By Dr. Cara Matocha, Functional Wellness Consultant

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Chances are you may not have heard of homocysteine, but this amino acid is quickly becoming noticed as an important player in a variety of diseases and is still largely overlooked by conventional medical doctors.

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Elevated homocysteine levels have been linked to a variety of health problems including:

• Atherosclerosis
• Blood Clots
• Heart Attacks and Strokes [1]
• Cognitive Decline and Brain Fog
• Dementia and Alzheimer’s Disease
• Anxiety, depression, and mood changes. [2]
• Osteoporosis and Fractures [2]
• Chronic Kidney Disease (CKD)
• Fatigue and Muscle Weakness

Homocysteine is at the center of important bodily processes such as the methylation cycle, detoxification, and neurotransmitter balance. Elevated homocysteine levels may denote underlying nutritional, metabolic, genetic, or physiological dysfunction that quietly lead to cardiovascular and neurological dysregulation.

Understanding what homocysteine is and how it impacts your body can be helpful for patients who have had trouble seeing success in addressing high blood pressure and other cardiovascular issues. Learning how to keep homocysteine levels at an optimal range will support your brain, heart, and overall well-being.

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What is homocysteine

Homocysteine is a chemical in the blood that is formed when the amino acid methionine is naturally broken down to be excreted in the urine. During this breakdown process, homocysteine can be recycled and reused to build other proteins. To recycle homocysteine, the body needs vitamins B12, B6, and folate. If these vitamins are deficient, homocysteine cannot be recycled efficiently and accumulates in the blood. An intake of too much methionine-rich animal protein without sufficient B vitamins may also push levels upward.

Furthermore, productive recycling requires the enzyme methylenetetrahydrofolate reductase (MTHFR). If mutations in the gene that makes the MTHFR enzyme exist, this enzyme may not activate optimally, leading to elevated homocysteine levels. Between 40-50% of the population has at least one MTHFR gene variant. Mild to moderate homocysteine elevations are common, while extremely high homocysteine elevations are uncommon. Excess homocysteine damages the inner lining of your arteries and reduces nitric oxide production, causing your blood vessels to stiffen and constrict [3].

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Why do our bodies produce Homocysteine?

The integrity of your DNA is so important that the human body has a special mechanism for repairing it. This special molecule is called S-adenosylmethionine (SAMe). SAMe sits next to DNA and delivers the basic material needed to make and repair molecules: single-carbon units in the form of methyl groups. Amino acids serve as raw material for important molecules such as neurotransmitters and proteins, and SAMe is made from the essential amino acid called methionine.

Oxidative damage occurs when electrons are knocked off molecules. When oxidative stress damages a DNA molecule, one of three things can happen: (1) Distortion of the information package presented by the dividing cell, perpetuating this distortion and altering the function of an entire line of cells (as is the case with cancer). (2) Distortion of the information package in one of your permanent un-dividing cells of the brain or immune system, either polluting or diminishing these irreplaceable cells. (3) Alteration of the DNA of a reproductive cell, harming future generations [4].

The repair molecule, SAMe, supplies the methyls (single carbon atoms) needed to replace the broken parts of the DNA. The intermediary in this process is folate, a B vitamin that plays a major role in cancer prevention by supporting the synthesis of healthy DNA and the repair of damaged DNA. Folate provides methyl groups for DNA methylation. Antioxidant mechanisms protect DNA, but its repair depends on an interconnected group of substances, including amino acids (the source of methyl groups), SAMe, folate, B12, and B6.

Methionine is a very special amino acid. Methionine has the special versatility of having methyls (single-carbon units), sulfur (with a quality of stickiness), and nitrogen (the defining ingredient of amino acids). With the help of folate, methionine becomes SAMe and donates its methyl groups to damaged DNA. Once it gives up its single carbon unit to the DNA molecule, SAMe becomes homocysteine. Only through proper detoxification processes or the replenishment of its methyl group can homocysteine be rendered harmless.

The body makes homocysteine because it is needed to make methionine’s most useful metabolite, reduced glutathione (RG). This is the most important metabolite in detoxification because it replenishes vitamin E. RG detoxifies substances created within the body through metabolism, transports them outside the body, and then returns for another load. But if it detoxifies substances that came in from outside the body, it takes the toxic load out but cannot return. This is why it is imperative to reduce your exposure to outside toxins as much as possible.

RG also has an important job of tending the fire that is needed to create important messenger molecules called leukotrienes. Lastly, the restoration of methionine from homocysteine depends on folate working with Vitamin B12 and B6. A lack of folate causes a buildup of homocysteine and insufficient DNA repair, which can lead to chromosome damage. Cancer arises in tissues that are constantly renewed, such as the mucous membrane of the lungs and the digestive, urinary, and reproductive tracts, when the supply of reparative methyls fails due to a lack of folate [5].

If you do not meet your need for folate, B6, or B12, then you have a one-in-fifty chance of being poisoned by your own homocysteine. The body rids itself of toxic substances using a sticky sulfur-oxygen group (sulfate), and when too much homocysteine is in the system, these sticky substances stick to healthy tissues, weakening them and creating further oxidative stress. This harms the blood vessels. Homocysteine will also liberate free radicals to do their mischief. If you eat a large amount of protein or take methionine supplements while having a weak mechanism for converting homocysteine back to methionine, you will unleash homocysteine to damage your body further.

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What your body is telling you through homocysteine

Elevated homocysteine levels mean your body has a problem getting rid of homocysteine, either during the remethylation process or the transsulfuration process. A problem within either one of these pathways will keep your body from clearing out homocysteine, allowing it to build up to unsafe levels. While both processes may need support through B vitamin supplementation, it is important to understand that homocysteine may not be the actual problem. Homocysteine acts as a warning that something else is wrong and needs to be addressed. Lowering homocysteine may not fix the root cause. When homocysteine levels are high, the goal is not to lower homocysteine levels as fast as possible. Instead, this should prompt a practitioner to keep looking for the root cause of the dysfunction.

A good practitioner will take the time to research possible causes. Methionine, SAMe, glycine, and serine levels, along with genetic markers, are all important to consider. Knowing these patients' genetic predispositions is also critical.

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Medications that can interfere with folate metabolism or reduce folate levels:

• Methotrexate and anticonvulsants
• Metformin (which is commonly used for diabetes)
• Proton pump inhibitors (can lower B12 absorption)
• Cholesterol-lowering drugs such as cholestyramine and niacin (can disrupt folate and homocysteine metabolism)

Lifestyle factors also contribute to higher levels of homocysteine, especially in people who consume too much alcohol, smoke, drink excessive amounts of coffee, or do not engage in a proper amount of physical activity.

It should also be noted that high homocysteine levels due to MTHFR gene variants can affect many other systems within the body. It is important to note these symptoms should a patient notice dysfunction in any of these areas. They include infertility, estrogen dominance, brain fog, anxiety low energy including digestive complaints [6].

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Managing homocysteine levels

With proper nutrition you can balance homocysteine levels.

• Methylfolate (B9) is required for new cell formation and DNA synthesis, as well as for converting homocysteine back to methionine. Food sources of folate include legumes and green leafy vegetables. Avoid taking folic acid.
• Riboflavin (B2) specifically supports homocysteine levels by helping to convert folate to the form necessary to convert homocysteine to methionine. It helps to convert food into usable energy and assists several antioxidant enzymes. Sources of riboflavin include salmon, eggs, and clean dairy products.
• Pyridoxine (B6) also helps convert food into usable energy and supports the formation of neurotransmitters, red blood cells, and DNA. This vitamin supports other B vitamins in lowering homocysteine levels. Food sources for pyridoxine include fish, poultry and nuts. ‍
• Cobalamin (B12) while also supporting the other B vitamins in maintaining healthy homocysteine levels, also helps to make red blood cells and is required for proper nerve function. It can be obtained through a diet rich in seafood (such as clams), poultry, and red meat.
• Choline is a nutrient not previously mentioned, but it is vital for cell membranes and some proteins. It is a precursor to betaine, which is a compound that supports the conversion of homocysteine to methionine. It aids in the transportation and metabolism of fat and cholesterol. Choline can be found in eggs, meat, and seafood.
• Vitamin C is not always discussed as an option for treating high homocysteine levels, the increased oxidative stress caused by higher homocysteine levels can quickly deplete vitamin C. Because Vitamin C is a powerful antioxidant and can neutralize free radicals, it may also be a valuable vitamin in treating high homocysteine levels.
• Betaine transfers methyl groups in metabolic pathways to convert toxic homocysteine into the beneficial amino acid L-methionine. ‍
• SAMe can also be considered for mood and methylation support.

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Suggested testing:

• Plasma homocysteine concentration (fasting preferred).‍
• It can be combined with other labs, such as B12, folate, methylmalonic acid (MMA), and vitamin D, to give a broader view of methylation and nutrient status.

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Preferred Homocysteine levels:‍

Functional medicine practitioners typically consider optimal homocysteine levels to be between 5–8 µmol/L.

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If you would like to learn more feel free to contact us to set up an appointment.

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*Nothing stated above is meant to diagnose, treat, or cure any illness or condition. Consult your healthcare practitioner for further information.

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References:

1)    https://medlineplus.gov/lab-tests/homocysteine-test/

2)    https://www.ncbi.nlm.nih.gov/books/NBK554408/

3)    Sen, U., Mishra, P. K., Tyagi, N., & Tyagi, S. C. (2010). Homocysteine to Hydrogen Sulfide or Hypertension. Cell Biochemistry and Biophysics,57(2–3), 49–58. https://doi.org/10.1007/s12013-010-9079-y

4)    MacDonald Baker, Sidney. Detoxification and Healing. McGraw-Hill Education, 11 Sept. 2003.

5)    Giovannucci, E. (2002). Epidemiologic studies of folate and colorectal neoplasia: a review. The Journal of Nutrition,132(8 Suppl), 2350S–2355S. https://doi.org/10.1093/jn/132.8.2350S

6)    Tito. (2018, July 18). Common MTHFR Gene Mutation Symptoms. MTHFR Support Australia. https://www.mthfrsupport.com.au/2018/07/5-common-mthfr-symptoms-and-how-to-manage-your-gene-mutation/

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