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Homocysteine - The Multidimensional Blood Marker

A key tool I often use in my Functional Nutrition practice is analyzing my clients' blood work. This proactive approach helps in identifying early signs of dysfunction, which differs from our current medical system. By examining blood work, I gain insight into my clients' functional health status, determining whether they are progressing towards optimal wellness or potentially facing health issues.

This approach contrasts with conventional medicine, which tends to view conditions in binary terms – you're either diabetic or you're not, leaving little room for nuance. As a Functional Nutritionist, my goal is to address concerns before they escalate. One way to support this is through ongoing monitoring of blood work and symptoms. This allows us to track trends and I can support my clients with personalized dietary, supplement, and lifestyle adjustments to guide my them towards optimal health.

One marker that I always include in my Comprehensive Panel is homocysteine. This marker is rarely ordered and is incredibly valuable. Read on to learn more about what this marker can indicate, why I include it, its importance to your health and longevity, and what you can do to get it back into better ranges!

What is Homocysteine? 

Homocysteine is an amino acid that is produced in the body as part of the normal process of methionine metabolism. Methionine is an amino acid that is obtained from dietary sources, such as meat, fish, and dairy products. When the body metabolizes methionine, it can be converted into homocysteine.

Homocysteine can be further metabolized through two main pathways: remethylation and transsulfuration. In the remethylation pathway, homocysteine is converted back into methionine with the help of certain enzymes and co-factors, such as vitamin B12 and folate (a form of vitamin B9). In the transsulfuration pathway, homocysteine is converted into other compounds, including cysteine.

Elevated levels of homocysteine in the blood are associated with deficiencies in vitamin B12, vitamin B6, and folate (B9). These vitamins play crucial roles in the metabolism of homocysteine, and their deficiencies can lead to an accumulation of homocysteine

Homocysteine is also a key player in the process of methylation, which is part of phase II detoxification in the liver. When homocysteine levels are elevated, this can be a sign the body is not detoxifying well and/or methylation is impaired (methylation is one of many pathways used in the liver for phase 2 detoxification)…we want this pathway working, just like we want all the detoxification pathways working. 

If there is a deficiency of B12, B6, and/or folate (B9), we will be unable to convert homocysteine to cysteine and methionine. When these nutrients are low, we will have higher homocysteine levels in our blood which can be problematic to our health. High homocysteine levels can accumulate to toxic levels, generating oxidative stress and the buildup of cholesterol that can cause arterial wall injury. When homocysteine is lingering in the blood it irritates the inner lining of arteries, veins, and over time makes them rough instead of smooth. This causes the arterial walls to thicken with atherosclerotic plaque as the cells that line the artery mix together with proteins and lipids. Eventually these plaques can cause degeneration of the arterial walls and a restriction of circulation, called atheroma. When an atheroma blocks blood to the heart, it causes a heart attack. When it blocks blood flow to the brain, it will cause a stroke. This process is also associated with high blood pressure and other cardiovascular issues.

As a functional nutritionist, my goal is to minimize as many risk factors as possible for my clients. Since heart disease and heart related deaths are so prevalent today, checking this marker can have a major impact. Many are familiar with other risk factors that are associated with heart disease, including family history, smoking, obesity, lack of exercise, diabetes and lipid imbalances, but homocysteine is rarely talked about and never checked in a regular blood work up. 

What causes homocysteine levels to go up?

B Vitamin Deficiencies

  • Homocysteine levels will increase when there is a deficiency in B12, folate (B9) and B6. 

  • A diet that is high in sugar and carbohydrates can deplete these key B vitamins. 

  • A vegan or vegetarian diet may be lacking the right nutrients to lower homocysteine levels. Specifically due to lower B12 intake with this type of diet which will lead to lower levels of these key vitamin.

Gut dysbiosis

  • Infections or imbalances of gut bacteria can cause dysbiosis, which can make one more susceptible to higher homocysteine. Often this is due to poor absorption of the very key nutrients needed to reduce homocysteine levels. 

  • Commensal bacteria in our gut also help to produce B vitamins, so if there is an imbalance this can contribute to B vitamin deficiencies as well. 

  • H. Pylori infection can cause a deficiency in B12 absorption, due to the fact that this bacterium affects our ability to absorb this vitamin, by decreasing our stomach acid. 


  • Chronic stress can impact the body's ability to metabolize homocysteine. Stress management techniques and a balanced lifestyle can play a role in supporting overall health, including homocysteine levels.


  • Certain medications, such as anticonvulsants, methotrexate (an immunosuppressant), metformin (used for diabetes), cholestyramine (used to lower cholesterol), birth control pills, and proton pump inhibitors, can interfere with B vitamin absorption or metabolism, impacting homocysteine levels.


  • Hypothyroidism, a condition where the thyroid gland doesn't produce enough thyroid hormones, can be associated with elevated homocysteine levels. Proper management of thyroid function is important for maintaining homocysteine balance.

  • A meta-analysis of 17 studies found that hypothyroid people not treated with levothyroxine (synthetic T4) had increased homocysteine levels, associated with the severity of hypothyroidism. When discovered and treated with levothyroxine (T4) treatment was effective in reducing homocysteine levels.

Dental health

  • Periodontal disease has been linked to increased homocysteine levels. Taking care of oral health through regular dental hygiene practices may contribute to overall cardiovascular health.


  • Genetic factors can influence how the body metabolizes homocysteine. Some individuals may have genetic variations that affect the efficiency of this process, potentially leading to higher levels of homocysteine.

  • Elevations in homocysteine can be caused by relatively common mutations in the MTHFR gene. 

    • MTHFR C677T. This mutation (the A allele) is associated with reduced enzyme activity, elevated total homocysteine levels and altered distribution of folate. People with one “A” allele for this mutation have a 35% lower and people with “AA” genotype 68% lower enzyme activity.

    • MTHFR A1298C. This mutation also impacts the MTHFR activity and homocysteine levels but to a lesser extent than C677T.

  • Other genes that can also have an impact on homocysteine levels are: 

    • CBS

    • MTR

    • MTRR

Alcohol and Smoking

  • Excessive alcohol consumption and smoking can contribute to elevated homocysteine levels. Both habits can affect the absorption and utilization of B vitamins in the body.

Kidney Disease

  • Impaired kidney function can lead to reduced clearance of homocysteine from the body, contributing to higher levels. Monitoring and managing kidney health are important in controlling homocysteine levels.

Health Implications of High Homocysteine

Heart Disease/Cardiovascular issues. 

  • Elevated levels of homocysteine damage the inner endothelial lining of blood vessels, promoting inflammation and oxidative stress in the vasculature. This increases the risk of atherosclerosis, a thickening and hardening of arteries caused by plaque buildup, and blood clots. Atherosclerosis is a primary cause of cardiovascular disease, including coronary artery disease (CAD), heart attack, heart failure, and stroke. 

Brain Imbalances

  • Studies show that nutritional interventions with homocysteine-lowering B vitamins slow the rate of brain atrophy in elderly with mild cognitive impairment. It is unclear if homocysteine directly causes brain atrophy or if these findings are related to vitamin deficiencies. Nevertheless, the evidence does support that homocysteine is neurotoxic and decreases blood perfusion to the brain. Elevated levels are associated with neurodegeneration progression, as observed in diseases like Alzheimer's disease.

  • There is also a correlation between high homocysteine levels and depression. In a study including over 900 middle-aged men, researchers found that individuals in the upper tertile for homocysteine levels had more than a two-fold increased risk for depression than those in the lowest tertile. Another study found that individuals with homocysteine levels greater than 12 µmol/L had significantly lower SAMe, mood-enhancing neurotransmitters, and red blood cell folate levels. 

Associated with Insulin Resistance

  • High levels of homocysteine, called hyperhomocysteinemia, are linked to insulin resistance, a condition where cells become less responsive to insulin. This association is due to several factors:

  • Impaired Insulin Signaling: Elevated homocysteine can disrupt insulin signaling pathways in cells, reducing their sensitivity to insulin and hindering glucose uptake.

  • Inflammation and Oxidative Stress: Hyperhomocysteinemia promotes inflammation and oxidative stress, both of which contribute to insulin resistance by disrupting cellular function and signaling.

  • Endothelial Dysfunction: Homocysteine damages blood vessel lining, leading to endothelial dysfunction, impairing blood flow and nutrient delivery to insulin-sensitive tissues.

  • Disruption of Methylation Pathways: Homocysteine is involved in crucial cellular processes like methylation, affecting gene expression and metabolism, thereby influencing insulin sensitivity.

Bone Building Effected

  • Osteoporosis and hip fracture are correlated with elevated homocysteine. Not only does homocysteine promote oxidative stress, but it also interferes with collagen cross-linking, altering the bone matrix composition and increasing bone fragility.

Who is a good candidate to get tested? 

Anyone who has a family history of heart disease, stroke, diabetes or cognitive degeneration.  Additionally, anyone who has already been diagnosed with any of these conditions should be monitoring their homocysteine levels.  Individuals who have a family history or personal history of alcoholism or kidney disease will also be at risk. And, anyone who knows or suspects they have a genetic predisposition. Anyone on a diet that is low in B12, folate or B6. Anyone with gut infections or history or not digesting well, anyone is taking the following medications that are known to deplete the necessary B vitamins that help keep homocysteine in check. Which is why I check everyone!

Strategies to Lower Homocysteine

Lowering homocysteine levels can be achieved through various dietary, lifestyle, and supplementation approaches. Here are some effective strategies:

Increase Intake of B Vitamins: Vitamins B6, B12, and folate (B9) are essential for homocysteine metabolism. Consuming foods rich in these vitamins can help lower homocysteine levels.

  • Folate (B9) - chicken and beef liver, asparagus, avocado, spinach (raw and cooked) as well as other dark leafy greens, green peas, oranges

  • Vitamin B6 - beef liver, tuna, salmon, chicken, egg yolk, dark leafy greens, bananas, papayas, oranges, cantaloupe

  • Vitamin B12 - organ meats, shellfish, fish, meat, poultry, eggs, dairy (especially those with live cultures)

Eat Foods Rich in Betaine: Betaine, found in foods like beets, spinach, quinoa, and wheat bran, can help lower homocysteine levels by facilitating its conversion to methionine.

Limit Alcohol Consumption: Excessive alcohol intake can interfere with the body's ability to metabolize and remove homocysteine. Limiting alcohol consumption or avoiding it altogether can help reduce homocysteine levels.

Quit Smoking: Smoking increases homocysteine levels and oxidative stress in the body. Quitting smoking can lead to a reduction in homocysteine levels and improve overall health.

Exercise Regularly: Regular physical activity can help lower homocysteine levels by improving circulation, reducing inflammation, and enhancing overall metabolic health.

Maintain a Healthy Weight: Obesity is associated with higher homocysteine levels. Maintaining a healthy weight through a balanced diet and regular exercise can help lower homocysteine levels.

Consider Supplementation: If dietary intake is inadequate or if there are absorption issues, supplementation with B vitamins (B6, B12, folate) may be necessary. However, it's essential to consult with a healthcare professional before starting any supplementation regimen.

Manage Stress: Chronic stress can contribute to elevated homocysteine levels. Practicing stress-reducing techniques such as meditation, yoga, deep breathing exercises, or spending time in nature can help lower stress levels and subsequently reduce homocysteine levels.

Get Enough Sleep: Poor sleep quality and duration have been linked to higher homocysteine levels. Aim for 7-9 hours of quality sleep per night to support overall health and lower homocysteine levels.

By incorporating these strategies into your lifestyle, you can effectively lower homocysteine levels and reduce the associated health risks. However, it's essential to consult with a healthcare professional before making significant dietary or lifestyle changes, especially if you have underlying health conditions or are taking medications.


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