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HOMOCYSTEINE

Updated 7/24/2013   


         Dr. Bernard Presser D.C.

5696 Magnolia Woods Drive

Memphis, TN 38134



 

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Elevated blood levels of homocysteine have been associated with and are being considered markers of coronary heart disease.  A vitamin, folic acid, lowers homocysteine levels, supposedly solving the problem.  Simple?  Or is there more to the story?

Homocysteine is a sulfur-containing amino acid, a component of proteins.  Another sulfur-containing amino acid, methionine, is the only known metabolic source of homocysteine. Methionine is an essential amino acid that is also the precursor of S-adenosyl methionine (SAMe), an important regulator of methyl metabolism.  With assistance from various other nutrients, homocysteine is made from the breakdown of methionine.  Both methionine and homocysteine are abundant in all animal proteins such as meats, fish, and eggs, and are found in lesser amounts in legumes, garlic, onions, corn, rice, and other grains.

Homocysteine can serve as an intermediate in the biosynthesis of cysteine, cystathionine, taurine, sulfate, and other metabolites that will be excreted in the urine.  Or, it can be remethylated (combined with a methyl group) back into methionine.  So homocysteine changes as part of biochemical processes.  It is when homocysteine is not changed but excessively accumulates in the blood that it is associated with health problems.  The conversion of homocysteine into other biochemicals involves processes catalyzed by enzyme systems requiring vitamins such as folate (folic acid), B12 (cobalamin), B6 (pyridoxine), and B2 (riboflavin).  Choline and betaine prevent accumulation of homocysteine and serve as co-enzymes to convert homocysteine to methionine.  Prevention of premature oxidation of homocysteine and its proper utilization by tissues depend on other nutrients including vitamin A complex, carotenoids, vitamin C complex (with its rutin and bioflavonoids), vitamin E complex (with its selenium component), glutathione, and various fatty acids.  Any abnormality in these enzyme systems or deficit of needed nutrients can contribute to excessive accumulation of homocysteine in blood.

What blood level is ‘high?'  Normal total homocysteine (homocysteine thiolactone, mixed disulfides, free homocysteine, and protein-bound homocysteine) ranges from 5 to 15 umol/L in the fasting state.  Anything above this is considered high, though some researchers think levels above 10 umol/L are high.  Also, fasting homocysteine levels alone are considered inadequate by scientists who believe a "methionine loading test" is needed, wherein a huge dose of isolated methionine is administered and the reaction interpreted to specify homocysteine metabolism.

The concentration of circulating homocysteine is determined by MANY factors including:  

     *A genetic mutation causing a decrease in the enzyme activity that converts homocysteine into methionine.  

     *Gender; men usually have higher levels than women.  

     *Getting older; levels rise with age.  

     *Race/ ethnicity.  

     *Tobacco use.  

     *Drinking eight or more cups of coffee a day.  

     *Consumption of hard liquor (less so with beer or wine).  Chronic alcohol abuse greatly elevates levels.  

     *Use of several common cholesterol-lowering drugs, including nicotinic acid (high-potency synthetic niacin), bile-acid-binding resins, and fibric-acid derivatives.  

     *Hormonal fluctuations or aberrations such as hypothyroidism and male subfertility.  

Levels are higher in postmenopausal women than in premenopausal women.  Exogenous sex steroids such as birth control pills or hormone replacement therapy (HRT) may induce changes.  

     *Complications or adverse outcomes of pregnancy such as preeclampsia, preterm birth, low birth weight babies, etc.  During normal pregnancy levels decrease markedly, probably due to hormonal changes.  

     *Vascular diseases such as thrombosis, atherosclerosis, arteriosclerosis, brain infarcts, stroke, peripheral vascular diseases.  

     *Chronic diseases such as bursitis, rheumatoid arthritis, several eye diseases, exfoliation syndrome, diabetes, chronic liver diseases, systemic lupus erythematosus, chronic renal diseases, cervical dysplasia, cervical cancer, other cancers, sickle cell disease, Raynaud's syndrome, Parkinson's disease, cognitive impairments, brain atrophy, poor recall, Alzheimer's disease, other dementias, lowered psychomotor speed.  

     *Lack of physical activity.  

     *Radiation injury.  

     *Overweight and obesity.  

     *Psychological factors such as hostility, stress, and anger.  Sufferers of depression are twice as likely to have high blood levels as people not depressed.  

     *Diet and nutritional deficiencies.  

The average American diet either does not provide sufficient amounts of or contributes to depletion of nutrients known to contribute to homocysteine metabolism.  Included are: folic acid (green leafy vegetables, whole grains, beans, oranges, root vegetables, etc.), vitamin B12 (meats, eggs, milk products, etc.; poor absorption may be due to digestive problems including a deficit of intrinsic factor which comes from gastric juices and is affected by intestinal bacteria), vitamin B6 (animal foods, some nuts, vegetables like broccoli and spinach, etc.), B2, betaine (trimethyl glycine) and choline (foods rich in methyl groups such as beets, green leafy vegetables, legumes, whole grains, liver, seafood, eggs, etc.) and other nutrients.  Components of the B complex may be less than adequate due to eating overcooked, over-processed, and over-refined foods.  For example, there is far more betaine and choline (the precursor of betaine) in WHOLE wheat than in refined wheat.

Obviously, homocysteine levels reflect far more than cardiovascular disease.  The question is, does a rise in homocysteine cause problems or do problems cause homocysteine levels to rise?  Research has yet to show that lowering homocysteine levels protects against heart disease.  Studies have shown that homocysteine damages vascular tissues in vitro (in test tubes) and impairs vessel elasticity.  What about in living people?  Volunteers whose homocysteine levels were experimentally elevated develop resistance to normal expansion in their blood vessels.  Is this reaction from the artificial elevation of homocysteine or from the homocysteine itself?  Other issues raise questions, such as:

     1. A correlation between homocysteine and cardiovascular risk is not always apparent.  For example, homocysteine levels are elevated in 20% to 30% of people with atherosclerosis, but 70% to 80% of people with atherosclerosis do not have elevated homocysteine.  A "comprehensive evaluation of the literature" shows that the effects of homocysteine on cardiovascular disease "are relatively weak."  Yet the benefits of nutrition on cardiovascular disease (including folic acid, B12, B6, B2, choline, etc.) are becoming increasingly evident.  The theory is that, when homocysteine is lowered, oxidative stress or thrombotic events (heart attacks, strokes, etc.) are reduced.  But some studies have shown this is not the case.

     2. Some researchers contend that elevated levels of homocysteine are a consequence of disease rather than a cause.  Study participants with the highest homocysteine levels have a much higher risk of heart attack, stroke, or death from any cause compared with participants with the lowest homocysteine.  This leads some to think homocysteine is a perilous cause of disease, but leads others to believe the increase occurs as a result of tissue damage.  When patients with genetically elevated homocysteine are ‘treated,' they nevertheless continue to have high homocysteine concentrations and "appear to experience no significant increase in vascular risk."  Study findings suggest that the connection between elevated homocysteine and vascular disease "is strongly enhanced after the vascular event [e.g., heart attack, stroke, etc.]."  Plasma homocysteine concentrations increase AFTER tissue damage due to acceleration of specific biochemical reactions that release homocysteine.  There is evidence that homocysteine is a natural regulator of leucocyte (white blood cell) behavior, activating various types of white blood cells and endothelial cells (like those lining blood vessels).  So "modest increases" in plasma homocysteine which develop during tissue damage and repair, "do not necessarily contribute to vascular damage or to increased thrombosis."  Some foods known to lower the risk and/or aid healing of cardio-vascular disease actually increase homocysteine concentrations for at least eight weeks.  These temporary increases "do not appear to have any adverse effects."  These foods are probably supporting biochemical processes of repair in which homocysteine plays a role.

     3. Even if homocysteine does promote cardiovascular disease, it is not known if lowering homocysteine will counter its effects.  Lowering plasma total homocysteine in a group of healthy men and women did not improve oxidative damage.  Folic acid or other vitamins may lower homocysteine levels, but the benefits may be due to reasons other than - or in addition to -homocysteine reduction.  At present, there are "no data" showing that lowering mild-to-moderate homocysteine levels reduces the risk of cardiovascular disease.  There are some data that indicate the risk of cardiovascular disease in individuals with very high total homocysteine is reduced by supplementation of vitamins that lower the homocysteine levels.  Yet what is considered a cardiovascular "risk" factor may or may not be involved in causing heart attacks or stroke.  And use of vitamins may help in other ways not related to lowering homocysteine levels.

"In nutritional epidemiology both measurement errors and strong associations between dietary factors, vitamin status, and lifestyle make data analysis especially challenging and standard statistical methods may not fully capture the complexities of the data."  Translation: People, their lives, and their foods are far too complicated and involve so many variables that a linear cause-and-effect relationship is next to impossible to prove between homocysteine levels and specific nutrients.  Many studies demonstrate that, in addition to folic acid intake, homocysteine values must be "interpreted in light of multiple factors."  Attempts to prove a simple homocysteine/ pathology connection and produce a simple therapeutic remedy are "complicated by the unfortunate abundance of public misinformation, if not overt propaganda."  Rash projections from studies on genetically-caused homocysteine elevation "obscure the reality that we remain uncertain" whether elevated homocysteine "causes, or merely marks, the presence of thrombovascular diseases."  It may be assumed that raised blood concentrations of homocysteine cause diseases, but "there is little substantial evidence to support this explanation."

Folic acid is usually used to lower homocysteine levels.  Yet studies are showing that a deficit of vitamin B12 is associated more closely with coronary atherosclerosis than folic acid. Folic acid and vitamin B12 together, rather than folic acid alone, is much more effective at lowering homocysteine concentrations and increasing coronary blood flow.  People with elevated homocysteine levels often have low levels of vitamin B12.  Supplementation with B12 results in decreased homocysteine but no improvement in blood vessel health or blood-clotting reduction.  Some studies found only vitamin B6 to be significantly associated with lower homocysteine levels; others found the level of B6 to be a better predictor of coronary disease risk than homocysteine.  Adequate levels of choline prevent homocysteine increases.  Choline deficiency can contribute to atherosclerosis.  Both choline and betaine (trimethyl-glycine) are effective in lowering homocysteine.  (Betaine is not the same as betaine hydrochloride, betaine with hydrochloric acid, a synthesized product used as a digestive aid.)

Vitamin C complex prevents "the impairment of flow-mediated (vascular) dilation" associated with methionine-loading and elevated homocysteine.  Vitamin E and C complexes appear to lower presumed ‘damaging' effects of homocysteine.  These nutrients play roles in inflammation and repair processes that aid tissue damage, so lowered homocysteine may reflect improved repair.  Ascorbic acid, a synthetic portion of the vitamin C complex, in doses between 500 and 1000 mg, may cause vitamin B12 deficiency and increase homocysteine levels. Large doses of isolated, synthetic niacin (often recommended to lower cholesterol) increase plasma homocysteine (by 17% with 1000 mg/day and 55% with 3000 mg).  Thiamin (B1) and riboflavin (B2) are essential to homocysteine metabolism.  Ultimately, intakes of ALL B vitamins have been found to be inversely related to plasma homocysteine concentration.  But homocysteine-lowering therapy with separated, manufactured, pharmacological B "vitamins" (not food complexes) "may be less effective than currently thought..."  Altering the DIET "may be a better alternative," since the consumption of folate-rich foods also increases intakes of many other nutrients in their natural complex, whole-package form.  The inter-connectedness of food components increases effectiveness and benefit.  Methionine-loading (administering a huge dose of the isolated amino-acid) elevates blood levels of homocysteine.  But a high-protein, high-methionine DIET does NOT raise homocysteine levels when compared to a low protein, low-methionine diet.  REAL food does not appear to be a problem, but a single amino acid separated from all its food co-dependents, coworkers, and natural balancers, can cause imbalances and tissue insult.  Studies have demonstrated that diets high in fruits and vegetables produce lower homocysteine levels.  These foods contain nutrients that support inflammation processes and tissue repair.  The MOST effective way to lower homocysteine is with a combination of many nutrients - as found in whole, natural foods.  Even garlic has been shown to lower homocysteine.

A rise in homocysteine is apparently a result of insult or damage and is part of the body's attempts to heal.  If homocysteine accumulates and remains too long, it could indicate continued injury and/or nutritional deficits.  Assuming that homocysteine is the CAUSE of heart disease or other disease is as presumptuous as attributing the pus in a skin boil to causing the original lesion. i

This website has excellent nutritional protocols for Homocysteine problems which are available in conjunction with the Symptom Survey.  Take the Symptom Survey to discover specifically what nutrition you need for your individual health problems.  I want to emphasize that the whole-food nutrition I recommend CANNOT be purchased in any retail store: so-called "health food" store, drug store, super market, etc.  The whole-food nutrition I recommend will help rebuild your body and help restore your health.  Those other products will only give you a pharmaceutical (drug) effect.  They will attempt to deal with your symptoms, which is the ONLY thing any drug can do, while leaving the state of your health unchanged.

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Originally published as an issue of Nutrition News and Views, reproduced with permission by the author, Judith A. DeCava, CNC, LNC.