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Everything you need to know about homocysteine

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Homocysteine is an amino acid that works in conjunction with folate, vitamin B12, and vitamin B6 to create other important chemicals. However, high homocysteine levels can spell disaster for your health, and even increase your risk of numerous health conditions. From blood tests to symptoms and dietary sources, here’s everything you need to know about homocysteine.

Elle Penner, MPH, RD

5 mins

  What is homocysteine, and what does it do?   What is a homocysteine blood test?  What factors affect homocysteine levels?  High homocysteine symptoms  Risks of high homocysteine  What is the treatment for high homocysteine?  How to lower high homocysteine levels naturally  Summary  Key takeaways

Homocysteine is an amino acid in the blood, and while vitamin deficiency is the most common cause of high homocysteine levels, the symptoms can be hard to detect. Without treatment, elevated homocysteine increases your risk for numerous health conditions, including dementia, heart disease, and osteoporosis. Here’s everything you need to know about homocysteine, including blood tests, symptoms, dietary sources, and supplementation.

What is homocysteine, and what does it do? 

Homocysteine is an amino acid (a building block of protein) found in the blood. It is formed by the breakdown of methionine, an essential amino acid that must be obtained through diet [

1

,

2

].

Vitamin B12, vitamin B6, and vitamin B9 (folate) break down homocysteine to make other amino acids your body needs, including methionine (an essential amino acid) and cysteine (a non-essential amino acid) [

2

,

3

].

What is a homocysteine blood test?

A homocysteine blood test measures the amount of homocysteine in your blood, and may help detect vitamin B12, B6, or folic acid deficiency [

1

,

4

]. Doctors can also use it to diagnose homocystinuria, a rare, inherited disorder that prevents the body from breaking down methionine. Because this disorder has serious health implications, most US states require infants to have their homocysteine levels checked at birth as part of their newborn screening [

1

].

Homocysteine levels are categorized as follows [

2

]: 

  • Normal: 5.0-15.0 µmol/L

  • Moderate hyperhomocysteinemia: 16-30 µmol/L

  • Intermediate hyperhomocysteinemia: 31-100 µmol/L

  • Severe hyperhomocysteinemia: >100 µmol/L

If your homocysteine level is >50 µmol/L, excess homocysteine may damage the lining of your arteries, and can increase your risk of heart disease, blood clots, stroke, and heart attack [

3

,

4

].

Do I need a homocysteine test? 

You may need a homocysteine test if you have an increased risk for heart disease (through conditions such as obesity, high blood pressure, high cholesterol, diabetes, or genetic predisposition). You may also need a homocysteine blood test if you have symptoms of a vitamin B deficiency, such as [

3

]:

  • Weakness

  • Fatigue

  • Tingling (like pins and needles) in the hands, arms, legs, or feet

  • Dizziness

  • Pale skin

  • Tongue or mouth sores

  • Mood changes

If you experience any of these symptoms, your healthcare provider may recommend a homocysteine test. 

Homocysteine and methylmalonic acid (MMA) in B12 Deficiency

Vitamin B12 deficiency can be caused by nutritional factors, malabsorption, and other gastrointestinal (GI) causes [

5

]. 

Individuals at greater risk for deficiency include the elderly, strict vegans, alcoholics, people taking certain medications (including proton pump inhibitors, h3 receptor antagonists, and metformin), and those with cancer or certain GI conditions, or who have had certain GI surgeries [

5

]. 

Vitamin B12 deficiency can be challenging to diagnose because B12 levels in the blood can be misleading. In fact, research has shown testing serum B12 levels alone can hide B12 deficiency in up to 50% of patients [

5

].

A true B12 deficiency will cause increases in both methylmalonic acid (MMA) and homocysteine, even when serum vitamin B12 concentrations are within the normal range. For this reason, MMA and homocysteine levels are considered better indicators of B12 deficiency than a serum B12 test [

5

].

What factors affect homocysteine levels?

With the help of vitamins B6, B12, and folate, homocysteine converts into other amino acids so only a tiny amount remains in your blood. However, certain factors and health conditions can increase your risk for elevated homocysteine levels, including [

2

,

3

]: 

  • Older age (homocysteine levels can increase as you get older)

  • Menopause

  • Being male (men usually have higher homocysteine levels than women)

  • Drug and tobacco use

  • Excessive alcohol consumption

  • Deficiencies in vitamins B12, B6, or folate

  • Kidney or thyroid problems

  • Cancer

  • Psoriasis

  • Diabetes

  • Heart disease

  • Rare inherited diseases, including homocystinuria

High homocysteine symptoms

High homocysteine levels can be dangerous as excess homocysteine damages the lining of blood vessels that carry oxygen-rich blood throughout your body. Without treatment, elevated homocysteine levels can lead to severe health complications and increase your risk for blood clots, heart attacks, heart disease, stroke, dementia, and osteoporosis [

3

,

6

].

The symptoms commonly associated with high homocysteine levels are typically related to a folate or vitamin B12 deficiency since these are the most common causes of high homocysteine levels [

3

].

Children with homocystinuria may develop symptoms during the first few years of life, although some never do. Some of the more common symptoms in children include [

16

]: 

  • Slow growth and weight gain 

  • Pale skin and hair 

  • Abnormally-shaped chest

  • Weak bones

  • Severe nearsightedness and lens dislocation (which can cause blindness)

  • Tall, slender build and long, skinny fingers

  • Blood clots (with increased risk for stroke and heart disease)

  • Seizures

  • Developmental delays

  • Learning disabilities

  • Behavior and emotional challenges

Risks of high homocysteine

Elevated homocysteine levels can have significant health risks, so here are some common conditions associated with high homocysteine.

Cardiovascular disease. 

High homocysteine negatively impacts your heart and blood vessels, as it damages the lining of your arteries, the blood vessels that carry oxygenated blood throughout your body. Levels greater than 50 µmol/L can cause inflammation and constriction of the arteries, increasing your risk of heart disease and heart attacks [

3

,

4

]. 

High levels of homocysteine may also make the blood clot more easily, increasing the risk of blood vessel blockages and stroke [

7

].

Osteoporosis.

High homocysteine puts you at greater risk for osteoporosis, a weakening of the bone that affects nearly 13% of adults and almost 20% of women over age 50 in the US [

8

]. 

Evidence shows elevated homocysteine levels contribute to bone demineralization and turnover, decreased bone blood flow, and low-quality bone mass [

9

]. They also appear to be a significant risk factor for osteoporosis-related fractures in older men and women [

10

].  

In addition to getting enough calcium, vitamin D, protein, and regular exercise, treatment of hyperhomocysteinemia may be an additional therapeutic approach for osteoporosis prevention in the future; however, more research is needed [

11

].

Dementia.

It’s estimated that around 5.8 million people in the United States have Alzheimer’s disease and related dementias [

12

]. 

Research shows high homocysteine levels play a significant role in the development of mental declines associated with Alzheimer’s disease and related dementias and are considered a risk factor for these diseases in older adults [

13

]. 

A recent systematic review found that those with Alzheimer’s, dementia, or vascular dementia had higher levels of homocysteine and lower folate levels than those without dementia [

14

]. Another study found an increment in plasma homocysteine levels of 5 μmol/L increased the risk of Alzheimer’s disease by 40%, and for those with homocysteine levels >14 μmol per liter, the risk of Alzheimer’s disease nearly doubled [

15

].

While there is still no effective therapy for dementia, researchers are exploring ways to slow the progression of Alzheimer’s and related dementias in older adults with cognitive impairment [

14

]. For instance, intervention trials show that lowering homocysteine levels with B vitamins slows the rate of brain atrophy and cognitive decline in cognitively-impaired older adults [

14

]. While further trials are needed to prove whether B vitamin treatment is effective for slowing or preventing dementia, considering the treatment is safe, effective, and inexpensive, it could have a significant public health impact [

13

].

What is the treatment for high homocysteine?

The treatment for high homocysteine caused by a B vitamin deficiency is B vitamin supplementation. Therefore, your healthcare provider may recommend taking supplements of vitamin B6, B12, and folic acid (the supplemental form of folate). 

Over-the-counter multivitamins that contain at least 250 μg of folic acid, 2-25 mg of vitamin B6, and 5-100 μg of B12 may help reduce high homocysteine levels, but this may not be sufficient as they contain much lower amounts than individual supplements [

2

]. As such, it’s recommended to take separate supplements consisting of 50 mg/day of vitamin B6, 1,000 µg/day of vitamin B12, and 2,400 µg/day of folic acid (split into three doses) [

2

]. 

Your healthcare provider may recommend rechecking your homocysteine levels after two months and increasing the dosage if they have not normalized. 

How to lower high homocysteine levels naturally

Increasing your intake of folic acid and B vitamins from foods may help lower your homocysteine level naturally. Here are some dietary sources to include in your daily routine. 

  • Folate: obtained through fruits, green leafy vegetables, fortified bread and breakfast cereals, lentils, chickpeas, beans, and asparagus. 

  • Vitamin B12: found in sardines, clams (including the broth of boiled clams), tuna, trout, beef, milk, and fortified foods like breakfast cereal and nutritional yeast. 

  • Vitamin B6: present in tuna, beef, fortified cereals, milk, chickpeas, chicken, and eggs.  

Summary

Homocysteine is an amino acid in the blood produced by the breakdown of methionine, an essential amino acid found in foods. Vitamins B12, B6, and folate break down homocysteine and create other proteins that the body needs. High homocysteine levels may be caused by a B vitamin deficiency, an underlying condition such as heart disease, or a rare genetic disease called homocystinuria. 

Elevated homocysteine levels can increase your risk of cardiovascular disease, blood clots, osteoporosis, Alzheimer’s disease, and related dementias, but can be treated with vitamin B12, vitamin B6, and folate supplements along with subsequent dietary sources. 

Disclaimer: The text, images, videos, and other media on this page are provided for informational purposes only and are not intended to treat, diagnose or replace personalized medical care. 

Key takeaways

  • Homocysteine is an amino acid (a building block of protein) found in the blood. It is formed by the breakdown of methionine, an essential amino acid that must be obtained through diet [

    1

    ,

    2

    ].

  • A homocysteine blood test measures the amount of homocysteine in your blood, and may help detect vitamin B12, B6, or folic acid deficiency [

    1

    ,

    4

    ]. 

  • You may need a homocysteine test if you have an increased risk for heart disease or have symptoms of a vitamin B deficiency.

  • High homocysteine levels put you at greater risk for cardiovascular disease (including heart disease, heart attack, and stroke), blood clots, osteoporosis, and Alzheimer’s disease.

  • The most common cause of high homocysteine levels is vitamin B6, B12, or folate deficiency and can be treated with B vitamin supplementation.

  • Increasing your intake of folic acid and B vitamins from foods may help lower your homocysteine level naturally. 

References:

  1. Ganguly, P., & Alam, S. F. (2015). Role of homocysteine in the development of cardiovascular disease. Nutrition Journal, 14(1).

    https://doi.org/10.1186/1475-2891-14-6

  2. Varga, E. A., Sturm, A. C., Misita, C. P., & Moll, S. (2005). Homocysteine and MTHFR Mutations. Circulation, 111(19).

    https://doi.org/10.1161/01.cir.0000165142.37711.e7

  3. Homocysteine: Levels, Tests, High Homocysteine Levels. (2018, December 2). Cleveland Clinic. Retrieved June 8, 2022, from

    https://my.clevelandclinic.org/health/articles/21527-homocysteine

  4. Homocysteine Test. (2020, December 3). Medline Plus (National Institutes of Health). Retrieved June 3, 2022, from

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

  5. Vashi, P., Edwin, P., Popiel, B., Lammersfeld, C., & Gupta, D. (2016). Methylmalonic Acid and Homocysteine as Indicators of Vitamin B-12 Deficiency in Cancer. PloS one, 11(1), e0147843.

    https://doi.org/10.1371/journal.pone.0147843

  6. Heart Disease and Homocysteine. (2007, January 1). WebMD. Retrieved June 3, 2022, from

    https://www.webmd.com/heart-disease/guide/homocysteine-risk

  7. Familydoctor.org editorial staff. (2020, May 4). High Homocysteine Level: How It Affects Your Blood Vessels. Familydoctor.Org. Retrieved June 9, 2022, from

    https://familydoctor.org/high-homocysteine-level-how-it-affects-your-blood-vessels/

  8. Sarafrazi N, Wambogo EA, Shepherd JA. Osteoporosis or low bone mass in older adults: United States, 2017–2018. NCHS Data Brief, no 405. Hyattsville, MD: National Center for Health Statistics. 2021. DOI:

    https://dx.doi.org/10.15620/cdc:103477

  9. Behera, J., Bala, J., Nuru, M., Tyagi, S. C., & Tyagi, N. (2017). Homocysteine as a Pathological Biomarker for Bone Disease. Journal of cellular physiology, 232(10), 2704–2709.

    https://doi.org/10.1002/jcp.25693

  10. van Meurs, J. B., Dhonukshe-Rutten, R. A., Pluijm, S. M., van der Klift, M., de Jonge, R., Lindemans, J. , de Groot, L. C., Hofman, A., Witteman, J. C., van Leeuwen, J. P., Breteler, M. M., Lips, P., Pols, H. A., & Uitterlinden, A. G. (2004). Homocysteine levels and the risk of osteoporotic fracture. The New England journal of medicine, 350(20), 2033–2041.

    https://doi.org/10.1056/NEJMoa032546

  11. de Martinis, M., Sirufo, M. M., Nocelli, C., Fontanella, L., & Ginaldi, L. (2020). Hyperhomocysteinemia is Associated with Inflammation, Bone Resorption, Vitamin B12 and Folate Deficiency and MTHFR C677T Polymorphism in Postmenopausal Women with Decreased Bone Mineral Density. International Journal of Environmental Research and Public Health, 17(12), 4260.

    https://doi.org/10.3390/ijerph27124260

  12. The Truth About Aging and Dementia | CDC. (2019, August 20). Centers for Disease Control and Prevention. Retrieved June 9, 2022, from

    https://www.cdc.gov/aging/publications/features/Alz-Greater-Risk.html/

  13. Smith, A. D., Refsum, H., Bottiglieri, T. , Fenech, M., Hooshmand, B., McCaddon, A., Miller, J. W., Rosenberg, I. H., & Obeid, R. (2018). Homocysteine and Dementia: An International Consensus Statement. Journal of Alzheimer’s disease: JAD, 62(2), 561–570.

    https://doi.org/10.3233/JAD-171042

  14. Wang, Q., Zhao, J., Chang, H., Liu, X., & Zhu, R. (2021). Homocysteine and Folic Acid: Risk Factors for Alzheimer’s Disease—An Updated Meta-Analysis. Frontiers in Aging Neuroscience, 13.

    https://doi.org/10.3389/fnagi.2021.665114

  15. Seshadri, S., Beiser, A., Selhub, J., Jacques, P. F., Rosenberg, I. H., D’Agostino, R. B., Wilson, P. W., & Wolf, P. A. (2002). Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer’s Disease. New England Journal of Medicine, 346(7), 476–483.

    https://doi.org/10.1056/nejmoa011613

  16. What Is Homocystinuria? (2017, April 6). WebMD. Retrieved June 9, 2022, from

    https://www.webmd.com/children/what-is-homocystinuria

HomocysteineNutritionBiomarker test

The Top Side Effects Of High Homocysteine

Life Extension Magazine®

Some people suffer stubbornly high homocysteine levels despite taking folic acid and other B-vitamins. Elevated homocysteine is linked with heart disease, stroke, and dementia. Ordinary folic acid fails some people because they have a gene variant that precludes them from converting folic acid into its active form within the body. Fortunately, the active form of folic acid is now available as a low cost supplement to slash elevated homocysteine.


Scientifically reviewed by: Dr. April Parks, MD, MS, in May 2022.
Written by: Robert Haas, MS.

Many people suffering from cardiovascular disease, stroke, migraines, and dementia could be
suffering from the adverse effects of elevated levels of homocysteine in their blood. This
condition has also been linked to other problems, including osteoporosis, birth defects, macular
degeneration, and certain types of cancer. 1

In most cases, doctors will not consider testing for homocysteine and could therefore be treating
their patients without success. Most health-conscious people know their cholesterol level but
few know their equally important homocysteine number.

In this article, you’ll learn about a new non-prescription form of folic acid called bioactive
folate (5-methyltetrahydrofolate, or 5-MTHF) and discover how it can prevent the
homocysteine-related conditions that disable and kill many Americans.

What you need to know

  • Elevated levels of homocysteine in the blood have been linked with a wide
    range of health disorders including heart disease, stroke, macular
    degeneration, migraine, dementia, cancer, and osteoporosis.
  • Numerous factors such as prescription drug use, smoking, alcohol, advancing
    age, and obesity contribute to elevated homocysteine levels.
  • B vitamins such as folic acid, vitamin B12, and vitamin B6 help the body
    maintain homocysteine levels within a healthy range.
  • Up to half of Americans carry a genetic variation that is linked with
    elevated homocysteine levels. This genetic variation impairs the ability to
    metabolize synthetic folic acid to its active form.
  • The active form of folic acid, called 5-methyltetrahydrofolate or 5-MTHF, is
    now available as a dietary supplement. 5-MTHF elevates plasma folate levels
    700% better than synthetic folic acid while effectively lowering
    homocysteine levels.
  • Together with other complementary nutrients like vitamin B12, vitamin B6,
    and betaine, 5-MTHF promises advanced protection against
    homocysteine-related disorders.

Why Doctors Don’t Check Homocysteine

Many mainstream doctors still accept classic lipid-related risk factors for heart attack and
stroke (e.g., high LDL and triglycerides and low HDL) as the gold standard upon which to base
treatment. They continue to ignore the fact that in many cases, high blood levels of
homocysteine also predict risk of vascular disease and stroke,
especially in the elderly.2

Dr. Kilmer McCully first described the connection between homocysteine and atherosclerosis in
1969. 3 His theory met with a rocky reception among
members of the Harvard University Medical School faculty where he taught and conducted research.
McCully’s revolutionary theory cast doubt on the widely accepted “lipid theory” of heart disease
favored by his peers.

Mainstream doctors in the 1970s ignored McCully’s groundbreaking research just as many continue
to do today. LDL levels (particularly elevated levels of oxidized LDL) remain an important risk
factor for cardiovascular disease, yet more than half of all heart attack victims have blood
cholesterol levels in the normal range.

The pharmaceutical industry encourages doctors to prescribe highly profitable lipid-lowering
drugs to prevent heart attack or stroke in their at-risk patients; there’s simply no monetary
incentive for selling non-patentable dietary supplements that perform as well as prescription
drugs in lowering homocysteine levels. There’s also little chance that drug sales reps will tell
doctors that a bioactive form of folic acid called 5-MTHF (5-methyltetrahydrofolate) is now
available as a non-prescription dietary supplement.

Many physicians remain unaware that elevated homocysteine levels can lead to depression,4 osteo-porosis,5,6 headaches,7
and macular degeneration.8,9 Yet these and other health
problems may be alleviated by lowering homocysteine blood levels.

Homocysteine, Stroke, and Folate

Stroke is the third largest cause of death in the US, ranking behind cardiovascular disease and
all forms of cancer.25

In 1998, the US and Canadian governments introduced a policy of folic acid fortification of
enriched grain products.26 In 2006, researchers
evaluated trends in stroke-related mortality before and after mandatory folic acid fortification
in both countries and, as a comparison, during the same period in England and Wales, where
fortification was not required. 27 They found that
average blood folate concentrations increased and homocysteine concentrations decreased in the
United States after fortification. In addition, between 1998 and 2002, there was an accelerated
decline in stroke mortality in the US with 12,900 fewer stroke deaths per year compared with the
established trend seen between 1990 and 1997. Similar data were also seen in Canada, where there
were 2,800 fewer stroke deaths per year between 1998 and 2002, while the decline in stroke
mortality in England and Wales did not change significantly during this time period.

Researchers concluded that folic acid supplementation could effectively reduce the risk of stroke
in primary prevention. The findings add to the growing body of evidence that supports the theory
that folic acid effectively reduces stroke death by reducing homocysteine levels in the blood.

Homocysteine, Alzheimer’s Disease, and Active Folate

Up to half of all Americans may carry a genetic variation that prevents the body, including the
brain, from optimally using folic acid.23 Scientists
believe that this genetic polymorphism may be linked with an increased risk of dementia.28 Fortunately, a non-prescription form of bioactive
folate, 5-MTHF, can cross the blood-brain barrier and effectively reduce homocysteine. Elevated
homocysteine has been linked with cognitive decline and Alzheimer’s disease.1,24,29

A 2002 study published in the New England Journal of Medicine reported that people with
high blood levels of homocysteine had a greater risk of developing Alzheimer’s disease.30 Dementia developed in 111 study participants, of whom
83 were diagnosed with Alzheimer’s disease over an eight-year follow up. In those with a plasma
homocysteine level greater than 14 µmol/L, the risk of Alzheimer’s disease nearly doubled.
Investigators concluded, “An increased plasma homocysteine level is a strong,
independent risk factor for the development of dementia and Alzheimer’s
disease.”

Active Folate: Relief For Migraine Sufferers

Migraine is a debilitating inflammatory blood vessel disease that may be triggered by damage
inflicted by elevated blood levels of homocysteine to the endothelium of blood vessels in the
brain.31

A recent study showed that treatment with B-complex vitamins, including 5-MTHF, might provide
relief for migraine sufferers including those with the MTHFR C677T genotype, which typically
limits the clinical effectiveness of supplemental folic acid. 7

Headache frequency and pain severity were also reduced. The treatment effect proved successful in
reducing homocysteine levels and migraine disability in study participants with the MTHFR C677T
genotype.7 Researchers have long suspected that
migraine headaches have a genetic component, because migraine sufferers often have family
members who also have the condition. Studies suggest that MTHFR polymorphisms may account for
the genetic predisposition to migraine in some individuals.32

Homocysteine’s Role in Macular Degeneration

Studies of homocysteine’s role in age-related macular degeneration (both wet and dry types)
reveal a strong link between the amino acid and the disease.

In a group of 2,335 study participants who had evidence of age-related macular degeneration as
detected from retinal photographs, researchers found that homocysteine blood levels greater than
15 µmol/L were associated with a more than three-fold increased likelihood of age-related
macular degeneration in participants under age 75 years. They found a similar association for
low vitamin B12 (under 125 pmol/L) among all study participants. Even in those with homocysteine
under 15 µmol/L, low serum B12 was associated with nearly four-fold higher odds of age-related
macular degeneration.8

In a larger and more recent study, Harvard researchers enrolled 5,442 women who were at high risk
for cardiovascular disease. The women were given a placebo or 2,500 mcg folic acid, 50 mg
vitamin B6, and 1,000 mcg vitamin B12. After seven years of treatment and follow-up, researchers
recorded 55 cases of macular degeneration in the B vitamin treatment group and 82 in the placebo
group. Investigators concluded that in women at high risk of cardiovascular disease, daily
long-term supplementation with folic acid, B6, and B12 significantly reduced the risk of
age-related macular degeneration. 9

Folate, Vitamin B12, and Birth Disorders

Published data provide strong evidence that folate deficiency during the periconceptional period
can lead to widespread alterations to DNA methylation in offspring, leading to disfigurement in
childhood (Figure 2 bottom left).33 DNA methylation is the key to the maintenance of gene
silencing, a process that relies on a dietary supply of methyl groups, as provided by B
vitamins. Up to one-third of all pregnant and lactating women in the US may not be meeting their
requirements for folate, despite mandatory folic acid-fortification of grain products.34

A long-term study demonstrated that women must begin supplementing with folate at least a year
prior to conception, which practically speaking is only possible if women take supplements on a
long-term daily basis. Women who took folic acid supplements for at least one year prior to
conception experienced a 70% lower risk of premature delivery between the 20th and 28th week of
gestation and a 50% decrease between the 28th and 32nd week compared with women who did not take
folic acid supplements.35

Numerous other studies confirm that folic acid supplementation reduces the risk of neural tube
defects and cleft lip and palate.36,37 Additional
research reveals that supplementing with vitamin B12 may also reduce the risk—up to five
times—of having a child with a neural tube defect, such as spina bifida.38

Homocysteine is a Risk Factor For Cancer

Emerging research suggests that elevated levels of homocysteine may be a risk factor for cancer. 39 A number of studies suggest that folate, through its effect on regulating DNA methylation and reducing homocysteine levels, may prevent cancers of the breast, bladder, lung, lymph, and colorectum.40-44

Conflicting evidence with respect to prostate cancer45 raises questions about the efficacy of folate for prostate cancer prevention. Some experts believe that when it comes to taking folate supplements, timing is everything. For example, some have proposed that folate may be beneficial when taken prior to old age because it decreases the likelihood of DNA mutations.

Why Ordinary B Vitamin Supplements May Not Lower Homocysteine

Many people who take B vitamin supplements are unable to sufficiently lower their homocysteine levels low enough to prevent disease.46 One possible reason is that folic acid, the form of the vitamin used in most supplements and enriched foods, is not bioavailable enough to sufficiently increase plasma folate levels in people with certain health problems or genotypes.

Researchers recently found that giving bioactive 5-MTHF to patients with coronary artery disease resulted in a 700% higher plasma folate concentration compared with folic acid. This difference was irrespective of the patient’s genotype.23 Compared with bioactive 5-MTHF, folic acid supplements were relatively ineffective in increasing blood folate concentrations.

Cooking and food processing destroy natural folates. Although red blood cells can retain folate for 40-50 days following discontinuation of supplementation, folic acid is poorly transported to the brain and is rapidly cleared from the central nervous system.1

Even though folic acid-fortified foods are ubiquitous in our food supply, and despite peoples’ best efforts to ensure adequate intake of the vitamin through supplementation, many individuals run the risk of not achieving sufficient plasma folate levels unless they supplement with bioactive folate.

Bioactive Folate: A New Supplement Effective at Lowering Homocysteine

Bioactive folate, or 5-MTHF, is the predominant biologically active form of folate in cells, the blood, peripheral tissues, and particularly the brain. 1 Until recently, 5-methyltetrahydrofolate was available only in expensive prescription medicines and medicinal food products. Now, this active form of folate, which provides increased bioavailability together with protection against homocysteine-related health problems, is available as a dietary supplement. Since 5-MTHF is the only form of folate used directly by the body, it doesn’t have to be converted and metabolized to be clinically useful, as does regular folic acid.1

Please Click Here for Figure 3

Folic acid, as used in ordinary dietary supplements and vitamin-fortified foods, must first be converted to bioactive 5-methyltetrahydrofolate in order to be clinically effective (Figure 3 to the Right). These steps require several enzymes, adequate liver and gastrointestinal function, and sufficient supplies of niacin (B3), pyridoxine (B6), riboflavin (B2), vitamin C, and zinc. 1

Another advantage of 5-MTHF is that it is unlikely to mask a vitamin B12 deficiency, a shortcoming of folic acid. Folic acid, when administered as a single agent, may obscure the detection of vitamin B12 deficiency (specifically, folic acid may reverse the hematological manifestations of B12 deficiency, while not addressing the neurological manifestations). Research has shown that bioactive 5-MTHF (5-methyltetrahydrofolate) is less likely than folic acid to mask vitamin B12 deficiency.1

Who Would Benefit From Taking 5-MTHF Supplements?

The low-dose requirements for 5-MTHF make it a relatively inexpensive supplement with superior clinical benefits over folic acid. People who would benefit from taking active folate include:

  • Those who desire to take advantage of 5-MTHF as a part of their anti-aging strategy due to its potency, low cost, and bioavailability.
  • Those with elevated risk factors for cardiovascular disease.
  • Those taking drugs known to interfere with the absorption or metabolism of folate (See sidebar below: “Drugs That Raise Homocysteine Levels. ”)
  • People with the gene variant MTHFR C677T.
  • Those who have stubbornly high homocysteine levels despite taking B-complex vitamins.

Individuals with the MTHFR C677T mutation are at higher risk of cardiovascular disease, stroke, pre-eclampsia (high blood pressure in pregnancy), and birth defects that occur during the development of the brain and spinal cord (neural tube defects).

How Much 5-MTHF Do You Need?

A daily dose of 800-1,000 mcg (0.8 to 1.0 mg) bio-active folate is typically used in research studies to achieve clinically beneficial reduction in elevated plasma homocysteine concentrations. Even doses of 200-400 mcg (0.2 to 0.4 mg) have been shown to achieve this effect.47

A number of drugs and medical food products on the market contain very high amounts (5,000 mcg or 5 mg) of 5-MTHF. Unless specifically prescribed by a physician, food and drug products that contain such high doses are probably not required to normalize homocysteine levels in most people with mild-to-moderate elevations.

Ancillary Supplements For Use With 5-MTHF

Individuals who wish to bring their elevated blood levels of homocysteine into the ideal range (under 8.0 µmol/L) may want to adopt a folate-boosting supplement protocol in addition to using bioactive folate 5-MTHF. This requires taking several supplements that work in concert to effectively reduce homocysteine and risk of disease. The following supplements can provide additional support:1

  • Riboflavin (vitamin B2): Plasma riboflavin has been shown to independently influence plasma homocysteine levels.48
  • Vitamin B6 (pyridoxine) helps reduce homocysteine levels by catalyzing the conversion of homocysteine to cysteine, which is then converted to the free-radical scavenger, glutathione (Figure 1 on Page 1).
  • Vitamin B12 (cobalamin) is required by the body to convert homocysteine to the amino acid, methionine, through the process of methylation (Figure 1 on Page 1).
  • A study of betaine (trimethylglycine) supplementation showed that a daily supplement of 6 grams betaine for 12 weeks reduced blood homocysteine values in healthy subjects. 49

Conclusion

Elevated levels of homocysteine have been linked with a diverse spectrum of health disorders ranging from cardiovascular disease, stroke, and cancer to migraine, dementia, and macular degeneration. Most conventional physicians fail to detect and treat elevated levels of homocysteine in the blood.

Folate is an essential nutrient for maintaining healthy homocysteine levels, yet up to half of Americans have a genetic inability to properly metabolize regular folic acid to its active form. Fortunately, the active form of folate is now available as a dietary supplement called 5-methyltetrahydrofolate, or 5-MTHF. By increasing blood folate levels 700% more effectively than ordinary folic acid, 5-MTHF offers advanced protection against the homocysteine-related disorders that threaten to compromise our longevity and well-being.

If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-800-226-2370.

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HOMOCYSTEIN – AN AMINO ACID THAT DAMAGES VESSELS

Earlier, we talked about how excess salt and sugar intake is a factor that threatens our blood vessels. Today we will talk about the amino acid homocysteine, since many do not even suspect what danger this amino acid can pose.

What is HOMOCYSTEIN?

To begin with, let us remind you that proteins consist of amino acids, which in turn are divided into nonessential (synthesized in the body) and irreplaceable (not synthesized in the body). So, homocysteine ​​ – is an amino acid that does not come from food, but is synthesized in the cells of the body, i.e. refers to replaceable. Further, under the influence of B vitamins and folic acid, homocysteine ​​is converted into harmless substances necessary for the body.

Why is a high level of homocysteine ​​in the blood dangerous?

  • Damages the inner wall of blood vessels, which in turn leads to the formation of cholesterol plaques in places of damage

  • Activates the blood coagulation system and leads to the development of atherosclerosis, arterial and venous thrombosis, which is fraught with a heart attack or stroke

  • During pregnancy, lead to gross malformations of the fetal nervous system

  • Increases the risk of miscarriage

What can cause an increase in homocysteine ​​levels?

  • Folate and B vitamins deficiency (B6, B12 and B1)

  • Coffee abuse (more than 4-5 cups per day)

  • Kidney dysfunction

  • Fermentopathies

Who is at risk?

  • Pregnant women with previous obstetric complications

  • Persons with a history of arterial / venous thrombosis, coronary heart disease

  • Women under the age of 50 with relatives who have had strokes, heart attacks, and thrombosis

  • smokers

  • Persons leading a sedentary lifestyle (obese)

  • Chronic alcohol abusers

How to prevent an increase in homocysteine?

  • Control the level of B vitamins and folic acid in the body.

  • Moderately consume foods sources of methionine, from which homocysteine ​​is synthesized (meat, cheese, cottage cheese, eggs).

  • More often include in the diet foods sources of omega-3 fatty acids and B vitamins (fatty fish, walnuts, flax seeds / oil, oatmeal, greens, beef liver)

  • Lead an active lifestyle (regular moderate physical activity).

  • Do not abuse coffee and alcohol

  • Quit smoking

Norms of homocysteine ​​for adults!

The average norm of homocysteine ​​in the blood is not more than 10 µmol/l.

For pregnant women and those planning a pregnancy – less than 8 µmol / l (in the 2-3rd trimester, no more than 4-6 µmol / l).

Increase from 10 to 20 µmol/l
– light,

20 to 29 moderate,

from 30 and above – severe.

Remember!
A high level of homocysteine ​​is not felt or manifested in any way, so it is recommended that people at risk have their levels checked periodically.

Homocysteine ​​- what is it?

Homocysteine ​​ is a sulfur-containing amino acid, which is a product of processing in the body of the essential amino acid methionine. They are rich in animal products, especially meat, dairy products (cottage cheese), eggs. Plasma homocysteine ​​is found predominantly in protein-bound form. Plasma total homocysteine ​​is the sum of free and conjugated homocysteine. Most of it undergoes reverse methylation with the formation of methionine. There are also options when it can irreversibly turn into cysteine ​​and glutathione.

Blood homocysteine ​​level normal

In adults, the level of homocysteine ​​is in the range of 10-11 µmol/l, in men this figure is higher than in women. With age, the level of homocysteine ​​begins to increase, but it is important to note that in women the rate of increase is higher than in men in this case. The increase in homocysteine ​​levels with age is due to the fact that there is a decrease in kidney function. Higher homocysteine ​​levels in men are initially due to greater muscle mass.

Vitamins B12, B6, folic acid are involved in the metabolism of homocysteine. In violation of the metabolism of homocysteine ​​due to genetic or functional defects in the enzymes involved in metabolic reactions, with a deficiency of essential vitamins, homocysteine ​​accumulates inside the cells in large quantities and enters the extracellular space, and then into the plasma. Further, accumulating in the human body, homocysteine ​​begins to attack the inner wall of the intima arteries, covered with endothelium.
Cholesterol and calcium are deposited on the damaged surface, forming an atherosclerotic plaque, which can lead to either a blood clot or rupture of the vessel with all the consequences (strokes, myocardial infarction, pulmonary embolism). An increase in the level of blood homocysteine ​​by 5 µmol/l leads to an increase in the risk of atherosclerotic vascular damage by 80% and 60% in men.

Why is high homocysteine ​​dangerous?

Individuals with elevated homocysteine ​​levels have an increased risk of Alzheimer’s disease and senile dementia. With a combination of elevated levels of homocysteine ​​and diabetes mellitus, vascular complications occur more often – peripheral vascular disease, nephropathy, retinopathy.
During pregnancy, an increase in the level of homocysteine ​​leads to disturbances in the fetoplacental circulation, which can be the cause of miscarriage and infertility as a result of implantation defects in the embryo. In the later stages of pregnancy, an increase in the level of homocysteine ​​is the cause of the development of chronic placental insufficiency and chronic intrauterine fetal hypoxia.
It is recommended to check the level of homocysteine ​​in all persons with a history of arterial and venous thrombosis, coronary heart disease. It is mandatory to check the level of homocysteine ​​in patients with previous obstetric complications and in women whose relatives had strokes, heart attacks and thrombosis under the age of 45-50 years.

Reference values:

– Men 6.26-15.01 µmol/l

– Women: 4.6-12.44 µmol/l

When does the level of homocysteine ​​in the blood rise?

  1. For deficiency of folic acid, vitamin B6, B12
  2. Genetic defects in enzymes involved in homocysteine ​​metabolism
  3. For renal insufficiency
  4. For severe psoriasis
  5. For proliferative diseases
  6. For hypothyroidism
  7. Smoking, alcoholism, coffee abuse
  8. When taking drugs such as cyclosporine, sulfasalazine, methotrexate, sulfasalazine, carbmazepine, nitrous oxide, 6-azauridine
  9. After suffering a new coronavirus infection (COVID-19)

Where can I get tested for homocysteine?

To date, a blood test for homocysteine ​​is a very affordable and common test. In our medical center VIP clinic-M, you can take an analysis at any convenient day and time. The clinic is within walking distance from Belomorskaya metro station and is open seven days a week.