Avoid an overlooked cause of stroke & dementia

As we age, levels of a harmful amino acid known as homocysteine increase.

Research indicates that homocysteine can be a major factor in the creation of strokes and heart attacks as well as crippling dementia.1,2

Lowering homocysteine can reduce one’s risk for catastrophic events.1-4

In the past few years, hundreds of papers on homocysteine and cardiovascular disease have been published. A February 2017 study stated that homocysteine levels are a powerful predictor of cardiovascular disorders.5

Homocysteine levels can be determined by a simple blood test and lowered with the proper forms of B6(pyridoxal 5-phosphate), B12 (as methylcobalamin), folate (as 5-methyltetrahydrofolate), and vitamin B2 (riboflavin-5-phosphate).6-17 It is important to ask yourself: When was the last time my doctor measured my homocysteine blood levels?

Optimizing homocysteine blood levels can be an important factor in reducing your risk of vascular disease and dementia.

An overlooked cardiovascular risk factor

Homocysteine levels rise as we age, a consequence of declining kidney function, B-vitamin deficiencies, and other factors such as impaired detoxification.18

Studies show that as many as 30% of patients 71 or older are deficient in vitamin B12, a critical cofactor in the body’s ability to naturally lower homocysteine.18,19 Deficiencies of B vitamins contribute to elevated homocysteine levels in up to 40% of patients aged 80 or over.18

Elevated homocysteine levels set off a series of harmful processes that include oxidative stress, inflammation, increased risk of clotting (thrombosis), and damage to endothelial function in arteries.20-25

Together, these properties contribute to decreased blood flow to vital organs, particularly the heart and brain. This increases the risk of a sudden obstructive blood clot, which triggers heart attacks and strokes, while chronically reduced blood flow in the brain contributes to dementia and cognitive decline.

Data supporting the role of high homocysteine and cardiovascular risks are compelling.


B vitamins lower homocysteine

  • High levels of homocysteine are associated with risks for numerous age-related disorders, such as heart attacks, strokes, arrhythmias, and neurodegenerative disorders.
  • High homocysteine is caused in part by a deficiency in B vitamins.
  • B-vitamin supplementation has been shown to lower homocysteine levels and reverse some of the conditions associated with their elevations.
  • It is now possible to say with some confidence that many of these age-related conditions may, in fact, be preventable through simple nutritional supplementation.


Homocysteine increases heart risks

Elevated homocysteine levels increase the risk of developing heart disease.

People with high homocysteine levels who also take the anticoagulant drug warfarin have a 23% increase in their risk for cardiovascular events of all kinds, a 38% increase in their risks of myocardial infarction (heart attack), and a 41% increase in the risk of death from all causes.26

Those same elevated risks apply to ischemic stroke—which is increased by 20%-32% in people with elevated homocysteine.24 These data make a strong argument for those taking anticoagulant drugs to optimize their homocysteine blood level.

Elevated homocysteine is associated with a 42% increase in the risk of narrowing of the carotid arteries, the main blood suppliers to the brain.27 That risk skyrockets to 189% in patients with diabetes, a known aggravator of atherosclerosis and cardiovascular disease.27 Carotid artery narrowing represents a major ischemic stroke risk.

People with excess homocysteine have a much higher risk for having microscopic bleeding that further contributes to the damage to brain tissue after a stroke. They also have an increased risk of poor outcomes even after being treated with “clot-busting” medications.28

High homocysteine interferes with recovery from heart attacks as well, as shown by a study of survivors who had coronary artery stenting (insertion of a tiny tube inside a blocked artery, see above). The people in this study with high homocysteine had a significant 30% higher rate of major adverse cardiac events (death, another heart attack, stroke, or the need for additional surgery), compared to those with normal levels.29


Additional heart risks

Studies show that people with high homocysteine are much more likely to have heart rhythm disturbances, especially atrial fibrillation, an irregular, often rapid heartbeat that causes poor blood flow.30,31 That’s critical, because homocysteine promotes excessive blood clotting, while atrial fibrillation predisposes us to blood-clot formation, specifically in the heart’s upper chambers (atria).18,32,33

If an atrial clot breaks free and becomes lodged in another part of the body, such as the lungs, where it causes a pulmonary embolism, or the brain, where it causes a stroke, the results are devastating.

In fact, increased homocysteine levels quadruple one’s risk for a stroke in the case of atrial fibrillation.18

Together, these data demonstrate the dangerous cardiovascular impact of the pro-clotting, pro-inflammatory, chemical stress-inducing homocysteine.

Let’s now turn to the effects of this metabolic toxin on the brain, cognition, and memory.


Homocysteine and dementia

Innovative physicians are beginning to recognize that elevated homocysteine is also a major factor in the development of a wide range of dementias.

Studies show that people with elevated homocysteine display cognitive problems and a nearly 100% elevated risk of dementia, compared with those having normal levels.34 A study of centenarians showed that individuals with normal cognitive function had lower homocysteine levels, compare with those having dementia.21

Both Alzheimer’s and Parkinson’s diseases—the leading causes of dementia in the aging population35—have shown powerful associations with blood homocysteine levels, as have non-Alzheimer’s dementias.36-39

Numerous studies have also found a clear link between high homocysteine levels and cognitive decline. For example, a 2016 meta-analysis pooling the results of 111 smaller studies showed that rising homocysteine levels correlate with cognitive decline, both in those with clear-cut dementias and the general population. This study emphasized that early detection of high homocysteine levels can be an important and effective test to prevent cognitive decline.40

Elevated homocysteine levels have also been shown to be closely related to the risk of decline in a wide range of specific cognitive functions. These include executive function (needed for sorting, prioritizing, and decision-making), attention, cognitive flexibility, and memory.41,42

In addition, people with elevated homocysteine levels suffer higher incidence of neurodegenerative conditions such as white-matter damage (leukoaraiosis), brain atrophy, accumulation of “junk proteins” like beta-amyloid that damage brain cells, and the resulting neurofibrillary tangles in brain cells.4,43,44

These findings make homocysteine reduction increasingly important in the quest to sustain cognitive function into advancing years.37,40,45




Life Extension scientists recently conducted an independent evaluation of homocysteine levels among Life Extension customers, including over 67,000 individual blood tests performed between January 2012 and April 2017.

Even using conservative levels to define excess homocysteine (>12 µmol/L), almost one quarter (23%) of individuals had high levels. While using a more aggressive cutoff, in line with many recent publications, nearly half (47%) showed dangerous homocysteine elevations of >10 µmol/L.

And if one uses Life Extension’s longstanding position that levels should be <8 µmol/L, 77% had higher-than-optimal levels.

Other findings from this study comport with published literature, showing that homocysteine elevations are most prominent among men and among older people.

These remarkable figures drive home the point that high homocysteine levels represent a massive problem, and that we are not yet doing enough, collectively, to protect ourselves from preventable age-related diseases.

Readers should respond to this finding by arranging for a homocysteine blood test and starting on the following B vitamins that support homocysteine detoxification:

  • Folate as 5-MTHF, 1,000 to 10,000 mcg
  • Vitamin B6 as pyridoxal 5’-phosphate, 100 to 200 mg
  • Vitamin B12 as methylcobalamin, 300 to 1,000 mcg
  • Vitamin B2 as riboflavin-5-phosphate, 25 to 100 mg


Effective homocysteine-reducing therapy

Studies show that people with B vitamin dietary deficiencies are more likely to suffer from both cardiovascular and brain disorders, with the common connection being a resulting rise in homocysteine.39,46-49

Numerous studies have demonstrated the benefit of supplementation with vitamins B2, B6, B12, and folate on homocysteine levels.10,50-56

Vitamin B2, also called riboflavin, helps facilitate the benefits of folate, which in turn is required to detoxify homocysteine.54 Vitamin B6 and its active form, called pyridoxal 5’-phosphate is required for the conversion of homocysteine into less toxic molecules.53 Vitamin B12, in the form of methylcobalamin, has been shown to lower homocysteine levels.6,8 And folate in its active form, 5-methyltetrahydrofolate or 5-MTHF, is superior at raising serum folate levels,57  which in turn translates into lower homocysteine levels.17

But while individual B vitamins can be effective for some, using a combination of these four key B vitamins provides an effective arsenal against elevated homocysteine levels.

Large meta-analysis studies suggest that lowering blood homocysteine levels by 25% would reduce the risk of coronary heart disease by up to 16% and the risk of stroke by up to 24%. These studies also indicate that we must find the optimum combination of B vitamins to achieve those results because each vitamin has a specific role to play regarding homocysteine balance.10

For example, it has now been shown that both riboflavin and folate must be present in ample quantities for optimal homocysteine-lowering.10,54,55 Yet some studies have shown that even people whose folate and riboflavin status has been restored by supplementation may not significantly lower high homocysteine levels until vitamin B6 is added to the equation.53

Research shows that healthy adults that use mixed B-vitamin supplementation consistently show improvement in homocysteine status and reduction of associated oxidative stress.52,56

Similar actions in the brain provide further evidence favoring mixed B-vitamin supplementation.

In patients who had recently suffered a stroke or near-strokes (transient ischemic attacks), supplementation significantly reduced the volume of brain white-matter hyperintensities (tiny markers of damage also called leukoaraiosis) in patients with the most severe lesions at baseline.50

Even more compelling data comes from a study of gray matter atrophy, which is shrinkage of the main “thinking” portions of the brain as seen in Alzheimer’s disease. In this study, elderly subjects with mild cognitive impairment (at increased risk for Alzheimer’s) who received B vitamins for 2 years experienced a slowing of brain shrinkage compared with placebo.51

Importantly, in those subjects, supplementation reduced shrinkage of brain areas especially vulnerable to Alzheimer’s damage by up to 7-fold.51




B vitamins help lower homocysteine levels, thereby reducing the risks of homocysteine-related diseases, including cardiovascular and neurological diseases.

Further analysis of an earlier trial reveals two new studies that have found that blood levels of omega-3 fats, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are important contributing factors to successful B-vitamin therapy.3,58

Both studies evaluated patients with mild cognitive impairment (MCI) at the start of the study, and followed them for two years to determine the combined impact of B-vitamin supplementation and omega-3 blood levels.

Both studies found better results in supplemented subjects overall, but not in every individual.

In one study, the outcome of interest was brain shrinkage or atrophy.3 It found that, among the B-vitamin-supplemented patients with higher levels of combined EPA and DHA, the rate of brain shrinkage was significantly (40%) slower, compared with placebo recipients.3

The other study’s outcome measure was cognitive decline, and B-vitamin-supplemented subjects were again evaluated according to their omega-3 levels.58

Here, scores on memory, cognition, and dementia rating improved in the B-vitamin-supplemented subjects according to their baseline omega-3 levels, with a particularly strong effect for levels of DHA.58

The bottom line?

Supplement with the recommended higher-dose B vitamins and with ample omega-3 fats from fish oil to optimize brain protection and slow brain aging.



A growing body of scientific evidence points clearly to the fact that some of our most feared age-related disorders can be prevented simply by lowering homocysteine levels.

High circulating homocysteine imposes enormous chemical stresses on tissues throughout the body, and raises our risks for heart attacks, arrhythmias, strokes, and neurodegenerative conditions.

A host of new studies is finding that B vitamin supplementation at ample doses can lower homocysteine levels and reverse some of the conditions associated with their elevations.

It’s also clear that assuring adequate omega-3 status in the blood potentiates the beneficial effects of B-vitamin supplementation.

With proper nutrition, some of the leading causes of death and disability can be prevented or at least decelerated—good news for all of us.

Homocysteine levels should be part of a yearly battery of blood tests to ensure a healthy, long life. Life Extension® advises that one should target their homocysteine levels below 10 umol/L with optimal numbers being <7-8 µmol/L.

Conventional reference ranges do not flag a homocysteine problem until blood levels reach 15 µmol/L. Published data reveal those with homocysteine blood levels between 10-15 umol/L suffer greater vascular risks.

Individuals with elevated homocysteine levels should begin supplementation with key B vitamins, especially higher doses of the activated form of folate (5-MTHF), and retest homocysteine blood levels after three months.



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