Heal Yourself At Home
DIY SOLUTIONS FOR YOUR HEALTH
Vitamin B12

Vitamin B12 (Cobalamin) – Energy Vitamin

Introduction to B12

B12 is the largest molecule of all the vitamins – also has a complex structure

B12 is unique among the vitamins containing a metal ion (cobalt) - explaining its name

In mammals, B12 is a cofactor for 2 enzymes:

SAME ( methyl group donor for methylation reactions, inlcuding methylation of DNA)

B12 found in significant amounts in animal foods, but neglible amounts in plant food

B12 absorption “journey”in the body

-Stomach acid and the protease enzyme pepsinfrees B12 from food - the free B12 then binds to an R protein (haptocorrin) - a glycoprotein released from the salivary glands and gastric mucosa.

-Pancreatic enzymes again release the B12 from R protein in the less acidic small intestine (duodenum) - allowing the free-again B12 to bind to intrinsic factor (IF), which was secreted by parietal cells of the stomach lining (gastric mucosa)

-After traveling to the ileum, intestinal lining receptors take up B12-IF complex - where its B12 is endocytosed by epithelial cells bound to transcobalamin to enter the liver, but only if calcium is present (supplied by the pancreas)

- Alternatively, B12 can be absorbed via the intestinal lining of the terminal ileum - by passive diffusion into the mesenteric veins, but this route has a very inefficient 1% absorption rate

Carmel R. Cobalamin (Vitamin B12). In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease. Philadelphia: Lippincott Williams & Wilkins; 2006:482-497.

-B12 is stored in the liver for about 1 –5 years –depending on amount consumed, amount absorbed and hepatic function B12

This antioxidant vitamin has many functions in the body

B12 has benefical functional roles in:

Maintaining energy levels –involved in metabolizing carbohydrate and fats

Neurological function /mental alertness/Stress

B12 health benefits - include:

Involved in adrenal hormone production

MELATONIN production

B12 deficiency is not uncommon and often goes unrecognized

Some misdiagnosed diseases may simply be a B12 deficiency – which has been referred to as a “silent epidemic”. Symptoms of B12-deficiency can parallel those of several diseases, misleading doctors to misdiagnosis of M.S., Alzheimer's, dementia, early Parkinson's disease, diabetic neuropathy, chronic fatigue syndrome and more.

Sally M Pacholok, Jeffrey J Stuart, Could it be B12? An Epidemic of Diagnoses 2nd Edition Feb 2011

A B12 deficiency needs to be timely addressed, since it can result in permanent damage – due to neuronal demyelination and axonal degeneration (called Wallerian degeneration - results from insult ro peripheral nerve fibers),which if left untreated will result in neuronal death.

Serum levels of B12 below 221 pmol/L (300 pg/mL) is the generally accepted level suggesting a tissue level deficiency

Rajan S, Wallace JI, Beresford SA, et al. Screening for cobalamin deficiency in geriatric outpatients: prevalence and influence of synthetic cobalamin intake. J Am Geriatr Soc, 2002;50:624-630.

B12 deficiency is commonly related to:

Food-cobalamin malabsorption syndrome (MOST COMMON REASON) –occurs when the stomach lining loses the ability to produce intrinsic factor, a protein that binds to B12 to enable its absorption whenit reaches the lower end of the small intestine;

You can be consuming B12 in animal products and still not be absorbing enough of it

Those over the age of 50 have limited ability to absorb B12

Pernicious Anemia progressive automimmune destruction ofstomach lining cells:

(1) Reducessecretion of B12-releasing gastric acid and enzymes

AND

(2) Antibodies bind to intrinsic factor preventing formation of B12-IF complex and consequently B12 absorption.

Intramuscular B12 shots are a common treatment, although high dose oral B12 delivers similar amounts (E.g. 1000mg supplies 1 mg B12 by passive absorption) .

Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998;92(4):1191-1198. (PubMed)

Lederle FA. Oral cobalamin for pernicious anemia. Medicine's best kept secret? JAMA. 1991;265(1):94-95.

Hathcock JN, Troendle GJ. Oral cobalamin for treatment of pernicious anemia? JAMA. 1991;265(1):96-97.

20-50% of those over 50 are unable to absorb natural (protein-bound) B12

Institute of Medicine. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin and choline. Washington, DC: National Academy Press 1998.

Shane B. Folic acid, vitamin B-12, and vitamin B-6. In: Stipanuk M, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W.B. Saunders Co.; 2000:483-518.

Herbert V. Vitamin B-12. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington D.C.: ILSI Press; 1996:191-205.

Symptoms of B12 deficiency include:

Megaloblastic anemia –diminished folate production, even in the presence of folate; a symptom of pernicious anemia; produces large, immature, hemoglobin-poor RBCs

Some diseases associated with B12 deficiency

Reference: Linus Pauling Institute

RDA for adult men and women is 2.4 mcgB12 /day

However, absorption or retention rate is related to the dose provided

Institute of Medicine. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid,biotin and choline. Washington, DC: National Academy Press 1998.

Dose Synthetic B12

(i.e. Non-protein bound)

Delivery Method

Absorption Rate

< 5 μg

Oral (w/ non-deficiency)

50-60%

>500μg

Oral (w/ non-deficiency)

1%

<40 μg

IM

93-100%

1000 μg

IM

15%

Natural B12 Sources

Food

Serving

Vitamin B12 (mcg)

Clams (steamed)*

3 ounces

84.0

Mussels (steamed)*

3 ounces

20.4

Crab (steamed)*

3 ounces

8.8

Salmon (baked)

3 ounces

2.4

Beef (cooked)

3 ounces

2.1

Nutritional yeast

1 T flakes

2.1

Milk (whole, 3.25%)

1 Cup

1.1

Yogurt (Plain, lowfat)

4 ounces

0.75

Egg (poached)

1 large

0.6

Brie (cheese)

1 ounce

0.5

Chicken (roasted)

3 ounces

0.3

Turkey (roasted)

3 ounces

0.3

USDA food composition database.

*There's a reason for the high B12 values in shellfish –i.e. a high bacterial load!

Who needs to supplement B12?

Non-vegan diet for healthy people should provide sufficient B12

The following persons should definitely supplement B12

- Strict vegetarians

-Women intending to get pregnant

It is prudent for those with conditions related to B12 malabsorption to empirically supplement B12 (especially given the lack of reliable diagnostic tests together with the low risk of B12supplementation)

-The “Over 50's”

- Those who have had:

- Those with:

(usually due to atrophic gastritis, common in over 50's) –need B12 in supplemental (non-protein bound) form since they can not depend on hydrochloric acid to cleave B12 from food.

E.g. Crohn's disease, Celiac's disease

Lambert D, Benhayoun S, Adjalla C, et al. Alcoholic cirrhosis and cobalamin metabolism. Digestion, 1997;58:64-71.

causes malabsorption

insufficient pancreatic secretions impedes cleavage of B12 from B12-R-protein complex, and therefore formation of the B12-IF complex

Andres E, Vidal-Alaball J, Federici L, et al. Clinical aspects of cobalamin deficiency in elderly patients. Epidemiology, causes,clinical manifestations, and treatment with special focus on oral cobalamin therapy. Eur J Intern Med, 2007;18:456-462.

-People taking meds that interfere with B12 absorption:

i.e. proton pump inhibitors (E.g. omeprazole, lansoprazole), H2-inhibitor antagonists (E.g. Tagamet, Pepsid, Zantac);

(laughing gas) (anaesthetic) - inhibits B12-dependent enzymes

-Also those with cirrhosis –diminishes liver's storage capacity of B12; Paradoxically, a degrading liver causes high serum B12 as it releases its stores, although despite raised serum levels, the tissues remain depleted.

Ermens AAM, Vlasveld LT. Significance of elevated cobalamin (vitamin B12) levels in blood. Clin Biochem, 2003;36:585-590.

Which is the best form of B12 supplement?

Supplemental forms of B12 are not bound to protein and therefore do NOT require the cleaving ability of gastric acid or pepsin (which is necessary for naturally occurring protein-bound B12) (The white cross in the picture depicts how protein-bound B12 must cleaved by gastric acid and pepsin before joining with intrinsic factor)

There are 3 forms of B12 to choose from found in supplements and fortified foods:

Hydroxycobalamin

Cyanocobalamin (popular form in supplements) –produced from hydroxocobalamin, the form produced by bacteria;

Methycobalamin (BEST, “Ready-to-go”, physiological form) – natural form produced in the body from bacterial hydroxycobalamin;

There are 3 main delivery methods for B12 i.e. Injection (IM), oral tablets or sublingual tablets or drops – study showed that all 3 methods have an equal affect at correcting B12 deficiency (study participants'average serum B12 was 100 pmol /L)

Delpre G, Stark P, Niv Y. Sublingual therapy for cobalamin deficiency as an alternative to oral and parenteral cobalamin supplementation. Lancet. 1999;354:740–741. PubMed

Sharabi, A., Cohen, E., Sulkes, J. and Garty, M. (2003), Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route. British Journal of Clinical Pharmacology, 56:635–638. doi:10.1046/j.1365-2125.2003.01907.x BJCP

–    B12 also available as a nasal spray (www.nascobal.com), skin patch or mouth spray

B12 in a multivitamin may be counterproductive – the late renowned B12 researcher Victor Herbert determined that many multivitamin supplements also contain B12 analogs (meaning they prevent B12 absorption by interacting with them)

Herbert V. Vitamin B-12. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington D.C.: ILSI Press; 1996:191-205.

Some good product choices:

Vegan B12 Sublingual - each melt-under-the-tongue tablet contains 1000mcg B12, also contains folic acid (400mcg) and B6 (2mg), all needed for MELATONIN production.

$9.99 +s/h for 90 tablets (3 month supply). Also tastes good!

Dose?

B12 Deficiency Replacement Doses

Oral or Sublingual (synthetic)

1000 μg/day for 1-4 weeks

B12 Maintenance Dose

Food-cobalamin Malabsorption

Perniceous Anemia

or No Ileal receptors

Oral or Sublingual (synthetic)

125-500 μg/day

1000 μg/day

Intramuscular (IM)

1000 μg / month

Replacement Dose for B12 Deficiency - 1000–2000 μg/day

Vidal-Alaball J, Butler CC, Cannings-John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev, 2005;20;(3): CD004655.

Recommended from 1 –4weeks

Andres E, Loukili NH, Noel E, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. Can Med Assoc J, 2004;171(3):251-259.

Oh RC, Brown DL. Vitamin B12 deficiency. Am Fam Physician, 2003;1;67(5):979-986

B12 doses to counter drug-induced malabsorption are undetermined

Since B12 is stored in the liver, it does not have to be supplemented every day - for example, 1000 ug tablets can be taken every other day or every third day for lower dose requirements. In figuring your dose you will need to somewhat compensate for the finding that a singular higher dose is not as well absorbed as when split into smaller doses. The exact compensation has not been determined for all doses and conditions so you will need to experiment for your specific case. Unused B12 is eliminated from the body

Pernicious anemia and lack of ileal receptors requires the high 1000 μg dose that relies on the 1% passive diffusion of B12 at the terminal ileum –a dose of 1000 μg would provide 100 μg B12 by this route without the need for gastric acid or intrinsic factor.

Painful IMB12-shots can be effectively replaced with HIGH oral doses that also rely on the 1% passive diffusion at the terminal ileum

B12 Toxicity?

No upper Intake Limit (UL) has been set for B12as there is little evidence of toxicity

Excess B12 is harmlessly eliminated

References

Liz da Silva Stacey McCray Vitamin B12: No One Should Be Without It. PRACTICAL GASTROENTEROLOGY ▪JANUARY 2009 Online Link

Linus Pauling Institute Online Link

AOX Links

ANTIOXIDANTS / VITAMINS

Related Links

Antioxidants - “Oxidant Damage Control”

FOOD / SUPPLEMENTAL ANTIOXIDANTS

Food/Supplemental Antioxidants

VITAMIN A

–   Vitamin A –   “Grass Vitamin”

VITAMIN B

–    Vitamin B9(Folate)

–    Vitamin B12 (Cobalamin) –“Energy Vitamin”

VITAMIN C

–    VitaminC –“God's Medicine”

–    Cfunctions / benefits in detail

–    Man does not produce C

–    Food sources of C

–    How to supplement C

–    Rath-Pauling Therapy

(strengthen connective tissue and reverse atherosclerosis/CVD)

–    Vitamin C Chemistry

VITAMIN D

–    Vitamin D –“The Sunshine Vitamin”

VITAMIN E

–    Vitamin E

VITAMIN K

–    Vitamin K –“ForKlotting and Kalcium”

–    K against Health Problems

–    How to obtain K?

PHYTONUTRIENTS

–    Dark Chocolate

MAJOR “IN-HOUSE”ANTIOXIDANTS

(Producedinside the body, but can be boosted via diet/supplementation)

–    Glutathione –“King of the Antioxidants"

Nebulizing Glutathione

–   Glutathione Peroxidase

–   Catalase

–   SOD

–   Alpha Lipoic Acid

–    CoEnzyme Q10 –“Spark and Dampener”

CoQ10 Health Benefits