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Balancing Homocysteine Levels: The Role of Essential Nutrients in Heart Health

Balancing Homocysteine Levels: The Role of Essential Nutrients in Heart Health 

Balancing Homocysteine Levels: The Role of Essential Nutrients in Heart Health 

Homocysteine is an amino acid naturally produced by the body. It’s normally kept in check by various nutrients but, if these nutrients aren't sufficient, homocysteine can rise to unsafe levels. Elevated homocysteine is associated with an increased risk of cardiovascular disease and other heart issues. [1]

Supplementing with specific vitamins, minerals, and other nutrients can help regulate homocysteine levels and support heart health. 

In this article, we'll explore the significance of homocysteine and identify the nutrients and natural remedies you can add to your diet or supplement regime. 

Defining homocysteine

Homocysteine is a sulfur-containing amino acid that occurs naturally in the body. It's produced as part of the process of breaking down another amino acid called methionine, which we get from the protein in our diet. Methionine is one of the eleven ‘essential’ amino acids that we must obtain from food as it cannot be produced by the body. [2]

Homocysteine is usually present only in very small amounts in our cells and for only a short time before it is converted to other constituents.

Normally, homocysteine is either converted back into methionine or transformed into another amino acid called cysteine. This conversion involves a range of B vitamins working together in a process called remethylation. [3]

However, if the remethylation process is disrupted or inefficient, homocysteine levels can rise in the body, leading to serious health issues.

High homocysteine levels: symptoms

While some with elevated homocysteine may not have any symptoms, those who are deficient in vitamin B12, B6, and folate could show symptoms associated with those deficiencies, such as fatigue, numbness/tingling, weight loss, and poor cognitive function. [4]

Risks of elevated homocysteine

High homocysteine - known clinically as hyperhomocysteinemia - is a risk factor for several diseases, including cardiovascular and neurological conditions. Prolonged exposure to high homocysteine can lead to the development of atherosclerosis, stroke, inflammatory syndromes such as osteoporosis and rheumatism, as well as neuronal pathologies including Alzheimer's and Parkinson's diseases. [5] Elevated homocysteine is also strongly associated with other conditions related to metabolic syndrome such as hypertension, which is correlated with type II diabetes mellitus (T2DM). [6]

What Does it Mean to be the “Best” Methylfolate

When chronically elevated, homocysteine promotes the formation of atherosclerotic plaques which can then lead to endothelial dysfunction, increased inflammation, and a higher risk of thrombophilia (blood clots). [7]

Studies show that 10% of all coronary artery disease is attributed to high homocysteine levels, and that a level higher than 5 μmol/l raises the risk of ischemic heart disease by 84%. [8]

Homocysteine also causes endothelial dysfunction by reducing nitrogen monoxide (NO), the main vasodilator of the endothelium, as well as increasing oxidative stress. These effects can cause severe damage to the walls of blood vessels, leading to vascular inflammation and atherosclerotic lesions. [9]  Homocysteine can also cause apoptosis (death) of endothelial cells and alters lipid metabolism, causing loss of function in cellular membranes. [10]

Essential nutrients for balance

The metabolism of homocysteine involves an important interaction between several different nutrients, namely folate, vitamin B6, and vitamin B12 (cobalamin).  

Two different pathways can be used to metabolize homocysteine. One is the methionine pathway, in which homocysteine is converted to methionine using folate and an enzyme called methionine synthase, which is dependent on vitamin B12. [11]

The other pathway is the “transsulfuration pathway”, in which homocysteine is converted to another amino acid, cysteine. This pathway requires an enzyme called cystathionine β-lyase, which is dependent on vitamin B6. 

Essentially, the regulation of homocysteine in the body depends on the availability of all three B vitamins: folate, vitamin B12, and vitamin B6. A deficiency in any of these nutrients can mean that homocysteine is not converted properly, resulting in elevated levels. It also means that SAMe is not created. 

Low vitamin B6 levels will result in homocysteine being primarily converted to S-adenosyl homocysteine (SAH) because the transsulfuration pathway is affected. Tetrapyrrole biosynthesis - which is needed to make vitamin B12 - will also be inhibited. As a result, SAH can accumulate, which inhibits methylation reactions dependent on S-adenosyl methionine (SAM). [12] This then reduces the synthesis of tetrahydrobiopterin (BH4), the essential cofactor required for creating the precursors to epinephrine, serotonin, and dopamine. [13] As a result, the accumulation of either homocysteine or SAH due to a lack of these B vitamins not only affects cardiovascular health but can also lead to depression and other mental health issues, along with neurotoxic effects. [14]


Dietary tips for homocysteine management

The homocysteine conversion process will not function properly if your body is lacking in methionine, folate, vitamin B12 and vitamin B6. This can occur due to poor diet and/or malabsorption, and/or problems with the metabolism or enzymatic processing of these nutrients. [15]

Increase folate-rich foods

Research suggests that increased folate intake may lower the risk of homocysteine-mediated cardiovascular disease. [16]

Good sources of folate include leafy green vegetables, beans, legumes, broccoli, organ meats such as liver, whole grains, lean poultry, citrus fruits, and avocado.

Increase B6 intake

Homocysteine can be converted to cysteine with the help of active vitamin B6, known as pyridoxal phosphate (P-5-P). P-5-P serves as a cofactor for about 160 reactions in the body, including the transformation of carbohydrates, lipids, amino acids, and nucleic acids. [17] Good sources of B6 include fish, organ meats, poultry, potatoes, grains, soy products, legumes, bananas, dried apricots, and prunes. [18]

Increase B12 intake

Homocysteine can be remethylated to methionine using vitamin B12. Deficiency in B12 is associated with various heart diseases mainly due to hyperhomocysteinemia. Each 5-μmol/L increase above 10 μmol/L of serum homocysteine is associated with a 20% increased risk of circulatory health problems. [19]

B12 is almost exclusively found in animal food products, including red meat, shellfish, poultry, fish, eggs, and dairy products. Some nutritional yeast products also contain vitamin B12. [20]

Increase methionine

A diet low in methionine can increase levels of inflammation in the body. Improving methionine intake is shown to modulate important biological processes associated with a high risk of cardiovascular disease. [21]

Methionine is found in high quantities in a balanced diet that contains nuts, beef, lamb, cheese, turkey, pork, fish, shellfish, soy, eggs, dairy, and beans. [22]

Increase antioxidants

Antioxidant-rich foods are often referred to as ‘heart health foods’ as they are shown to boost serum antioxidant capacity and decrease oxidative stress, helping to protect against inflammation and heart disease. [23] Interestingly, taking antioxidants as dietary supplements does not seem to have the same beneficial effect. [24] Foods rich in antioxidants include red beans, blueberries, pinto beans, cranberries, artichokes, blackberries, apples, pecans, dark leafy greens, and other brightly coloured fruits and vegetables. [25]


The role of supplements

Although nutrients are best sourced from the diet, not everyone is able to obtain the B vitamins they need from food alone. Vegetarians and vegans are typically low in B12 due to a lack of animal products in their diets. People with malabsorption disorders may also be unable to metabolize and absorb sufficient nutrients from food. 

In these cases, nutritional supplements can help to fill any gaps in the diet. 

Methyl-Life® offers a range of methylated vitamins for heart health and other supplements for people who have difficulty metabolizing certain nutrients, particularly folate. Methylfolate - the active form of folate - is ideal for those with MTHFR genetic mutations as it can be used immediately by the body. Methyl-Life’s® Methylfolate 5 mg contains the internationally patented Magnafolate® PRO and provides a highly bioavailable source of folate to support cardiovascular health. 

For more comprehensive heart support, L-Methylfolate 7.5mg + B12 provides both methylfolate and active B12: both of which are required for the proper breakdown of homocysteine. These nutrients are also vital for healthy mood and cognitive function. 

Those requiring a therapeutic dose of methylfolate and B12 would be advised to try L-Methylfolate 15mg + B12, which contains the added benefit of inositol for optimal methylation support. 

Methyl-Life® is renowned for its expertise in MTHFR-related health issues while strictly adhering to all FDA guidelines. Methyl-Life® also provides educational support for those looking to understand more about MTHFR and their health.

The takeaway

Managing homocysteine requires folate, vitamin B6, and vitamin B12. These B vitamins play crucial roles in converting homocysteine to other useful nutrients that support healthy daily functioning. If any of these B vitamins are lacking in the body, homocysteine will not be converted, and may accumulate to harmful levels. High homocysteine is one of the most serious risk factors for heart disease and stroke. 

Plenty of foods contain all three of these B vitamins, which makes it easy to support your intake of B vitamins through diet. For those who struggle with malabsorption or MTHFR mutations, supplementing with active folate (methylfolate) and active B12 is your best bet. 



























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    - Katie Stone



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