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Nutritional Science
Homocysteine : A 21st Century Model of Nutritional Medicine
Home | Homocysteine : A 21st Century Model of Nutritional Medicine | Cell Salts or Tissue Salts


                   Nutrition and Homocysteine


      Homocysteine is a non-essential amino acid in the body which, when elevated,is a risk factor for a variety of of illnesses that involve the disciplines of Cardiology, Neurology, Gynaecology, Geriatrics and Genetics.  The purpose of this article is to show how this model of a dysfunctional metabolic pathway is responsive to simple, safe and cost-effective vitamins and nutrients. This type of medical approach involving " Functional Testing and Medicine ", supports the concept of incremental disease, which sees health as a continuum ranging from optimal functioning to acute illness.


            My journey with homocysteine began on June 30,1988, when Lindenbaum and colleagues reported in th New England Journal of Medicine ( 1988: 318:1720-8 ),that out of 140 consecutive patients with neuropsychiatric abnormalities due to viatamin B12 deficiency,28 percent had no evidence of anaemia or macrocytosis ( enlarged red blood cells ). Instead, the authors found elevated levels of methylmalonic acid and homocysteine,biochemical markers of B12 deficiency. With appropriate

therapy, these levels were reduced with subsequent symptom improvement.

Following this landmark article, William beck, MD, of Massachuesetts General Hospital, wrote an editorial in the New England Journal of Medicine by asking. " Could it be that vitamin B12 injections given over the years for vague symptoms were in fact justified ? "


      Homocysteine elevations in the urine and blood occur if vitamin- and nutrient-dependent enzymes are not functioning properly, therefore blockinmg homocysteine breakdown. The most common blockage occurs from lack or malfunction of a vitamin B6-dependent enzyme ( cystathione B-synthase), which is important in the removal of sulfur from the homocysteine-methionine cycle. Vitamin B12 also plays a role in this pathway. When homocysteine is remethylated back to methionine, any one of three inadequate amounts of vitamin B12, folic acid and/or betaine ) can cause elevations in levels of homocysteine. Choline is another nutrient important in keeping homocysteine leverls low.



           Cardiovascular Disease


           Elevated levels of homocysteine  are now recognised as an independent risk factor for cardiovascular disease,regardless of the traditional risk factors. In fact, in some studies,elevated levels of homocysteine have correlated better with cardiovascular disease incidence than do cholesterol levels. Elevated levels of homocystein have been observed in patients with coronary artery disease, peripheral vascular

disease, intermittent claudication, strokes : cerebro-vascular accidents, cardio-vascular accidents, thrombosis, and angina pectoris. In a recent Journal of the American Medical Association article ( 1992 ); 268(7): 877-881 ), a sample of 271 males who developed heart attacks had levels of homocysteine which were significantly higher than controls. The authors noted that elevated levels of homocysteine can be easily treated with folic acid,vitamin B6, B12, betaine and choline. In another recent study, researchers from South Africa found moderately elevated levels of homocysteine in  44 apparently healthy men. These men supplemented with very moderate doses of nutrients ( vitamin B6 at 10 mg, folic acid at one mg and 400 mcg of vitamin B12 ), which resulted in normalization of homocysteine concentrations within a six week period. The authors concluded in this study that, since elevated homocysteine levels are a risk factor for premature occlusive  vascular

disease, appropriate vitamin B therapy may be efficient,safe and cost-effective in controlling homocysteine levels. The fact that cardiovascular disease costs us, as a nation, approximately $108.9 billion per year, suggests that there should be some impetus to aggressively study and evaluate the role of these simple,safe and low-cost nutrients in order potentially to reduce this independent risk factor for cardio-vascular disease.




             It is very interesting that homocysteine levels have been elevated in patients who have had recurrent miscarriages ( spontaneous abortions ) and abruptio placentae, a premature separation of the placenta. There is also some suggestive evidence, though debatable, that elevated homocysteins levels are placing women who take birth control pills at greater risk of thrombosis. It is almost common knowledge now, and has been recommended by our own public Health Service and Centers for Disease Control, that females of reproductive  age should have adequate amounts of folic acid ( at

least 400 mcg per day ), especially prior to and early on in their

pregnancy in order to help prevent neural tube defects. Elevated homocysteine levels have been documented to be higher in some mothers wh have had neural tube defect in infants. Another area where homocysteine assessment may be of valve is in the prevention of cervical dysplasia and/or cancer. Researchers at the University of Alabama have noted that low folic acid levels allow the cervix to become more susceptible to the papilloma virus, which is a causative agent for cervical dysplasia and possibly subsequent increased risk of

cervical cancer. Recently, it has been reported that female dental personnel exposed to nitrous oxide have had an increased  problem with infertility. One of the proposed explanations is that nitrous oxide interferes with vitamin B12 metabolism , which affects the ability to achieve pregnancy. An excellent study would be an assessment of homocysteine levels in female dental personnel to see if those who suffer from infertility have elevated levels.




     As mentioned previously, in the landmark article by Lindenbaum et al, homocysteine may be an excellent screening  marker for the development of a wide variety of neurologic disorders. Elevated homocysteine levels have been associated with genetic disorders resulting in mental retardation of young children, reduced cognition,dementia in the elderly and ASIDS patients,depression and in neurologic conditions such as multiple sclerosis . Multiple sclerosis patients have been noted to have slightly enlarged red blood cells and elevated levels of homocysteine . It has been stated in the literature that mulitiple sclerosis patients should be screened for elevated levels of homocysteine and/or methylmalonic acid since these metabolites can be elevated up to a year before there are actual sign of vitamin B12 deficiency in the blood. A case report was given of a 46-year-old female who had painful paresthesias associated with right leg weakness, and was presumed to have had a diagnosis of multiple sclerosis. For 15 years, this patient was admitted approximately every 18 months for a flare-up of her symptoms. Her neurologic situation continued to deteriorate and eventually , she was found to have low serum levels of vitamin B12. When she was treated with vitam B12 injections 1,000mcg daily for one week, followed by weekly injections,after six months her right leg increased in strength and there was a reduction in her large blood cells as well as homocysteine

and methylmalonic acid levels.


                     The elderly are a population in which homocysteine assessment could yield significant benefits. Dr. Russell, the associate director of the United States Department of Agriculture's Nutrition Research Center on Aging at Tufts University, is concerned  that significant portions of the older population in nursing homes, and the elderly not functioning well at home, may have undiagnosed vitamin B12 deficiency. If B12 levels are low normal, Dr. Russell would follow-up with an assay of homocysteine and methylmalonic acid, which are functional tests for B12. In one study, 17 percent of geriatric in-patients with major depression had elevated homocysteine levels, without evidence of classic folic acid or B12 deficiency . In the discussion of this paper the question, " How does one screen for subtle or subclinical vitamin deficiencies?" was answered with homocysteine being the perfect model since it can indicate deficiencies even with vitamin blood levels being normal. In can be envisioned that in the near future, homocysteine levels in the blood or urine will be assessed routinely at a minimal cost for a variety of conditions involving neurological,cardiac and gynaecological problems. Aids patients are another population in which vitamin B12 deficiency can significantly affect neurologic function. Dementia is one of the most debilitating aspects of AIDS. There is evidence that vitamin B12, homocysteine and methylmalonic acid assessment may be able to catch these deficiencies earler oln, and with treatment help slow the progression of neurologic impairment.



          Inborn Errors of metabolism


          The subject of inborn errors of metabolism is an area which necessitates homocysteine evaluation. These genetic disorders result in children and newborns who have a variety of neurologic abnormalities including epilepsy , cleft lip and delayed development. For these fully expressed inborn errors of metabolism, much larger doses of the homocysteine lowering nutrients are required. At a recent American College of Clinical pathologists and College of Pathologists joint meeting, it was stated that if the health practitioner only investigated vitamin B12 status when the red blood cells were big ( macrocytosis ), this would be a very "antiquated and inefficient " approach. The new standard for B12 uses serum methylmalonic acid and homocysteine

According to these researchers who have tested over 20,000 blood

Samples from the Cleveland Clinic foundation and the University of

Colorado Health Science in Denver.


                Homocysteine Assessment


    One laboratory which does excellent work in this area of homocysteine assessment is Meta-metris Research laboratories

In Norcross, Georgia. Informationm regarding this test and practitioners who utilize it can be obtained by calling (404) 466-5483.


       In can easily be envisioned that,in the near future, homocysteine levels in the blood or urine will be assessed routinely at a minimal cost for a wide variety of conditions involving neurological,cardiac and gynaecological problems. Homocysteine evaluation  may also extend to areas such as lung cancer, where vitamin B12 injections have long been anectotally noted to help patients, for all mental health and hospitalized

Patients, reproductive work-ups and alcoholism, among others.

       One does not have to look much further into the future to see that functional testing of other nutrients will be developed and refined.

This attempt to optimize bodily function by interviewing with these low-cost and simple nutrients will address more specifically,the underlying causes of the multitudes of degenerative diseases and illnesses, while at the same time preserving our health-care dollar and reducing the amount of crisis care which is at present stressing our ailing health-care system. This realization of  21st century medicine is really not that far off and can be propelled by consumer demand and understanding.


- Dr. Kirk Hamilton




I wish to extend my great appreciation and thanks to the staff

and management of Pahang Pharmacy Sdn. Malaysia for

calling on me and sending me  Hocygard which contains

the nutrients: Folic Acid, B6 and B12  . Hocygard is

packed  as  a community service item with minimal profit







       A Risk factor for Heart Disease


    Most people today know that high cholesterol , high blood pressure,diabetes, smoking, overweigt and lack of exercise are factors

most stronly asscociated with increased rtisk of development of coronary

heart disease. However, clinical studies have identified another important

risk factor called Homocycteine. A high blood level of Homocycteine is

found to be of equal risk in causing heart diseases as compared with high

blood cholesterol or smoking. The higher your blood homocysteine level,

the higher your risk of suffering a heart attack.



        What is Homocysteine ?


     Homocysteine is a natural amino acid metabolite of the amino acid called

Methionine. Methionined is present in all proteins and is known as an essential amino acid because it cannot be manufactured by the body, and requires a supply from dietary proteins. Methionine is ewquired for proper growth and maintenance of cells in the body. Proteins from animal sources,

Such as meat, eggs or jmmilk are abundant in methionine. Proteins from plant

Sources such as grains ( rice ), vegetables and fruits have less amount of methionine than protein from animal sourses.



    How does the body maintain a safe level of Homocysteine ?     


  During normal metabolism within the body,excess methionine is broken

Down into Homocysteine . Homocysteine can be reconverted back to methion ine. This process is controlled by Vitamin B12 and Folic Acid and is a revesible process. The body has another

process to render Homocysteine harmless by converting Homocysteine to cysteine and other compounds which are excreted in the urine. The second process is controlled by Vitamin B6 and is irreversible. Therefore, Folic Acid and Vitamin b12 protect blood vessels against damaging g effects opf Homocysteine by converting Homocysteine  to methionine,which does not cause damage unless it is reconverted back to Homocysteine. Vitamin B6

protects blood vessels by converting Homocysteine to cysteine and other compounds that are excreted in the urine.



                    Is a high Homocysteine level a health problem ? 


      A build-up of Homocysteine in the body leads to over production of a highly reactive form of Homocysteine. This reactive form can cause damage to the lining cells of blood vessels. Once the lining of the blood vessels is damaged, there seems to be an attraction of LDL cholesterol ( bad cholesterol ) which may act as a b andage, trying to help heal the lining cells. This causes a plaque to be formed in the walls of the coronary blood vessels. The plaque may grow in size and can cause a blockage in the blood vessels that carry blood to the heart. The result is a heart attack.



                     What is a normal Homocysteine level ?  



        A Homocysteine level of below 15  umol/L of blood is considered normal. Levels of 15umol/L and above are associated with increased risk of arteriosclerosis and the higher the Homocysteine level, the higher the risk. Blood  test is available . You should discuss with your doctor whether to check your Homocysteine level.



                    Who are likely to have high Homocysteine level ?



       Some people are born with high Homocysteine level due to genetic defect. This is very rare, more commonly due to defect of an enzyme  called

Methylenetetrahychrofolate  Reductase ( MTHFR ).  People who consume  huge proportion of meat and dairy products with high concentration of methionine would require increased amounts of Vitamin B6 , B12 and Folic Acid to keep blood vessels of Homocysteine down to a safe range . However,

Vitamin B6,B12 and Folic Acid are very sensitive and are very easily destroyed by the harsh physical and chemical treatments involved in food

Processing , refining an d preservation. For people who consume a high proportion of refined foods they are likely to be lacking in Vitamin B6, B12 and Folic Acid. Vitamin B12 is obtained only from foods of animal origin.

Thus, strict vegetarian diet can lead to serious vitamin B12 deficiency. Deficiency of Vitamin 6, B12 and folic Acid can lead to a build-up of Homocysteine in blood.



             Food Sources of Vitamin 6, B12 and Folic Acid.    


   Good plant sources of Vitamin B6 include whole grains,legumes,banana,nuts,seeds and vegetables like spinach, brussel sprouts and cauliflower. Folic Acid is found in high concentration in green

leafy vegetables. Vitamin B12 is found only in animal-based foods such as meat, fish and eggs.


                What can you do to lower the Homocysteine level ?



       Eat a well balanced diet and to include plenty of vegetables and fruits. If possible eat more fresh food and less refined food.

       Take  a daily supplement that provides adequate amounts of

Vitamin B6, Vitamin B12 and Folic Acid. The adequate amounts

Should preferably be above the recommended daily allowances.



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