How Vitamin B12 can help prevent disease
METHYLATION: The folate – B12 – Methionine – Homocysteine pathway
Folate, also known as tetrahydrofolate, can be utilized in the body by two different pathways; either for DNA and red blood cell synthesis (erythropoiesis) or it can be used in the folate-B12-methionine-homocysteine pathway (what a mouth-full).
Tetrahydrofolate, after being metabolized to its 5-methyl tetrahydrofolate form, will transfer its methyl group to a cobalamin molecule to from methylcobalamin (the active form of vitamin B12). This same methyl group is transferred to homocysteine to later form methionine. Methionine is later transformed into S-adenosyl methionine (SAM), its methyl group is then later used in other methylation reactions in the body and is turned back into homocysteine.
In the absence of vitamin B12, the 5-methyl tetrahydrofolate is not able to transfer its methyl group to transform homocysteine into methionine. Homocysteine levels then rise, DNA production and erythropoiesis slow down. This is known as the methyl-folate trap.
In the case of folate deficiency, DNA synthesis and red blood cell formation can be compromised. However, folate can be used to produce DNA and red blood cells, potentially masking vitamin B12 deficiency.
Methionine is an essential amino acid that can be found in high quantities in (in descending order) fish, chicken, eggs, red meat, and dairy. Dogs that have been trained to detect cancer through smell are actually detecting high levels of methionine in a certain region of the body due to skin, lung, or colon cancer.
Studies have shown that restricting methionine in diets helps elongate life and provokes the starvation of cancer cells. Lowering the intake of methionine reduces the rate of free radical (a type of reactive oxygen species) production, which causes a decrease in the formation of DNA mutations and cancer cell formation, decreasing the rate of aging and disease, and increasing longevity.
Unfortunately, restricting the consumption of methionine through a strict vegan diet is not a common recommendation amongst physicians. Plant-based diets provide protein with much lower amounts of methionine than diets containing meat and dairy, not to mention an increased concentration of antioxidants and micronutrients which have a myriad of other health benefits.
Homocysteine is a non-essential amino acid that is a product of the metabolism of methionine in the body and is associated with inflammation. There are three known pathways for homocysteine to be broken down in the body; one using vitamin B6 (pyridoxine), another using choline, and the most important pathway to take into consideration, especially for those following a plant-based diet, is the pathway using the active form of vitamin B12 (methylcobalamin) and vitamin B9 (folate). Without enough of one of these four substrates, accumulation of homocysteine occurs.
Cyanocobalamin (the form of vitamin B12 most commonly found in supplements) is decyanated to cobalamin and then is reduced into methylcobalamin, which is then used as a coenzyme to convert homocysteine into methionine in a pathway called methylation.
Hyperhomocysteinemia is a medical condition that in which there are high levels of homocysteine in the blood. Technically when there is a level of homocysteine of 15 umol/L or more it is considered to be hyperhomocysteinemia, even though levels of just 14 umol/L have been associated with a 4 fold increase in developing Alzheimer’s disease.
Homocysteine blood levels of 10 umol/L or less are considered to be ideal. This, however, is a relatively expensive blood test to have done, it may not available in all clinics or laboratories and may not be covered by insurance.
Unfortunately, most doctors still overlook the health risks associated with elevated homocysteine. Blood levels of homocysteine tend to be high in people who eat a lot of animal protein and consume small amounts of fruits and leafy green vegetables. However, because of low levels of vitamin B12 in a plant-based diet, vegans who do not supplement their diets properly actually tend to have even higher homocysteine levels than meat eaters.
Cardiovascular and Kidney Disease
Homocysteine is toxic to blood vessels and can cause endothelial cell (the cells that line arteries and veins) injury that leads to inflammation of the vessels, later progressing to atherosclerosis (hardening and narrowing of the arteries) and eventually ischemic injury such as heart attacks, strokes, limb ischemia and posterior amputation, especially of the legs.
It is a known risk factor for developing thrombosis (blood clots) and has also been associated with microalbuminuria, small amounts of protein (albumin) in the urine which can be an early indicator of kidney dysfunction. Under normal circumstances, the kidneys do not filter albumin which is why it is a marker of renal disease.
Homocysteine can also break down and inhibit the synthesis of collagen, elastin, and proteoglycans, which are three major components of arteries.
Homocysteine is also toxic to neural cells, high levels increase the risk of developing neurodegenerative disease. It has been associated with mild cognitive impairment, vascular dementia, Alzheimer’s disease and schizophrenia. Peripheral neuropathy (disease of the nerves in arms and legs) can also be accredited to homocysteine.
High homocysteine levels should especially be controlled in people with high blood pressure and/or high uric acid in blood levels, as the risk of vascular dementia increases up to 10.5 times in these patients.
The risk to develop Alzheimer’s disease has been found to have a 4.2 fold increase in patients with hyperhomocysteinemia, while physical activity, low saturated fat intake and proper omega-3 fatty acid intake have been found to be protecting factors.
High homocysteine levels are correlated with increased mortality in patients with type II diabetes. Even in patients who are considered to be prediabetic have substantially more endothelial damage when associated with high homocysteine levels. Preexisting peripheral neuropathy, a common complication of type-2 diabetes, can be exacerbated by poor homocysteine control.
All diabetic patients should have aggressive control of homocysteine levels and should supplement their diets with vitamin B12.
The Pure Doctor’s Recommendations:
- A plant-based diet: The best way to restrict methionine in the diet, which helps to prevent cancer and lead to a longer life than if you were to have a diet rich in animal products.
- Vitamin B12: I strongly recommend that all vegans and plant-based dieters take vitamin B12 supplements, as they are very safe to take, they are inexpensive and have many other benefits for your health. Meat eaters and vegetarians should also consider vitamin B12 supplementation as it is common amongst the general population, not just vegans.
- Folate and Vitamin B6: I also recommend considering supplementing your diet with folate and vitamin B6, especially if you do not get enough leafy greens and seeds into your diet.
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