UNIVERSE SCIENCE EXPLORATION

ABSTRACT
This document serves to counteract the problems of vitamin
B12 being faced by people of today. It therefore gives quality
information on vitamin B12 for academic and professional
use. This article covers the introduction, dietary sources,
digestion and absorption, functions, symptoms, deficiency
and recommendations.

BY: KUMBIRAI GWAMANDA

VITAMIN B12
You are what you digest and absorb not what you eat.
Edited by: Ashbold J Tembo & Munyaradzi Nhambure
ACKNOLEDGEMENTS

I would like to thank the co-founders of Universe Science Exploration (UScE), Ashbold John
Tembo and Munyaradzi Emmanuel Nhambure for the undying support they gave to me
during the compilation of this document.

VITAMIN B12

INTRODUCTION

Vitamin B12 (Cobalamin) is a water soluble vitamin with the molecular formula
C63H88CoN14O14P. It comprises of a tetrapyrrol ring structure with a central cobalt ion.
Methyl-cobalamin is the transport and coenzyme form whereas Adenosyl-cobalamin is the
storage and coenzyme form. It possesses the following properties;

i) Absorbs directly into the blood stream by endocytosis.

ii) Transported freely in the blood stream.

iii) Circulate freely hence it is not stored therefore there is need to be taken every 2-3 days to

avoid deficiency.

iv) Toxicity levels are reached when supplemented.

DIETARY SOURCES

Table 1: Recommended Dietary Allowances (RDAs) for Vitamin B12

Age Male Female Pregnancy Lactation
0–6 months* 0.4 mcg 0.4 mcg
7–12 months* 0.5 mcg 0.5 mcg
1–3 years 0.9 mcg 0.9 mcg
4–8 years 1.2 mcg 1.2 mcg
9–13 years 1.8 mcg 1.8 mcg
14+ years 2.4 mcg 2.4 mcg 2.6 mcg 2.8 mcg
Vitamin B12 is naturally found in animal products richly in organ meats, including fish,
meat, poultry, eggs, milk, and milk products. Vitamin B12 is generally not present in plant
foods, but fortified breakfast cereals are a readily available source of vitamin B12 with high
bioavailability for vegetarians. Some nutritional yeast products also contain vitamin B12.
Fortified foods vary in formulation, so it is important to read product labels to determine
which added nutrients they contain.

DIETARY SUPPLEMENTS

In dietary supplements, vitamin B12 is usually present as cyanocobalamin, a form that the
body readily converts to the active forms methylcobalamin and 5-deoxyadenosylcobalamin.
Dietary supplements can also contain methylcobalamin and other forms of vitamin B12.

Existing evidence does not suggest any differences among forms with respect to absorption
or bioavailability. However the body’s ability to absorb vitamin B12 from dietary
supplements is largely limited by the capacity of intrinsic factor. For example, only about 10
mcg of a 500 mcg oral supplement is actually absorbed in healthy people.

In addition to oral dietary supplements, vitamin B12 is available in sublingual preparations as

tablets or lozenges. These preparations are frequently marketed as having superior
bioavailability, although evidence suggests no difference in efficacy between oral and
sublingual forms.

PRESCRIPTION MEDICATION

Vitamin B12, in the form of cyanocobalamin and occasionally hydroxocobalamin, can be

administered parenterally as a prescription medication, usually by intramuscular injection.
Parenteral administration is typically used to treat vitamin B12 deficiency caused by
pernicious anaemia and other conditions that result in vitamin B12 mal-absorption and severe
vitamin B12 deficiency.

Vitamin B12 is also available as a prescription medication in a gel formulation applied

intranasal, a product marketed as an alternative to vitamin B12 injections that some patients
might prefer. This formulation appears to be effective in raising vitamin B12 blood levels,
although it has not been thoroughly studied in clinical settings.

DIGESTION AND ABSOPTION

Vitamin B12 is found in protein rich foods mostly of animal origin. Enzymatic protein
digestion starts in the stomach. Stomach pH is acidic and ranges from 1 to 3. Pepsinogen
from chief cells is converted to pepsin by HCl produced by the parietal cells. Pepsin optimal
pH is 2. During protein digestion pepsin breaks peptide bonds between tyrosine and
phenylalanine amino acids producing peptide fragments and few amino acids thereby
releasing the vitamin B12.

In the mouth during mastication, vit B12 is partially digested and a link (B12-R protein) is
formed. R protein is produced by salivary glands and it helps protect vit B12 from intestinal
bacteria. In the small intestines R protein is released by trypsin from the pancreas. Salivary
glands also secrets Haptocorin/a-binda/trans-cobalamin 1 which then travels to the stomach.
Pepsin then liberates vit B12. Liberated vit B12 have high affinity for trans-cobalamin in the
stomach. A complex of trans-cobalamin 1-VB12 complex is thus formed, which then travels
to the duodenum. Parietal cells in the stomach also releases intrinsic factor and is also active
in the duodenum. Proteases from the pancreas breaks down the Ab-VB12 complex and
liberates the vit B12 again. Now in the duodenum liberated vit B12 has high affinity for
intrinsic factor. A VB12-IF complex is thereby formed and it travels towards the ileum. The
ileum has intrinsic factor binding receptors. The complex is endocytosed and absorbed into
the plasma, and approximately 56% is absorbed. When released in the plasma 20% of the vit
B12 binds to trans-cobalamin 11, and 80% remains bound to trans-cobalamin 1. Trans-
cobalamin 11 is responsible for delivering vit B12 to body tissues. Trans-cobalamin 1
remains in circulation and rendering for cellular delivery by trans-cobalamin 11.

FUNCTIONS

Vitamin B12 is required for proper red blood cell formation, neurological function in
myelination, and DNA synthesis. Vitamin B12 functions as a cofactor for methionine
synthase and L-methylmalonyl-CoA mutase. Methionine synthase catalyses the conversion of
homocysteine to methionine. Methionine is required for the formation of S-
adenosylmethionine, a universal methyl donor for almost 100 different substrates, including
DNA, RNA, hormones, proteins, and lipids. L-methylmalonyl-CoA mutase converts L-
methylmalonyl-CoA to succinyl-CoA in the degradation of propionate, an essential
biochemical reaction in fat and protein metabolism. Succinyl-CoA is also required for
haemoglobin synthesis.

DEFICIENCY
Humans do not have the bacteria which synthesises vit B12 hence it is regarded essential.
Due to this and the fact that it is a water soluble vitamin humans are susceptible to its
deficiency. The deficiency of vit B12 / Hypocobalaminemia refers to the reduced blood
levels. The most common causes include reduced intake, the use of certain medications,
genetics, malnutrition, malabsorption, and chronic stomach inflammation, intestinal parasite,
thyroid disorders e.g. Hypothyroidism and Hashimoto. This disorder leads to reduced
stomach acid which is the major cause of the deficiency. Symptoms of low stomach acids
include acid reflux, gas, and bloating. Celiac Disease is a gluten intolerant disorder. This is
when one is sensitive to gliadin, part of the protein gluten, found in wheat, rye, barley, and
oats.

Lack of intrinsic factor, due to pernicious anaemia. Pernicious anaemia is an autoimmune

disease that affects the gastric mucosa and results in gastric atrophy. This leads to the
destruction of parietal cells, achlorhydria, and failure to produce intrinsic factor, resulting in
vitamin B12 mal-absorption. If pernicious anaemia is left untreated, it causes vitamin B12
deficiency, leading to megaloblastic anaemia and neurological disorders, even in the presence
of adequate dietary intake of vitamin B12.

WHO IS AT RISK?

The main causes of vitamin B12 deficiency include vitamin B12 mal-absorption from food,
pernicious anaemia, postsurgical mal-absorption, and dietary deficiency. However, in many
cases, the cause of vitamin B12 deficiency is unknown. The following groups are among
those most likely to be vitamin B12 deficient.

OLDER ADULTS

Atrophic gastritis, a condition affecting 10%–30% of older adults, decreases secretion of

hydrochloric acid in the stomach, resulting in decreased absorption of vitamin B12.
Decreased hydrochloric acid levels might also increase the growth of normal intestinal
bacteria that use vitamin B12, further reducing the amount of vitamin B12 available to the
body.

Individuals with atrophic gastritis are unable to absorb the vitamin B12 that is naturally
present in food. Most, however, can absorb the synthetic vitamin B12 added to fortified foods
and dietary supplements. As a result, the IOM recommends that adults older than 50 years
obtain most of their vitamin B12 from vitamin supplements or fortified foods. However,
some elderly patients with atrophic gastritis require doses much higher than the RDA to avoid
subclinical deficiency.

INDIVIDUALS WITH PENICIOUS ANAEMIA

Pernicious anaemia, a condition that affects 1%–2% of older adults, is characterized by a lack
of intrinsic factor. Individuals with pernicious anaemia cannot properly absorb vitamin B12
in the gastrointestinal tract. Pernicious anaemia is usually treated with intramuscular vitamin
B12. However, approximately 1% of oral vitamin B12 can be absorbed passively in the
absence of intrinsic factor, suggesting that high oral doses of vitamin B12 might also be an
effective treatment.

INDIVIDUALS WITH GASTROINTESTINAL DISORDERS

Individuals with stomach and small intestine disorders, such as celiac disease and Crohn's
disease, may be unable to absorb enough vitamin B12 from food to maintain healthy body
stores. Subtly reduced cognitive function resulting from early vitamin B12 deficiency might
be the only initial symptom of these intestinal disorders, followed by megaloblastic anaemia
and dementia.

INDIVIDUALS WHO HAVE HAD GASTROINTESTINAL SURGERY

Surgical procedures in the gastrointestinal tract, such as weight loss surgery or surgery to
remove all or part of the stomach, often result in a loss of cells that secrete hydrochloric acid
and intrinsic factor. This reduces the amount of vitamin B12, particularly food-bound vitamin
B12 which the body releases and absorbs. Surgical removal of the distal ileum also can result
in the inability to absorb vitamin B12. Individuals undergoing these surgical procedures
should be monitored preoperatively and postoperatively for several nutrient deficiencies,
including vitamin B12 deficiency.

VEGETARIANS
Strict vegetarians and vegans are at greater risk than lacto-ovo vegetarians and non-
vegetarians of developing vitamin B12 deficiency because natural food sources of vitamin
B12 are limited to animal foods. Fortified breakfast cereals are one of the few sources of
vitamin B12 from plants and can be used as a dietary source of vitamin B12 for strict
vegetarians and vegans.

PREGNANT AND LACTATING WOMEN WHO FOLLOW STRICT VEGETARIAN

DIET AND THEIR INFANTS

Vitamin B12 crosses the placenta during pregnancy and is present in breast milk. Exclusively
breastfed infants of women who consume no animal products may have very limited reserves
of vitamin B12 and can develop vitamin B12 deficiency within months of birth. Undetected
and untreated vitamin B12 deficiency in infants can result in severe and permanent
neurological damage.

SYMPTOMS

Vitamin B12 deficiency is characterized by megaloblastic anaemia, fatigue, weakness,

constipation, loss of appetite, and weight loss. Neurological changes, such as numbness and
tingling in the hands and feet, can also occur. Additional symptoms of vitamin B12
deficiency include difficulty maintaining balance, depression, confusion, dementia, poor
memory, and soreness of the mouth or tongue. The neurological symptoms of vitamin B12
deficiency can occur without anaemia, so early diagnosis and intervention is important to
avoid irreversible damage. During infancy, signs of a vitamin B12 deficiency include failure
to thrive, movement disorders, developmental delays, and megaloblastic anaemia. Many of
these symptoms are general and can result from a variety of medical conditions other than
vitamin B12 deficiency.

FOLIC ACID AND VITAMIN B12

Large amounts of folic acid can mask the damaging effects of vitamin B12 deficiency by
correcting the megaloblastic anaemia caused by vitamin B12 deficiency without correcting
the neurological damage that also occurs. Moreover, preliminary evidence suggests that high
serum folate levels might not only mask vitamin B12 deficiency, but could also exacerbate
the anaemia and worsen the cognitive symptoms associated with vitamin B12 deficiency.
Permanent nerve damage can occur if vitamin B12 deficiency is not treated. For these
reasons, folic acid intake from fortified food and supplements should not exceed 1,000 mcg
daily in healthy adults.

RECOMMENDATIONS

From a Nutritionist point of view, since most cases of vit B12 deficiency are caused by
malabsorption and not inadequate dietary intake, intake of the following helps to increase the
bioavailability of the ingested vit B12. Vinegar, Bananas (Potassium), and mineral rich foods
helps to lower stomach pH and hence increase absorption of the vit B12. Lastly there is need
to continued eating vit B12 rich foods such as Organ food i.e. Chicken liver, beef liver, fish
(sardine), raw dairy products, and foods with probiotics. Maintenance of a healthy gut
through avoiding gluten inflammatory foods of the gut in the diet is recommended.

REFERENCES

1. Herbert V. Vitamin B12 in Present Knowledge in Nutrition. 17th ed. Washington,

DC: International Life Sciences Institute Press, 1996.
2. Herbert V, Das K. Vitamin B12 in Modern Nutrition in Health and Disease. 8th ed.
Baltimore, MD: Williams & Wilkins, 1994.
3. Combs G. Vitamin B12 in The Vitamins. New York: Academic Press, Inc., 1992.
4. Zittoun J, Zittoun R. Modern clinical testing strategies in cobalamin and folate
deficiency. Sem Hematol 1999;36:35-46. [PubMed abstract]
5. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin,
Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and
Choline. Washington, DC: National Academy Press, 1998.
6. Clarke R. B-vitamins and prevention of dementia. Proc Nutr Soc 2008;67:75-81.
[PubMed abstract]
7. Klee GG. Cobalamin and folate evaluation: measurement of methylmalonic acid and
homocysteine vs vitamin B(12) and folate. Clin Chem 2000;46:1277-83. [PubMed
abstract]
8. Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood.2008;112:2214-21.
[PubMed abstract]
9. Gueant JL, Safi A, Aimone-Gastin I, Rabesona H, Bronowicki J P, Plenat F, et al.
Autoantibodies in pernicious anemia type I patients recognize sequence 251-256 in
human intrinsic factor. Proc Assoc Am Physicians 1997;109:462-9. [PubMed
abstract]
10. Kapadia CR. Vitamin B12 in health and disease: part I—inherited disorders of
function, absorption, and transport. Gastroenterologist 1995;3:329-44. [PubMed
abstract]
11. Johnson MA. If high folic acid aggravates vitamin B12 deficiency what should be
done about it? Nutr Rev 2007;65:451-8. [PubMed abstract]
12. Andrès E, Federici L, Affenberger S, Vidal-Alaball J, Loukili NH, Zimmer J, et al.
B12 deficiency: a look beyond pernicious anemia. J Fam Pract 2007;56:537-42.
[PubMed abstract]
13. U.S. Department of Agriculture, Agricultural Research Service. 2011. USDA
National Nutrient Database for Standard Reference, Release 24. Nutrient Data
Laboratory Home Page, http://www.ars.usda.gov/ba/bhnrc/ndl .
14. Subar AF, Krebs-Smith SM, Cook A, Kahle LL. Dietary sources of nutrients among
US adults, 1989 to 1991. J Am Diet Assoc 1998;98:537-47. [PubMed abstract]
15. Tucker KL, Rich S, Rosenberg I, Jacques P, Dallal G, Wilson WF, et al. Plasma
vitamin B12 concentrations relate to intake source in the Framingham Offspring
Study. Am J Clin Nutr 2000; 71:514-22. [PubMed abstract]
16. Yazaki Y, Chow G, Mattie M. A single-center, double-blinded, randomized
controlled study to evaluate the relative efficacy of sublingual and oral vitamin B-
complex administration in reducing total serum homocysteine levels. J Altern
Complement Med 2006;12:881-5. [PubMed abstract]
17. Sharabi A, Cohen E, Sulkes J, Garty M. Replacement therapy for vitamin B12
deficiency: comparison between the sublingual and oral route. Br J Clin Pharmacol
2003;56:635-8. [PubMed abstract]
18. Suzuki DM, Alagiakrishnan K, Masaki KH, Okada A, Carethers M. Patient
acceptance of intranasal cobalamin gel for vitamin B12 replacement therapy. Hawaii
Med J 2006; 65:311-4. [PubMed abstract]
19. Slot WB, Merkus FW, Van Deventer SJ, Tytgat GN. Normalization of plasma vitamin
B12 concentration by intranasal hydroxocobalamin in vitamin B12-deficient patients.
Gastroenterology.1997; 113:430-3. [PubMed abstract]
20. Bialostosky K, Wright JD, Kennedy-Stephenson J, McDowell M, Johnson CL.
Dietary intake of macronutrients, micronutrients and other dietary constituents:
United States 1988-94. Vital Heath Stat 11 2002;(245):1-158. [PubMed abstract]
21. Ervin RB, Wright JD, Wang CY, Kennedy-Stephenson J. Dietary intake of selected
vitamins for the United States population: 1999-2000. Advance Data from Vital and
Health Statistics; no 339. Hyattsville, Maryland: National Center for Health Statistics.
2004.
22. Carmel R. Cobalamin, the stomach, and aging. Am J Clin Nutr 1997;66:750-9.
[PubMed abstract]
23. Carmel R. Malabsorption of food cobalamin. Baillieres Clin Haematol 1995;8:639-55.
[PubMed abstract]
24. Vidal-Alaball J, Butler CC, Cannings-John R, Goringe A, Hood K, McCaddon A, et
al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.
Cochrane Database Syst Rev 2005 ;( 3):CD004655. [PubMed abstract]
25. Butler CC, Vidal-Alaball J, Cannings-John R, McCaddon A, Hood K, Papaioannou
A, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12
deficiency: a systematic review of randomized controlled trials. Fam Pract 2006;
23:279-85. [PubMed abstract]
26. Markle HV. Cobalamin. Crit Rev Clin Lab Sci 1996;33:247-356. [PubMed abstract]
27. Bernard MA, Nakonezny PA, Kashner TM. The effect of vitamin B12 deficiency on
older veterans and its relationship to health. J Am Geriatr Soc 1998; 46:1199-206.
[PubMed abstract]
28. Healton EB, Savage DG, Brust JC, Garrett TF, Lindenbaum J. Neurological aspects
of cobalamin deficiency. Medicine 1991; 70:229-44.
29. Bottiglieri T. Folate, vitamin B12, and neuropsychiatric disorders. Nutr Rev
1996;54:382-90. [PubMed abstract]
30. Monsen ALB, Ueland PM. Homocysteine and methylmalonic acid in diagnosis and
risk assessment from infancy to adolescent. Am J Clin Nutr 2003; 78:7-21. [PubMed
abstract]
31. Chanarin I. Adverse effects of increased dietary folate. Relation to measures to reduce
the incidence of neural tube defects. Clin Invest Med 1994; 17:244-52. [PubMed
abstract]
32. Huritz A, Brady DA, Schaal SE, Samloff IM, Dedon J, Ruhl CE. Gastric acidity in
older adults. J Am Med Assoc 1997;278:659-62. [PubMed abstract]
33. Andrews GR, Haneman B, Arnold BJ, Booth JC, Taylor K. Atrophic gastritis in the
aged. Australas Ann Med 1967;16:230-5. [PubMed abstract]
34. Johnsen R, Bernersen B, Straume B, Forder OH, Bostad L, Burhol PG. Prevalence of
endoscopic and histological findings in subjects with and without dyspepsia. Br Med J
1991;302:749-52. [PubMed abstract]
35. Krasinski SD, Russell R, Samloff IM, Jacob RA, Dalal GE, McGandy RB, et al.
Fundic atrophic gastritis in an elderly population: Effect on hemoglobin and several
serum nutritional indicators. J Am Geriatr Soc 1986;34:800-6. [PubMed abstract]
36. Carmel R. Prevalence of undiagnosed pernicious anemia in the elderly. Arch Intern
Med 1996; 156:1097-100. [PubMed abstract]
37. Suter PM, Golner BB, Goldin BR, Morrow FD, Russel RM. Reversal of protein-
bound vitamin B12 malabsorption with antibiotics in atrophic gastritis.
Gastroenterology 1991; 101:1039-45. [PubMed abstract]
38. Carmel R, Sarrai M. Diagnosis and management of clinical and subclinical cobalamin
deficiency: advances and controversies. Curr Hematol Rep 2006;5:23-33. [PubMed
abstract]
39. Sumner AE, Chin MM, Abraham JL, Gerry GT, Allen RH, Stabler SP. Elevated
methylmalonic acid and total homocysteine levels show high prevalence of vitamin
B12 deficiency after gastric surgery. Ann Intern Med 1996; 124:469-76. [PubMed
abstract]
40. Brolin RE, Gorman JH, Gorman RC, Petschenik A J, Bradley L J, Kenler H A, et al.
Are vitamin B12 and folate deficiency clinically important after roux-en-Y gastric
bypass? J Gastrointest Surg 1998; 2:436-42. [PubMed abstract]
41. Doscherholmen A, Swaim WR. Impaired assimilation of egg Co 57 vitamin B 12 in
patients with hypochlorhydria and achlorhydria and after gastric resection.
Gastroenterology 1973;64:913-9. [PubMed abstract]
42. Commonwealth of Massachusetts, Betsy Lehman Center for Patient Safety and
Medical Error Reduction. Expert Panel on Weight Loss Surgery, Executive Report,
2007.
43. von Schenck U, Bender-Gotze C, Koletzko B. Persistence of neurological damage
induced by dietary vitamin B12 deficiency in infancy. Arch Dis Childhood
1997;77:137-9. [PubMed abstract]
44. Kaiser L, Allen LH. Position of the American Dietetic Association: nutrition and
lifestyle for a healthy pregnancy outcome. J Am Diet Assoc 2008;108:553-61.
[PubMed abstract]
45. National Institutes of Health. Third report of the National Cholesterol Education
Program Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults (Adult Treatment Panel III). Bethesda, MD: National
Cholesterol Education Program, National Heart, Lung, and Blood Institute, National
Institutes of Health, September 2002. NIH Publication No. 02-5215.
46. Refsum H, Nurk E, Smith AD, Ueland PM, Gjesdal CG, Bjelland I, et al. The
Hordaland Homocysteine Study: a community-based study of homocysteine, its
determinants, and associations with disease. J Nutr 2006;136(6 Suppl):1731S-40S.
[PubMed abstract]
47. Schulz RJ. Homocysteine as a biomarker for cognitive dysfunction in the elderly.
Curr Opin Clin Nutr Metab Care 2007; 10:718-23. [PubMed abstract]
48. American Heart Association Nutrition Committee, Lichtenstein AH, Appel LJ,
Brands M, Carnethon M, Daniels S, et al. Diet and lifestyle recommendations revision
2006: a scientific statement from the American Heart Association Nutrition
Committee. Circulation 2006; 114:82-96. [PubMed abstract]
49. Malinow MR. Plasma homocyst(e)ine and arterial occlusive diseases: a mini-review.
Clin Chem 1995; 41:173-6. [PubMed abstract]
50. Selhub J, Jacques PF, Bostom AG, D'Agostino RB, Wilson PW, Belanger AJ, et al.
Association between plasma homocysteine concentrations and extracranial carotid-
artery stenosis. N Engl J Med 1995; 332:286-91. [PubMed abstract]