FOLIC ACID

For many women, an easy way to be sure you're getting enough folic acid is to take a vitamin with folic acid in it. The U.S. Public Health Service recommends that all women who could possibly become pregnant get 400 micrograms (or 0.4 mg) of folic acid every day. This could prevent up to 70% of some types of serious birth defects. But to do this, women need folic acid before they get pregnant. That's why you should always get enough folic acid every day even if you're not thinking about a baby any time soon. Folic acid has been added to some foods, such as enriched breads, pastas, rice, and cereals.  A few cereals have 100 percent of the folic acid you need.

No one expects an unplanned pregnancy. But they happen -  every day. In fact, about half of all pregnancies are not planned.  That's why you should get enough folic acid every day if there's any chance you could get pregnant.  Because by the time you know you're pregnant, your baby's brain and spine are already formed.

Folic acid prevents breast cancer

 A team of American and Chinese researchers has discovered that folic acid (folate) is highly effective in preventing breast cancer in both pre- and postmenopausal women. Their investigation involved 1321 women with breast cancer and 1382 healthy controls. The women were between the ages of 25 and 64 years when they enrolled in the Shanghai Breast Cancer Study during 1996-98.
The researchers found a clear correlation between dietary intake of folic acid and the risk of breast cancer. Women with a daily intake of 345 micrograms or higher had a 38 per cent lower risk than did women with an intake of less than 195 micrograms – after adjustment for total vegetable, fruit and animal food intake. The protective effect of folic acid was even more pronounced in women who also had a high dietary intake of vitamin B6, vitamin B12 and methionine. Women with a daily intake equal to or higher than 345 micrograms of folic acid, 8.47 micrograms of vitamin B12, 2 mg of vitamin B6, and 1.9 grams of methionine had a 53 per cent lower risk of breast cancer than did women with daily intakes at or below 195 micrograms of folic acid, 1.32 micrograms of vitamin B12, 1.35 mg of vitamin B6, and 1.27 grams of methionine.
Researchers believe that folic acid exerts its protective effect by preventing errors in DNA replication and by helping to regenerate methionine, a vital component in DNA synthesis. They also point out that both vitamin B12 and vitamin B6 are vital cofactors required for folic acid to "do its job". NOTE: Most multivitamins have levels of folic acid, vitamin B6 and vitamin B12 well above the levels found to be beneficial in the Shanghai study.
 

Folic acid protects against pancreatic cancer

Although pancreatic cancer accounts for only 2 per cent of all cancers worldwide it is the fifth leading cause of cancer deaths in the US. The five-year survival rate is less than 5 per cent. Researchers at the National Cancer Institute and the Finnish National Public Health Institute now report that an adequate folic acid intake can materially reduce the risk of developing the cancer. Their study included over 27,000 healthy male smokers aged 50 to 69 years when enrolled in 1985. Thirteen years later 157 of the men had developed cancer of the pancreas. A review of dietary records revealed that the men with a daily dietary folate intake of more than 373 micrograms/day had half the risk of pancreatic cancer than did the men with an intake of less than 280 micrograms/day. This significant risk reduction held true even after adjusting for other potential risk factors. As expected, the most serious risk factor was smoking. Men who smoked more than 25 cigarettes a day had an 82 per cent higher risk than men who smoked less than 14 a day. The researchers found no correlation between the risk of pancreatic cancer and alcohol consumption or dietary intake of methionine, vitamin B6 or vitamin B12.
Supplementing with folic acid seemed to have a slightly negative effect. The researchers point out that the supplement takers had significantly more health and alcohol-related problems than did the non-takers and that the number of supplement takers was too small to draw statistically significant conclusions. They caution that the issue could be clouded by earlier findings from animal experiments that, while folic acid supplementation may be effective in preventing cancer from starting, it may actually enhance tumor development at a later stage.
 

Folic acid requirements defined

 The U.S. government has mandated the fortification of all cereal grains with 0.14 mg (140 micrograms) of folic acid per 100 grams of grain. The aim of this measure is to reduce the risk of women giving birth to babies with neural tube defects (spina bifida). The fortification would theoretically supplement a person's diet with about 0.1 mg (100 micrograms) of folic acid per day.
Folic acid supplementation has also been found useful in lowering homocysteine levels and thereby reducing the incidence and mortality from ischemic heart disease (angina and heart attack). A dosage of 1 mg (1000 micrograms) per day has been found to result in about a 25 per cent decrease in homocysteine concentration; this is estimated to correspond to a 15 per cent reduction in mortality from ischemic heart disease. Higher dosages (up to 5 mg/day) have not been found to have any greater effect than the 1 mg/day dose. British researchers have now addressed the question of how much folic acid (in supplement form) is needed to achieve the maximum homocysteine reduction. Their clinical trial involved 151 patients with ischemic heart disease who were randomized to receive 0.2 mg, 0.4 mg, 0.6 mg, 0.8 mg, 1 mg or a placebo daily for a three-month period. The participants' blood levels of folate and homocysteine were measured before the start of supplementation, at the end of the supplementation period, and three months later. The maximum median reduction in homocysteine levels (23 per cent) was observed at a supplementation level of 0.8 mg/day. The currently recommended daily intake of 200-400 micrograms/day achieved only a 10 per cent reduction in homocysteine levels. Homocysteine levels returned to their pre-trial levels after three months without supplementation indicating that folic acid supplementation must be continuous and indefinite if homocysteine levels are to be kept in check. The researchers conclude "It would be reasonable for clinicians to consider advising patients with ischemic heart disease to take 0.8 mg (800 micrograms) of folic acid each day."
 

Crohn's disease patients need folic acid

 People with inflammatory bowel disease (Crohn's disease and ulcerative colitis) tend to be at greater risk for thromboembolic events (blood clots) such as stroke and peripheral venous thrombosis. Researchers at the Chaim Sheba Medical Center believe they may have found the reason for this. They studied 105 men and women with active Crohn's disease and compared their blood levels of homocysteine (a known risk factor for blood clots), folic acid and vitamin B12 to the levels found in 105 healthy controls. They found that homocysteine levels were significantly higher in patients with mild to moderately active Crohn's disease and that folic acid and vitamin B12 levels were significantly lower. The average level of folic acid was 5.9 pg/mL (normal range is 5 to 17 pg/mL). The researchers point out that it is well established that increased folate levels correspond to lower homocysteine levels. They conclude that patients with Crohn's disease may benefit from supplementing with folic acid.
 

Folic acid helps heart disease patients

Several studies have concluded that high homocysteine levels are associated with coronary artery disease (CAD). It is believed that homocysteine promotes atherosclerosis through increased oxidative stress and by "encouraging" dysfunction of the lining of the arteries (endothelial dysfunction). It is generally accepted that folic acid supplementation will lower homocysteine levels, but whether folic acid supplementation will also reduce the endothelial dysfunction responsible for the initiation and progression of atherosclerosis is less certain.
Medical researchers at the Queen Elizabeth II Health Sciences Centre now report that supplementation with 5 mg/day of folic acid significantly decreases endothelial dysfunction. The extent of endothelial dysfunction is determined by measuring the blood flow through the brachial artery in the arm (flow-mediated dilation or FMD). The clinical trial included 75 patients with CAD. The patients were randomized into three groups. One group took 5 mg of folic acid daily for four months; the second group took 5 mg of folic acid plus 2000 mg of vitamin C plus 800 IU of vitamin E per day; the third group was given a placebo. At the end of the trial patients in the folic acid group had increased their blood plasma level of folate by 475 per cent (from 14 nmol/L to 80 nmol/L) and decreased their homocysteine level by about 11 per cent. FMD improved significantly as well (from 3.2 to 5.2 per cent). Patients in the folic acid plus antioxidant group increased their folate level by 438 per cent, reduced homocysteine by 9 per cent, and improved FMD from 2.6 to 4.0 per cent. The researchers point out that the FMD improvement seen in the folic acid supplemented groups is similar to that seen with statin drugs and ACE inhibitors. They conclude that four months of folic acid supplementation is safe and significantly reduces endothelial dysfunction in patients with established coronary atherosclerosis.

Folic acid and heart disease

High homocysteine levels are associated with an increased risk of heart disease. High homocysteine levels have also been linked to a relative folic acid deficiency. Researchers at the Centers for Disease Control and Prevention now report that low blood levels of folic acid are associated with a substantially increased risk of dying from cardiovascular disease. Their study involved 689 adults aged between 30 and 75 years who were free of heart disease at the start of the study in 1976-1980. After 12 to 16 years of follow-up 122 of the participants without diabetes had died - 49 of them from heart disease. Among the participants with diabetes, 52 in all, 25 died - 12 of them from heart disease.
In the non-diabetic group there was a clear association between blood levels of folate and death from heart disease. The participants with folate levels below 10 nmol/L had a 2.64 times higher age and sex adjusted risk of dying from cardiovascular disease than did the participants with levels above 16.8 nmol/L. Even when adjusting for other risk factors (education level, race, cigarette smoking, alcohol consumption, cholesterol levels, blood pressure, and body mass index) the death rate among the participants with low folate status was still 2.28 times higher than among the people with higher levels. The observations made in the non-diabetic group tended to parallel those in the diabetes group, but because of the small sample size in the diabetes group the observed trends were not statistically significant.
The researchers conclude that at least a third of the participants had folate levels at baseline (1976-1980) so low that they would be in the high-risk category for dying from cardiovascular disease. They urge further work to determine if recent efforts to fortify the US food supply with folic acid are sufficient to decrease the proportion of the population at risk for heart disease because of insufficient folate levels.
 

Supplement recommendations for chronic fatigue syndrome

Dr. Melvyn Werbach, MD of the UCLA School of Medicine has just published a thorough review of nutritional deficiencies involved in chronic fatigue syndrome (CFS). These include deficiencies in vitamin C, coenzyme Q10, magnesium, zinc, sodium, l-tryptophan, l- carnitine, essential fatty acids, and various B vitamins. He points out that there is some evidence that the deficiencies are caused by the disease itself rather than by an inadequate diet. He suggests that the deficiencies not only contribute to the symptoms of CFS but also impair the healing process. Although the results of supplementation trials involving CFS patients have been inconclusive so far Dr. Werbach nevertheless recommends that CFS patients be given large doses of certain supplements for at least a trial period to see if their symptoms improve. His recommendations are:

Folate deficiency linked to Alzheimer's disease

 Studies have shown that low concentrations of folic acid (folates) in the blood are associated with an increased risk of dementia and Alzheimer's disease (AD). Researchers at the University of Kentucky now report that low folate levels are directly associated with a high degree of atrophy of the cerebral cortex. Their study involved 30 nuns who had blood samples drawn and analyzed prior to their death between the ages of 78 and 101 years. Autopsies of the brains showed a clear negative association between folate levels and atrophy of the neocortex and this association was especially strong among the nuns who had been diagnosed with Alzheimer's disease. The average folate level in the nuns with significant AD was 45 nmol/L as compared to 61 nmol/L in the nuns without significant AD. It is interesting that the average blood levels of folate was 104 nmol/L in the nuns taking multivitamin pills as compared to only 36 nmol/L in those not taking supplements.

Atherosclerosis and folic acid

A high blood level of homocysteine (a sulfur-containing amino acid derived from methionine) has been associated with the development of atherosclerosis. High homocysteine levels can be reduced by supplementation with folic acid; however, it is still uncertain whether this reduction actually lowers the risk of atherosclerosis. Now researchers at the University Hospital Vrije Universiteit report evidence that supplementation with folic acid and vitamin B6 is associated with a decreased occurrence of abnormal exercise electrocardiographs - important markers for atherosclerosis. The study involved 158 siblings of 167 patients with premature atherothrombotic disease. The study participants (siblings) had no signs of arterial disease when entering the study, but were obviously at greater risk of developing atherosclerosis than normal. The participants underwent a methionine-loading test at the start of the study and were subsequently divided into two groups. One group of 104 had high homocysteine levels after the methionine-loading test while the second group of 54 siblings had normal levels. Each group was subsequently randomized to receive either 5 mg folic acid plus 250 mg vitamin B6 daily for a two-year period while the other group received a placebo. At the end of two years all participants had an electrocardiogram, an ultrasound measurement of the carotid and femoral arteries, and a determination of their ankle-brachial pressure index at rest and after exercise. As expected, the vitamin treatment was associated with a significant drop in both fasting homocysteine concentration and postmethionine homocysteine concentration. Blood plasma content of folic acid increased 13-fold and that of vitamin B6 9-fold in the supplement group. There was no apparent effect of vitamin treatment on ankle-brachial pressure indices or ultrasound measurements; however, the incidence of new abnormal exercise electrocardiograms was much lower in the vitamin group (6 versus 14 in the placebo group). The researchers conclude that vitamin therapy lowers the risk of an abnormal exercise electrocardiogram by 60 per cent independent of other risk factors such as age, sex, baseline level of postmethionine homocysteine, cholesterol levels, smoking habits, and the presence of hypertension or diabetes. Although the trial involved participants at high risk for atherosclerosis the researchers see no reason why the results should not be applicable to healthy individuals.
 

Niacin treatment increases homocysteine levels

 Niacin (vitamin B3) has been used effectively to reduce elevated cholesterol levels. Niacin therapy is particularly desirable because it reduces the level of low- density lipoproteins (LDL - the "bad" cholesterol) and increases the level of high-density lipoproteins (HDL - the "good" cholesterol). A recent trial which evaluated the effect of treating high cholesterol levels with both niacin and the cholesterol-lowering drug colestipol found that the treated patients increased their blood plasma levels of homocysteine. High homocysteine levels have been associated not only with an increased risk for heart disease, but also with an increased risk for stroke, intermittent claudication, and hypothyroidism.

B vitamins and atherosclerosis

 High blood levels of the amino acid homocysteine have been associated with an increased risk of atherosclerosis. Homocysteine is formed in the body from methionine (an amino acid found in proteins) in a process that can be blocked by folic acid and vitamins B6 and B12. High homocysteine levels can induce endothelial dysfunction (a narrowing of the arteries) which in turn is believed to be a precursor of atherosclerosis. Researchers at the National Taiwan University Hospital now report that homocysteine-induced endothelial dysfunction can be avoided or very significantly ameliorated by supplementing with folic acid and vitamins B6 and B12.

Vitamin C supplementation may increase vitamin E and folate stores in elderly people

A study of the vitamin C status of 677 noninstitutionalized elderly people (age 60 to 98 years) was carried out in the Greater Boston area between August 1981 and December 1983. The study was based on detailed blood analyses and three-day food intake and nutrient supplement records. The study involved 235 males (82 of whom used vitamin C supplements) and 442 females (195 of whom used supplements). The average daily vitamin C intake from diet alone was 142 and 136 mg/day for males and females respectively. The mean daily supplement dose was 300 mg. The study found no significant correlation between plasma ascorbic acid (AA) level and age; however, there was a clear correlation between vitamin C intake and plasma AA level. None of the subjects taking supplements were found to be deficient in plasma AA levels; however, 6% of male non-users and 3% of female non-users were found to be marginally deficient. There was no significant correlation between vitamin B-6 status and plasma AA level nor was vitamin B-12 status affected. The study supports the hypothesis that vitamin C spares vitamin E in elderly people. Neither copper nor iron absorption seemed to be affected by plasma AA levels. However, the folate status was substantially better (by 25%) in supplement users as compared to non-users.
 

Women urged to supplement with folic acid

 The Public Health Service in the U.S.A. recently issued a statement urging women of child-bearing age to ensure that they consume 400 micrograms of folic acid a day. Folic acid is present in leafy dark vegetables and citrus fruits, but even a well balanced diet may not provide 400 micrograms per day; thus the need for supplementation. Recent studies in England and Hungary have shown that folic acid is important in preventing neural tube defects. Dr. Godfrey Oakley of the Centers for Disease Control estimates that 2,500 children are born with neural tube defects in the United States each year. He predicts that one half to three quarters of these cases can be prevented if women of child-bearing age ensure an adequate intake of folic acid at all times. NOTE: Neural tube defects usually occur before a woman realizes that she is pregnant.
 

Supplementation urged

It is becoming increasingly clear that fruits, vegetables, fiber, and antioxidant vitamins are potent protectors against many forms of cancer. Now folic acid has been added to the list. A recent study shows that increased dietary intake of folic acid significantly reduces the risk of developing adenomas (tumors) of the colon and rectum. Dr. Gladys Block of the University of California points out that only 9% of all Americans consume the recommended five or more servings a day of fruits and vegetables. She recommends that serious consideration be given to fortifying food and/or urging people to use antioxidant supplements so as to reduce the incidence of cancer.
 

Vitamin A may protect against breast cancer

Evidence is mounting that a high intake of fruits and vegetables is protective against most cancers. It is not entirely clear which components of the fruits and vegetables provide the protection but vitamin C and beta carotene have long been top contenders. Now researchers at the Harvard Medical School report that folic acid may provide significant protection against colon cancer. The scientists found that men and women with a high intake of folic acid (including supplements) had a 35 per cent less risk of developing adenomatous colon polyps (the precursors to colon cancer) than did people with a low intake. A high fiber intake was also found to lower the colon adenoma risk. Thus people who consumed about 30 grams/day of fiber had a 50 per cent lower risk than did people who consumed about 12 grams/day. The researchers also report on the latest findings in the Nurses' Health Study concerning breast cancer. Between 1980 and 1988 about 1500 cases of breast cancer occurred in the study group. The scientists found no correlation between the risk of breast cancer and the intake of fat or the intake of vitamins C and E. However, a high intake of vitamin A was found to correspond to a 20 to 30 per cent reduction in breast cancer risk. The researchers believe that both beta carotene and preformed vitamin A from animal sources (including supplements) have a protective effect. They point out that women who already have a high dietary intake of vitamin A may benefit little from further supplementation; however, among women whose dietary intake was low, the scientists found a 50 per cent reduction in breast cancer risk associated with the use of vitamin A supplements.
 

Niacin effective in the treatment of atrial fibrillation

Dr. Abram Hoffer, a world-renowned psychiatrist in Victoria, reports on the successful treatment of six patients with atrial fibrillation. One 76 year old physician who suffered from atrial fibrillation was completely cured after starting a vitamin supplementation program which included megadoses of niacin and folic acid. Other patients report complete disappearance of their irregular heart beat symptoms after supplementing with high doses of niacin, folic acid, and vitamin B-12. Dr. Hoffer believes that one of the main causes of atrial fibrillation is excessive stress. High levels of stress release large amounts of adrenalin which in turn is oxidized to adrenochrome. Adrenochrome is known to cause fibrillation and other cardiac dysfunctions. Adrenochrome is a natural free radical and is primarily produced in the heart tissue, but circulates in the blood throughout the body. It can cross the blood-brain barrier and excessive amounts of it are believed to be a main cause of schizophrenia. Antioxidants protect against the formation of excessive amounts of adrenochrome and schizophrenics have been successfully treated with large amounts of niacin and ascorbic acid. Penicillamine has also been successfully used in the treatment of schizophrenia. Dr. Hoffer points out that adrenochrome is not all bad. He believes that the leucocytes use adrenochrome to destroy abnormal cells like cancer cells and that we therefore need a certain amount of adrenochrome in order to control cancer. The fact that schizophrenics rarely develop cancer supports this hypothesis. Dr. Hoffer concludes that we need a certain amount of stress in order to produce enough adrenochrome to enable our leucocytes to kill bacteria and tumor cells. However, we also need an adequate supply of natural antioxidants such as vitamins C and E and beta-carotene in order to neutralize an excess of adrenochrome after its work is done.

Folate helps prevent heart disease

 Several recent studies on the causes of coronary disease have concluded that a high blood level of homocysteine is an important risk factor. A recently completed study, the Physicians' Health Study, showed that men with a high homocysteine level had a three times higher risk of suffering a myocardial infarction (heart attack) than did men with lower levels. Elevations of homocysteine levels can be due to relatively rare genetic defects but are most likely caused by a lack of folate (folic acid) in the diet. Studies have shown that the level of homocysteine in the blood is inversely proportional with the level and dietary intake of folate. A minimum daily intake of 400 micrograms per day of folate is required to maintain a stable low level of homocysteine. A folate intake of 1 to 2 mg per day, which is generally safe, is usually sufficient to reduce high homocysteine levels even if they are not due to inadequate folate consumption. It is estimated that 40 per cent of Americans get too little folate and that over 20 per cent have homocysteine levels high enough to result in vascular disease.
 

Heavy drinkers need folate

 Researchers at the Harvard Medical School report that heavy drinking (more than two drinks a day) combined with a low intake of folate and methionine triples the risk of developing colon cancer. Their study involved almost 48,000 male health professionals in the United States and covered the period 1986 to 1992. During this period 205 new cases of colon cancer were diagnosed in the study group. The researchers also discovered that men who drank more than two drinks per day, but had a high folate or methionine intake, had no greater risk of developing colon cancer than did non-drinkers. The greatest protective effect was found with a methionine intake in excess of 2.44 grams/day and a folate intake of 646 micrograms/day or greater. A high methionine and folate intake did not significantly lower the risk of getting colon cancer among light drinkers and non-drinkers. The risk of getting colon cancer was somewhat higher among wine drinkers than among beer and liquor drinkers. The researchers recommend that alcohol drinkers increase their intake of methionine-rich foods (poultry, fish, and low-fat dairy products); they do not recommend supplementation with methionine as an excess can increase blood homocysteine levels. A high homocysteine level is now believed to be a risk factor for coronary heart disease. A high intake of folate-rich foods (fresh fruit, vegetables, and whole-grain foods) is also recommended including the use of multivitamin supplements if necessary. The researchers believe that the combination of large amounts of alcohol and insufficient amounts of methionine and folate in the diet leads to abnormalities in the methylation of DNA. This may contribute to the development of cancer by activating tumor development genes and deactivating tumor suppressor genes. (88 references)
 

Folic acid helps prevent cleft lip and palate

Researchers at the California Birth Defects Monitoring Program and the Oakland Children's Hospital report that mothers can decrease their risk of giving birth to a child with orofacial clefts (cleft lip or palate) by increasing their intake of folic acid prior to and immediately following conception. The investigation involved 731 mothers who had given birth to a child with an orofacial cleft and 734 mothers with a non-malformed child. The researchers found that mothers who had taken multivitamins containing folic acid (0.4-0.8 mg) during the period from one month before through two months after conception had a 25 to 50 per cent reduction in the risk of giving birth to a child with orofacial clefts. Earlier research has shown that a mother who has already given birth to one child with orofacial clefts can reduce her risk of having another child with orofacial clefts by a factor of six if she takes multivitamin pills and 10 mg/day of folic acid.

Folic acid helps prevent coronary heart disease

 A high level of homocysteine in the blood has been clearly implicated in heart disease, stroke and peripheral vascular disease. Homocysteine is an amino acid which is not found in protein as such, but is involved in the metabolism of other amino acids (methionine and cysteine). The average blood level of total homocysteine in male adults is about 10 micromol/L. Now researchers at the University of Washington confirm that people with a higher than normal level of homocysteine have a greater risk of developing vascular disease. The researchers evaluated 17 studies dealing with the link between homocysteine levels and the risk of coronary artery disease (CAD). They found that men with a level of 15 micromol/L had a 60 per cent greater risk of developing CAD while the increased risk for women was 80 per cent. The risk for cerebrovascular disease (stroke) was found to be almost twice as high in men and women with elevated (15 micromol/L) homocysteine levels. The risk of developing peripheral vascular disease (eg. intermittent claudication) was found to be almost seven times higher among people with elevated homocysteine levels. The researchers conclude that a high homocysteine level is an independent risk factor for vascular disease and that a 5 micromol/L elevation results in the same increase in CAD risk as a cholesterol increase of 0.5 mmol/L (20 mg/dL).

Homocysteine linked to known cardiovascular risk factors

It is generally accepted that a high blood level of homocysteine is a significant risk factor for cardiovascular disease. Several studies have found that patients with coronary heart disease have homocysteine levels which are 20 to 30 per cent (2 to 3 micromol/liter) higher than those of healthy control subjects. A recent study found that a 5 micromol/l increase in homocysteine level is associated with a 60 to 80 per cent increase in the risk of coronary artery disease and a 50 per cent increase in the risk of cerebrovascular disease (stroke). Researchers from the University of Bergen now report that homocysteine levels are closely linked with other known risk factors for cardiovascular disease. Their study involved a total of 7,591 men and 8,585 women between the ages of 40 and 67 years. None of the participants had a previous history of diabetes, hypertension, coronary heart disease or cerebrovascular disease. The researchers found that men tend to have higher homocysteine levels than women and that these levels increase significantly with age. Cigarette smoking is closely connected with homocysteine levels and women smokers tend to have higher levels than male smokers. When age, sex, and cigarette smoking is combined the effect becomes vastly magnified. A 65-67 year old man who is a heavy smoker has a homocysteine level 4.8 micromol/l higher than a never-smoking woman aged 40-42 years; this would correspond to a 60 to 80 per cent higher risk for coronary heart disease.

Elevated homocysteine levels linked to stroke risk

 Evidence is rapidly accumulating to the effect that a high homocysteine level in the blood is a potent risk factor for cardiovascular disease. Homocysteine is an amino acid formed in the metabolism of methionine. A high level of homocysteine can be inherited, but far more often is due to a deficiency of the vitamins required to metabolize it (folic acid, vitamin B- 6, and vitamin B-12). A team of British and Norwegian medical researchers now report that men with a high homocysteine level have a vastly increased risk of suffering a stroke (ischemic). Their study involved 5,661 middle-aged men whose blood was sampled in the period 1978 to 1980. By 1991 141 of the men had suffered a stroke. The researchers compared the homocysteine level in the blood from the stroke victims with the level in blood from matched controls who had not had a stroke or heart attack during the follow-up period. They found that men with a total homocysteine level of more than 15.4 micromol/liter had an almost five times greater risk of having a stroke than did men with a more normal level of less than 10.3 micromol/liter. The increased stroke risk held true even after adjusting for obesity, hypertension, diabetes, cigarette smoking, alcohol consumption, social class, lung capacity, and level of HDL cholesterol. Elevated homocysteine levels can be normalized by ensuring an adequate intake of folic acid and other B vitamins.
 

Broccoli is not enough

A team of researchers from the University of Ulster and Trinity College in Dublin report that eating folate-rich foods such as broccoli and spinach does not result in improved folate status. An adequate folate status is especially important in women of child-bearing age as low folate levels in the blood can lead to the birth of babies with neural tube defects. Recent research has also shown that an adequate folate status is crucial in the prevention of heart disease. The study involved 41 women aged 17 to 40 years. The women were randomly assigned to one of five groups. Group I was given 400 micrograms/day of a folic acid supplement, Group II received 400 micrograms/day of folate by eating folic-acid-fortified foods, Group III received 400 micrograms/day of folate through the consumption of folate-rich food, Group IV received dietary advice on how to increase their intake of folate from food, and Group V served as a control group. At the end of the three-month experiment only the women in Groups I and II showed a significant increase in the folate content of their red blood cells. The researchers conclude that it is misleading to advise women to rely on the consumption of folate- rich foods as a means of maintaining an adequate folate status. The only way an adequate status can be ensured is by taking supplements or by consuming foods fortified with folic acid.
 

Heart disease linked to folate deficiency

 Researchers at Health Canada report that a lack of folate (folic acid) increases the risk of death from coronary heart disease (CHD) significantly. Their study began in 1970 and involved 5056 men and women aged 35 to 79 years. During the 15-year follow-up period there were 165 deaths from CHD. The researchers conclude that people with low folate levels (<6.8 nmol/L [3 ng/mL]) have a 69 per cent greater risk of dying from CHD than do people with high levels (>13.6 nmol/L [6 ng/mL]). They also confirm that smoking, hypertension, diabetes, and high cholesterol levels are potent risk factors for cardiac death with relative risk rates of 1.72, 2.37, 2.26, and 2.91 respectively. Low folate levels have also been linked to an increased risk of carotid artery stenosis, neural tube defects, cervical dysplasia, and rectal cancer. It is believed that an adequate level of folate is required in order to avoid high blood levels of homocysteine, a known risk factor for both CHD and cerabrovascular disease. The researchers point out that an estimated 88 per cent of American adults consume less folate than required to produce low, stable homocysteine levels. They also point out that the bioavailability (absorption) of folate from food is significantly less than that from folic acid supplements.
 

Vitamins prevent heart attacks

 Researchers at the Harvard Medical School confirm that a high blood level of homocysteine is a potent risk factor for a first heart attack (myocardial infarction). Homocysteine is an amino acid formed during the metabolism of methionine (an amino acid found in proteins). The researchers measured the blood plasma levels of homocysteine, vitamin B-6, vitamin B-12, and folate (folic acid) in 130 Boston area residents who had suffered a first heart attack. The results were compared to levels found in 118 matched controls. The homocysteine levels were an average 11 per cent higher in the heart attack victims than in the controls. A high homocysteine level (>11.2 micromol/L) corresponded to a five-fold increase in heart attack risk over the incidence rate at a low level (<7.2 micromol/L). The increase in risk was linear with a 3 micromol/L increase in homocysteine level corresponding to a 35 per cent increase in heart attack risk. The researchers also found that high blood levels of vitamin B-6 and folic acid provide significant protection against heart attacks. No clear assocation was found between vitamin B-12 levels and heart attack risk. There was a strong inverse relationship between homocysteine levels and folate levels indicating that an adequate folate intake is essential to normalizing homocysteine levels. The researchers found that homocysteine levels were lowest at a folate intake of 350-400 micrograms/day and recommend a daily folate intake of 400 micrograms/day (the current RDA is 200 micrograms/day).
 

Vitamins may help prevent strokes in lupus patients

 Systemic lupus erythematosus (SLE) patients have an increased risk of suffering strokes, heart attacks, and other arterial thrombotic events such as gangrene of the fingers. It is believed that this higher risk is at least partially related to a greater propensity among SLE patients to develop premature atherosclerosis. High concentrations of homocysteine (a sulphur-containing amino acid) have previously been linked to an increased risk of stroke and coronary artery disease. Now researchers at the Johns Hopkins Medical Institutions report that many SLE patients have high homocysteine levels and that these higher levels correspond to a significantly increased risk for stroke and other thrombotic events. The study involved 337 SLE patients who were followed for an average of 4.8 years. The average age of the patients was 35 years and 93 per cent of them were women. The researchers found that 15 per cent of the patients had raised homocysteine levels (greater than 14.1 micromol/liter). They also noted a strong inverse correlation between homocysteine levels and the levels of folic acid and vitamin B- 6 in the blood. After adjusting for other relevant risk factors the researchers conclude that SLE patients with elevated homocysteine levels have a 2.4 times higher risk of having a stroke and a 3.5 times higher risk of having an arterial thrombotic event. The researchers suggest that supplementation with folic acid and vitamin B-6 may help prevent thrombotic events in SLE patients. Other studies have found a clear inverse correlation between homocysteine levels and vitamin B-12 levels. This correlation was not observed in the present study - most likely because the patients were relatively young and therefore less likely to be deficient in vitamin B-12.
 

Folate and vitamin E protect against colon cancer

Colorectal adenomas are benign tumors (polyps) in the large intestine that are believed to be precursors of colon cancer. Researchers at the University of North Carolina now report that women with a high intake of folate (folic acid) and men with a high intake of vitamin E have a much reduced risk of developing colorectal adenomas. Their study involved 645 patients who underwent colonoscopy in the period between July 1988 and March 1991. Of these patients, 236 were found to have adenomas or cancer while 409 had no polyps and were used as a control group. After adjusting for other variables the researchers conclude that women with an average (mean) daily intake of 398 micrograms or more of folate have a 60 per cent reduced risk of developing colorectal adenomas as compared to women with a mean daily intake of 130 micrograms or less. The RDA of folate is only 180 micrograms. High intakes of iron (25 mg/day or more) and vitamin C (278 mg/day or more) were also found to have a protective effect among women. Among men the most protective micronutrient was vitamin E. Men whose daily vitamin E intake averaged 34 IU or higher were found to have a 65 per cent reduction in their risk of developing colorectal adenomas as compared to men with a mean daily intake of 5 IU or less. The RDA of vitamin E for men is only 10 IU. A high intake of calcium was also found to have a significant protective effect among men. Men whose average daily intake was 1400 mg or more reduced their risk by 56 per cent as compared to men whose daily intake was 400 mg or less. The researchers point out that many of the patients with high intakes of the protective micronutrients were using supplements and question whether the normal American diet contains enough of these micronutrients to offer any significant protection.
 

Folic acid important for kidney patients

Patients with end-stage renal disease often die from a heart attack or other cardiovascular complications. Researchers at the Cleveland Clinic Foundation now provide compelling evidence that this increased risk of cardiovascular disease among kidney patients is, to a large extent, due to the fact that they tend to have high blood concentrations of homocysteine (an amino acid formed in the metabolism of methionine). The study involved 176 dialysis patients with end-stage renal disease. The researchers found that the kidney patients had much higher homocysteine concentrations in their blood than does the normal population (26.6 versus 10.1 micromol/liter). They also discovered that kidney patients who had a homocysteine level above 27.8 micromol/liter were three times more likely to suffer a cardiovascular event than were kidney patients with lower concentrations. Not surprisingly, the researchers also found that kidney patients who suffered cardiovascular events had lower levels of folate, vitamin B-12, and vitamin B-6 (pyridoxine) than did kidney patients who did not suffer such events. The researchers conclude that kidney patients may need more vitamin B-6 supplementation than previously thought. They also suggest that supplementation with folic acid (15 mg/day or more) together with adequate doses of vitamins B-12 and B-6 may be effective in counteracting the increased risk of cardiovascular disease found among patients with end-stage renal disease.
 

Folate deficiency linked to depression

A low or deficient blood level of folate (folic acid) has been detected in 15 to 38 per cent of adults suffering from depression. There is now increasing evidence that supplementation with therapeutic amounts of folate can significantly improve the condition of depressed patients. In a recent trial involving 20 elderly patients with depressive disorders, treatment with 50 mg/day of methylfolate was associated with an 81 per cent response rate within six weeks. Folate supplementation (15 mg/day of methylfolate) has also been found to markedly improve the effect of treatment with standard antidepressants. Researchers at the Harvard Medical School point out that many drugs, some chronic diseases (eg. rheumatoid arthritis), certain cancer treatments, alcoholism, and a poor diet can all lead to a folate deficiency and the potential for depression. They conclude that folate supplementation may play a useful role in the treatment of depression, but caution that the daily dosage required has to be carefully determined as too high a dose may cause sleeping problems, irritability, and hyperactivity.
 

Vitamin supplementation could save billions in health care costs

It is estimated that the treatment of preventable illnesses absorbs as much as 70 per cent of total health care costs in the United States. Researchers at the Roche Vitamins Laboratory have just published a study which clearly demonstrates that nearly $20 billion in hospital charges alone could be saved every year if all women of childbearing age were to supplement with zinc and folic acid and if all people over 50 years of age were to supplement with vitamin E. The researchers evaluated all reports available in the MEDLINE database dealing with the association between vitamin intake and the incidence of disease. There are more than 4600 babies born every year in the United States with neural tube defects. Research has shown that 70 per cent of these cases could be prevented if all women of childbearing age were to supplement with 0.4-0.8 mg of folic acid daily in addition to having a daily dietary intake of 0.15-0.2 mg folate. Cardiovascular birth defects and complications associated with low birth weight incur hospital charges of almost $6 billion/year. These conditions could be largely prevented if women of childbearing age supplemented with folic acid plus 15-20 mg of zinc per day. Vitamin E supplementation is an effective preventive measure against coronary heart disease and heart attacks. Several large-scale studies have shown that men and women who supplement with 100 IU/day of vitamin E for two or more years reduce their risk of fatal coronary disease and non-fatal heart attacks by 40 per cent. Another large study found that older people (mean age: 62 years) can reduce their risk of having a heart attack by over 75 per cent by supplementing with 400 IU/day or more of vitamin E for 1.4 years or more. The researchers point out that in addition to major health care cost savings other benefits of supplementation include better quality of life, longer life, and increased productivity. They also point out that the level of supplements required for effective disease protection cannot be obtained through even the most healthful diet. NOTE: This work was funded and performed by Hoffmann-LaRoche Inc., a major manufacturer of vitamins and pharmaceuticals.
 

Major new risk factor for heart disease discovered

It is becoming increasingly evident that an elevated blood level of homocysteine is a potent risk factor for cardiovascular disease. Recent studies also suggest that high homocysteine levels may be associated with kidney disease, psoriasis, breast cancer, and acute lymphoblastic leukemia. Extensive past research has shown a close link between the development of neural-tube defects in babies and the mother's homocysteine level prior to and during pregnancy. Researchers at the University of British Columbia have just released a major report which summarizes the current knowledge about homocysteine and its effect on health. Homocysteine is formed in human tissues during the metabolism of methionine, a sulfur- containing essential amino acid. A normal, desirable level is 10 micromol/L or less. A level of 12 micromol/L is considered borderline and levels of 15 micromol/L or above are considered to be indicative of increased risk for cardiovascular disease. Several factors (age, smoking, vitamin deficiencies, and genetic abnormalities) have been linked to increased homocysteine levels. Medications that interact with folate such as methotrexate, carbamazepine, phenytoin, and colestipol/niacin combinations have also been linked to increased homocysteine levels. The researchers reviewed 23 studies dealing with the association between atherosclerosis and homocysteine levels and found that patients with vascular diseases had an average level of homocysteine that was 26 per cent higher than the level in healthy subjects. One study found that a homocysteine level of 4 micromol/L above normal corresponds to a 41 per cent increase in the risk of developing vascular disease. Another study estimates that the lives of 56,000 Americans could be saved every year if average homocysteine levels were lowered by 5 micromol/L. The researchers conclude that abnormally high homocysteine levels are a potent risk factor for cardiovascular and several other diseases. They point out that elevated homocysteine levels can, in most cases, be safely and effectively lowered by supplementation with as little as 400 micrograms per day of folic acid. Other researchers have found that a combination of folic acid (0.4-10 mg/day), vitamin B-12 (50-1000 micrograms/day), and vitamin B-6 (10-300 mg/day) is highly effective in lowering homocysteine levels. (153 references). Medical doctors at the University of Wisconsin echo the findings of the Canadian researchers in a separate report and describe a case of a 57-year-old man who lowered his homocysteine level from 29 micromol/L to 2 micromol/L by supplementing with 800 micrograms/day of folic acid for two months.
 

Folic acid and vitamin B-6 prevent heart attacks

Researchers at the Harvard School of Public Health have just released a major study which shows that a higher intake of folic acid and vitamin B-6 (pyridoxine) protects women against nonfatal heart attacks (myocardial infarction) and fatal coronary heart disease (CHD). The study involved over 80,000 female nurses who in 1980 completed food frequency questionnaires. The questionnaires were updated in 1984, 1986 and 1990 and also gathered information on the use of vitamin supplements. By 1994 658 of the women had suffered a nonfatal heart attack (MI) and 281 had died of coronary heart disease. Statistical analysis showed that women whose intake of folate (folic acid) exceeded 545 micrograms/day had a 31 per cent lower risk of having a heart attack or fatal CHD than did women whose intake was less than 153 micrograms/day. Similarly, women whose intake of vitamin B-6 was greater than 5.9 milligrams/day had a 33 per cent lower risk. Women with the highest intake of both folate and vitamin B-6 had a 45 per cent lower risk than women with the lowest combined intake. These risk reductions were independent of other cardiovascular risk factors such as smoking, hypertension, alcohol consumption, and the intake of fiber, vitamin E and saturated, polyunsaturated and trans- fatty acids. Multivitamins and other vitamin supplements were by far the largest contributors to the intakes of both folate and vitamin B-6.

Folic acid and homocysteine

Many studies have shown that patients with vascular disease, especially coronary heart disease, have higher blood homocysteine levels than do healthy controls. It is clear that the elevated homocysteine levels precede the onset of disease and is unrelated to other risk factors. Epidemiological studies have shown that a prolonged lowering of homocysteine levels of just 1 micromol/liter (in the range of 10-15 micromol/l) could theoretically result in a 10 per cent reduction in risk. It is known that homocysteine concentrations are inversely proportional to blood levels of folic acid (folate), vitamin B-12, and vitamin B-6 and that homocysteine levels can be lowered by supplementing with these vitamins. Medical researchers at the Radcliffe Infirmary have reviewed the results of trials aimed at lowering homocysteine levels by vitamin supplementation. The trials involved 1114 people with a mean age of 52 years (23 to 75 years); the average (mean) duration of treatment was six weeks and the median baseline blood concentrations of homocysteine and folate were 11.8 micromol/l and 11.6 nanomol/l respectively. The researchers found that daily supplementation with 0.5-5.0 mg of folic acid reduces homocysteine concentrations by 25 per cent. The reduction was significantly greater among patients with high initial homocysteine levels, but did not seem correlated with the amount of folic acid taken in the range of 0.5 to 5.0 mg. Supplementation with vitamin B-12 (0.5 mg/daily on average) lowers homocysteine levels by an additional seven per cent, but no effect was noted for vitamin B-6 supplementation with an average (mean) intake of 16.5 mg/daily. The researchers conclude that oral supplementation with at least 0.5 mg of folic acid and 1.0 mg of vitamin B-12 on a daily basis would lower homocysteine concentration by 3-4 micromol/l theoretically corresponding to a 30-40 per cent reduction in the risk of developing vascular disease. They recommend that further large scale studies be done to evaluate the efficacy and safety of long term use of folic acid and vitamin B-12 as a means of reducing the incidence of vascular disease among high risk subjects.
 

Low folate levels link to strokes and dementia

Researchers at the University of Calgary report that elderly people with low blood levels of folic acid (folate) are more likely to suffer a stroke than are people with normal to high levels. Their study involved 1171 subjects aged 65 years and older who were enrolled in the Canadian Study of Health and Aging. The researchers found that participants with a folate level below 9.3 nmol/L had a relative risk for ischemic stroke of 1.37. They also discovered that people with low folate levels were more likely to be depressed or demented, tended to have a history of weight loss, and were more apt to rate their health as poor. The researchers conclude that folate deficiencies in elderly people can have serious implications and point out that these deficiencies are easily, inexpensively, and rapidly correctable through supplementation.
 

Multivitamin use and colon cancer

A deficiency of folate (folic acid) prior to and during preganancy increases the risk of giving birth to a baby with neural tube defects. A lack of folate has also been linked to an increased risk of cardiovascular disease. Now researchers at the Harvard Medical School report that women with a high folate intake decrease their risk of developing colon cancer by as much as 75 per cent. Their study which began in 1980 involved 88,756 female nurses. The nurses completed food frequency questionnaires in 1980, 1984, 1986, and 1990 and also provided information about their use of vitamins, lifestyle factors, and family history which could affect their risk of colon cancer. During the period from 1980 to June 1994 442 of the women developed colon cancer. Statistical analysis showed that women who had supplemented with multivitamins containing folic acid (>400 micrograms/day) for 15 years or more had a four times lower risk of colon cancer than did women whose daily intake had been 200 micrograms/day or less. This association remained true after adjusting for age, family history of colorectal cancer, aspirin use, smoking, weight, degree of physical activity, and intake of red meat, alcohol, methionine and fiber. Adjustment for intake of vitamins A, C, D, E and calcium did not alter the folate/colon cancer correlation. However, it was clear that the benefits of folate became evident only after 15 years or more of supplement use although smaller statistically non-significant risk reductions were noted after five years. The risk reduction associated with folate supplementation was particularly evident among women with low methionine levels. Folate is essential in the regeneration of methionine and a deficiency may lead to abnormalities in DNA synthesis and repair - mechanisms which may influence the development of colon cancer. The researchers found a significantly stronger correlation between the intake of folate from supplements and a reduced colon cancer risk than between the intake of dietary folate and reduced risk. They ascribe this to the relatively low bioavailability of folate from food sources and conclude that long term use of multivitamins containing folic acid reduces the risk of colon cancer in women. Other studies have shown that folic acid supplementation also reduces colon cancer risk in men. NOTE: Certain birth control pills and drugs such as methotrexate can markedly lower folate levels in the body.
 

Folate levels and colon cancer risk

Cancer of the colon or rectum is now the second most common cause of cancer deaths in the United States. There were almost 200,000 new cases and over 59,000 deaths from colorectal cancer in 1996 alone. Colon cancer is preceded by the occurrence of malignant polyps (adenomatous polyps); non-malignant polyps (hyperplastic polyps) may also be present in the colon and rectal area. Researchers at the University of Toronto have just completed a study which shows that the folate (folic acid) level in the lining (mucosa) of the colon is significantly lower among patients with malignant polyps than among patients with benign polyps. Their study involved 30 patients over the age of 18 years who had been referred to the New England Medical Center for colonoscopy. Biopsies of normal mucosa (at least 10 cm from polyps) showed that the presence of adenomatous polyps was associated with a significantly lower mucosal folate level than was the presence of hyperplastic polyps. Although mucosal folate levels correlated reasonably well with the folate concentration in blood serum and red blood cells, these indicators were not sufficiently sensitive to predict whether polyps would be malignant or not. Blood levels of homocysteine were found to correlate well with mucosal folate levels and an elevated homocysteine level was also found to correlate with the presence of adenomatous polyps. The researchers suggest that people with malignant polyps may have an impairment in their folate metabolism which would account for their higher homocysteine levels.
 

New RDAs for folate

 Folates occur naturally in foods such as spinach and broccoli. Folic acid is a synthetic form of folate used in supplements and fortified foods. A folate deficiency has been linked to neural tube defects, cardiovascular disease, and colon cancer. The Food and Nutrition Board of the US Academy of Sciences has recently updated the Recommended Dietary Allowances for folate. They are now 400 micrograms/day for adults, 600 micrograms/day for pregnant women, and 500 micrograms/day for lactating women. Folic acid has been found to be 1.7 times more bioavailable than folate from food so 100 micrograms of folic acid has the equivalent effect of 170 micrograms of food folate. The Tolerable Upper Intake Level for supplemental folic acid has been set at 1000 micrograms/day based on the observation that an intake of 5 mg or more per day may hide the progression of neurologic disorders in patients suffering from a deficiency of vitamin B12.
 

Alzheimer's disease and folic acid

 An inadequate intake of folic acid is firmly associated with an increased risk of vascular disease and, among women of childbearing age, with a significantly heightened risk of giving birth to a baby with neural tube defects. Now a team of researchers from the universities of Oxford and Bergen (Norway) report that low folate levels are associated with an increased risk of developing Alzheimer's disease (AD). Their study which spanned the period 1988 to 1996 involved 164 patients with a clinical diagnosis of AD and 108 control subjects. The AD diagnosis was confirmed by autopsy in 76 of the 164 patients who died during the study. The researchers found that AD patients had significantly lower blood levels of folic acid and vitamin B12 (cobalamin) than did controls. They also had significantly higher levels of the amino acid homocysteine. Homocysteine is a strong risk factor for vascular disease and its level has been found to be inversely proportional to the level of folic acid in the blood. Study participants with homocysteine concentrations equal to or higher than 14 micromol/liter were found to have a 4.5 fold higher risk of AD than did participants with a homocysteine level at or below 11 micromol/liter. This association held true even when corrected for age, sex, social class, cigarette smoking, and level of apolipoprotein E epsilon 4 (a known risk factor for the development of AD). Study participants with folate levels in the lower third of the overall distribution had a 3.3 fold higher risk of AD when compared to subjects in the upper third. Similarly, participants in the lower third of vitamin B12 levels had a 4.3 times higher risk of AD as compared to subjects in the upper third. The researchers also observed that disease progression was more rapid among AD patients with high initial homocysteine levels. They conclude that high homocysteine levels are an important risk factor for AD and that this risk can be significantly reduced by ensuring an adequate intake of folic acid and vitamin B12. They suggest that daily supplementation with 0.5 to 5 mg of folic acid and 0.5 mg of vitamin B12 (cyanocobalamin) will lower the typical homocysteine levels found in Western populations by about a third.

Vitamin B-12 increases efficiency of folic acid

 There is increasing evidence that high blood levels of the amino acid homocysteine increases the risk of vascular disease, coronary heart disease, neural tube defects, and Alzheimer's disease. Folic acid supplementation is known to lower homocysteine levels and laws have recently been passed in the United States mandating folic acid fortification of bread and cereal. Now researchers at the University of Bonn report that folic acid's homocysteine lowering capacity can be markedly increased by also supplementing with vitamin B-12 (cobalamin). Their study involved 150 young, healthy women (average age of 24 years) who after a four-week washout period were randomized into three groups. Group 1 received a daily supplement of 400 micrograms of folic acid, group 2 received 400 micrograms/day of folic acid and 6 micrograms/day of vitamin B-12, and group 3 received 400 micrograms/day of folic acid and 400 micrograms/day of vitamin B-12. After four weeks the average concentration of plasma homocysteine had dropped by 11 per cent in group 1, 15 per cent in group 2, and 18 per cent in group 3. The researchers noted that study participants with high initial homocysteine concentrations benefitted more from supplementation than did women with lower initial homocysteine levels. It was also noted that vitamin B-12 levels increased significantly over the four-week period in the women whose supplements included vitamin B-12. This provides further proof that oral vitamin B-12 is indeed adequately absorbed. The researchers conclude that the benefits of folate supplementation can be markedly enhanced by the addition of vitamin B-12. They point out that vitamin B-12 deficiency is widespread especially among the elderly. The addition of vitamin B-12 to folic acid supplements also prevents the possibility that supplementation with just folic acid could mask pernicious anemia resulting from a vitamin B-12 deficiency which in turn may lead to irreversible nerve damage.
 

Low-dose folic acid supplementation is effective

An elevated level of homocysteine is a risk factor for cardiovascular disease, stroke, and Alzheimer's disease and also increases the risk of a pregnant woman giving birth to a baby with neural tube defects. Supplementation with folic acid is known to lower homocysteine levels, but it is not known exactly how much is required and how long it takes to become effective. Researchers at the Nijmegen University Hospital have just completed a study aimed at answering these questions. The trial involved 144 healthy women (with normal homocysteine levels) between the ages of 18 and 40 years. The women were randomly allocated to one of three groups. Group 1 received 500 micrograms of folic acid daily for a four-week period, group 2 received 500 micrograms every second day (250 micrograms/day), and group 3 received a placebo. Blood samples were taken at the start of the trial and after one, two and four weeks when the supplementation phase ended. Samples were also taken four and eight weeks after the end of the supplementation to see how long its effect would last. Supplementation with both 500 micrograms/day and 500 micrograms every second day was found to be effective. Homocysteine levels decreased by an average 22 per cent in the women taking 500 micrograms/day and by 11 per cent in the ones taking 500 micrograms every second day. The level of folate in plasma and red blood cells also increased significantly. The homocysteine levels increased again when supplementation was stopped, but were still well below original levels eight weeks later. The major part of the drop in homocysteine level in the 500 micrograms/day group took place within the first two weeks. In view of the fact that neural tube defects develop in the third or fourth week of pregnancy it may be worthwhile to start taking folic acid immediately after missing the first period; although, of course, it would be better to start four weeks before a planned pregnancy. The magnitude of the observed drop in homocysteine concentration upon supplementation was found to be highly dependent on the initial level. Women with high levels (14.3 micromol/L) experienced a drop of around 4 micromol/L while women with lower initial levels only experienced drops of about 1 micromol/L.
 

Folic acid deficiency implicated in hearing loss

Hearing loss is the most common impairment among the elderly after heart problems, hypertension, and arthritis and affects more than 28 million Americans. Researchers from the Centers for Disease Control and Prevention and the University of Georgia believe that age-related hearing loss may be partially caused by vitamin deficiencies. They have just released a report which supports this hypothesis. Their study involved 55 healthy women between the ages of 60 and 71 years. The women were all given a hearing test using a diagnostic audiometer according to Standard S3.6 of the American National Standards Institute and also had fasting blood samples taken. The blood samples were analyzed for serum vitamin B12, serum folate, and folate levels in the red blood cells. The researchers discovered that women with impaired hearing (less than 20 dB hearing level) had a 38 per cent lower serum level of vitamin B12, a 31 per cent lower folate level in the red blood cells, and a 25 per cent lower folate level in the blood serum. They speculate that poor folate and vitamin B12 status may somehow lead to deterioration of the nerves and blood vessels supplying the auditory system perhaps through a mechanism involving homocysteine.

Folic acid and colon cancer

 Colorectal cancer (cancer of the colon or rectum) is the third-leading cancer in the United States with more than 130,000 new cases reported every year. Previous research has shown that a high consumption of meat and a low intake of fruits and vegetables substantially increase the risk of developing colorectal cancer. Now researchers at the New York University School of Medicine report that women with a low level of folate (folic acid) in their blood serum have twice the risk of colorectal cancer than do women with higher levels. Their study involved 15,785 women who were part of the New York University Women's Health Study begun in 1985. By the end of 1994 105 of the women had developed colorectal cancer. These women were matched with 523 controls and folate intake and blood levels of folate and homocysteine were compared. Women with the highest serum level of folate (more than 31 nanomol/L) had about half the risk of developing colorectal cancer than did women with levels below 12 nanomol/L. Women with the highest levels of homocysteine (more than 12 micromol/L) had a 70 per cent increase in risk compared with women whose levels were below 8 micromol/L. About 39 per cent of the total folate intake reported came from vitamin/mineral supplements. The researchers conclude that folates may protect against colorectal cancer, but recommend larger clinical trials to further support this contention.
 

A daily vitamin pill helps combat atherosclerosis

 A high blood level of the amino acid homocysteine has been linked to an increased risk of atherosclerosis and thrombosis. It is known that oral supplementation with folic acid will lower homocysteine levels to acceptable norms, but it is not clear just how much folic acid is required to achieve this effect. Now researchers at the Cleveland Clinic Foundation report that the amount of folic acid (400 micrograms) found in most multivitamin preparations is sufficient to lower homocysteine levels in heart disease patients. Their experiment involved 95 patients who had either had a heart attack or suffered from advanced atherosclerosis. The patients were divided into four groups with one group receiving 400 micrograms/day (0.4 mg/day) of folic acid, one group receiving 1 mg/day, one group receiving 5 mg/day, and the fourth group receiving a placebo. All patients receiving folic acid also received 12.5 mg of vitamin B6 per day and 500 micrograms of vitamin B12. After 90 days the plasma homocysteine levels had dropped from 13.8 to 9.6 micromol/L in the 400 micrograms/day folic acid group, from 13.0 to 9.8 micromol/L in the 1 mg/day group, and from 14.8 to 9.7 micromol/L in the 5 mg/day group. Also after 90 days the plasma levels of folic acid had risen from 28 nanomol/L in the placebo group to 63 nmol/L in the 400 micrograms/day supplement group, to 80 nmol/L in the 1 mg/day group, and to 162 nmol/L in the 5 mg/day group. Vitamin B6 levels rose from 75 nmol/L to about 250 nmol/L in the supplemented groups and vitamin B12 levels rose from about 300 picomol/L to 525 picomol/L. The researchers conclude that a daily dose of 400 micrograms of folic acid combined with vitamins B6 and B12 will normalize homocysteine levels in heart disease patients.
 

Parkinson's patients on l-dopa need folic acid

People suffering from Parkinson's disease have an increased risk of heart attacks and strokes. A team of German and Swiss medical researchers believe they have uncovered the reason for this and propose a simple solution to the problem. The researchers studied a group of 48- to 73-year-old people. Fifteen of them had Parkinson's disease and were treated with levodopa plus decarboxylase inhibitor (Sinemet), 15 had Parkinson's disease, but were not treated as yet, and 15 were healthy controls. All study participants had their homocysteine levels measured after a 10-hour fast. The drug-treated Parkinson's patients had an average level of 17.3 micromol/L as compared to 9.1 micromol/L in the untreated group, and 9.2 micromol/L in the group of healthy controls. Other research has found that men with a level of 15 micromol/L increase their risk of coronary heart disease by 60 per cent while women increase it by 80 per cent. The risk of a stroke at the 15 micromol/L is two to five times higher than at the 10 micromol/L level in both men and women and the risk of peripheral vascular disease (eg. intermittent claudication) is seven times higher among people with elevated levels. The researchers believe that prolonged treatment with levodopa and decarboxylase inhibitor increases the blood level of homocysteine resulting in a greater risk for heart disease and stroke. They point out that elevated homocysteine levels can be lowered easily and effectively by supplementation with folic acid (400-800 micrograms per day or more depending on homocysteine level). The research team concludes that Parkinson's patients who are treated with levopoda should have their homocysteine levels monitored on a regular basis and should supplement with folic acid as required. (Editor's Note: Folic acid is non-toxic and no cases of overdosing have ever been reported. In these times of tight medical resources it would seem reasonable to suggest that Parkinson's patients on levopoda routinely supplement with 400-800 micrograms per day - unless, of course, their physician has specific objections to this).
 

Folates and cancer prevention

Folates (derivatives of folic acid) play a key role in the synthesis, repair, and methylation of DNA. It is therefore not surprising that a deficiency in this essential B vitamin has been implicated in Alzheimer's disease, atherosclerosis, heart attack, stroke, osteoporosis, depression, dementia, cleft lip and palate, hearing loss, Raynaud's phenomenon, and of course, neural tube defects.
There is now also evidence that a folate deficiency may be involved in the development of certain cancers. Dr. Young-In Kim, MD of the University of Toronto presents an overview of the current knowledge regarding the role of folates in cancer prevention. Some 20 studies have been published regarding the association between colorectal cancer (cancer of the colon or rectum) and folate status. Collectively, these studies suggest that people with a high intake of folates can reduce their risk of developing colorectal cancer by about 40 per cent when compared to people with low intakes. A study involving almost 90,000 American female nurses concluded that nurses who had been supplementing with 400 micrograms/day or more of folic acid for 15 years or more had a 75 per cent reduction in the risk of colorectal cancer when compared to people who did not supplement. The evidence concerning folates and breast cancer is not quite as clear. Studies have shown that even moderate alcohol consumption increases the risk of breast cancer and that this risk can be counteracted by supplementing with folic acid. The jury is still out on whether folate supplementation reduces the risk among non-drinkers although one study did show that postmenopausal women could decrease their risk of developing breast cancer by supplementing with folic acid. Another study involving 300 premenopausal women found a 50 per cent lower risk among women whose intake exceeded 304 micrograms/day. Other studies, however, have failed to confirm this effect.
A major study involving over 29,000 male, Finnish smokers found that those who developed pancreatic cancer had a significantly lower blood serum level of folate than did those who did not. A baseline serum folate level above 4.45 ng/mL was associated with a 55 per cent risk reduction when compared to levels below 3.33 ng/mL. An Australian study found a 64 per cent difference in risk between men with the highest folate intake and those with the lowest intake.
Dr. Kim concludes that a moderate increase in folate intake can materially help reduce the risk of certain cancers, but cautions that people who already have cancer should not increase their folate intake as there is evidence that high folate levels may accelerate the growth of existing tumours.
 

FOLIC ACID FORTIFICATION

Background:

The U.S. Public Health Service recommended in September 1992 that all women of childbearing age consume 400 micrograms (ug) of folic acid daily to reduce their risk of having a pregnancy affected with spina bifida or other neural tube defects. Folic acid is a B vitamin. For women, this amount of folic acid on a daily basis spina bifida or anencephaly, both of which are neural tube defects (NTDs) in the baby.

PHS suggested several approaches by which this level could be reached:

• Improved dietary habits
• Fortification of the U.S. food supply
• Daily use of folic acid supplements by women throughout their childbearing years.

FDA Action:

In keeping with the recommendations of PHS and the FDA Food Advisory Committee called to study these issues, the Food and Drug Administration is requiring that folic acid be added to specific flour, breads and other grains. These foods were chosen for fortification with folate because they are staple products for most of the U.S. population, and because they have a long history of being successful vehicles for improving nutrition to reduce the risk of classic nutrient deficiency diseases.

These fortified foods include most enriched breads, flours, corn meals, rice, noodles, macaroni and other grain products.

Under the terms of the new rule:

• Fortification levels will range from 0.43 milligrams to 1.4 mg per pound of product.

   

• Fortification of grain products at these levels will allow the daily intake from all sources to remain below the recommended upper limit of 1 mg per day.

   

• The amount of folic acid that will be consumed through foods fortified at these levels is considered safe for all population (age/gender) groups.

   

• Manufacturers will be allowed to make claims on the labels that the fortified products contain folic acid and that adequate intake of the nutrient may reduce the risk of neural tube defects.

FDA also emphasizes that adequate levels of folic acid, in the form of folate, can be obtained by eating natural sources such as:

• Leafy dark green vegetables
• Legumes (dried beans and peas)
• Citrus fruits and juices
• Most berries

In addition, women can assure adequate intake by taking dietary supplements containing folic acid.

The new rule takes account of the finding in PHS' recommendation that total folate consumption should be kept under 1 mg per day. This is because higher intake may complicate the diagnosis of pernicious anemia, one form of vitamin B12 deficiency, which especially affects older people.

Neural Tube Defects:

Neural tube defects, including spina bifida and anencephaly, are a common birth defect.

• Approximately 2,500 infants are born each year in the U.S. with an NTD. About half this number are though to be related to inadequate folate intake by the mother. Other NTDs have different causes that are not well understood.

   

• Spina bifida is a condition in which the spinal cord is exposed. A majority of babies born with spina bifida grow to adulthood with varying degrees of disability, ranging to problems with bowel and bladder control, and paralysis. Many may require a series of operations and other treatments.

   

• In anencephaly, infants die shortly after birth because most or all of the brain is absent.

Since NTDs develop very early in pregnancy (18-30 days after conception), often before a woman knows she is pregnant, it is essential that adequate intake of folic acid be maintained throughout the childbearing years.

Women who have had a prior NTD-affected pregnancy are at high risk of having a subsequent affected pregnancy. When these women are planning to become pregnant, they should consult their physicians for advice.

Pernicious Anemia & Recommended Daily Limit:

Because the effects of high intakes of folic acid are not well known, but do include complicating the diagnosis of vitamin B12 deficiency, care should be taken to keep total folate consumption under 1 mg per day, except under the supervision of a physician.

                                           Micrograms
                                    (per 100 g of food-3.5 oz)
 
dark-green leafy vegetables                  120-160
 
other vegetables                              40-100
 
fruits (particularly citrus)                  50-100
 
beans (legumes)                               50-300
 
whole grains                                  60-120
 
breakfast cereals                            100 or 400

                                                                     PRESCRIPTION FOR WELLNESS