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Vitamin B12 and Methylcobalamin

      Vitamin B12, one of the B vitamins, is a water soluble vitamin that plays a key role in the normal functioning of the brain and nervous system, and the formation of blood. B12 is essential for DNA synthesis, fatty acid synthesis, production of the mood-affecting substance SAMe (S-adenosyl-L-methionine) and cellular metabolism. Vitamin B12, folic acid, vitamin b6 and other methyl donors control homocysteine levels. An excess of homocysteine is associated with an increased risk of heart disease, stroke, osteoporosis and Alzheimer's disease.

      Vitamin B12 works in close partnership with folic acid in the synthesis of DNA and RNA as well as the synthesis of molecules important for the maintenance of the integrity of the genome.

      Vitamin B12 is not synthesized in the human body. It is synthesized by certain bacteria, in particular those found in the digestive system of ruminant animals. Food sources of B12 include shellfish, liver, caviar, octopus, fish, crab, lobster, beef, lamb, eggs, and cheese.

Forms of B12

      Vitamin B12 exists in several chemical forms. A synthetic form, cyanocobalamin, is commonly used in pharmaceutical products and nutritional supplements. The human body is capable of converting the synthetic form into the biologically active natural forms methylcobalamin and adenosylcobalamin.

      Methylcobalamin is the neurologically active form of B12. It is the methylcobalamin form of B12 that has been used in most European and Japanese studies showing efficacy against neurological disease. The liver converts only about 1% of ingested cyanocobalamin into methylcobalamin. Because of the superior biological activity of methylcobalamin and the relatively low conversion rate of cyanocobalamin to methylcobalamin, it is recommended that only the methyl form be used as a nutritional supplement.

Vitamin B12 Deficiency

      Vitamin B12 deficiency has the potential to cause severe, irreversible damage to the brain and nervous system. Even at levels only slightly below the normal, such symptoms as depression, fatigue and poor memory can occur. The neurological effects of the vitamin deficiency may occur even in the absence of anemia. This is particularly true in those who are over 60 years old.

      The main syndome of vitamin B12 deficiency is pernicious anemia, also called Addison's anemia and Beirmer's disease. In addition, several other types of anemia are associated with B12 and/or folic acid deficiency. Individual symptoms found in cases of vitamin B12 deficiency may include the following:

  • Change in mental status
  • Loss of concentration ability
  • Memory loss
  • Insomnia
  • Impaired bladder and bowel control
  • Confusion
  • Depression
  • Intermittent diarrhea and constipation
  • Anorexia and weight loss
  • Abdominal pain
  • Age related hearing loss
  • Fatigue
  • Muscle weakness
  • Numbness and tingling in hands and feet (paresthesias)
  • Loss of vibratory and position sensation
  • Abnormalities of gait
  • Alzheimer's disease
  • Shortness of breath
  • Palpitations
  • Sore mouth and tongue

      Vitamin B12 deficiency may result from poor absorption through the digestive system, vegetarian diets deficient in B12 and from certain disease processes. Anyone with elevated homocysteine, psychiatric disorders, eating disorders, sleep disorders or elderly is potentially B12 deficient. These conditions are more likely caused by diet induced B12 deficiency than a lack of intrinsic factor. All may respond to oral B12 supplements.

      Older people produce less intrinsic factor, and are thus more vulnerable to B12 deficiency.

B12 and Homocysteine

      Homocysteine is an amino acid that is not obtained from the diet. It is biosynthesized in the human body from the amino acid methionine. Homocysteine can be converted to methionine or cysteine with the aid of B vitamins. Homocysteine levels can be elevated by deficiencies of folic acid (B9), pyridoxine (B6) or B12. Elevated homocysteine levels have been associated with many degenerative diseases including heart disease, arteriosclerosis and osteoporosis.

      Research findings demonstrate that oral supplementation with B12 alone reduced homocysteine levels in most individuals, but not all. Dramatic reductions in homocysteine levels were experienced by some individuals who took 2000 mcg. of B12 orally for 4 weeks. B12 injections also reduced homocysteine and worked faster than oral B12. Those who did not respond to B12 were found to have a folic acid deficiency. Vitamin B12 and folic acid work synergistically to recycle homocysteine back to methionine by the methylation cycle. During the 1950s, B12 was frequently given to heart patients. This practice was discontinued when new drugs were introduced. B12, folic acid and B6 are now getting new consideration as the role of homocysteine in heart and cardiovascular health is being recognized.

Absorption of Oral B12

      It has long been believed that B12 supplements taken orally were not absorbed very well and that for therapeutic effect B12 injections were necessary. Recent research has, however, demonstrated that oral B12 supplements are much better absorbed than previously believed, alleviating the need for injections for many individuals. Normally, Intrinsic Factor is secreted by the stomach to help the body absorb B12. Patients with pernicious anemia lack intrinsic factor. This lack of intrinsic factor may be associated with insufficient stomach acid. Some may also have antibodies to intrinsic factor resulting from an autoimmune process.

Vitamin B12 and Sleep

      Studies show that B12 acts directly on the pineal gland to provoke a faster release of melatonin at night which resets the sleep-wake cycle. B12 also causes melatonin levels to drop off faster in the morning. Very serious sleep-wake disorders have been successfully treated with vitamin B12 in the methylcobalamin form, although it may not work for everyone.

B12 and Cancer

      There is some epidemiological evidence that B12 may protect against certain types of cancer. A couple of clinical studies have shown that a combination of B12 and folic acid significantly reduces the number of abnormal bronchial cells thought to be cancer cell precursors. The mechanism of the possible anticarcinogenic effect of B12 is unclear. Abnormal DNA methylation patterns are characteristic of neoplastic cells. Decreased SAMe and thymidylic acid levels may also lead to increased errors in DNA replication, increased DNA strand breaks and defective DNA repair. B12, especially methylcobalamin is a methylating agent with the potential to correct these errors.

      In one of study, supplementation with 10 milligrams of folic acid daily, combined with 500 micrograms of vitamin B12 daily, for four months, produced a significant reduction in the number of subjects who exhibited the abnormal bronchial cells believed to be cancer precursors.

B12 Dosage

      The U.S. RDA, for vitamin B12, the value used for nutritional supplement and food labeling purposes, is 6 micrograms daily.

      The dose of oral B12 supplements for sleep disorders is 3000 mcg a day, while 2000 mcg a day has proven useful in lowering homocysteine and correcting B12 deficiency. In published studies, it took four weeks for the sleep effect, and four months for the homocysteine lowering effect, so be patient. People with degenerative diseases, including alzheimer's, should take very high doses in the range of 3-4000 mcg, supplemented with SAMe.

B12 Interactions with Drugs

      Several medications are known to either decrease the absorption of B12 or reduce B12 levels in the system. These include:

  • Alcohol
  • Aminosalicylic acid
  • Antibiotics
  • Hormonal contraceptives
  • Chloramphenicol
  • Colchicine
  • Colestipol, Cholestyramine
  • H2 receptor antagonists - Including cimetadine, famotidine, nizatidine, and ranitidine
  • Metformin (Glucophage)
  • Neomycin
  • Nicotine
  • Nitrous Oxide
  • The anticonvulsants Phenytoin (Dilantin),phenobarbitral, primidone (Mysoline)
  • Proton Pump Inhibitors including omeprazole (Prilosec, Losec), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix, Pantoloc), and esomeprazole (Nexium)
  • Zidovudine (AZT, Combivir, Retrovir)

      This list is not likely complete. For due diligence:

  • Ask your pharmacist about vitamin and mineral interaction for all the medications that you are taking.
  • Ask your doctor to test your blood levels for key vitamins like vitamin B12 and vitamin D.
  • As a preventive measure, take a good multi-vitamin and multi-mineral supplement.
  • If you have any of the symptoms on the deficiency list, consider taking a high dose supplement of the methyl form of B12.

Vitamin B12 and Folic Acid Interactions

      Because B12 and folic acid act synergistically, both should be supplemented together.

      Taking folic acid supplements alone may correct megaloblastic anemia, but not the neurological damage of B12 deficiency. Because of this, B12 should always be taken with folic acid supplements.

      Because B12 did not reduce homocysteine levels in patients with a folic acid deficiency, folic acid should always be given with B12 supplements.

B12 Side Effects and Adverse Reactions

      There are no reported side effects or adverse reactions to oral B12 supplements even in high doses.

      There have been rare adverse reactions to B12 injections. It is unclear whether this was from the B12 or the additives and preservatives in the injectable form.





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