sub-optimal, in that although adequate in preventing clinical folate deficiency (i.e. megaloblastic anaemia) in most people, they are generally insufficient to achieve a folate status associated with the lowest risk of NTDs. Natural food folates have a limited ability to enhance folate status as a result of their poor stability under typical cooking conditions and incomplete bioavailability when compared with the synthetic vitamin, folic acid (as found in supplements and fortified foods). Current folate recommendations to prevent NTDs (based primarily on folic acid supplementation) have been found to be ineffective in several European countries. In contrast, in North America and Chile, the policy of mandatory folic acid-fortification has proven itself in terms of lowering the prevalence of NTD, but remains controversial because of concerns regarding potential risks of chronic exposure to high-dose folic acid. In the case of vitamin B12, the achievement of an optimal status is particularly difficult for many older people because of the common problem of food-bound B12 malabsorption. Finally, there is evidence that riboflavin status is generally low in the UK population, and particularly so in younger women; this warrants further investigation.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Intake and status of folate and related B-vitamins: considerations and challenges in achieving optimal status
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Intake and status of folate and related B-vitamins: considerations and challenges in achieving optimal status
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Intake and status of folate and related B-vitamins: considerations and challenges in achieving optimal status
      Available formats
Corresponding author
*Corresponding author: Professor Helene McNulty, fax +44 028 70323023, email
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

7 JW Miller , MG Garrod , AL Rockwood , MM Kushnir , LH Allen , MN Haan & R Green (2006) Measurement of total vitamin B12 and holotranscobalamin, singly and in combination, in screening for metabolic vitamin B12 deficiency. Clin Chem 52, 278285.

9 AL Morkbak , RM Heimdal , K Emmens , A Molloy , AM Hvas , J Schneede , R Clarke , JM Scott , PM Ueland & E Nexo (2005) Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project. Clin Chem Lab Med 43, 10581064.

10 AM Hvas & E Nexo (2005) Holotranscobalamin – a first choice assay for diagnosing early vitamin B deficiency? J Intern Med 257, 289298.

12 M Wolters , A Strohle & A Hahn (2004) Cobalamin: a critical vitamin in the elderly. Prev Med 39, 12561266.

17 S Liu , R West , E Randell , (2004) A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects. BMC Pregnancy Childbirth 4, 2029.

25 M Eichholzer , O Tonz & R Zimmermann (2006) Folic acid: a public-health challenge. Lancet 367, 13521361.

26 LD Botto , A Lisi , E Robert-Gnansia , (2005) International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working? BMJ 330, 571576.

28 MA Honein , LJ Paulozzi , TJ Mathews , JD Erickson & L-YC Wong (2001) Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA 285, 29812986.

29 P De Wals , F Tairou , MI Van Allen , (2007) Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med 357, 135142.

30Homocysteine Studies Collaboration (2002) Homocysteine and risk of ischemic heart disease and stroke. JAMA 288, 20152022.

31 DS Wald , M Law & JK Morris (2002) Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 325, 12021208.

32 P Frosst , HJ Blom , R Milos , (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10, 111113.

33 B Wilcken , F Bamforth , Z Li , (2003) Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet 40, 619625.

34 M Klerk , P Verhoef , R Clarke , HJ Blom , FJ Kok & EG Schouten (2003) MTHFR 677C>T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 288, 20232031.

35 SJ Lewis , S Ebrahim & G Davey Smith (2005) Meta-analysis of MTHFR 677C → T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate. BMJ 331, 10531056.

36 Q Yang , LD Botto , JD Erickson , RJ Berry , C Sambell , H Johansen & JM Friedman (2006) Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation 113, 13351343.

37 X Wang , X Qin , H Demirtas , J Li , G Mao , Y Huo , N Sun , L Liu & X Xu (2007) Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 369, 18761882.

40 BF Cole , JA Baron , RS Sandler , (2007) Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 297, 23512359.

41 JA McMahon , TJ Green , CM Skeaff , RG Knight , JI Mann & SM Williams (2006) A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med 354, 27642772.

42 J Durga , MP van Boxtel , EG Schouten , FJ Kok , J Jolles , MB Katan & P Verhoef (2007) Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 369, 208216.

43 Y Sato , Y Honda , J Iwamoto , T Kanoko & K Satoh (2005) Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA 293, 10821088.

44Homocysteine Lowering Trialists' Collaboration (1998) Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomized trials. BMJ 316, 894898.

45 SJPM Eussen , LCPGM de Groot , R Clarke , (2005) Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency. A dose finding trial. Arch Intern Med 165, 11671172.

47 H McNulty , LC Dowey , JJ Strain , A Dunne , M Ward , AM Molloy , LB McAnena , JP Hughes , M Hannon-Fletcher & JM Scott (2006) Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C → T polymorphism. Circulation 113, 7480.

49 EP Quinlivan , J McPartlin , H McNulty , M Ward , JJ Strain , DG Weir & JM Scott (2002) Importance of both folic acid and vitamin B-12 in reduction of risk of vascular disease. Lancet 359, 227228.

50 G Liaugaudas , PF Jacques , J Selhub , IH Rosenberg & AG Boston (2001) Renal insufficiency, vitamin B-12 status, and population attributable risk for mild hyperhomocysteinemia among coronary artery disease patients in the era of folic acid-fortified cereal grain flour. Arterioscler Thromb Vasc Biol 21, 849851.

51 AM Molloy , S Daly , JL Mills , PN Kirke , AS Whitehead , D Ramsbottom , MR Conley , DG Weir & JM Scott (1997) Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: implications for folate intake recommendations. Lancet 349, 15911593.

52 PF Jacques , AG Bostom , RR Williams , RC Ellison , JH Eckfeldt , IH Rosenberg , J Selhub & R Rozen (1996) Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93, 79.

53 K Yamada , Z Chen , R Rozen & RG Matthews (2001) Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. Proc Natl Acad Sci U S A 98, 1485314858.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 13
Total number of PDF views: 166 *
Loading metrics...

Abstract views

Total abstract views: 264 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 27th May 2017. This data will be updated every 24 hours.