Vitamin B12 has many crucial functions in the body. You need it for the formation of healthy, fully mature red blood cells and to regenerate folic acid, another B vitamin mostly known for its role in preventing birth defects.
Vitamin B12 also supports brain function, maintains the health of your nervous system and helps in DNA synthesis.
A moderate vitamin B12 deficiency can cause symptoms such as fatigue, lack of focus and pins and needle sensation in the extremities. Worse yet, long-term deficiency has the potential to cause permanent damage to your nervous system and may increase your risk of dementia.
Can a vitamin B12 deficiency also affect your heart health? Research indicates that vitamin B12 deficiency is related to increased cardiovascular risk. And this could be attributed the role of B12 in the metabolism of homocysteine (Hc), an amino acid whose high levels are associated with many health conditions.
What is homocysteine?
Homocysteine is an amino acid, naturally produced in the body during the metabolism of methionine. Methionine is a protein found in foods such as meat, eggs, fish, dairy and in some vegetables. When you consume these foods, methionine is degraded into homocysteine.
Your body can deal with some amounts of homocysteine in the blood, but high levels circulating in the bloodstream are known to cause inflammation and serious damage to the heart, brain and nervous system health.
The role of vitamin B12 in homocysteine metabolism
In the body, homocysteine is recycled back into methionine and cysteine with the help of B vitamins.
Homocysteine is metabolized through two pathways:
- Homocysteine is converted into methionine with the help of enzymes that use vitamin B12 and folate as co-factors. This is called the re-methylation pathway. Methionine is further activated into S-adenosyl-methionine or SAM, a molecule that donates its methyl group to proteins, phospholipids, myelin, neurotransmitters and DNA.
- Homocysteine is converted into cysteine with the help of enzymes that use vitamin B6 as a co-factor. This is called the transculturation pathway and cysteine produced here is used in the synthesis of glutathione.
A deficiency in B12, folate and vitamin B6 results in high homocysteine levels. What does it mean for your health?
High levels of homocysteine and your health
High levels of homocysteine in the body, also called hyperhomocysteinemia, is bad news for your health. While it may not cause any symptoms, high levels have been associated with many health risks.
Studies show increased levels of homocysteine could be an important bio-marker for conditions like dementia, Alzheimer’s, atherosclerosis and heart disease.
In fact, emerging studies suggest that it could also be used as a biomarker for vitiligo, a condition which is marked by the appearance of white spots or patches on the skin. Supplementation with B12 may help patients suffering from this condition. 
Older adults often have low B12 levels and high Hc levels. A study found that high Hc levels may degenerate nerve function in the elderly. These findings are important as impaired nerve function can reduce strength and physical performance in older adults. 
The good news is that one can get their homocysteine levels tested. Most importantly, supplementation with nutrients such as vitamins B12, B6, folate, magnesium and zinc can help you maintain your levels within a healthy range. You can also lower your Hc levels by eating more green leafy vegetables, giving up smoking and alcohol, and eliminating foods rich in methionine such as red meat and dairy.
Here is a list of possible causes of elevated Hc levels:
- Vitamin B12, B6 and folate deficiency
- Low thyroid levels
- Magnesium deficiency
- Kidney disorders
- Use of certain medications such as metformin, levodopa and nitrous oxide
- Excessive consumption of coffee and alcohol
- A family history of certain medical conditions
Elevated levels of this amino acid are considered as a prominent risk factor for heart disease. It has been associated with atherosclerosis, coronary artery disease, stroke, and blood clotting disorders.
Increased homocysteine damages the endothelium (the inner lining of the blood vessels) and increases the risk of atherosclerosis (thickening and hardening of arteries). Homocysteine impairs endothelial function through various other mechanisms such as increasing coagulation of the blood, increasing oxidative stress, reducing the levels of HDL cholesterol molecules and upregulating adhesion molecules that increases the burden of plaque within the arteries.
Studies show that increased levels of homocysteine could be a risk factor for coronary heart disease.   CHD develops when plaque build-up and inflammation damage coronary arteries, major blood vessels that supply blood and oxygen to the heart. This damages and narrows down the coronary arteries, increasing the risk of heart attack.
A study showed that elevated levels of Hc and low levels of folic acid and vitamin B12 are related to coronary artery disease, including chest pain, unstable and stable angina, and heart attack. 
This 2014 study found that high Hc levels may cause arterial stiffness in the elderly, concluding, “a clear association between homocysteine level and aortic stiffness in elderly, indicating that homocysteine may be involved in artery stiffening in older (people).” 
Vitamin B12 and thrombosis
It has been found that Hc may increase the risk of thrombosis, formation of blood clots within a blood vessel. Increased homocysteine contributes to thrombosis through many mechanisms including enhancing aggregation of platelets.
This means when you have high levels of homocysteine, your blood clots more easily, which increases the risk of blocked arteries. A clot in your blood vessel can cause stroke and heart attack.
A 2017 study found that vitamin B12 and folic acid can reduce the risk of thrombosis in patients with deep vein thrombosis in lower extremity. Researchers reported that this could be as a result of reduced levels of Hc. 
Vitamin B12 and heart palpitations
Heart palpitation is described as a feeling that your heart is pounding or rapidly fluttering in the chest. Stress, anxiety, anemia, certain medications, magnesium deficiency and B12 deficiency can cause irregular or abnormal beating of your heart, something that feels like you have either missed a heart beat or your heart is beating more faster than it should.
In fact, this is one of the common symptoms of having B12 deficiency. Though harmless in most cases, these sensations in your chest can be frightening. Heart palpitations, without any other symptoms like chest pain, dizziness and shortness of breath, could be a sign that you are deficient in B12. Get your B12 levels tested, especially if you are a vegetarian.
Don’t take recurring heart palpitations lightly. Chronic issues do run a risk of heart failure. Talk to your doctor about your condition as soon as possible.
Vitamin B12 and stroke
Stroke occurs when the blood circulation to the brain is interrupted. High blood pressure, smoking, unhealthy diet, lack of physical activity, obesity, diabetes, stress and excessive alcohol consumption are some important risk factors for stroke. These risk factors can be managed by making some positive changes to your lifestyle, which may help you reduce the risk of stroke.
There are other factors that are out of your control such as age, gender (women are at an increased risk of stroke), heredity and a history of a previous stroke. There is nothing you can do to control these risk factors, but did you know vitamin B12 deficiency also contributes to stroke and cognitive decline? In fact, B12 deficiency is common in people with stroke.
Studies suggest that increased Hc levels increases the risk for ischemic strokes.  Ischemic stroke occurs when one of the blood vessels supplying blood and oxygen to the brain is blocked or plugged. It is usually caused by the formation of blood clot in the arteries.
Excessive homocysteine causes damage and inflammation in the blood vessels. It also increases the formation of blood clots. All these changes lead to an impaired flow of blood in the brain. High levels of Hc and the resulting injury to endothelium can be reduced by improving your levels of B vitamins especially vitamin B12, folate and vitamin B6. This may help reduce your stroke risk.
In a 2017 study the researchers suggested that vitamin B12 supplementation may benefits patients with stroke and those with MTHFR mutation who have vitamin B12 deficiency. 
Vitamin B12 supplements in reducing heart disease risk?
The role of elevated homocysteine in increased risk of heart disease, including impaired endothelial function, damage in arteries, blood coagulation, heart attack and stroke, is well understood. What is also clear is the role of vitamin B12, B6 and folic acid in keeping the levels of this potentially harmful amino acid in a balanced and harmless range.
Does this mean supplementation with B12 and folic acid might help in preventing or reducing your risk of cardiovascular disease? Unfortunately, this line of thought needs more scientific evidence as the findings from various studies are mixed.
There is some indication that reducing Hc levels, with the help of B vitamins, may reduce cardiovascular risk in people who have suffered stroke. For example, one analysis concluded that, “Older individuals with stroke were more likely to benefit from B vitamin therapy than younger individuals. These findings can help inform the future design of clinical trials of tHcy-lowering therapy for cardiovascular risk reduction after stroke.” 
Are you at risk of vitamin B12 deficiency?
Vitamin B12 is not found in plant-based foods. You can only get it from food products sourced from animals, such as organ meats, beef, eggs, shellfish, fish and dairy. This means vegetarians are at a very high risk of developing a B12 deficiency unless they are eating foods that are fortified with B12 and folic acid.
In addition, vitamin B12 absorption is a complex process and entirely depends on sufficient gastric acid, enzymes, calcium levels and intrinsic factor (transport protein that binds to free B12 in the body). Age and certain drugs and health conditions affect B12 absorption by reducing gastric acid, intrinsic factor and calcium levels in the body.
For example, thinning of stomach lining with age reduces the secretion of intrinsic factor, which is a protein that binds to the free B12. This conjugation of B12 and intrinsic factor is absorbed by the small intestine, which has receptors for intrinsic factor. That is why you need intrinsic factor for effective absorption of B12.
Other factors that cause B12 shortage in the body include:
- Long term use or proton pump inhibitors (drugs used to treat ulcers and GERD)
- Pernicious anemia (an autoimmune disorder where the immune system destroys cells that produce intrinsic factor)
- Weight loss surgery
- Excessive use of alcohol
Vitamin B12 deficiency can be easily prevented or corrected by eating B12 rich foods or taking supplements. In some cases, such as pernicious anemia or diabetes, foods or oral supplements may not work, and you might need intramuscular injections to restore your blood levels.
Liposomal vitamin B12 supplements are also very effective in people with absorption issues. Supplements that are formulated using liposomes improve the bioavailability and absorption of the nutrients. These forms of dietary supplements don’t undergo the typical digestion process and are delivered directly to the cells and tissues for absorption and utilization.
- Sabry et al. Serum levels of homocysteine, vitamin B12, and folic acid in vitiligo. The Egyptian Journal of Dermatology and Venerology. 2014
- Lishear et al. Vitamin B12 and Homocysteine Levels and 6-Year Change in Peripheral Nerve Function and Neurological Signs. J Gerontol A Biol Sci Med Sci. 2012
- Shah et al. Correlation of hyper-homocysteinemia with coronary artery disease in absence of conventional risk factors among young adults. J Saudi Heart Assoc. 2018
- Mahalle et al. Vitamin B12 deficiency and hyperhomocysteinemia as correlates of cardiovascular risk factors in Indian subjects with coronary artery disease. J Cardiol. 2013
- Ma et al. Serum high concentrations of homocysteine and low levels of folic acid and vitamin B12 are significantly correlated with the categories of coronary artery diseases. BMC Cardiovasc Disord. 2017
- S. Zhang, Y.Y. Bai, L.M. Luo, W.K. Xiao, H.M. Wu, P. Ye Association between serum homocysteine and arterial stiffness in elderly: a community-based study J Geriatr Cardiol. 2014.
- Shu et al. Effects of folic acid combined with vitamin B12 on DVT in patients with homocysteine cerebral infarction. Eur Rev Med Pharmacol Sci. 2017
- He Y et al. Homocysteine level and risk of different stroke types: a meta-analysis of prospective observational studies. Nutr Metab Cardiovasc Dis. 2014
- Zacharia e al. Recurrent stroke in a patient with vitamin B12 deficiency and MTHFR mutation. Neurol Clin Pract. 2017
- Towfighi et al. Homocysteine-lowering therapy and risk of recurrent stroke, myocardial infarction and death: the impact of age in the VISP trial. Cerebrovasc Dis. 2014