How prevalent is vitamin B 12 deficiency among vegetarians? - Pawlak 2013

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How prevalent is vitamin B 12 deficiency among vegetarians? Roman Pawlak, Scott James Parrott, Sudha Raj, Diana Cullum-Dugan, and Debbie Lucus Veg eget etar aria ians ns ar aree at ri risk sk fo forr vi vita tami min n B12 (B1 (B12) 2) defic deficien iency cy due to sub subopti optimal mal int intake ake.. The goal of the present literature review was to assess the rate of B12 depletion and  deficiency among vegetarians and vegans. Using a PubMed search to identify  relevant publications, 18 articles were found that reported B12 deficiency rates from fr om st stud udie iess th that at id iden enti tifie fied d de defic ficie iency ncy by me meas asur urin ing g me meth thyl ylma malo loni nicc ac acid id,, holo-tr hol o-trans anscob cobala alamin min II, or bot both. h. The defi deficie ciency ncy ra rates tes re report ported ed for spe specifi cific  c   populations were as follows: 62% among pregnant women, between 25% and  almost alm ost 86% amo among ng chi childr ldren, en, 21– 21–41% 41% amo among ng ado adoles lescen cents, ts, and 11– 11–90% 90% amo among ng the elderly. Higher rates of deficiency were reported among vegans compared with vegeta veg etaria rians ns andamong ind indivi ividua duals ls who hadadher hadadhered ed to a veg vegeta etaria rian n die diett sin since ce birth compared with those who had adopted such a diet later in life. The main finding of  this review is that vegetarians develop B12 depletion or deficiency regardless of  demographic characteristics, place of residency, age, or type of vegetarian diet. Veget Ve getari arians ans sho should uld thu thuss tak takee pre preven ventiv tivee mea measur sures es to ens ensure ure ade adequa quate te int intake ake of thi thiss vitamin, including regular consumption of supplements containing B12. © 2013 International Life Sciences Institute

INTRODUCTION

Vitamin B12   (B12) Vitamin (B12) has the lar larges gestt and most com comple plexx 1 chemical structure of all vitamins. It is named cobalamin becausee cobal becaus cobaltt is a part of its chemical structure. structure. Cobalamin ami n bel belong ongss to a gro group up of cob cobalt alt-co -conta ntaini ining ng com compou pounds nds 2,3 known as corrinoids. Some of these compounds are biologically inactive in humans, while methylcobalamin and adenosylcobalamin are biologically active. Hydroxycobalamin cobala min and cyanoc cyanocobalam obalamin in const constitute itute two additi additional onal forms that may be metabo metabolized lized into eithe eitherr meth methylcob ylcobalalamin or adenosylcobalamin and can thus play functional roles in human cells. B12 is an essential nutrient important in transferring the meth methyl yl group in a methio methionine nine synthase-requiri synthase-requiring ng reaction, which converts homocysteine to methionine. This reaction activates folate, which can be utilized in

DNA synthesis. B12 is also needed in the synthesis of  myelin and thus the maintenance and repair of neural axons. In addition, B12 is essential for the synthesis of  energy in mitochondria and for erythropoiesis in bone marrow.4,5 B12 is only synthesized by microorganisms and is, thus,, not foun thus found d in foods of plant origin, except except through contamination with soil or by exposure to foods containing B12, such as milk solids during processing or in foods fortifi for tified ed wit with h thi thiss vit vitami amin. n.3,6 Sin Since ce veg vegeta etaria rians ns hav havee limited natural natural sources sources of of B12 (milk, dairy dairy,, and eggs), eggs), the presen pre sence ce of B12 in pla plantnt-bas based ed die diets ts dep depend endss on the inclusion/exclusion of foods of animal origin, consumption of foods fortified with B12, B12, or the use of B12 supplements. Although B12 deficiency was once thought to be extremely rare except among strict vegetarians, it is now  known that B12 deficie deficiency ncy is relatively common among

Affiliations: R Pawlak  is Affiliations: R  is with the Department of Nutrition Science, East Carolina University, North Carolina, USA.  SJ Parrott  is   is with the Department of Nutritional Sciences, School of Health Related Professions, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA. S USA.  S Raj  is  is with the Department of Public Health, Food Studies and Nutrition, Syracuse University, Syracuse, New York, USA. D Cullum-Dugan is Cullum-Dugan is with Namaste Nutrition, Watertown, Massachusetts, USA.  D Lucus is Lucus  is with the Sutter Medical Foundation, Roseville, California, USA. Correspondence: R Pawlak , Department of Nutrition Science, East Carolina University, Rivers West 337, Greenville, NC 27858, USA. E-mail: Correspondence: R [email protected]. pawlakr@ecu. edu. Phone:  + 1-252-328-2350. Key words: cobalamin, deficiency, deficiency, vegetarians, vegans, vegans, vitamin B 12

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doi:10.1111/nure.12001 Nutrition Reviews® Vol. 71(2):110–117 

people adhering to all types of vegetarian diets, including lacto-ovo-vegetarian, and other population subgroups, such as the elderly.7,8 Although a variety of assessment techniques have been used to assess B12 status, e.g., serum or plasma B12, mean corpuscular volume (MCV), homocysteine (tHcy), holo-transcobalamin II (holo-TCII), and serum or urinary methylmalonic acid (MMA), the newest research findings indicate that MMA and holo-TCII are the most accurate, while serum or plasma B12 and MCV are unreliable.3,5,9 Herbert9 suggested that holo-TCII shows a degree of B12 depletion while MMA indicates the extent of deficiency. He further indicated that the progression from normal B12 status to deficiency passes through a stage called depletion and that holo-TCII is the best marker of this stage, while MMA is the best marker of  B12 status when stores are exhausted and deficiency has been reached.9 Herbert (as well as others) also suggested that more than one assessment technique should be used to determine B12 status. As reported by Antony,10 researchers who reported B12 status among vegetarians based on the use of serum B12 level as a marker of B12 status likely underestimated the rate of deficiency due to the inherent inaccuracy of this assessment method. The goal of the present review was to assess B12 depletion and deficiency among people adhering to different types of   vegetarian diets based on studies that reported B12 status from measurements of serum holo-TCII and/or serum or urinary MMA. To achieve this goal,a PubMed search was performed using the following key words: B12, cobalamin, vegetarians,vegans, and deficiency. The titles and abstracts of the resulting publications were then screened to identify  manuscripts in which reports of B12 status among vegetarians were based on the use of holo-TCII, MMA, or both. The reference lists of manuscripts selected initially  were then checked to search for additional manuscripts that may not have been identified in the initial PubMed search. Research manuscripts that reported the use of  either of the two assessment techniques, but reported only means or medians without percentages of the sample with abnormal values, were excluded. RESULTS

A total of 18 manuscripts meeting the inclusion criteria were identified.11–28 The studies included very heterogeneous samples that incorporated pregnant women,14 infants,27 children,24,26 adolescents,11,23,28 adults, and the elderly.12,13,15–26 They included male and female participants who adhered to different types of vegetarian diets: semi-vegetarian, macrobiotic, lacto-vegetarian (LV) or lacto-ovo-vegetarian (LOV), vegan, and vegan raw food. Two of the reviewed manuscripts utilized urinary MMA, Nutrition Reviews® Vol. 71(2):110–117 

eight used serum MMA, one used both urinary and serum MMA, while seven reported the use of both MMA and holo-TCII (four of these studies reported separate rates for depletion and deficiency, while three described a rate for participants who had both low holo-TCII and elevated MMA). Assessment of what constituted deficiency was the same across studies for holo-TCII (<35 pmol/L) and urinary MMA (>4.0  m g/mg creatinine), while the serum MMA cutoff value varied widely, from >260  m mol/L to >0.75 m mol/L. Assessment subjects included individuals of various ethnic backgrounds and living in a variety of countries, such as China (including Hong Kong),21,22 Germany,13,16–20,24 Ethiopia,14 India,25 New Zealand,26 the Netherlands,11,16,19,24,28 Norway,27 Oman,17 and the United States.23 Pregnant women

Only one of the studies included pregnant women.14 This study was conducted in Ethiopia and included participants whose diet was based on either maize or enset. The reported prevalence of B12 deficiency, defined as MMA >271 nmol/L, was 62%. Infants and children

One study reported the prevalence of B12 deficiency  among 41 Norwegian infants.27 Deficiency (MMA >0.43  m mol/L) was detected among 85.4% of the sample. Two studies, one from the United States23 and the other from New Zealand (evaluating Asian Indian migrants),26 examined the prevalence of B12 deficiency among children. The American children followed a macrobiotic diet, while the Asian Indians in New Zealand were LOVs. The prevalence of B12 deficiency was estimated to be 55% among US children (67% among children who followed a  vegetarian diet all their life versus 25% among other vegetarian children) and 50% among children of Asian Indian origin. B12 deficiency was defined as urinary  MMA >4.0 mmol/mol creatinine in the US study and serum MMA >430 nmol/L in the New Zealand study. Adolescents

Two of the reviewed studies assessed B12 deficiency  among children and adolescents (ages 9–15 years).11,28 In both cases, participants adhered to a macrobiotic diet in the first 6 years of their lives and subsequently switched to an LV, LOV, or omnivorous diet. Prevalence of deficiency  was 41% in one of the two studies,with deficiency defined as MMA >290 nmol/L; in the other study, deficiency  prevalence was 21% with deficiency defined as MMA >410 nmol/L. 111

Adults and the elderly

Twelve studies assessed B12 deficiency in non-pregnant adults, including young adults and the elderly.12,13,15–25 The prevalence of depletion or deficiency was reported as follows: 32% and 43% among young adult LVs or LOVs and vegans, respectively,with deficiency defined as MMA >271 nmol/L; 47% among raw food vegans, with deficiency defined as MMA >4.0  m g/mg creatinine; from 30% through 76% of adults depending on the definition of  deficiency (MMA >4.0  m g/mg creatinine versus MMA >0.260  m mol/L); and 90% among vegans (depletion defined as holo-TCII <35 pmol/L). Prevalence among  vegans in the United Kingdom was 11%. However, the criterion for deficiency used in this study was two to three times higher than in most other studies. Detailed features of the studies, including rates of  depletion and deficiencies, are listed in Table 1. DISCUSSION

In this review, the rates of B12 depletion and deficiency  were assessed through an evaluation of published studies that included participants adhering to different types of   vegetarian diets. One of the main findings is that vegetarians develop B12 deficiency (assessed with holo-TCII, MMA, or both) regardless of demographic characteristics, place of residency, age, or the type of vegetarian diet consumed. In the past, it was assumed that only strict  vegetarians (vegans) were at risk for B12 deficiency, but for some time now, and as this review confirms, it has been known that not only vegans commonly develop B12 depletion or deficiency.7,8,29 Depending on the criterion used, the prevalence of B12 depletion or deficiency  among vegetarians ranged from about 11 to 90%. Lower rates were reported in studies that used less stringent deficiency criteria (e.g., MMA >0.75  m mol/L vs >0.271  m mol/L) and in studies in which participants met two different deficiency criteria (e.g., low holo-TCII and elevated MMA). In three of the four studies that reported rates of depletion (low holo-TCII) and deficiency  (elevated MMA) separately, the rate was higher for holoTCII than for MMA. The deficiency rate among infants and children was at least equal to that of adults and the elderly. Higher rates were reported among children who followed a vegetarian lifestyle from birth, compared to those who adopted it later in life.17,23 This finding is likely due to low maternal B12 stores that resulted in low stored B12 in offspring during infancy and childhood. Two of the reviewed studies reported B12 deficiency  separately among LVs or LOVs and vegans.18,19 Herrmann et al. 200118 found that 32% of the LOVs and LVs were B12 deficient, while the rate was 43% among vegans. 112

Herrmann et al. 200319 additionally found that 31% of the LOVs and LVs who took B12-containing supplements were deficient, compared to 68% of LOVs and LVs who did not take such supplements. Surprisingly, the rate of  deficiency was higher among vegans who used B12containing supplements (88%) than among those who did not use them (83%). On the other hand, in a study by  Gilsing et al.,15 the prevalence of B12 deficiency was the lowest (11%) among vegans, 19% of whom used B12 supplements.15 However, Gilsing et al.,15 used the least stringent criteria of B12 deficiency (MMA >0.75 m mol/L  versus 271 nmol/L in several other studies). The fact that even supplement users were diagnosed with deficiency  may be due to two factors: 1) using them less frequently  than needed and 2) using supplements with a lower dose than needed to maintain adequate B12 status. While supplements have been shown to be effective in correcting B12 deficiency,10,12,30,31 according to one study, the dose of B12 in a supplement should be about 100 times higher than the RDA. 3 Also, in cases of deficiency, a dose thatis at least 200 times higher than the RDA may need to be ingested to achieve the most desirable results.32 Although B12 deficiency is associated with a host of  adverse symptoms, Herrmann et al.,17 indicated that none of the vegetarians included in their study had clinical symptoms despite the fact that about two-thirds of the sample had B12 depletion or deficiency, as indicated by  both low holo-TCII and elevated MMA.According to the stages of B12 deficiency developed by Herbert,9 although this is not always the case, clinical manifestations of B12 deficiency (stage IV) develop after biochemical deficiency  is present (stage III). In addition, Herbert suggested that low holo-TCII is an indication of B12 depletion and elevated MMA indicates a deficiency.9 Thus,symptoms of  deficiency, at least the severe symptoms, may not be seen with low values of holo-TCII or even in higher-thannormal values of MMA. However, one has to be careful with concluding that biochemical indicators of B12 deficiency in vegetarians are not associated with any adverse symptoms. Deficiency symptoms of this vitamin may be mild to severe. Mild symptoms, such as lethargy or forgetfulness may not even be detected or may be associated with other issues, such as aging or tiredness due to other reasons. One should also keep in mind that even some hematological symptoms, such as elevated mean corpuscular volume of erythrocytes, may not be shown in biochemical assessments. This is because such symptoms may be masked by either iron deficiency or high intake of  folate. Vegetarians are more likely to have both. In addition, Herbert suggested that while it may take a relatively  long time for B12 stores to be depleted, once depleted, symptoms of deficiency, of which some are irreversible, may occur rapidly.9 Furthermore, Herrmann and Geisel33 suggested that the function of B12-dependent enzymes, Nutrition Reviews® Vol. 71(2):110–117 

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    s     n     n     )     a     n     a     y     a      i      )     m     r     s     y     g     6     e     A      0    e      5      G     9      7    v   –      7   –      9      3     1      1     =     (      2      (      d      6      3      (      N    y     s     n     e     a     )     y     d     2      l     a     n     s     0    n     2     :     a     V      5    a     )     m    m     :     s     e      O      )      L      V    g     n    r     a     e     r     e      i      O    n     a     r      G    o    g     n     L     r     a     r      (     t      4     s     a     r     o      5     e      O     (  ,      L     s     e     g    s     g     e     n    n    e     a      V     v     a     a     g      L     a     n      6    g     i      4     a     n      i      9    e     d     n    a     3     d     v      I     =     e     =    e       N      M       N     M

     2     e     r      1     e      B     w      )     e      )     y     y     r     m      5    e      4     o      7    w      6      h   –       w     )      4    m      5     o      1      f     s     r      2      h      (     o    e     (     y     w     )     y      3    s     u      8     f     s      7      5      (     s      4    o    r      3     t     :      7     e     :     s     n     )     s     )      V    e     e     1     u    e      O    m    g     (     s     g      L     s     t     e     n     n    n     r      l     n     a     a     r     a     e     (     r     o    p     (     s     p    e     g     m     e     e     e      V     g     v     l      L     u     s     g     a     9     p    a      6     2     n     p    n      6     1     a     2     u    a     =     B    e     =    s     e       N      M       N      M

    m     o      d     g     n      i      K      d     e     t      i     n      U

    e      h     t     s      d     d     n    n     a     a     l     y     r     e     n     h     a     t     e     m     r      N     e      G

    n     a      i      d     n     I      )     a     n   -     s     t     n    n     m     r      i     a     r     e     s     a     y     g      G      (      A     i     n     n     d    m     a     n     a     m     m     r     a     i     m     e      O      G

    e      h     t     s      d     d     n    n     a     a     l     y     r     e     n     h     a     t     e     m     r      N     e      G

     l .     a     5     t     1     e     )      0     g     1     n     0      i      2     s     (      l      i      G

     l .     a     t     e      1     n     6     n     )     a     3      0      0     m     r      2     r      (     e      H

     l .     a     t     e      1     n     7     n     )     a     9      0      0     m     r      2     r      (     e      H

     l .     a     t     e      1     n     9     n     )     a     3      0      0     m     r      2     r      (     e      H

    o      h    n      )      1     w    a      )  .      6  ,  .      3     n    r      4      1      (     e     o   -      (     y     y     m    e     z     t      8      8     o     i  .  .     e     7    n     2     w    a     i     e     4     t     m      d     2     :     m     :     n    a     d     )      )     a      D    n     D     n     d    e      S      S      (     g    e     s     a     (     a     e      b     e    g     e     r     m     e       g     g     p    u     s     t     a     v     a     e      9    n    s     n     5     n      9    o    n    a     6     a     =    c     e     e     =    e       N      M       N     M

    a      i     p     o      i      h     t      E

    n     a     d      f      i     o     s     n     a      A      A     s      l      f      A     e     M     o     v     M      M     e      %      l      d     9     M     w    e     t     6    o     t     o      l     a     v     d    g      d     l     e    n    n     e     e    a     i     n     s     d      i     r      b     d    n     a     o      %     m    n     c     a      2     ;     o     I     m    c      I      7     c     I     r     a     I     :      %      C    e     s     C      I      I      0     d     T      G     n   -     f     a     T        C     6    a     o      i     o      T     :      l      h   -      A     o    o     d     l     o     o      %     n     h      l      h     %      I     o     M      5      6      H     M      5      6

     %      f      0     o      9      d      %     n      6     a      8     s      d      V     n      O     a     s      L     r      V     o      O     s      L     r      V     s     o      L      V      f     s     o      V      O      L     s      L     r     n      %      f     o    a      3    s     o     s     g      7     :     n     a     %    s     e      I      V      L     v      I     g     1      C    e     6    n      f      f     a     v     :     g     o    o      T   -      f      A     e     o      %      %      l     o     v      2     3     o      M      3     4      H      M

     2      1

     )      0      0      0      2      (     n     o     s      d      l     a     n     o      D

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     l .      3     a     1     t      )     e     5      l      0      0     e      2     s     (      i     e      G

     l .     a     4     t     1     e     )      8     n     0      0     o     s     (      2      b      i      G

     l .     a     t     e      1     n     8     n     )     a     1      0      0     m     r      2     r      (     e      H

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    y     c     n     e      i     c      fi     e      d      f     o     e     t     a      R

     %      f      6     o      2      1      7      B     r      d      %     n      4     e     n      7      i      h     a      A      i     t     m     s      d     t     a     M     e      V     n      (      i     v     M      O     a     s      (      d      %      L      V     r  .     n      8     o      O      %      2     a      2      L     s      3      4      L     r     :      V      /     o     :      L     y     y     l      %      f     c     o     c      %     s     o      V     n    m     n      2     1     e      3     8      L      i     e     p     )      i     :      %      f     c     :      A     c     0     L      /      fi     )      A      1     s     o      fi      l      5      6     n     e      M     :      %    s     e     1    o     d    n      I     o     M      M       <    m      i      I     a     g     7      d      M     r     e     e      l      C    e     5     n     a    t     e      m     l     e     y      T     r     v     :     g     i     t      b   -      f      i      4     a     n    v  .      i     r     m     s     o    o     A    e     e     0     u     n      l      fi     v      l     c     s     r      i     o      M     e     o     e     r      H      M      D      P      S     U

     L      /      l     o     m      L      /     n     t      d      l     o     1     n    e      7     :     e     s      I     m     u     I     p     2      C       >     m     a     T     s     :   -      5     s     i     r     o      3      A     e     e       <     s     t      l     s     i     r     o      M      A    c      H      M

     L      /      l      L     o      /      l     m     o      L      m      /      l     m      6     o      m     2  .     :      I      0     0      I     m      C    p      6       >      T     :      2  .     :   -      5      3     A     0     A     o      l       <     M      >     M     o      H      M      M

    s     s     a     l     e  ,      d     a     c     s      i     t      V    e     m     n     o      O      i      fi     9      b      L     e     4     o     r      d    ;     r     o     y     c      l     s     s     a      V     n     k     a     e      )     m      L     i     r     e      5     a     w      1     y     a      4      (     t      6      d  ,     e     ;     y     s     y      7     y  .     e     s     e     c     g      )     n     n    s     6     V      0      1      5     w    t     e    a     e     e     4     O     v      7      1     o     i      l   -     o     :      L     5      l   –      i     a   –    n     5     l      d    g      )   –     t     s     y     7     o    n    e     t      1    e  .      f      D     l      l     v     m    a     m     r      1     t     e      2      2      S     e     s     u      l     e     (     a     9     s      f      d    :     s      i     o    :      d    :      i     e     t     e      2     0     m     c     r     a     e      (      4     e     a     g     h     g     g     m    g     t     e     g     c      2      6      j     n     n      0     e     1     n     a  ,     n      1     a      2     a     b    g     1     d     i      d      8     a      1     r      4     r     u      1     n    t      7     r     a     n    n     s     e     e     e     v     a     e     a     a     =    g     =    g     l     =      l     e     =    e     g       N     A      N     A     A       N      M       N     A

    a     n      i      h      C

    g     n     o      K     g     n     o      H

    w     e      N      (     s     e     )     t     a     t      d     n      S     l     a      d    g     e     n     t      E      i     n      U

     1      2

     2      2

     3      2

    s     t     n     a     p      i     c      i     t     r     a      P

     l .     a     t     e      2     n     0     n     )     a     5      0      0     m     r      2     r      (     e      H

     L      /      l     o     m     n      1      7      2       >     :      A      M      M

    s     n     a      i     r     a     t     e     g     e     v     e     s     e     n      i      h      C     e     s      l     a     r     a     m    e     e     y      f      5      3     5      1       >      1     :     =    e     g       N     A

     )      )     y     y      6      1      6      7   –   –      0      5      3      2      (      (     y     n     y      4      0    e      4      5    m     :     s     )     :      )     e     V    e    o     g     O    g    w     n     L     n    e     a     s     (     r     r     a     r     s     r     e     s     n     o     (      i     a     a     e     s     e    n    e     g    g     V    g     h    y     e     a     L     a     C     5     v     n     4     n     9     5      0     i     a     1     a     1       >      5     d     1     i      d     1     :     =    e     =    e     =    e     g       N     M       N     M       N     A

     d     e     u     n      i      t     n     o      C     e     c       1     n     e      e     r       l     e       b      f      a     e       T      R

     %      5      7     :      %      I      I      6      C     7      T   -     :     o     A      l     o     M      H     M

     d     e     t     r     o     p     e     r     t     o      N

     d     e     t     r     o     p     e     r     t     o      N

    y     n     a     m     r     e      G

     L     :      l     :      /      l     o    e      A    o     A     e     m    n     n      M      i      /      M    m     g    n     l      i     n      M      i      m      M     y     m    t     o     i     t      4     a     m    a      /     r  .     m     a     g    e      0     r     m    e     u     n      m    r     c     0     c     r       >     i     r  .     e      S      U      4

    t     x     e     t     t     u      b      %      8      5     s     w     o      h     s     e     r      %     u     5     g     8      i      F     s  .     t     r     r     a     o     e     p      l     c     e     r     n      U

    a      h      d     g     t      h     n     r      i     t      i     ;     s     e      i     w     e      h     s  ,     t      h    n     w     h     s     n     d    a     s     t      h     o    a     e      h     n     w     t     o    t     n     n     o    m    n     e     e     o    m      7    r     c     n      2     m      d      i      1      f      l     m     s      8     o     i      9     4      h      4     c     t      7     f     e     d     o   –     n      i     e      3      8     a     2     d    t      i     r     n   –     :     a     n     d     4      1     i     e      f      h    o     :     e     p      d    e     s     r     m    o    t     e     t     e     d     r      l      0      l     u    m      i     a     3     o     t     t     o      d      h      A      C      N

    n     o      i     t     a     r     u      d     t     e      i      D

    y     r     t     n     u     o      C

114

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methionine synthase and methylmalonyl-CoA mutase, are already impaired at stage III deficiency. This may lead to a variety of problems, including hyperchomocysteinemia, which is associated with many health problems.2 Food sources of B12

The Institute of Medicine’s recommended dietary allowance (RDA) of B12 needed to meet an adult’s requirement as 2.4  m g per day. B12 is synthesized only by  microorganisms, and this is why natural food sources of B12 are limited to meats and foods of animal origin. Clams and beef liver are the highest sources of B12, containing about 84 and 71  m g of B12 in a 3 oz serving. 6 The amount of B12 found in a chicken varies from about 3.3  m g in the entire chicken liver to 0.03  m g in a chicken’s neck.6 Pork contains between 0.3 m g of B12 in each sausage patty to about 11.4  m g in pork liver.6 The content of B12 in fish ranges from about 9  m g in one half of a fillet of sockeye salmon to about 0.5  m g in a 3 oz serving of  yellowfin tuna.6 Vegetarian sources of B12 include milk, which contains between 0.3 and 0.4  m g/100 g of B12, with an absorption rate of about 65%. The B12 content of cheese or cottage cheese ranges from 20 to 60% that of milk. The amount of B12 in a whole egg is between 0.9 and 1.4 m g/ 100 g. B12 can be destroyed by heat and, thus, boiling milk can destroy 30–50% of B12, depending on the duration of cooking. 2,6,34 In the United States, many commercial food products are fortified with B12, including a variety of breakfast cereals, soy milk, and certain soy meat analogs. These foods contain B12 in amounts ranging from less than the RDA to more than 200% of the RDA. Supplements and fortified foods.  In the United States and some other countries, pharmacies and health food stores alike offer B12-containing supplements, mostly as cyanocobalamin. Other forms of this vitamin, such as methylcobalamin and hydroxycobalamin, are also available. The doses of cyanocobalamin used in supplements include 100, 250, 500, 1,000, 3,000 and 5,000  m g. Nutritional yeast may also be fortified with B12, and approximately two tablespoons typically contains the amount equal to the US RDA. Results of a study conducted by Donaldson12 showed, however, that supplements were more effective than nutritional yeast in correcting deficiency. Prevention and treatment of deficiency

Vegetarians have very limited and vegans have no food sources that naturally contain B12.2 Biochemical values of  B12 deficiency among vegetarians correlate with B12 intake.23,33 While it is theoretically possible to ingest an Nutrition Reviews® Vol. 71(2):110–117 

adequate amount of B12 from milk, dairy products, and eggs or from foods fortified with B12, not all vegetarians and few vegans consume the required amount of these products.Also, as indicated by this review, B12 deficiency  is common among people adhering to all types of vegetarian diets, which could indicate that adequate intake might be much harder to achieve than it may seem or that other factors, in addition to relatively low intake, play a role in deficiency development. It should be emphasized that a study performed in the New England region of the United Stated found that deficiency among macrobiotic  vegans reached 30% in adults and 55% in children. 23 This is important because many foods including cereal or soy  products are fortified with B12 in this country. Thus, while B12 deficiency can theoretically be avoided by consuming milk, dairy, eggs, foods fortified with B12 and by  using nutritional yeast, a prudent strategy to prevent B12 deficiency should include the use of B12 supplements. Supplements, when taken in an adequate dose, are very  effective in both the prevention and treatment of B12 deficiency and are very cost effective.12 However, many   vegetarians, for different reasons, refuse to take B12 supplements.29 This is largely due to various misconceptions, including the belief that it takes many years for B12 deficiency to develop.7 This belief assumes that most people have adequate stores of B129; however, this is very  unlikely, especially in long-term vegetarians and vegans. Results of studies that included either Asian Indians or children consuming a macrobiotic diet, with both groups consuming a vegetarian diet from birth, showed they had higher rates of B12 deficiency than subjects who adhered to vegetarianism for a shorter time period.17,25 Studies do not support the position that it takes up to 20 or 30 years to develop a deficiency.7 According to Donaldson,12 47% of the sample developed a deficiency, and most of these individuals had adhered to a raw vegan diet for between 23 and 49 months or about 2–4 years. In a study conducted by Herrmann et al.17 66% of German participants who had adhered to a vegetarian diet for at least 2 years were found to be B12 deficient. A healthy enterohepatic circulation is needed for efficient B12 absorption.9 B12 is secreted with bile and can be reabsorbed. As pointed out by Herbert,9 the rate of  reabsorption of B12 can reach up to 100%; however, B12 can only be reabsorbed in the presence of intrinsic factor. Vegetarians can be considered a group at high risk for atrophic gastritis, which affects intrinsic factor synthesis. This is, in part, due to the fact that vegetarians are at higher risk for iron deficiency. Iron deficiency can contribute to gastric mucosa damage, which leads to atrophic gastritis. Atrophic gastritis is associated with synthesis of  weaker hydrochloric acid and an inability to synthesize intrinsic factor. Both conditions can lead to a reduced or absent ability to absorb B12. 115

Many people who adopt a vegetarian or vegan lifestyle do so for health reasons. Since B12 deficiency is associated with higher risk of some of the very health conditions vegetarians are trying to avoid (e.g., occlusive  vascular disease, Alzheimer’s disease/dementia, osteoporosis, etc.),35,36 this knowledge might encourage vegetarians to take B12 supplements. Thus, public health campaigns targeting vegetarians should include messages conveying the risk of developing specific health conditions due to B12 deficiency. Some scientists have proposed that flour be fortified with B12. Fortification of flour with folic acid contributed to increases in the folic acid content of red blood cells, decreases in total homocysteine, and consequent reductions in rates of neural tube defects. 37 It is reasonable to assume that a similar preventive measure with B12 would have the same effect in terms of reducing rates of B12 deficiency. B12 deficiency is associated with a variety of  health issues, including low mineral density,17 increased risk for heart disease,35,36 and neural tube defects.35,36 Thus, the fortification of flour with B12 could prove to be the most cost-effective solution in terms of prevention of  these and other B12 deficiency-related symptoms and conditions.

4. 5.

6.

7. 8. 9. 10. 11.

12.

13. 14.

15.

16.

CONCLUSION

17.

The present review of the literature regarding B12 status among vegetarians shows that the rates of B12 depletion and deficiency are high. It is, therefore, recommended that health professionals alert vegetarians about the risk  of developing subnormal B12 status. Vegetarians should also take preventive measures to ensure adequate intake of this vitamin, including the regular intake of B12 supplements to prevent deficiency. Considering the low  absorption rate of B12 from supplements, a dose of at least 250  m g should be ingested for the best results.3

18.

Acknowledgments

24.

19.

20.

21.

22.

23.

25.

All authors met the authorship criteria specified in the guidelines for authors and no person was omitted from the list of authors.

26.

Declaration of interest.  The authors have no relevant interests to declare.

28.

REFERENCES

27.

29. 30.

1. 2. 3.

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