Elevated Homocysteine Levels

Elevated Homocysteine Levels: Overview

A study at the National Institute on Aging found that homocysteine does more than just damage the arterial wall.  As a major consequence of folic acid deficiency – a particular problem with the elderly – elevated homocysteine impairs DNA repair.

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Diagnosis and Tests

There is at the time of writing no universally agreed standard for defining "low", "optimal", "normal", "elevated" and "high" levels when it comes to homocysteine.  The upper level for "normal" is generally taken to be 10-11µmol/L, although some go as high as 15 or even 17.  Wikipedia, for example, states that "elevated" is defined as over 10.4µmol/L for women and 11.4µmol/L for men, and that the "therapeutic target" (or ideal level) is below 6.3µmol/L.

Many doctors believe that what some consider to be "normal" levels are in fact quite dangerous.  Studies have shown that stroke risk starts to rise rapidly as homocysteine levels exceed 7µmol/L, with the risk of stroke being 70-80% higher in individuals with levels exceeding 11µmol/L.

S-Adenosylhomocysteine, which is the precursor of homocysteme, appears to be a more sensitive marker for differentiating cardiovascular patients from control subjects than homocysteine.  [Am J Clin Nutr, 2001;74: pp.723-9]

Signs, symptoms & indicators of Elevated Homocysteine Levels:

Lab Values - Chemistries

Conditions that suggest Elevated Homocysteine Levels:

Aging

Premature/Signs of Aging

A recent large-scale prospective study of 4700 Norwegian men and women between the ages of 65 and 67 revealed that higher levels of homocysteine in plasma were associated with a significantly increased risk of mortality.  For each 5 mmol/L increase in plasma homocysteine levels, the number of deaths from all causes in this "youthful" senior population jumped by 49%.  This included:

  • a 50% rise in deaths from cardiovascular disease
  • a 26% rise in deaths from cancer
  • a 104% rise in deaths from other causes.

These dramatic results may indicate a need for more routine screening in the elderly population.  [Am J Clin Nutr 2001;74: pp.130-6]

Alzheimer's Disease

People with elevated levels of homocysteine have nearly double the risk of developing Alzheimer's disease, according to a report from researchers at Boston University.  The findings, which come from the long-running Framingham Study, are the first to tie homocysteine levels measured several years before with later diagnosis of Alzheimer's and other dementias.  The report, which appeared in the New England Journal of Medicine, provides some of the most compelling evidence yet of an association between high plasma homocysteine and eventual significant memory loss.

Circulation

Atherosclerosis

Multiple studies indicate that 15-30% percent of patients with premature occlusive vascular disease have moderately elevated total plasma homocysteine concentrations.  [ JAMA 1992; 268: pp.877-81]

Coronary Disease / Heart Attack

Elevated homocysteine levels are believed to exacerbate oxidative injury to blood vessels and increase pro-clotting mechanisms linked to stroke and heart attack.

Stroke

Stroke risk appears to rise as soon as homocysteine levels reach 7µmol/L, accelerating rapidly as levels rise beyond that.

Mental

Depression

Nutrients which lower elevated homocysteine levels, including the B-vitamins, are related to depression in several ways [Am J Psy 1997;154: pp.426-428].  The methyl group provided by normal homocysteine metabolism is necessary for the production of depression-relieving neurotransmitters such as serotonin and dopamine.  The B-vitamins are also crucial in the direct synthesis of the brain neurotransmitters.  [J Affect Disord.  1986;10: pp.9-13; Psychosomatics.  1980;21: pp.926-929]

Musculo-Skeletal

Osteoporosis - Osteopenia

Elevated homocysteine levels disrupt collagen-forming processes in the body and raise the likelihood of developing osteoporosis.

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Risk factors for Elevated Homocysteine Levels:

Autoimmune

Ulcerative Colitis

Because people with inflammatory bowel disease (IBD), like ulcerative colitis and Crohn's disease, have a much higher risk of both thromboses and osteoporosis, a team of researchers from McGill University in Montreal explored the idea that homocysteine excess may play an important role in this chronic gastrointestinal disease.

To test this hypothesis, they measured homocysteine levels in the plasma of 65 patients with IBD and in 127 healthy controls.  Their results revealed a striking difference: The patients with IBD had nearly a six-fold increased incidence of hyperhomocysteinemia (homocysteine levels above the normal range) compared to controls.

About one in every seven patients in the IBD group had hyperhomocysteinemia.  As expected, those with vitamin B12 deficiency tended to have higher homocysteine levels.  Yet researchers were also surprised to find that 80% of the IBD patients with hyperhomocysteinemia had normal blood levels of vitamins.

This suggests that homocysteine imbalances could be an early warning sign of B-vitamin deficiency inside cells – one that occurs well before vitamin levels actually decline in serum.  It is still too early to tell if treating high homocysteine could actually reduce IBD symptoms in patients.

Importantly, as homocysteine levels rose in the patients with IBD, so did the clinical ratings of IBD disease severity, including its length of duration and the use of steroid medications to treat it.  [Am J Gastroenterol.  2001 96(7): pp.2143-9]

Crohn's Disease

Homocysteine levels are increased in patients with Crohn's disease.  [Am J Gastroenterol.  2000 Dec;95(12): pp.3498-502]

Nutrients

Vitamin B-Complex Requirement

Homocysteine imbalances could be an early sign of B-vitamin deficiency inside cells, one that occurs well before vitamin levels actually decline in serum.  "Homocysteine may, in fact, be a more sensitive marker of vitamin B12, B6 or folate deficiency and... may precede deficiency of circulating vitamins." [Am J Gastroenterol.  2001 96(7): pp.2143-9]

Organ Health

Chronic Renal Insufficiency

Homocysteine levels in patients suffering from chronic renal failure are significantly elevated at an early stage.  The kidney plays a very significant role in homocysteine metabolism but this does not occur during chronic renal failure.  In addition, there is a decreased extra-renal catabolism, which contributes to the hyperhomocysteinemia state.  [Hyperhomocysteinemia: A Role in The Accelerated Atherogenesis of Chronic Renal Failure?, Netherlands Journal of Medicine, 1995;46: pp.244-251]

Symptoms - Food - Preferences

Elevated Homocysteine Levels suggests the following may be present:

Organ Health

Chronic Renal Insufficiency

Homocysteine levels in patients suffering from chronic renal failure are significantly elevated at an early stage.  The kidney plays a very significant role in homocysteine metabolism but this does not occur during chronic renal failure.  In addition, there is a decreased extra-renal catabolism, which contributes to the hyperhomocysteinemia state.  [Hyperhomocysteinemia: A Role in The Accelerated Atherogenesis of Chronic Renal Failure?, Netherlands Journal of Medicine, 1995;46: pp.244-251]

Recommendations for Elevated Homocysteine Levels:

Psychological

Stress Management

It was recently found that periods of stress increase serum homocysteine, an amino acid known to be a significant risk factor for coronary artery disease.

Vitamins

Folic Acid

A deficiency of vitamin B12 is associated with elevated homocysteine levels and folic acid is essential for its proper metabolism.

Vitamin B12 (Cobalamine)

Since most people with a high homocysteine level don't get enough folic acid, vitamin B6 or B12 in their diet, supplementing with these vitamins helps return homocysteine to normal levels.

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