Homocysteine is an amino acid normally found in small amounts in the blood. High homocysteine levels in the blood can also cause cholesterol to change to something called oxidized low-density lipoprotein (LDL), which is more damaging to the arteries. In addition, high homocysteine levels can make blood clot more easily than it should, increasing the risk of blood vessel blockages. These, in turn, may increase a person’s risk of stroke, heart attack (myocardial infarction), and pulmonary embolism. Also, increased homocysteine levels may promote the formation of blood clots in the deep veins of the legs (called deep venous thrombosis, or DVT).
Blood levels of homocysteine may increase if a person’s diet is deficient in certain B vitamins (folic acid, vitamin B6, and vitamin B12). High levels of homocysteine in the blood can be lowered with adequate dietary intake of these B vitamins.
In addition to dietary deficiency of B vitamins, there are other factors that may increase a person’s blood homocysteine level, including:
- A family history of elevated blood homocysteine.
- Age. Blood homocysteine levels rise with age in both men and women.
- Gender. Blood homocysteine levels are higher in men than in women. The reason for this is not totally understood but may be related to differences in muscle mass, hormones, or kidney function.
- Kidney disease. The level of homocysteine in the blood increases in kidney disease because the kidneys do not properly filter homocysteine from the blood.
- Medication use. Certain medications increase blood homocysteine levels. These medications include anticonvulsants (such as phenytoin), methotrexate, cyclosporine, levodopa, theophylline, niacin, and cholestyramine.
- Homocystinuria.
- The more a steak is cooked, the more homocysteine you’ll produce in digesting it, so don’t choose ‘well-done’ if you are having a problem in this area.
Homocysteine testing may be most valuable in evaluating the overall risk of heart disease for people who have a strong personal or family history of heart disease but who do not have other risk factors that can be controlled (such as smoking or high blood pressure).
S-Aadenosylhomocysteine, which is the precursor of homocysteme, appears to be a more sensitive marker for differentiating cardiovascular patients from control subjects than homocysteine.
Conditions that suggest Elevated Homocysteine Levels
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:
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 – having 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]
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]
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]
Schizophrenia
Extreme homocysteinuria can result in mental retardation and seizures.
Osteoporosis / Risk
Elevated homocysteine levels disrupt collagen-forming processes in the body and raise the likelihood of developing osteoporosis.
Increased Risk of 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.
Risk factors for Elevated Homocysteine Levels
High homocysteine levels
Counter Indicators
Normal/low homocysteine levels
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]
Kidney Failure
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]
Typical/high Metformin use
See the link between this question and Megaloblastic Anemia.
Vegan/raw food diet
Elevated Homocysteine Levels suggests the following may be present
Kidney Failure
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
Coffee (Coffea genus)
Two weeks of administration of caffeine tablets (870 mg/d) or coffee (0.9 L paper-filtered coffee providing 870 mg/d caffeine) increased plasma homocysteine concentrations in a well-controlled study of 48 adult volunteers. Caffeinated coffee increased homocysteine levels approximately twice as much as caffeine alone. [Am J Clin Nutr 2002;76(6): pp.1244-8]
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.
Vitamin Folic Acid
An analysis of 92 studies concluded that higher serum homocysteine concentrations are associated with an increased risk of cardiovascular disease and that daily supplementation with folic acid (800mcg per day) may reduce serum homocysteine levels adequately to reduce the risk of ischemic heart disease, deep vein thrombosis, and stroke. [BMJ 2002;325(7374): pp.1202-6]
A Netherlands study concluded that those people with a genetically reduced capacity to process homocysteine were only at increased risk for heart disease when their folic acid levels were low.
Key
| Weak or unproven link |
| Strong or generally accepted link |
| Proven definite or direct link |
| Very strongly or absolutely counter-indicative |
| May do some good |
| Highly recommended |
| Reasonably likely to cause problems |
Glossary
Amino Acid
An organic acid containing nitrogen chemical building blocks that aid in the production of protein in the body. Eight of the twenty-two known amino acids are considered "essential," and must be obtained from dietary sources because the body can not synthesize them.
Cholesterol
A waxy, fat-like substance manufactured in the liver and found in all tissues, it facilitates the transport and absorption of fatty acids. In foods, only animal products contain cholesterol. An excess of cholesterol in the bloodstream can contribute to the development of atherosclerosis.
Low-Density Lipoprotein
(LDL): Also known as "bad" cholesterol, LDLs are large, dense, protein-fat particles composed of a moderate proportion of protein and a high proportion of cholesterol. Higher levels of LDLs are associated with a greater risk of cardiovascular disease.
Stroke
A sudden loss of brain function caused by a blockage or rupture of a blood vessel that supplies the brain, characterized by loss of muscular control, complete or partial loss of sensation or consciousness, dizziness, slurred speech, or other symptoms that vary with the extent and severity of the damage to the brain. The most common manifestation is some degree of paralysis, but small strokes may occur without symptoms. Usually caused by arteriosclerosis, it often results in brain damage.
Pulmonary
Pertaining to the lungs.
Embolism
Obstruction of a vessel by an abnormal body, usually a detached blood clot.
Thrombosis
Formation of blood clots causing vascular obstruction.
Folic Acid
A B-complex vitamin that functions along with vitamin B-12 and vitamin C in the utilization of proteins. It has an essential role in the formation of heme (the iron containing protein in hemoglobin necessary for the formation of red blood cells) and DNA. Folic acid is essential during pregnancy to prevent neural tubular defects in the developing fetus.
Vitamin B6
Influences many body functions including regulating blood glucose levels, manufacturing hemoglobin and aiding the utilization of protein, carbohydrates and fats. It also aids in the function of the nervous system.
Cobalamin
Vitamin B-12. Essential for normal growth and functioning of all body cells, especially those of bone marrow (red blood cell formation), gastrointestinal tract and nervous system, it prevents pernicious anemia and plays a crucial part in the reproduction of every cell of the body i.e. synthesis of genetic material (DNA).
Hormones
Chemical substances secreted by a variety of body organs that are carried by the bloodstream and usually influence cells some distance from the source of production. Hormones signal certain enzymes to perform their functions and, in this way, regulate such body functions as blood sugar levels, insulin levels, the menstrual cycle, and growth. These can be prescription, over-the-counter, synthetic or natural agents. Examples include adrenal hormones such as corticosteroids and aldosterone; glucagon, growth hormone, insulin, testosterone, estrogens, progestins, progesterone, DHEA, melatonin, and thyroid hormones such as thyroxine and calcitonin.
Niacin
(Vitamin B-3): A coenzyme B-complex vitamin that assists in the breakdown of carbohydrates, fats and proteins. Essential for the health of the skin, nerves, tongue and digestive system. It is found in every cell of the body and is necessary for energy production. Niacin is also needed for DNA formation.
Cardiovascular
Pertaining to the heart and blood vessels.
Ulcerative Colitis
(Colitis ulcerosa): Ulceration of the colon and rectum, usually long-term and characterized by rectal bleeding or blood in the stool, frequent urgent diarrhea/bowel movements each day, abdominal pain.
Crohn's Disease
Chronic inflammatory disease of the gastrointestinal tract. The most common symptoms are abdominal pain, often in the lower right area, and diarrhea. Rectal bleeding, weight loss, and fever may also occur. Bleeding may be serious and persistent, leading to anemia.
Osteoporosis
A disease in which bone tissue becomes porous and brittle. The disease primarily affects postmenopausal women.
Chronic
Usually Chronic illness: Illness extending over a long period of time.
Gastrointestinal
Pertaining to the stomach, small and large intestines, colon, rectum, liver, pancreas, and gallbladder.
Serum
The cell-free fluid of the bloodstream. It appears in a test tube after the blood clots and is often used in expressions relating to the levels of certain compounds in the blood stream.
Steroid
Any of a large number of hormonal substances with a similar basic chemical structure containing a 17-carbon 14-ring system and including the sterols and various hormones and glycosides.
Metabolism
The chemical processes of living cells in which energy is produced in order to replace and repair tissues and maintain a healthy body. Responsible for the production of energy, biosynthesis of important substances, and degradation of various compounds.
Neurotransmitters
Chemicals in the brain that aid in the transmission of nerve impulses. Various Neurotransmitters are responsible for different functions including controlling mood and muscle movement and inhibiting or causing the sensation of pain.
Serotonin
A phenolic amine neurotransmitter (C10H12N2O) that is a powerful vasoconstrictor and is found especially in the brain, blood serum and gastric membranes of mammals. Considered essential for relaxation, sleep, and concentration.
Dopamine
A neurohormone; precursor to norepinephrine which acts as a stimulant to the nervous system.
Seizure
While there are over 40 types of seizure, most are classed as either partial seizures which occur when the excessive electrical activity in the brain is limited to one area or generalized seizures which occur when the excessive electrical activity in the brain encompasses the entire organ. Although there is a wide range of signs, they mainly include such things as falling to the ground; muscle stiffening; jerking and twitching; loss of consciousness; an empty stare; rapid chewing/blinking/breathing. Usually lasting from between a couple of seconds and several minutes, recovery may be immediate or take up to several days.
Chronic Renal Failure
(CRF) Irreversible, progressive impaired kidney function. The early stage, when the kidneys no longer function properly but do not yet require dialysis, is known as Chronic Renal Insufficiency (CRI). CRI can be difficult to diagnose, as symptoms are not usually apparent until kidney disease has progressed significantly. Common symptoms include a frequent need to urinate and swelling, as well as possible anemia, fatigue, weakness, headaches and loss of appetite. As the disease progresses, other symptoms such as nausea, vomiting, bad breath and itchy skin may develop as toxic metabolites, normally filtered out of the blood by the kidneys, build up to harmful levels. Over time (up to 10 or 20 years), CRF generally progresses from CRI to End-Stage Renal Disease (ESRD, also known as Kidney Failure). Patients with ESRD no longer have kidney function adequate to sustain life and require dialysis or kidney transplantation. Without proper treatment, ESRD is fatal.
Anemia
A condition resulting from an unusually low number of red blood cells or too little hemoglobin in the red blood cells. The most common type is iron-deficiency anemia in which the red blood cells are reduced in size and number, and hemoglobin levels are low. Clinical symptoms include shortness of breath, lethargy and heart palpitations.