Vitamin B12 and Disease

Vitamin B12 and the associated amino acids methionine and cysteine are essential to avoid specific symptoms of anemia and the deleterious effects of inflammation.

Vitamin B12, cobalamin, cannot be made by the human body and requires a protein secreted by stomach cells, intrinsic protein, for uptake from the diet or from gut bacteria. In the absence of dietary B12, individuals can develop pernicious anemia. Since vitamin B12 is used by enzymes involved in nucleic acid synthesis, the rapidly dividing cell of the blood show the first symptoms. Another feature of pernicious anemia is the production of autoimmune antibodies against gastric intrinsic protein. This means that even if the diet is supplemented with vitamin B12, the anemic patient would show no improvement. Historically, the cure was beef liver juice containing B12 already bound to intrinsic factor.

I enjoyed learning about the autoimmune aspect of pernicious anemia, because when I examined the sequence of the human intrinsic factor, I found the expected pairs of basic amino acids that I associate with strong heparin binding, uptake and presentation of allergens.  I would predict that pernicious anemia results when intrinsic factor is presented to the immune system as a result of inflammation of the stomach or intestines. Subsequently, anti-intrinsic protein antibodies block B12 uptake. Pernicious anemia is commonly associated with pathogen attack on stomach tissue by Helicobacter pylori, the stomach ulcer and gastric cancer bacterium. Treatment for B12 deficiency has to bypass the required binding to intrinsic factor and uses injection or inhalation of B12 supplements.

There is also a group of proteins that bind to B12 in the human body and apparently block uptake of B12 by pathogens. These proteins are called “R binder” proteins and are present in the body in the same pattern as lactoferrin, an antibacterial protein that binds iron, another critical limited nutrient needed by pathogens.

B12 is used by enzymes to hold methyl groups as the groups are moved from one place to another on a substrate molecule. So B12 is needed to donate a methyl group to homocysteine to regenerate the amino acid methionine. In the absence of B12, homocysteine accumulates in the blood and begins to react with the cysteines and lysines of proteins. It is particularly reactive with enzyme active sites and inactivates lysyl oxidase, which cross-links collagen and elastin that are needed for the integrity of heart and smooth muscle.

Inability to regenerate methionine also eliminates the essential functions of its derivative S-adenosylmethionine, SAM, which is involved in polyamine synthesis and cysteine synthesis. Cyseine is an essential amino acid that is one of the three amino acids in glutathione, the major antioxidant of cells. Thus, a methionine deficiency can result in severe oxidative stress and inflammation.

Disruption of normal nutrition, gut flora and uptake can result in deficiencies of vitamin B12, methionine and cysteine, with a subsequent cascade of oxidative events leading to inflammation, autoimmunity and degenerative diseases. It seems likely that a similar scenario could be associated with loss of physical activity and muscle mass (sarcopenia) of aging. As the older person’s energy requirements decrease, less food will be required, but the composition will need to be adjusted carefully to maintain a healthy gut flora and avoid vitamin and amino acid deficiencies. I would not be surprised if the diets of most older people are grossly inadequate to avoid deleterious chronic inflammation. Poorly managed inflammation could account for most of the symptoms of aging and its associated degenerative diseases.

On a closing note, alcohol consumption has be associated with both hangovers and decreased risk of cardiovascular disease. The hangovers are due to alcohol conversion to acetaldehyde. Reaction of acetaldehyde with cysteine may be both a cure for hangovers and a partial explanation for increased longevity associated with moderate consumption of alcohol. Moderate and consistent alcohol consumption may cause an increase in cysteine storage as a compensation for losses due to alcohol intake. If the alcohol adapted person has higher stores of cysteine, there may be a simultaneous increase in cellular glutathione with a corresponding decrease in oxidative stress and inflammation. Decrease in inflammation is associated with increased longevity. Supplementation with cysteine prior to alcohol consumption eliminates a hangover and may also make you live longer!