Introduction
Homocystein is a
homologue of the naturally-occurring amino acid cysteine
differing in that its
side-chain contains an additional methylene (-CH2-) group before the thiol
(-SH) group.
Introduction
Alternatively, homocysteine
can be derived from methionine by removing the latter's terminal Cε methyl
group.
Homocysteine is not
obtained from the diet; it is a normal temporary and chemically reactive
reaction product that can be measured in blood!!
In blood, it is found
bound to albumin and to hemoglobin.
It affects enzymes with
cysteine-containing active sites, for example, it inhibits lysyl oxidase a key
enzyme in the production of collagen and elastin, two main structural proteins
in artery, bone and skin
Elevated
homocysteine
Deficiencies of the
vitamins folic acid (B9), pyridoxine (B6), or B12 (cyanocobalamin) can lead to
high homocysteine levels.
Supplementation with
pyridoxine, folic acid, B12 or trimethylglycine (betaine) reduces the
concentration of homocysteine in the bloodstream.
Increased levels of
homocysteine are linked to high concentrations of endothelial asymmetric
dimethylarginine.
Elevations of
homocysteine also occur in the rare hereditary disease homocystinuria and in
the methylene-tetrahydrofolate-reductase polymorphism genetic traits.
Common levels in
Western populations are 10 to 12 and levels of 20 μmol/L are found in
populations with low B-vitamin intakes (New Delhi) or in the older elderly
(Rotterdam, Framingham).
Women have 10-15% less homocysteine
during their reproductive decades than men which may help explain the fact they
suffer myocardial infarction (heart attacks) on average 10 to 15 years later
than men.
How Much Is
Safe?
Children with
genetically elevated homocysteine levels experienced heart disease similar to
the heart disease found in middle-aged patients.
People with elevated
homocysteine levels are more likely to have strokes, Alzheimer's disease and
dementia, kidney disease, diseases of the eye, erectile dysfunction, and,
especially, heart disease.
Homocysteine
and Heart Disease
Having an elevated
homocysteine level is an independent risk factor for heart disease.
A highly elevated
homocysteine level was associated with a more than 3-fold increase in the risk
of heart attack over a 5-year period.
It causes thickening of
the intima, or inner wall of the arteries.
homocysteine has been
shown to affect the production of nitric oxide, a substance that causes
arteries to relax and blood flow to increase.
Having an elevated
homocysteine level has been associated with:
–
First and second heart attacks .
–
Coronary artery disease.
–
Total cardiovascular mortality.
–
Adverse outcomes after coronary balloon
angioplasty.
–
Heart failure.
Homocysteine Levels
Normal—5 to 15 µmol/L
Moderate—16 to 30
µmol/L
Intermediate—31 to 100
µmol/L
Severe—Above 100 µmol/L
People try to keep
their homocysteine level between 7 µmol/L and 8 µmol/L.
A homocysteine level
over 12 µmol/L should be treated aggressively.
One study found that
each 3-µmol/L increase in homocysteine caused a significant increase in the
risk of having a heart attack.
Homocysteine:
Linked to Diseases of Aging
elevated homocysteine levels
have been linked to the following disorders or diseases:
–
Stroke—Homocysteine's effect on the arteries
that supply the brain with blood (carotid arteries) is similar to its effect on
the arteries in the heart.
–
Vascular disease—There is evidence that
homocysteine combines with low-density lipoprotein (LDL) cholesterol and
contributes to the creation of plaque inside artery walls.
–
Homocysteine has also been implicated in the
formation of blood clots, which can cause a heart attack, stroke, or peripheral
vascular disease.
Liver disease—Elevated
homocysteine and low levels of SAMe are linked to liver toxicity and cirrhosis.
Homocysteine likely
contributes to liver damage, leading to the formation of fibrin, clots, and
vascular complications.
Kidney disease—The
kidneys filter, reabsorb, and metabolize amino acids, including homocysteine.
In kidney failure, homocysteine levels rise due to improper kidney filtration.
–
Folic acid, trimethylglycine, and vitamins B6
and B12 reduce homocysteine in people with kidney failure.
–
High doses of folic acid can normalize
homocysteine levels. Once kidney failure occurs, folic acid is much less
effective, and high doses of vitamin B12 are required to help normalize
homocysteine levels
Thyroid
conditions—Elevated homocysteine levels may contribute to accelerated heart
disease among people who have hypothyroidism.
Alzheimer’s disease and
dementia—High levels of homocysteine indicate impaired methylation in the
brain. Individuals with Alzheimer's disease have been shown to have elevated
homocysteine levels.
Depression—Depression
has been linked to low levels of folic acid in women. Low folic acid levels
have been shown to decrease the effectiveness of the antidepressant fluoxetine
(Prozac®), and vitamin B6 may alleviate depression.
Erectile dysfunction—Homocysteine has been shown to
reduce the production of nitric oxide. Nitric oxide causes blood vessels to
relax, increasing blood flow to organs and tissues. In one case study, a man with
erectile dysfunction, who also had a genetic defect that causes elevated
homocysteine levels, did not initially respond to treatment with sildenafil
(Viagra®). However, after treatment with 5000 micrograms (mcg) of folic acid
and 1000 mcg of vitamin B12, his erectile dysfunction was successfully treated
with sildenafil.
Diseases of the eye
Homocysteine's ability to damage blood vessels also
has implications for the tiny blood vessels in the eye. Elevated homocysteine
levels are associated with serious eye conditions, including glaucoma and
macular degeneration. A study showed that homocysteine levels of 11.6 µmol/L
were the average concentrations in patients who had central retinal vein occlusion.
Why Homocysteine
Levels Rise?
–
They rise naturally as we age.
–
Genes also play a large role in the body's
metabolism of homocysteine.
–
Coffee and alcohol consumption increase
homocysteine levels.
–
Eating foods that contain large amounts of
methionine, such as red meat and chicken, increase blood levels of
homocysteine.
–
low intake of foods rich in vitamin B, such as
green leafy vegetables, may also increase homocysteine levels.
In addition, the
following pharmaceuticals are associated with elevated homocysteine levels:
–
Fenofibrate—Used in the treatment of high cholesterol.
–
Niacin—Used in the treatment of lipid management.
–
Metformin—Used to treat diabetes.
–
Antiepileptic drugs—Used to control seizures.
–
Levodopa—Used to manage Parkinson's disease.
–
Methotrexate—Used to treat cancer, psoriasis, arthritis,
and lupus.
. The Life Extension Foundation's approach to lowering
homocysteine relies on several principles:
–
Directly addressing high homocysteine levels by
increasing metabolization of homocysteine. Nutrients that increase
metabolization of homocysteine fall into two categories:
•
those that increase the remethylation of
homocysteine back into SAMe, and
•
those that act along the transsulfuration
pathway to remove excess homocysteine from the body.
Routine blood testing
to monitor homocysteine levels. This should include genetic testing to check
for abnormalities. Slight genetic defects in as few as two enzymes may cause
moderate hyperhomocysteinemia. the most serious form of hyperhomocysteinemia
(homocystinuria) is caused by an extremely rare genetic disorder.
Addressing the damage
directly caused by homocysteine. This may mean supplementing with antioxidants
and other nutrients to reduce damage caused by homocysteine.
Managing underlying
conditions—including high blood pressure, coronary artery disease, diabetes,
and hypothyroidism—that are associated with a high homocysteine level.
The B Vitamins: A
Powerful Weapon:
Management of hyperhomocysteinemia begins with
folic acid, vitamin B6, and vitamin B12. To varying degrees, folic acid and
vitamin B12 increase the remethylation of homocysteine back into SAMe. Vitamin
B6 is necessary for the conversion of homocysteine into glutathione along the
transsulfuration pathway.
TMG and Zinc:
Bringing Homocysteine Under Control:
–
TMG (trimethylglycine) and zinc, both of which
enhance the action of B vitamins.
–
TMG operates along a different pathway than the
B vitamins. its activity is limited to the liver and kidneys.
–
Zinc acts in concert with vitamin B6 to promote
remethylation of homocysteine to methionine.
–
Zinc is also needed for the conversion of
homocysteine to cysteine and glutathione.
Inhibiting the
Formation of Homocysteine:
Not all the
homocysteine created is released directly into the bloodstream as free
homocysteine. In fact, less than 1 percent of the homocysteine in the blood is
free. The majority, about 98 to 99 percent, is bound to proteins in the blood
and considered stored.
This store of
homocysteine may be released in response to decreased methylation or oxidative
damage, or in response to other influences.
Nutrients that have
been shown to inhibit the release of homocysteine include:
–
Creatine—Somewhere between 50 and 90 percent of
the SAMe required by the body goes into the production of creatine.
Supplementation with creatine diminishes the need for SAMe, reduces formation
of homocysteine, and the need for homocysteine remethylation.
–
Choline-producing nutrients—SAMe is involved in the
production of choline. By taking choline-producing nutrients, your body
produces less SAMe, which reduces the amount of homocysteine needed.
Choline-producing nutrients include cytidine diphosphate (CDP) choline,
lecithin, alpha-glycerylphosphorylcholine, and choline chloride.
Recommendations
It is important to
begin your homocysteine-lowering program by working with a qualified physician
and taking the necessary blood tests to evaluate your risk. To help lower your
homocysteine level, the Life Extension Foundation suggests:
–
Folic acid—4000 to 8000 mcg daily
–
Vitamin B12—1 to 2 mg daily
–
Vitamin B6—100 to 200 mg daily
–
SAMe—400 mg two to four times daily
–
TMG—2 to 4 grams daily
–
Zinc—30 to 90 mg daily
–
CDP choline—250 to 500 mg daily
–
Micronized creatine—500 mg (in capsule form) four to eight times
daily
–
N-acetyl-cysteine—600 mg (in capsule form) one to two times
daily on an empty stomach
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