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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
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
Differential radioassay
the human body, in foods of animal origin (meat, poul-
TABLE 1
Cobalamin and analogue levels in 6-d 200 C-dehydrated feces collections from six men
Radioassay
Folate (g/24 h):
Patient L. /eichmanniit Corrimoids Cobalamins Analogues L casei
human stool is from analogues (Table 1). In this process age 60. We have calculated that everybody in the United
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
Hyp.rs.gmentation No No No No No Yb Yb
M.*ll4malonaI.+* No No No No No 1 Yb
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
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
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-