Vitamin B-i 2: plant sources, requirements, and assay

Victor Herbert, MD, JD

ABSTRACF Vitamin B-l2 is of singular interest in any discussion of vegetarian diets be-
cause this vitamin is not found in plant foods as are other vitamins. Many ofthe papers in the
literature give values of vitamin B-12 in food that are false because as much as 80% of the
activity by this method is due to inactive analogues of vitamin B-l2. Am J Clin Nuir
l988;48:852-8

KEY WORDS Vitamin B-l2, vitamin B-l2 analogues, corrinoids, cyanocobalamin,

vegans

Introduction tion with plant food is external contamination with bac-

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teria, often of fecal origin. In one of the less appetizing
Vitamin B-l2 is of singular interest in any discussion
but more brilliant experiments in the field of vitamin B-
of vegetarian diets because this vitamin is not found in 12 metabolism in the 50s, Sheila Callender (7) in En-
plant foods as are other vitamins. Confusion about what
gland delineated that human colon bacteria make large
sources may yield vitamin B-b2 to strict vegetarians has
amounts of vitamin B-b2. Although the bacterial vita-
arisen because the standard US Pharmacopeia (USP) as-
mm B-l2 is not absorbed through the colon, it is active
say for vitamin B-l2 does not assay only vitamin B-12
for humans. Callender studied vegan volunteers who had
(1). In the USP method the content of vitamin B-l2 of
vitamin B-l2 deficiency disease characterized by classic
any given food is determined by making a water extract megalobbastic anemia. She collected 24-h stools, made
ofthat food and feeding the extract to a bacterium (Lac- water extracts ofthem, and fed the extract to the patients,
tobacillus leichmannii). The quantity ofvitamin B-l2 is thereby curing their vitamin B-l2 deficiency. This exper-
determined by the amount of bacterial growth. The iment demonstrated clearly that 1) colon bacteria of veg-
problem is that what is active vitamin B-b2 for bacteria
ans make enough vitamin B-l2 to cure vitamin B-12 de-
is not necessarily active vitamin B-12 for humans (1-6).
ficiency, 2) the vitamin B-b2 is not absorbed through the
Many of the papers in the literature give values of vita-
colon wall, and 3) if given by mouth, it is absorbed pri-
mm B-l2 in food that are false because as much as 80% marily in the small bowel. Vitamin B-12 is one of those
ofthe activity by this method is due to inactive analogues
few nutrients absorbed primarily from the lower half of
of vitamin B-l2. In this paper we review the origins of
the small bowel (3, 4, 6).
vitamin B-l2 and its analogues, the effect of vitamin B-
12 structure on absorption, assay methods for the vita-
mm, and issues relating to the requirements for the Structure of vitamin B-12 and analogues
vitamin.
The structure of the vitamin B-12 molecule is shown
in Figure 1. This molecule (cobalamin) consists of four
Origins ofvitamin B-12
basic parts, the core of which is almost identical to the
There is no active vitamin B-12 in anything that grows heme ofhemogbobin, suggesting ontogenic development
out ofthe ground; storage vitamin B-l2 is found only in from the same precursor. This core structure (corrin)
animal products where it is ubiquitous and where it is differs from heme in only two things: the attached metal
ultimately derived from bacteria (1, 2, 4). All the vitamin in corrin is cobalt (it is iron in heme) and one ofthe alpha
B-b2 in plants is there fortuitously in bacteria contami- methene bridges(there are four in heme) is missing; there
nating the food. That contamination is usually on the are only three alpha methene bridges in the corrin nu-
outside of the plant but occasionally is internal. For cx- cleus. The corrin nucleus is the central structure of all
ample, in certain pulses in India in the nodules and on the corrinoids.
the root some bacteria ofthe rhizobium species grow and Corrinoids are cobalt-containing cyclic structures in
produce small amounts ofvitamin B-l2. They also pro-
duce analogues ofvitamin B-b2 (1, 4). From the Mt Sinai School ofMedicine, New York, New York.
The more frequent source of vitamin B-l2 in associa- 2 Reprints not available.

852 Am J C/in Nuir l988;48:852-8. Printed in USA. © 1988 American Society for Clinical Nutrition
 VITAMIN B-12: SOURCES AND REQUIREMENTS 853

charcoal columns contained cyanide, which exchanged

with the naturally present adduct groups attached to the
cobalt. The cyanide stabilized the vitamin B-12 mole-
cube, which otherwise is so unstable that exposure to light
alone can destroy it.
Cyanocobalamin is not vitamin active for humans un-
til the cyanide is removed within the body. This fact is
dramatically illustrated in the rare infant born with a de-
fect in the ability to enzymatically remove cyanide from
various substances. Such infants are unable to use cyano-
cobalamin as vitamin B-12 because they cannot remove
the cyanide from it (8). In fact, such infants, when they
(Factor Viol have a vitamin B-l2 deficiency, are made worse by giving
them cyanocobalamin because for them it acts as an anti-
metabolite. This was demonstrated by Rosenblatt and
his group at Yale Medical School (8) in studies of chib-
FIG 1. The structural formula ofvitamin B-l2. From reference 1. dren with genetic defects in vitamin B-l2 metabolism.

Differential radioassay
the human body, in foods of animal origin (meat, poul-

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try, eggs, fish, milk, and milk products), and in the bacte- How does one, then, differentiate the nonvitamin ana-
ria, which make not only vitamin B-b2 but also various bogues from the true B-12, which is vitamin active for
analogues thereof (1-6). Vitamin B-l2 and all its ana- humans, because it cannot be done by microbiologic as-
bogues are corrinoids. The human uses as vitamin B-b2 say? This is done by differential radioassay (1, 3, 6). The
only those corrin nuclei to which are added the three mixture of vitamin B-l2 and vitamin B-l2 analogues is
other basic parts ofthe cobalamin molecule: aminopro- assayed for the total content ofcorrinoids (ie, total B-12)
panol, sugar, and a nucleotide (5). To use it as a vitamin, by using a binder that attaches primarily to the cornn
the human cell must see it as depicted in Figure 1, ie, as nucleus. Such a binder is ubiquitous in human and ani-
a cobalamin with no alterations except in the R adduct. mal tissues; it is a heterogenous glycoprotein called R (for
Cobalamins remain vitamin active for humans with a rapid mobility on electrophoresis) binder. It is also called
variety of R adducts, which are named cobalamin with transcobalamin 1+111 (TC 1+111), haptocorrin, or coba-
whatever is attached to cobalt as a prefix. Thus, we have bophilin (4, 6). R binder attaches only to the corrin nu-
hydroxocobalamin (Fig 1), aquocobalamin, 5’-deoxy- cleus and thereby measures the total number of corrin
adenosylcobalamin, methylcobalamin, and cyanocobal- nuclei (true B-l2 plus noncobalamin analogues). Then
amin among the naturally occurring human-active and the vitamin B-12 active for humans (ie, cobalamin) is
potentially human-active forms ofvitamin B-12 in van- assayed by using a substance which attaches to both ends
ous foods. ofthe cobalamin molecule, the corrin end and the nude-
One can sequentially remove parts of the vitamin B- otide end. The substance that accomplishes this is intrin-
12 molecule, add side chains, or alter it in other ways. In sic factor (IF), first discovered by William Castle at Ha-
such cases it ceases to be a cobalamin and thus is not a yard and the molecule that makes it possible to absorb
vitamin for humans. However, it may remain a corn- free vitamin B-b2. This gastric parietal-cell secretion is a
noid vitamin for one or more ofa wide variety of simpler glycoprotein that attaches specifically to vitamin B-b2
life forms, such as algae and bacteria, which need only with a high affinity coefficient but does not attach to ana-
the corrin nucleus for vitamin activity in contrast to hu- bogues of vitamin B-l2 (9). When we use IF as a binder,
mans who need the entire cobalamin structure for vita- we essentially measure only the cobalamins in the mix-
mm B-12 activity. As noted, in addition to cobalamin, ture.
bacteria synthesize a number of vitamin B-12 analogues By subtracting the value for cobalamin determined us-
that are noncobalamin comnoids and therefore not vita- ing pure IF(true B-l2) from the value for total corrinoids
mm active for humans. determined by using R binder (total B-l2), we determine
the amount of analogues by difference, hence the term
Cyanocobalamin is stable but not vitamin active differential radioassay of analogues.
(noncobalamin) analogues = total B-l2
Cyanocobalamin is the form in most pharmaceutical
preparations because adding cyanide stabilizes the mole- -trueB-l2 (1)
cube. This was accidentally learned when vitamin B-l2
was first isolated in the eluate from charcoal columns (4). Fecal contamination as a vitamin B-12 source in vegans
The fortuitous reason that the beautiful red crystalline
cobalamin structure came out of the charcoal columns When we apply differential radioassay to human stool,
intact, but not out of other columns, was because the we find that an enormous amount of vitamin B-l2 in
854 HERBERT

TABLE 1
Cobalamin and analogue levels in 6-d 200 C-dehydrated feces collections from six men

Feces 8-12 (pgJ24 h)*

Radioassay
Folate (g/24 h):
Patient L. /eichmanniit Corrimoids Cobalamins Analogues L casei

1 32.9 52.9 1.7 51.2 94.5

2 37.36 70.3 1.1 69.2 61.3
3 31.4 103.3 1.6 101.7 150.7
4 12.5 29.8 2.1 27.7 230.7
5 72.9 1 14.8 12.8 102.0 576.7
6 28.1 46.3 0.6 45.7 56.8
i±SEM(g/24h) 35.6 ±20.0 69.5 ±13.6 3.31 ±1.08 66.25±12.5 195.11±80.8
j: SEM (ILg/g) 1.83 ± 0.52 3.63 ± 0.33 0.159 ± 0.068 3.47 ± 0.32 10.53 ± 3.66
* The dehydration process destroys approximately one-third each of cobalamim and analogues as compared with fresh (refrigerated) feces.
Therefore, actual content is 150% ofthe values in the above table. Reprinted from reference 1.
t Not alkali boiled. Boiling in alkali destroys --85% ofstool growth activity for L leichmannii(ie, -.‘85% is 8-12 by L /eichmannii assay).

human stool is from analogues (Table 1). In this process age 60. We have calculated that everybody in the United

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24-h stools are collected over 6 d and dehydrated down States will develop vitamin B-12 deficiency by age 127;
to a few ounces of powder. These results represent two- it will be difficult to prove us wrong!
thirds ofthe vitamin B-12 and analogue content because The sequence ofevents in developing vitamin B-l2 de-
approximately one-third ofeach is destroyed in the dehy- ficiency is indicated in Figure 2 (12). Long before gastric
dration procedure. Correcting for this loss, we find that IF is lost we lose our gastric acid and gastric digestive
normal, 24-h human stool output contains 100 g of - enzyme secretion and the ability to absorb vitamin B-12
total B-12 (vitamin B-12 plus analogues) of which only from foods. This is because vitamin B-l2 is peptide
,-,.,5 g is cobalamin (vitamin B-l2-active for humans) bound in milk and all other foods. To be absorbed, the
and 95% are various analogues (1). vitamin must first be cleaved from its peptide bonds.
From Callender’s work we know that a water extract This cleavage is brought about by gastric acid and diges-
of stool will correct human vitamin B-b2 deficiency. tive enzymes.
Therefore, although about 19 out of 20 B-l2 molecules Negative vitamin B-l2 balance characterized by the
in the stool are not active vitamin B-12, these analogues inability to absorb vitamin 8-12 from food can be diag-
do not block the absorption of that one vitamin B-l2 nosed by a food Schilling test (ie, vitamin B-l2 in an om-
molecule when gastric intrinsic factor secretion is nor- elet is not absorbed). Doscherholmen (3, 13) showed that
mal. However, some analogues do compete with vitamin the inability to absorb vitamin B-b2 from food can occur
B-l2 for absorption and may block residual vitamin B- in a 1-3 y period during which crystalline vitamin B-l2
12 absorption when it is already impaired (3, 10). is still normally absorbed (ie, the standard Schilhing test
The fact that stool vitamin B-l2 can be important in gives normal results). This occurs because there is still
human vitamin B-l2 economy was delineated by James substantial IF secretion but the gastric acid and enzyme
Halsted (1 1) working with Iranian vegans who did not secretion has been lost. It only takes -‘-20% ofnormal IF
get vitamin B-b2 deficiency. It was difficult to under- secretion for normal absorption of0.5-l.5 g vitamin B-
stand why these people, who were strict vegetarians (veg- 12(3,6).
ans) for religious reasons, did not get vitamin B-l2 defi-
ciency. Halsted went to Iran and found that they grew
B-12 produced by intestinal bacteria
their vegetables in night soi/(human manure). The vege-
tables were eaten without being carefully washed and the What is the role of intestinal bacteria above the colon
amount of retained vitamin B-l2 from the manure-rich in vitamin B-l2 absorption? We have seen that the 5 ig
soil was adequate to prevent vitamin 8-12 deficiency. of vitamin B-l2 made by colon bacteria per 24 h is of
Thus, strict vegetarians who do not practice thorough little, ifany, value to individuals unless they ingest some
hand washing or vegetable cleaning may be untroubled of their own feces because vitamin B-12 is not absorbed
by vitamin B-l2 deficiency. across the colon mucosa. If one takes gastric aspirates
from humans and looks for quantities ofviable bacteria,
Limitations of the standard Schilling test one finds that as the gastric pH becomes closer to neutral
the quantities of bacteria gradually increase (1). In the
As we get older we gradually develop, on a genetically normal, healthy, acid-secreting stomach, there are very
determined basis, gastric atrophy. About 1 person in 100 few bacteria. As we grow older and our gastric acid secre-
has vitamin B-l2 deficiency through gastric atrophy by tion decreases, gradually more bacteria grow in our
 VITAMIN B-l2: SOURCES AND REQUIREMENTS 855

Stage:
Uv B,2
Excess
uznEes4
Positive
Balance
B,2
Norm
Negative
Balance
B,2 B,2 B,2 -Deficient
_
B,2 -Deficiency
Anemia

HOIOTC II

RBC+WBC B,2

HIoTCII(pn) >50 >40 >30 ‘#{176} <12 <12

TCII%sat. >5% >5% >5% l_<5s I _______

<2% <1% <1%

Haloh(pg/M) >500 >300 >150 >150

1<150 1 <100 <100

dU Suppression Normal Normal Normal Normal Normal Abnormal Abnormal

Hyp.rs.gmentation No No No No No Yb Yb

TBnIt%$at. >50% >40 >15% >15% >15% <15% <10%

H % s. >50% >40 >20% >20% >20% <20% <10%

RBCFolate(ng/mI) >160 >160 >160 >160 >160 <140 <100

Erihrocyt.s Normal Normal Normal Normal Normal Normal Mwoovalocytlc

MCV Normal Normal Normal Normal Normal Normal EI#{149}vatsd

H.moob Normal Normal Normal Normal Normal Normal Low

TC II Normal Normal Normal Normal Normal Elevatsd Elsvatsd

M.*ll4malonaI.+* No No No No No 1 Yb

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MyalIn Damage No No No No No Friquint

FIG 2. Sequential stages ofvitamin B-12 status. sCyanocobalamin excesses (injected or intranasal) produce tram-
sient rise in B-l2 analogues on B-l2 delivery protein (TC II); the significances of rises is unknown. tTBBC, total
B-l2 binding capacity. tIn serum and urine. From reference 12.

stomachs and upper small bowel(Fig 3)(1). This is a very cum where we have the highest colony count before the
interesting phenomenon and we need to explore whether colon. Of particular importance may be bacteroides,
these bacteria release any unbound vitamin B-b 2. which are present in the upper halfofthe small intestine
The average American omnivore or vegetarian who is and which make both vitamin B-l2 and analogues. Al-
not a vegan get vitamin B-l2 from food in which the vita- bert, Mathan, and Baker(1 5) found that Lactobaciii, the
mm B-b2 is peptide bound. There is adequate vitamin streptococci, the bacteroides, and other enteral bacteria
B-12 in milk or milk products for the needs ofany person in the small intestine made primarily vitamin B-12.
with normal gastric, pancreatic, and intestinal secretions However, their studies used microbiologic assays with
and functions. However, as noted, a negative vitamin B- organisms that grow on some noncobalamin comnoids.
12 balance may result when those secretions are de- It is thus uncertain how much ofthose bacterial products
creased. Thus the potential contribution of gastric and were cobalamin rather than noncobalamin comnoids.
small intestine bacteria to overall vitamin B-b2 nutriture
is of interest.
There is normal distribution of viable bacteria in the Enterohepatic circulation of vitamin B-i 2
small intestine and the quantity ofbacteria increases pro-
The enterohepatic circulation of vitamin B-12 is of
gressiveby (Fig 4) (1) down the small intestine to the cc-
crucial importance in human vitamin B-12 economy
particularly for vegetarians (4, 6). The reason is that any-
L -I/---- where from 1 to 10 ig of vitamin B-l2 is secreted in the
9-
08-

+ 5

<: I

Cstrc
Gastric pH oChiOrhydro
Duodenum Jeunum Itsum
Lscloboc.II. S*’co’ cwrs (,w,obw.o (Mswbscwb Dw*1*o bhdsbicIs,w
FIG 3. Increasing stomach bacteria with decreasing gastric pH.
From reference 14. FIG 4. Flora ofthe small intestine. From reference 14.
856 HERBERT

down into the ileum, where it attaches to specific recep-

tors for the vitamin B-b2-IF complex (Fig 5) and is then
absorbed (9).
Pancreatic secretion not only digests the R binder and
releases the food vitamin B-b2 but also digests the R
binder that comes out in the bile with vitamin B-l2 at-
tached to it, thereby allowing that vitamin B-12 also to
migrate to IF and then be absorbed across the ileum (16).
Thus, a healthy pancreas is ofcrucial importance in the
absorption ofvitamin B-b2 (17).
The ileal receptor is not just for IF but, as we showed
25 y ago, is a key-and-lock receptor for the complex of
vitamin B-l2 and IF. That is a very important distinction
because the receptor is for the complex and there can be
some absorption ofvitamin B-l2 (an incomplete key) in
the absence of IF and there is evidence that does in fact
occur. This direct vitamin B-l2 absorption can be
blocked by analogues and is an area of active research
right now (3). Shaw delineated that the main site of ab-
FIG 5. The ileal vitamin B-12-intrinsic factor(IF) receptors. sorption of analogues is in the ileum just as is the main
site ofabsorption ofvitamin B-12 itself(18).

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There are two separate mechanisms for vitamin B-12
bile each day. Nobody needs > 1 jzg vitamin B-b2/d. We absorption: the IF-dependent physiologic mechanism
normally reabsorb much of the vitamin B-b2 in bile se- and the mass-action pharmacologic mechanism whereby
cretions. In addition, enterohepatic circulation has the 1% of any quantity of free vitamin B-b2 is absorbed by
effect of removing unwanted analogues from the body, diffusion across the ileum (Table 2) (1, 4, 6).
returning vitamin B-12 relatively free of analogues (3,
16, 17).
The vegetarian often may be getting more vitamin B- Needed dietary intake of vitamin B-i2
12 by reabsorption from bile than from external foods. How much vitamin B-12 do we need? No more than
This would be true for those who eat very little animal g daily (2). Figure 6 is the laboratory
1 data ofan mdi-
protein. The reabsorption of bile vitamin B-b2 explains vidual, aged 54 y, with relatively early pernicious anemia
why it takes -20 y to run out of vitamin B-12 and get
(PA), the form of vitamin B-b2 deficiency disease that is
vitamin B-b2 deficiency disease after one stops consum-
due to inadequate or absent secretion of gastric IF. This
ing dietary B-b2 but only 3 y to run out and get vitamin individual, when given just 1 g cyanocobabamin/d by
B-l2 deficiency disease if one stops absorbing the vita- injection, had a beautiful hematobogic response with a
mm (3, 4, 6).

TABLE 2
The mechanism of vitamin B-i 2 absorption
Absorption of2 vs 30 g oral cyanocobalamin without vs with
intrinsic factor’
In the average omnivorous American diet there are 5-
15 tg of vitamin B-12 (2). The food vitamin B-b2 has to Vitamin B-l2 in 48-h urinet
be removed from its peptide bonds in the food by prote-
ases and acids in the stomach. When removed from food, After2goral After 30 igoral
it does not immediately attach to IF but rather to the cyanocobalamin cyamocobalamin

ubiquitous R binder, which has a higher affinity for corri- Subject B-l2 B-l2+IF B-12 B-l2+IF
noids (including cobabamin) than does IF. Because we all
regularly swallow our own saliva, and saliva is loaded I 0.02 0.36 0.24 0.18
with R binder, the vitamin B-b2 split from peptides in 2 0.01 0. 17 0.44 0.45
3 0.01 0.35 0.48 0.60
our food attaches to R binder and not to IF. Similarly,
4 0.02 0.14 0.16 0.24
the vitamin B-b2 secreted in bile (along with analogues)
5 0.01 0. 1 1 0. 12 0.27
is attached to R binder. Vitamin B-12 cannot be ab-
sorbed or reabsorbed as long as it is attached to R binder. Average 0.02 0.23 0.29 0.35
The pancreas secretes proteases which, at the slightly C When 2 or 30 g ofB-l2 is fed to patients with pernicious anemia,
alkaline pH of the upper intestine, selectively digest the there is - 1% urinary excretion in a Schilling test (suggesting ‘-3%
R binder, releasing its vitamin B-12, which then for the diffusion absorption?) Reprinted from reference 1.
first time is taken up by the dilute-alkali-resistant IF not t Flushed into urine in 48 h by injection of 1 mg nonradioactive
in the acidic stomach but in the mildly alkaline upper cyanocobalamin at 0 time and again at 24 h after the oral dose of B-12.
small bowel. The vitamin B-12-IF complex then passes IF, hog intrinsic factor concentrate.
 VITAMIN 3-12: SOURCES AND REQUIREMENTS 857

PLASMA IRON (yiq/l00 ml) 1401 8 42 for vitamin B-12 are lower than previous recommenda-
PLASMA FOLATE (nuq/mI) 47 22 21 7. 5.3
tions (2).
LASMAT.
.!_#s,s!.) 24 26 Se ase 571 348

Sources of vitamin B-i 2

Fermented products, such as soy products bike tem-

24 peh, do not contain substantial amounts ofB-b2 (1). The
amounts given on the labels cannot be trusted because
they were obtained by the US Pharmacopeia (USP) assay
method, which sellers ofproducts containing vitamin B-
12 are required to use.
The label-stated content of vitamin B-l2 is in fact the
content of all comnoids in which L leichmannii grows
and not just cobalamin. It should say corrinoids rather
than vitamin B-12. The Food and Drug Administration
W.M. 54;78kq
t!oMl.AMlN (I4 dolly, l.rn.)I (FDA) was petitioned several years ago to require vita-
PERNICIOUS -IS -10 -5 0 5 0 15 20 25 mm B-b2 assay for true vitamin B-12 and analogues and
ANEMIA I TIME (Days)
-Word D..t-..4-.--DIst Dsvoid Of Fruit Juics, FrssliVsg.,LIvsr perhaps the assay will eventually be changed.
We studied several types oftempeh, including Original

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FIG 6. Excellent hematologic response ofpatient with vitamin B-12 Soy Tempeh, a Rhizobus oligosporus culture with a label
deficiency (pernicious anemia) to I pg/vitamin B-l2/d. (To convert
claim of 160% of the US RDA for vitamin B-12 per 4
gFe/l00 mL to imol/L, multiply by 0.1791. To convert mg folate/
oz. Using the differential radioassay we found there was
mL to nmol/L, multiply by 2.266. To convert pg vit B-12 to pmol/L,
multiply by 0.7378.)
practically no vitamin B-l2 in it (1).
We also studied most of the spirulinas sold in health
food stores as sources ofvitamin B-12; there is practically
no vitamin B-l2 in them. The so-called vitamin 8-12 is
sharp increase in very young red cells and reticulocytes
almost exclusively analogues of vitamin B-b2 and we
and a rise to normal in red cell count, hemoglobin, and
have extracted the two largest peaks of analogues and
hematocrit. Characteristically, as happens when one
they actually block vitamin B-12 metabolism. We sus-
treats vitamin B-12 deficiency, the serum Fe plummets,
pect that people taking spirulina as a source of vitamin
in this case from 180 to 8 over the first 10 d, as the plasma
B-12 may get vitamin B-12 deficiency quicker because
Fe is drawn into the formation of new hemoglobin for
the analogues in the product block human mammalian
the new red cells.
cell metabolism in culture and we suspect they will also
Nobody needs more than 1 zg/d because 1 &g would
do this in the living human. Remember that the label
actually treat and return to normal people with no stores claim of vitamin B-12 is actually a claim of comnoid
of vitamin B-12 (2). The average omnivorous human, if content, not vitamin B-12 content.
one does sequential studies each decade, has a progres- The vegan diet, if it is a diet exclusively of products
siveby rising liver level of vitamin B-b2 throughout life, that grow out ofthe ground, which are then well washed,
indicating the average omnivore is eating much more vi- contains no vitamin B-12 except trace amounts in some
tamin B-12 than needed and is in continuous positive rhibozium-bacteria-containing root nodules. Careful
balance and progressively storing the excess. There is studies from England (19) on several hundred vegans
nothing about continuous positive balance that is inher- showed that they all eventually get vitamin B-l2 defi-
ently desirable (12). ciency disease with anemia and pancytopenia, low white
What is the minimal daily amount we need? Less than counts, low red counts, low platelet counts, and slowed
1 g. In studies carried out at Harvard with then research DNA synthesis (19). Vegans all eventually have slowed
fellow Louis Sullivan, we showed that one can treat vita- DNA synthesis, which is corrected by vitamin B-12. My
mm B-12 deficiency with as little as 0. 1 tg/d (2). At this advice to the vegan parents of a vegan child is that you
bevel stores are not rapidly replenished and the response have to provide a supply of vitamin B-l2. Yeast grown
is submaximal but it only takes 0. 1 g to produce a re- on vitamin B-b2-enriched medium is only the answer
sponse. when some of the vitamin B-12-enriching medium is
The minimum daily requirement (MDR) for vitamin mixed in with the yeast that is eaten because the yeast
B-12 to sustain normality is probably in the range of itselfdoes not contain active vitamin B-b2; it contains a
.-0. 1 tg, 0.2-0.25 tg/d absorbed from food is probably lot ofanalogues but not active vitamin B-12. Differential
adequate for anybody (2). There are no objective pub- radioassay show that all the vitamin B-b2 is accounted
lished data that larger amounts ofvitamin B-b2 have any for by vitamin B-12-enriched medium rather than by
added value for greater health or longer life. The current the yeast itself. Vegans must get a source for vitamin B-
Canadian Recommended Dietary Allowances (RDA) 12. It can be 1 tg/d of vitamin B-12 in a tablet or in
and the recent Recommended Dietary Intakes (RDI) something else but it has to be cobabamin.
858 HERBERT

Bindra et al (20) note that vegetarians who boil their balamin but about 100 pg of apparent analogue (and 200 g of
milk before drinking may destroy much ofthe milk vita- folate). Trans Assoc Am Phys l984;97: 161-71.
mm B-l2 and place themselves at risk; they also sug- 2. Herbert V. Recommended dietary intakes (RDI) ofvitamin B-l2
in humans. Am J Qin Nutr l987;45:671-8.
gested that the high dietary fiber levels of Punjabi diets
3. Herbert V. The 1986 Herman Award Lecture. Nutrition science as
may increase fecal excretion ofvitamin B-b2 (20).
a continually unfolding story: the folate and vitamin B-l2 para-
digm. Am J Oin Nutr 1987;46:387-402.
Vitamin B-i2 as snake oil 4. Herbert V, Colmam, N. Folic acid and vitamin B-12. In: Shils M,
Young V, eds. Modern nutrition in health and disease. 7th ed. Phil-
Just before this conference, Time magazine inquired adeiphia: Lea & Febiger, 1988:388-416.
about the latest California health food fad: sniffing vita- 5. Herbert V. Vitamin B-l2. In: Olson RE, ed. Present knowledge in
nutrition. 5th ed. Washington, DC: Nutrition Foundation, 1984:
mm B-l2 gel up the nose. Like most health food fads,
347-64.
it was created by entrepreneurs with heavy advertising
6. Herbert V. Biology ofdisease: megaloblastic anemias. Lab Invest
budgets and light consciences. The heavily promoted fad 1985;52:3-19.
moved east to just about every health food store across 7. Callender ST, Spray, OH. Latent pernicious anemia. Br J Haema-
the United States. Given a deceptive name suggesting en- tol l962;8:230-40.
ergy, it is falsely represented as giving an energy boost, 8. CooperB, Rosenblatt D. Inherited defectsofvitamim B-l2 metabo-
which, ofcourse, is biochemically impossible because vi- lism. Ann Rev Nuts l987;7:29l-320.
tamin B-12 neither supplies nor releases energy except in 9. Cannel R, Rosenberg AH, Lau K-S, StreiffRR, Herbert V. Vita-
the vitamin B-12--deficient individual. Vitamin 8-12 is mm B-l2 uptake by human small bowel homogenate and its en-
involved in intermediary metabolism as a catalyst much hancement by intrinsic factor. Gastroenterology l969;56:548-55.
10. Kanazawa 5, Kondo H, Terada H, Okuda K. R-binder blocks co-

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bike a traffic cop at an intersection.
balamin analogue binding to intrinsic factor-cobalamin receptor.
Like many other pharmaceutical agents, vitamins are
Fed Proc l984;43:1859(abstr).
absorbed better through the nasal mucosa than through 1 1. Halsted JA, Carroll J, Rubert S. Serum and tissue concentration of
the alimentary mucosa. However, the increased percent- vitamin B,2 in certain pathologic states. N Engl J Med l959;260:
age absorption of vitamin B-l2 through the nasal route 575-80.
is of no value whatsoever to the person with a normal 12. Herbert V. Stating nutrient status from too little to too much by
serum vitamin B-b2 level. All that vitamin B-l2-normal appropriate laboratory tests. In: Livingston GE, Vanderveen JE,
people get from wasting their money on vitamin B-12 IaconoJM, eds. Nutrition statusassessment ofthe individual. New
nasal gels is expensive urine. In addition, the gel may be York: American Health Foundation (in press).
allergenic for some. Nasal gel vitamin B-l2 gets no more 13. Doscherholmen A, McMahom J, Ripley D. Inhibitory effect of eggs
on vitamin B-l2 absorption: description of a simple ovalbumim
vitamin 8-12 into the bloodstream than a 10-fold greater
“Co-vitamin B-l2 absorption test. Br J Haematol 1976;33:261-
oral dose and may not be as reliable as injected vitamin
72.
B-l2 (2 1). The FDA has been petitioned to stop the sale 14. Drasar, BS, Hill MJ. Human intestinal flora. New York: Academic
ofthe gel as a food supplement. Press, 1974.
What is the RDA for vitamin 8-12? The suppressed 15. Albert Mi, Matham VI, Baker Si. Vitamin B-l2 synthesis by hu-
(3) 1980-85 RDA appears in the April 1987 issue of the man small intestinal bacteria. Nature l980;283:781-2.
American Journal of Clinical Nutrition (2) as the RDI 16. Kamazawa S, Herbert V. Mechanism ofenterohepatic circulation
(for which read “ 1985 RDA”) for vitamin B-l2. RDI is ofvitamin B-l2; movement ofvitamim B-l2 from bile R-binder to
the international term used by the World Health Organi- intrinsic factor due to the action ofpancreatic trypsin. Trans Assoc
zation (WHO) and many other countries. RDA is a term Am Physicians 1983;96:336-44.
17. Hei-zlich B, Herbert V. The role ofthe pancreas in cobalamin (vita-
used primarily in the United States. We (the 1980-85
mm B-l2) absorption. Am J Gastroenterol l984;79:489-93.
RDA Committee) reduced the RDA for vitamin B-l2 to
18. Shaw 5, Meyers S, Colman N, Jayatilleke E, Herbert V. The ileum
2 ig for adults (which is still more than anybody needs) is the major site ofabsorptiom ofvitamin B-l2 analogues. Fed Proc
because there was no scientific basis for higher amounts l987;46:(abstr).
(2). As delineated above, nobody needs that much, there 19. Chanarim I, Malkowska V, O’Hea A-M, Rinsler MG, Price AB.
is no evidence that it has any value whatsoever for hu- Megaloblastic anemia in a vegetarian Indian community. Lancet
mans and, as we discover more and more about excesses l985;2:l 168-72.
ofany nutrient, we discover hams we did not know cx- 20. Bindra OS, Gibson R, Berry M. Vitamin B-l2 and folate status of
isted (12, 21, 22). It will probably turn out eventually that East Indian immigrants living in Canada. Nutr Res(in press).
too much vitamin B-b2, like too much of anything, is 21. Herbert V, Stopler T, Huebscher T. Nasal vitamin B-12 gel may
not be a reliable alternative to injectable vitamin B-l2; both bind
harmful(l2).
preferentially to TC II and produce analogue incrementjust on TC
II. Blood l987;70(suppl):45A(abstr).
References 22. Herbert V. The inhibition of some cancers and the promotion of
others by folic acid, vitamin B-l2, and theirantagonists. In: Butter-
1. Herbert V, Drivas 0, Mamusselis C, Mackler B, Eng J, Schwartz E. worth CE Jr, Hutchinsom ML, eds. Nutritional Factors in the In-
Are colon bacteria a major source of cobalamim analogues in hu- ductiom and Maintenance of Malignancy. New York: Academic
man tissues? 24-hour human stool contains only about 5 sg of co- Press, 1983:273-87.