One of the most powerful ways we can support our clients is to identify risk factors their doctors typically do not assess. One such marker we always recommend including as part of a comprehensive blood panel is homocysteine. Rarely will a doctor order this marker, even though it is inexpensive and incredibly valuable.
Homocysteine is a sulfur-containing amino acid that naturally occurs in all humans. When it becomes elevated it can significantly increase the risk for cardiovascular disease, stroke, Alzheimer’s disease (AD), and osteoporosis. Homocysteine is also a key player in the process of methylation, a phase II liver detoxification pathway and when it is elevated, detoxification is impaired.
Homocysteine should be present in small amounts in the blood but when there is a deficiency of B12, B6, and/or B9 (folate), it is unable to convert to cysteine and other beneficial compounds. Essentially, elevated homocysteine is a deficiency of, and/or an inability to absorb, these crucial B vitamins. Extremely high plasma homocysteine is linked to a rare genetic disorder called homocystinuria; however, even mildly elevated levels can be problematic.
With the rate of heart disease and heart-related deaths so prevalent today, functional nutritionists must be focused on helping clients eliminate as many risk factors as possible. Most of us are familiar with many of them, including family history, smoking, obesity, lack of exercise, diabetes, and lipid imbalances. Less well-known and rarely talked about is the fact that when these vital B vitamins are lacking, homocysteine can accumulate to toxic levels, generating oxidative stress and the buildup of cholesterol that can cause arterial wall injury. High levels of homocysteine irritate the inner lining of arteries and 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 protein and lipids. Eventually these plaques cause degeneration of the arterial walls and a restriction of circulation, which is called atheroma. When an atheroma blocks blood to the heart, it causes a heart attack. When it blocks blood flow to the brain, it is a stroke.
The famous Framingham study gave researchers an ideal opportunity to observe homocysteine levels over several years in 1092 people who initially had no memory issues, well before there was any evidence of dementia. The study found that elevated homocysteine levels doubled the chance that a study participant would develop AD and each 5 mmol/liter elevation in homocysteine increased the risk of AD by 40%. The association between elevated homocysteine and AD was found to be strong and independent of age, sex, APOE genotype, and other known risk factors for dementia and AD. (1)
Another study looked at the association between levels of circulating homocysteine and the risk of osteoporotic fracture. The results showed that increased homocysteine appears to be a strong independent factor for osteoporotic fractures in older men and women. The link between these two problems is thought to involve an interference by homocysteine in collagen cross-linking. Additionally, lower amounts of collagen cross-links have been found in patients who have high homocysteine levels. (2)
Homocysteine levels can vary with age, sex, diet, and genetics. It is typically found at higher concentrations in men than women and it’s estimated that roughly 5-10% of the population present with high lab values. While homocysteine values vary from lab to lab, the conventional lab reference range is typically <14.5 umol/L. As with other blood markers, IRH recommends utilizing a tighter optimal, or functional range when measuring homocysteine. The functional range for homocysteine is <7. The New England Journal of Medicine reported on a study that looked at mortality from coronary artery disease and homocysteine levels and found that a homocysteine blood level between 9 and 15 correlated with an 8.6% risk of dying from coronary artery disease while a homocysteine value of >15 correlated with a 24.6% death rate. (3)
Yet another study, done in Japan, looked at homocysteine and the risk of stroke. The control group, representing normal risk, had homocysteine levels of <7 umol/L. When homocysteine levels were between 7 and 9, there was 26% greater risk of a stroke. When homocysteine was between 9-11, they found a 31% increased risk and, incredibly, those with a homocysteine level above 11 had a 74% increased risk of stroke. (4)
Once elevated homocysteine has been identified, what do we do about it?
While it’s difficult to address with diet alone, we always include dietary recommendations. B12 is primarily found in animal-based foods, folate is high in dark leafy greens, and B6 can be found in bananas, poultry and fish. Moderating alcohol and caffeine can also help keep homocysteine levels in check. Even when dietary sources of these nutrients are adequate, the ability to digest and absorb them is key so ensure your client is producing adequate hydrochloric acid. Supplementation with methylated forms of these nutrients has been shown to effectively reduce homocysteine levels. We always recommend appropriate testing to determine initial need and ongoing dosing.
Despite all of the research and evidence regarding the many risks of high homocysteine levels, the American Heart Association does not recommend including homocysteine in routine screenings. That means it’s really up to us as functional practitioners to educate our clients about this important and valuable marker.
(1) https://pubmed.ncbi.nlm.nih.gov/11844848/
(2) https://www.nejm.org/doi/full/10.1056/NEJMoa032546#
(3) https://pubmed.ncbi.nlm.nih.gov/9227928/
(4) https://pubmed.ncbi.nlm.nih.gov/15159287/
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FAQ
These frequently asked questions expand on the key clinical concepts in this article and provide additional context for practitioners using homocysteine as part of a comprehensive functional blood assessment.
What is homocysteine, and why is it an important marker in functional nutrition?
Homocysteine is a sulfur-containing amino acid that serves as an important functional marker because elevated levels may indicate nutrient deficiencies, impaired methylation, and increased chronic disease risk. It is rarely included in routine blood work despite being inexpensive and clinically valuable. Functional practitioners often use it as part of a comprehensive blood panel to identify risks that may otherwise go unnoticed.
Why do functional practitioners recommend testing homocysteine?
Functional practitioners recommend testing homocysteine because elevated levels may reveal nutritional and metabolic dysfunction before more advanced disease develops. The marker provides insight into methylation status and potential deficiencies in key B vitamins that support cardiovascular, neurological, and overall health.
What causes elevated homocysteine levels?
Elevated homocysteine most commonly results from a deficiency of vitamin B12, vitamin B6, or folate (vitamin B9), or an inability to properly absorb these nutrients. When these vitamins are insufficient, homocysteine cannot be efficiently converted into cysteine and other beneficial compounds. Age, sex, diet, and genetics can also influence homocysteine levels.
What is the functional range for homocysteine?
The article recommends a functional homocysteine range of less than 7 µmol/L. While many conventional laboratories use a reference range of less than 14.5 µmol/L, functional practitioners use a narrower optimal range to identify potential dysfunction earlier.
How is homocysteine connected to methylation?
Homocysteine is a key component of the methylation cycle. Elevated homocysteine may indicate impaired methylation, which can negatively affect phase II liver detoxification. Because methylation depends on adequate B-vitamin status, deficiencies may contribute to reduced detoxification capacity.
How can elevated homocysteine affect cardiovascular health?
Elevated homocysteine is associated with increased cardiovascular disease risk because it may contribute to oxidative stress and injury to the inner lining of blood vessels. Over time, this irritation can promote plaque formation, arterial thickening, reduced circulation, and an increased risk of heart attack or stroke.
What is the relationship between homocysteine and Alzheimer’s disease?
Research cited in the article found that elevated homocysteine was associated with a substantially higher risk of Alzheimer’s disease. One study reported that elevated levels doubled the likelihood of developing Alzheimer’s disease, and every 5 µmol/L increase in homocysteine was associated with a 40% increase in risk.
How is elevated homocysteine associated with osteoporosis?
Elevated homocysteine has been associated with an increased risk of osteoporotic fractures in older adults. The proposed mechanism involves interference with collagen cross-linking, which may weaken bone structure and contribute to fracture risk.
How does stroke risk change as homocysteine increases?
The article cites research showing that stroke risk increased progressively with higher homocysteine levels.
Specifically:
- Less than 7 µmol/L served as the reference group.
- 7–9 µmol/L was associated with a 26% greater stroke risk.
- 9–11 µmol/L was associated with a 31% greater stroke risk.
- Greater than 11 µmol/L was associated with a 74% greater stroke risk.
What dietary strategies may help lower elevated homocysteine?
Diet can support healthy homocysteine metabolism, although the article notes that diet alone is often insufficient.
Recommended food sources include:
- Vitamin B12 from animal-based foods
- Folate from dark leafy greens
- Vitamin B6 from bananas, poultry, and fish
Moderating alcohol and caffeine intake may also help support healthy homocysteine levels.
Why is digestion important when addressing elevated homocysteine?
Adequate digestion is important because clients must be able to absorb the B vitamins required for normal homocysteine metabolism. The article specifically recommends ensuring adequate hydrochloric acid production so that vitamin B12, folate, and vitamin B6 can be properly utilized.
Can supplementation reduce elevated homocysteine?
Yes. According to the article, supplementation with methylated forms of vitamin B12, vitamin B6, and folate has been shown to effectively reduce homocysteine levels. Appropriate laboratory testing should be used to determine both the need for supplementation and ongoing dosing.
Why isn’t homocysteine included in routine medical screening?
Despite research linking elevated homocysteine with multiple chronic diseases, the article notes that the American Heart Association does not recommend routine homocysteine screening. As a result, functional practitioners often play an important role in educating clients about the value of this marker and including it as part of a comprehensive assessment.
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ABOUT THE AUTHOR
Anne Fischer Silva’s journey in the field of functional nutrition over the last 23 years began in a functional medicine practice, where she learned the power of objective testing. From there she opened her own business, A New Leaf Nutrition, where she built a wait-list distance practice. Anne has taught nutrition courses in Washington, Hawaii, and California, and hosted a radio show, “Health-Wise”, for 3 years. She helped develop the original curriculum for the Nutritional Therapy Association, was a lead instructor with NTA for 8 years, and she continues to lecture nationally on a variety of health topics. Anne founded the Institute of Restorative Health in 2013 with the sole purpose of training other nutrition professionals how to address complex issues with their clients and achieve the same stellar results she gets in her practice.
The core principles Anne built the Institute of Restorative Health upon are the importance of nutrient-dense foods and balancing biochemistry. From there, she looks for the deeper underlying issues by utilizing a variety of testing techniques and customized healing methods to restore optimal function and health.
Anne received her certification in functional nutrition from Advanced Integrated Medical Institute in Washington, DC in 2000 and she is a Master Restorative Health Practitioner and Functional Nutritional Therapy Practitioner.
In 2022, Anne decided to pursue new and different aspects of holistic wellness and left the Institute of Restorative Health in the hands of her dear friend and business partner, Margaret Floyd Barry.
