B-12 2000

Today's literature indicates that with B6, B12 and folic acid deficiencies, homocysteine buildup is a major factor behind many degenerative diseases of today. Briefly, vitamin B12  (cyanocobalamin), an essential water-soluble nutrient belonging to the B complex, is required in extremely small amounts for cell division and growth. As an enzyme, it is involved in the metabolism of protein, fats and carbohydrates. B12 assists in the utilization of single carbon methyl groups from folic acid to form the amino acid methionine, and the making of thymine, a building block of DNA, etc. Methionine is a critical building block for cellular proteins, and is also the raw material for cysteine, acetylcholine, epinephrine, choline, taurine, etc.  In the pathway of methionine to cysteine, the amino acid homocysteine is produced which the body cannot utilize and it is B6 dependent to be converted to cysteine. With folic acid and B6 present, B12 can also convert homocysteine back to methionine. Thus all three have a part in preventing homocysteine buildup. 

“Vitamin B12 and Folate in Relation to the Development of Alzheimer's Disease,” Rieder CRM, Fricke D, Neurology, November 2001;57(1 of 2):1742. This letter to the editor comments on the role of vitamin B12 and folate in Alzheimer's disease. Vitamin B12 is a cofactor in several metabolic pathways, and its deficiency has been associated with dementia. Dementia that is caused by vitamin B12 deficiency may not be accompanied by anemia. Vitamin B12 deficiency results in reduced conversion of homocysteine to methionine, resulting in elevated homocysteine levels. Vitamin B12 deficiency can result in demyelination. Cognitive changes can occur from central demyelination. Elevated homocysteine levels have been associated with poor word recall in the elderly. Elevated homocysteine levels have been associated with an increased risk of atherosclerosis and stroke. Elevated homocysteine may be directly toxic to endothelium or may be thrombogenic. Patients with vascular dementia were found to have significantly higher homocysteine levels. Increased homocysteine levels increase the risk of silent brain infarction in the elderly. Serum cobalamin evaluation for cobalamin deficiency is not completely sensitive nor specific. In patients with poor levels of vitamin B12, the authors feel that homocysteine and methylmalonic tests should be done to confirm cobalamin deficiency.

"Homocysteine - A Pathophysiological Cornerstone in Obstetrical and Gynecological Disorders?" Obwegeser R, et al, Hum Reprod Update, 1999;5(1):64-72. Homocysteine is a thiol-containing amino acid, which is the demethylated derivative of the essential amino acid methionine and therefore is an intermediate in the methionine cycle.  For remethylation, methionine synthase, vitamin B12 as coenzyme and folic acid (methyl donor) as substrate are required, while for trans-sulfuration, cystathionine beta-synthase and vitamin B6 as coenzyme are needed. Untreated women with classic homocystinuria have fetal loss rates of almost 50%.  Some studies have shown that 25-33% of women with recurrent pregnancy loss have hyper-homocysteinemia.  Homocysteine may play a role in neural tube defects through a disruption in the methionine cycle.  Vitamin B12, and especially folic acid, can be of benefit in the prevention of neural tube defects.  Elevated cortisol and estrogens may reduce homocysteine values in pregnancy. Total homocysteine levels are significantly higher in the plasma of postmenopausal women. It is noted that synthetic estrogens such as ethinylestradiol, the most common estrogen in oral contraceptives, may act differently from natural estrogens used for hormone replacement therapy in postmenopausal women.  It is noted that women who use oral contraceptives show more vitamin deficiencies, especially of vitamins B6 and B12 and folate, which may impair the methionine cycle. There is a wide spectrum of conditions in obstetrics and gynecology where a disturbed methionine cycle seems to have an important influence on pathophysiology. Hyperhomocysteinemia is suspected to be a contributing factor for recurrent early pregnancy loss. One major field of disturbances influenced by homocysteine is vascular damages. These vascular alterations during pregnancy may cause gestosis, eclampsia and fetal growth retardation. It is well known that periconceptional folic acid supplementation (which lowers hyperhomocysteinemia) can prevent the development of neural tube defects of the fetus. Besides, hormonal replacement therapy and most oral contraceptives have been shown to influence methionine cycle in different ways. There are many reports that show the positive influence of folic acid supplementation on clinical situations. In one scientific paper, women with a history of a prior pregnancy that resulted in a fetus with a neural tube defect were taking 4 mg of folic acid periconceptionally. The number of recurrent neural tube defects was decreased by 72% as compared to the control group. The administration of vitamins B12 and B6 and folic acid is safe. No major adverse effects are known. It is known that folate supplementation successfully can treat mild or moderate cervical dysplasia within young women taking oral contraceptives.  A majority of tumor cell lines are considered to be "methionine-dependent." In gynecology, there are reports suggesting that certain types of ovarian cancer and cervical neoplasia might be associated with alterations in the methionine cycle. Vitamins B6 and B12 and folic acid should be considered as potential therapies. (To not recommend concurrently in view of the information in the literature is negligence at minimum.)

"Oral Contraceptive Use and Bone Mineral  Density in Premenopausal Women: Cross-Sectional, Population-Based Data From the  Canadian Multicentre Osteoporosis Study," Prior JC, Kirkland SA, Joseph L, et  al, Can Med Assoc J, October 16,  2001;165(8):1023-1029.In evaluating 524 women ( mean age  of 36.3 years), 454 had used oral contraceptives (mean age  upon initiating use was 19.8 years, mean duration of use of 6.8 years). Mean bone mineral density values were lower in the oral contraceptive users and were significantly lower in the spine and trochanter. The bone mineral density of the spine in oral contraceptive users was 1.03 g/cm2 vs 1.07 g/cm2 in those who had never used oral contraceptives. Bone mineral density was not related to the duration of use nor to gynecological age at first use. 

"Homocysteine Metabolism in Pregnancies Complicated by Neural-Tube Defects," James L. Mills, M.D. The Lancet, January 21, 1995; 345:149-51. A major study in Dublin collected blood on pregnant women. After the pregnancy outcomes were known, they went back and pulled out the specimens from the women who had neural tube defects and started measuring vitamin levels.  They found that not only was folate associated with neural tube defects, but it looked as if B12 was independently a risk factor for neural tube defects and homocysteine might even be that much more prognostic or sensitive for assessing vitamin B12 levels. It was the interaction between folate and B12 that was the critical factor.  The place where folate and B12 interacted is in the enzyme methionine synthase, which is the enzyme that converts homocysteine to methionine. This gave a very strong indication as to where to look. These women were not folate deficient nor were they B12 deficient. It wasn't simply a case of women who were generally undernourished or generally had poor nutrition who have the neural tube defects.  Most of the women in this study had perfectly normal levels of B12 and perfectly normal levels of folate. They were just in the lower range of normal. (Were there sufficient B6-dependent cysteine levels?)  

"Distribution of and Factors Associated With Serum Homocysteine Levels in Children:  Child and Adolescent Trial for Cardiovascular Health," Osganian SK, et al, JAMA, April 7, 1999;281(13):1189-1196. In studying 3,524 U.S. schoolchildren aged 13 and 14 years from the Child and Adolescent Trial for Cardiovascular Health (completed in 1994), it was found that homocysteine levels in children were significantly lower than those seen for adults.  A small percentage of children were potentially at elevated risk for future cardiovascular disease.  Serum folic acid may be a determinant of homocysteine levels in children.  The distribution range of homocysteine values was from 0.1 to 25.7 umol/l.  The mean was significantly higher in boys than girls, blacks than whites or Hispanics, and for nonusers of multivitamins compared with users.  Smokers had higher levels of homocysteine than nonsmokers.  Serum homocysteine levels were significantly inversely correlated with serum levels of folic acid, vitamin B12 and vitamin B6.  Serum homocysteine levels were not significantly associated with serum lipid levels or family history of cardiovascular disease.  

The day may come when homocysteine will be a screening tool on almost every chemistry profile, since its elevation is a risk factor for cardiovascular, cerebrovascular and peripheral vascular diseases, gynecological conditions including neural tube defects, recurrent miscarriages and other related conditions, neuropsychiatric disorders, and in such conditions as multiple sclerosis.

Consider oral therapy of 2000 ug/d. It has been shown that several thousand micrograms per day orally is as effective as 1000 ug/month given IM, even in some of the most difficult patients with pernicious anemia. This may be a good alternative to intramuscular injections. As indicated, it is good to include folic acid and B6. Biotics Research's B12 -2000 Lozenges each contain 6 mg of B6 (as Pyridoxal -5-phosphate), 800 mcg of Folic Acid and 2000 mcg of B12 (as cobalamin). For easy patient compliance, they have an excellent taste as also containing mannitol, sorbitol and natural lemon flavor, magnesium stearate (vegetable source) and stearic acid (vegetable source). Taken as lozenges, there is a better activating of the intrinsic factor involved in proper absorption. Consider also Methionine-200. Each capsule contains 200 mg of L-Methionine, 20 mg of L-Lysine HCl and 5 mg of L-Cysteine HCl, all in a vegetable culture base with 20 mcg of Superoxide Dismutase and 20 mcg of Catalase.