Vitamin A
Vitamin B1
Vitamin B2
Vitamin B3
Vitamin B4
Vitamin B5
Vitamin B6
Vitamin B9
Vitamin B12
Vitamin B15
Vitamin B17
Vitamin C
Vitamin D
Vitamin D2
Vitamin D3
Vitamin E
Vitamin H
Vitamin K1
Vitamin K2
Vitamin K3
Vitamin K4
Vitamin L
Vitamin M
Vitamin P

Folic acid(Vitamin M)

Recommend Site


CAS: 118-92-3

Product Description
Folic Acid is developed by importing, digesting and absorbing the foreign advance production craft. Its quality conforms to USP24¡¢BP98¡¢GB7302£­87 and 2000 edition standard of the "People's Republic of China Animal Remedy Pharmacopoeia",the product has exported to European and American and the Southeast Asia area.
¡¾Chemical Name¡¿ N-4-[(2-amido-4-oxo-1,4-dihydro-6-terene)methylamino]benzoyl-L-glutamic acid
¡¾M.F.¡¿ C19H19N7O6
¡¾M.W.¡¿ 441.40
¡¾Properties¡¿ yellow or orange crystalline powder, no smell and no odor. Do not solvable in water and ethanol, easy to dissolve in sodium hydroxide or sodium carbonate's dilute solutions.
¡¾Item index¡¿ Item GB7302£­87 "China Animal Remedy Pharmacopoeia"2000 Enterprise internally control standard
content(£¥) 95.0¡«102.0 95.0¡«102.0 98.0¡«102.0
loss on drying (£¥) ¡Ü8.5 ¡Ü8.5 ¡Ü7.0
residue on ignition(£¥) ¡Ü0.5 ¡Ü0.1 ¡Ü0.1

Health starts with the individual cells of our body. If our cells are healthy so are we. Healthy cells, in turn, depend on the continued, faultless replication of our DNA. DNA can be seriously damaged through attacks by free radicals so an adequate antioxidant status is essential to cell health. However, it is becoming clear that antioxidants alone are not enough to protect our DNA; more and more research points to the B vitamin folic acid as being equally or perhaps even more important in ensuring proper DNA replication. It is not surprising that a folic acid deficiency has been implicated in a wide variety of disorders from Alzheimer's disease to atherosclerosis, heart attack, stroke, osteoporosis, cervical and colon cancer, depression, dementia, cleft lip and palate, hearing loss, and of course, neural tube defects.

Folic acid (folinic acid, folacin, pteroylglutamic acid) is essential for the synthesis of adenine and thymine, two of the four nucleic acids that make up our genes, DNA and chromosomes. It is also required for the proper metabolism of the essential amino acid methionine that is found primarily in animal proteins. A folic acid deficiency has been clearly linked to an elevated level of homocysteine, a sulfur-containing amino acid. High homocysteine levels, in turn, have been linked to cardiovascular disease and a host of other undesirable conditions.

It is unfortunately, estimated that 88 per cent of all North Americans suffer from a folic acid deficiency. Obviously, the standard diet does not supply what we need. This has led to the fortification of cereals and other foodstuffs to try to ensure a minimum daily intake of 0.4 mg/day. Although beans and green vegetables like spinach and kale are good sources of folic acid, relatively few people eat lots of vegetables and cooking destroys most of the folate anyway. Realizing the poor availability from the diet many medical researchers now advocate daily supplementation with folic acid. Because folic acid needs the catalysts vitamins B12 and B6 to carry out its functions effectively it is usual to supplement with a combination of the three. Dosage recommendations for folic acid vary between 0.4 mg/day and 10 mg/day or more depending on the severity of the deficiency and the health problem to be overcome. The RDA for adults is now 0.4 mg/day and 0.6 mg/day for pregnant women. Recommendations for vitamin B12 generally range from 0.5 to 1.0 mg/day and for vitamin-B6 from 10 to 250 mg/day.

Supplementation with folic acid and vitamins B6 and B12 costs only pennies a day and yet it is indeed hard to imagine an investment that would pay greater dividends in protecting your health.

Folic acid research article:

Folic Acid and Heart Disease?

Vitamin therapy reduces restenosis after angioplasty
ENCINITAS, CALIFORNIA. Angioplasty (percutaneous coronary intervention or PCI) is used to open up (dilate) coronary arteries so as to produce a more abundant blood supply to the heart. The beneficial effect of angioplasty is, unfortunately, often short-lived with 40% or more of the opened artery segments closing up again (restenosis) within 6 months of the operation.

A team of American researchers now reports that the incidence of restenosis in smaller coronary arteries can be markedly reduced by decreasing homocysteine levels through supplementation with folic acid and vitamins B6 and B12. Their double-blind, randomized clinical trial involved 205 patients who underwent angioplasty to open up small (diameter less than 3 mm) coronary arteries that were at least 50% blocked (stenosis). Half the participants received 1 mg folic acid, 400 micrograms vitamin-B12, and 10 mg vitamin-B6 on a daily basis while the other half received a placebo. After 28 weeks (plus or minus 6 weeks) 42% of the control group had experienced restenosis as compared to only 15% of the vitamin-treated patients; this is a relative reduction in restenosis rate of 66%. The benefit of homocysteine lowering therapy was highest among patients treated with balloon angioplasty only (82% relative risk reduction) and significantly less in patients who had stents implanted. The benefits were also higher among patients with high levels of low-density lipoprotein cholesterol.

The researchers conclude that homocysteine lowering therapy with vitamins significantly reduces the risk of restenosis in patients treated with PCI for stenosis of small coronary arteries.
Schnyder, Guido, et al. Effect of homocysteine-lowering therapy on restenosis after percutaneous coronary intervention for narrowing in small coronary arteries. American Journal of Cardiology, Vol. 91, May 15, 2003, pp. 1265-69

Congestive heart failure and homocysteine
FRAMINGHAM, MASSACHUSETTS. Congestive heart failure (CHF) is a serious health problem among the elderly. The main risk factors are advancing age, high blood pressure (hypertension), diabetes, obesity, heart valve disease, and having experienced a heart attack. Researchers involved with the Framingham Heart Study now report that a high blood level of homocysteine, a sulfur-containing amino acid, is an independent risk factor for CHF. Their study involved 1547 women and 944 men between the ages of 60 and 95 years. All participants were free of CHF and had not suffered a heart attack at the start of the study. After 8 years of follow-up 156 (6.2%) participants (88 women) had developed CHF. The researchers found that women in the highest quartile of homocysteine level (13.7 ?64.6 micromol/L) had a 4 times higher risk of CHF than did those in the lowest quartile (3.5 ?8.9 micromol/L). Even women with only slightly elevated homocysteine levels (9.0 ?11.0) had twice the risk of women in the lowest quartile. The risk for men in the highest quartile (14.5 ?219.8 micromol/L) was 50% higher than for men in the lowest quartile (4.1 ?9.5 micromol/L); however, a significant increase was not observed until the level exceeded 11.8 micromol/L. The risk estimates are those obtained after adjusting for age, smoking, valve disease, systolic blood pressure, antihypertensive medication use, echocardiographic left ventricular hypertrophy, diabetes, ratio of total cholesterol to high-density lipoprotein, alcohol intake, body mass index, serum creatinine, interim recognized or unrecognized myocardial infarction, and baseline examination.

The researchers urge further trials to determine if reducing elevated homocysteine levels through supplementation with folic acid, vitamin B6 and vitamins B12 will reduce the risk of CHF.
Vasan, Ramachandran S., et al. Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction. Journal of the American Medical Association, Vol. 289, March 12, 2003, pp. 1251-57

Editor comment: Homocysteine levels can be safely and effectively lowered by daily supplementation with 400-800 micrograms of folic acid, 50-100 mg of vitamin-B6 (pyridoxine) and 1 mg of vitamin-B12 (cyanocobalamin) taken sublingually.

Folic acid and heart disease
HYATTSVILLE, MARYLAND. 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.
Loria, Catherine M., et al. Serum folate and cardiovascular disease mortality among US men and women. Archives of Internal Medicine, Vol. 160, November 27, 2000, pp. 3258-62

Folic acid helps heart disease patients
HALIFAX, CANADA. 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. [61 references]
Title, Lawrence M., et al. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. Journal of the American College of Cardiology, Vol. 36, September 2000, pp. 758-65

Atherosclerosis and folic acid
AMSTERDAM, THE NETHERLANDS. 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.
Vermeulen, E.G.J., et al. Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial. The Lancet, Vol. 355, February 12, 2000, pp. 517-22

B vitamins and atherosclerosis
TAIPEI, TAIWAN. 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.

The study involved two men and fourteen women between the ages of 41 and 55 years. At the start of the study all participants had their blood levels of homocysteine and their blood flow through the brachial artery measured after a 10-14 hour overnight fast. They were then given an oral methionine loading test to simulate the intake of a high protein meal. Four hours later their average homocysteine level had increased from 7 micromol/L to 22.7 micromol/L and the blood flow (flow-mediated vasodilation) had decreased by 40 per cent. The experiment was repeated, but this time 5 mg of folic acid was given together with the methionine; the results were similar to those obtained in the first experiment indicating that folic acid does not act immediately as an "antidote" to a high intake of methionine. The participants were then given 5 mg of folic acid, 100 mg of vitamin B6, and 0.5 mg of vitamin B12 daily for five weeks. At the end of the five weeks their average homocysteine level had decreased to 5.2 micromol/L. The methionine loading test was repeated. Four hours later the average homocysteine level among the participants had increased to 17 micromol/L, but there was no statistically significant difference in blood flow before and after the methionine loading test. The researchers conclude that short-term (five weeks) administration of folic acid and vitamins B6 and B12 will reduce post-methionine load homocysteine levels and eliminate or ameliorate endothelial dysfunction (an early manifestation of atherosclerosis).
Chao, Chia-Lun, et al. Effect of short-term vitamin (folic acid, vitamins B6 and B12) administration on endothelial dysfunction induced by post-methionine load hyperhomocysteinemia. American Journal of Cardiology, Vol. 84, December 1, 1999, pp. 1359-61

A daily vitamin pill helps combat atherosclerosis
CLEVELAND, OHIO. 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.
Lobo, Arlene, et al. Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12. American Journal of Cardiology, Vol. 83, March 15, 1999, pp. 821-25

Low folate levels link to strokes and dementia
CALGARY, CANADA. 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.
Ebly, Erika M., et al. Folate status, vascular disease and cognition in elderly Canadians. Age and Aging, Vol. 27, July 1998, pp. 485-91

Folic acid and vitamin B6 prevent heart attacks
BOSTON, MASSACHUSETTS. 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.

The researchers found a linear decline in the risk of CHD with increased folate intake (5.8 per cent decrease for each 100 micrograms/day increase in intake) in the range between 150 to 700 micrograms/day. They conclude that the lowest risk was among women whose folate intake was above 400 micrograms/day and whose vitamin B-6 intake was above 3 milligrams/day. These values are considerably higher than the current Recommended Daily Allowances (RDAs) of 200 micrograms and 1.6 milligrams respectively. The researchers also point out that almost 90 per cent of all American women have a folate intake below 400 micrograms/day with the average national intake being only 224 micrograms/day. A high folate intake was found to be particularly important among women who consumed one or more alcoholic drinks per day. In this group those with the highest folate intake reduced their risk of MI and CHD by an astounding 73 per cent when compared to women with a low intake. The researchers were not able to evaluate the benefits of supplementation with more than 1000 micrograms/day of folate.
Rimm, Eric B., et al. Folate and vitamin B-6 from diet and supplements in relation to risk of coronary heart disease among women. Journal of the American Medical Association, Vol. 279, February 4, 1998, pp. 359-64
McCully, Kilmer S. Homocysteine, folate, vitamin B-6, and cardiovascular disease. Journal of the American Medical Association, Vol. 279, February 4, 1998, pp. 392-93 (editorial)

Heart disease linked to folate deficiency
OTTAWA, CANADA. 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 cerebrovascular 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.
Morrison, Howard I., et al. Serum folate and risk of fatal coronary heart disease. Journal of the American Medical Association, Vol. 275, No. 24, June 26, 1996, pp. 1893-96

Vitamins prevent heart attacks
BOSTON, MASSACHUSETTS. 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 association 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).
Verhoef, Petra, et al. Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B-6, B-12, and folate. American Journal of Epidemiology, Vol. 143, No. 9, May 1, 1996, pp. 845-59

Folic Acid and Homocysteine?

Homocysteine reduction with folic acid
WAGENINGEN, THE NETHERLANDS. There is growing evidence that a high blood level of the amino acid homocysteine is associated with an increased risk for heart attack, stroke, atherosclerosis, Raynaud’s phenomenon, and Alzheimer’s disease. Folic acid is known to reduce homocysteine levels and is also effective in preventing neural tube defects. However, it has not been clearly established exactly how much folic acid is needed on a daily basis in order to achieve maximum homocysteine reduction.

Researchers at Wageningen University now report that a daily intake of 400 micrograms of folic acid will reduce homocysteine levels by an average of about 22%. The clinical trial involved 308 Dutch men and women between the ages of 50 and 75 years. The participants were randomized to receive a placebo or 50, 100, 200, 400, 600 or 800 mcg/day of folic acid for a 12-week period. At the end of the trial homocysteine concentrations had dropped by about 10% in the groups receiving 50 or 100 mcg/day, by 22% in the 400 mcg/day group, and by about 25% in the groups receiving 600 and 800 mcg/day. The researchers conclude that about 90% of the maximum homocysteine reduction obtainable through folic acid supplementation can be achieved by supplementing with 400 micrograms daily.
van Oort, Floor VA, et al. Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study. American Journal of Clinical Nutrition, Vol. 77, May 2003, pp. 1318-23

Low-dose folic acid supplementation is effective
NIJMEGEN, NETHERLANDS. 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.
Brouwer, Ingeborg A., et al. Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. American Journal of Clinical Nutrition, Vol. 69, January 1999, pp. 99-104

Vitamin B12 increases efficiency of folic acid
BONN, GERMANY. 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 benefited 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.
Bronstrup, Anja, et al. Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women. American Journal of Clinical Nutrition, Vol. 68, November 1998, pp. 1104-10

Folic acid and homocysteine
OXFORD, ENGLAND. 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.
Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. British Medical Journal, Vol. 316, March 21, 1998, pp. 894-98

Major new risk factor for heart disease discovered
VANCOUVER, CANADA. 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.
Moghadasian, Mohammed H., et al. Homocysteine and coronary artery disease. Archives of Internal Medicine, Vol. 157, November 10, 1997, pp. 2299-2308
Fallest-Strobl, Patricia C., et al. Homocysteine: A new risk factor for atherosclerosis. American Family Physician, Vol. 56, October 15, 1997, pp. 1607-12

Vitamins may help prevent strokes in lupus patients
BALTIMORE, MARYLAND. 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.
Petri, Michelle, et al. Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus. The Lancet, Vol. 348, October 26, 1996, pp. 1120-24

Elevated homocysteine levels linked to stroke risk
LONDON, ENGLAND. 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.
Perry, I.J., et al. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. The Lancet, Vol. 346, November 25, 1995, pp. 1395-98

Homocysteine linked to known cardiovascular risk factors
BERGEN, NORWAY. 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.

Exercise has a beneficial effect on homocysteine levels with vigorous exercise in the 40-42 year age group having homocysteine levels 0.8-0.9 micromol/l lower than sedentary people. A low diastolic blood pressure and heart rate were both associated with benefically lower homocysteine levels. Serum cholesterol levels were also found to be related to homocysteine levels with lower cholesterol levels corresponding to lower homocysteine levels. People who took vitamin supplements, which usually contain folic acid, were found to have an average 1.35 micromol/l lower homocysteine level than people who did not supplement. A diet rich in fresh fruit and vegetables was also found to be beneficial with people eating fruit and vegetables at least six times a week having a 0.79 micromol/l lower homocysteine level than people eating fruit and vegetables once a week or less. The researchers conclude their report by raising the crucial question "Is a high homocysteine level the cause of cardiovascular disease or merely a marker of susceptibility to cardiovascular disease?" The Norwegian team believe that high homocysteine levels actually may cause vascular disease and raise the intriguing possibility that people who are at an elevated risk for cardiovascular disease (smokers, sedentary people, people with high blood pressure and cholesterol levels, and older people) may actually lower their risk by increasing their intake of vitamins or more specifically, folic acid.
Nygard, Ottar, et al. Total plasma homocysteine and cardiovascular risk profile. Journal of the American Medical Association, Vol. 274, No. 19, November 15, 1995, pp. 1526-33

Folic acid helps prevent coronary heart disease
SEATTLE, WASHINGTON. 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).

The researchers also evaluated 12 studies concerning the connection between dietary intake of folic acid and homocysteine level. They found that folic acid is very effective in lowering homocysteine levels. An intake of 400 micrograms per day (the level found in most supplements) lowers the homocysteine level by about 6 micromol/L. The researchers conclude that over 44,000 lives could be saved every year if just half the population of the United States were to supplement with 400 micrograms per day of folic acid. Unfortunately, recent surveys have shown that 88 per cent of American adults have a daily intake of folic acid below 400 micrograms. The researchers warn that an increased intake of folic acid may mask a vitamin B-12 deficiency and recommend that 1 mg of vitamin B-12 be added to all supplements containing 400 micrograms of folic acid. They also recommend that consideration be given to fortifying grain products with 350 micrograms of folic acid per 100 grams of grains. This strategy would have the added advantage of making it easier to prevent neural tube defects in new born babies.
Boushey, Carol J., et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Journal of the American Medical Association, Vol. 274, No. 13, October 4, 1995, pp. 1049-57

Folate helps prevent heart disease
BOSTON, MASSACHUSETTS. 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.
Stampfer, Meir J. and Malinow, M. Rene. Can lowering homocysteine levels reduce cardiovascular risk? The New England Journal of Medicine, Vol. 332, No. 5, February 2, 1995, pp. 328-29

Requirements and Supplementation

Grain fortification with vitamin B12?
DUBLIN, IRELAND. Since 1998 it has been mandatory to fortify grain-based foods with folic acid in the United States. Recent reports indicate that this measure has resulted in a 19 per cent decrease in the incidence of neural tube defects. A similar fortification program is being considered in the UK. Irish researchers now suggest that the fortification protocol should include not only folic acid, but also vitamin B12. They point out that folic acid supplementation also lowers the level of homocysteine, a potent risk factor for heart and vascular disease. However, a recent trial carried out by the Dublin researchers clearly showed that as blood levels of folic acid increased through supplementation, blood levels of vitamin-B12 became the limiting factor. In other words, additional folic acid as well as additional vitamin B12 is required in order to attain the maximum reduction in homocysteine levels. Four to five hundred micrograms per day of folic acid were found to increase folic acid levels by 80 to 180 per cent and lower homocysteine levels by about 30 per cent in both men and women. Both folate and homocysteine levels tended to revert to their pre-supplementation levels after 10 weeks of no supplementation; this shows that continuous supplementation is necessary in order to keep homocysteine levels under control.
Quinlivan, E.P., et al. Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease. The Lancet, Vol. 359, January 19, 2002, pp. 227-28 (research letter)

Older people need folic acid
High blood levels of homocysteine are associated with an increased risk of cardiovascular disease, particularly among the elderly. Folic acid will lower homocysteine levels, but how much is needed? Scottish researchers conclude that a total intake of 926 micrograms/day is required to remove the homocysteine-related risk from 95 per cent of people between the ages of 65 and 75 years. It would be very difficult to obtain this amount from the diet so supplementation or fortification is required. NOTE: Folic acid supplements should always be taken in conjunction with vitamin-B12 and preferably vitamin-B6 as well.
Quarterly Journal of Medicine, Vol. 95, January 2002, pp. 27-35

Folic acid requirements defined
CHICHESTER, UNITED KINGDOM. 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.?br> Wald, David S., et al. Randomized trial of folic acid supplementation and serum homocysteine levels. Archives of Internal Medicine, Vol. 161, March 12, 2001, pp. 695-700

New RDAs for folate
GAINESVILLE, FLORIDA. 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.
Bailey, Lynn B. Dietary reference intake for folate: the debut of dietary folate equivalents. Nutrition Reviews, Vol. 56, October 1998, pp. 294-99

Vitamin supplementation could save billions in health care costs
PARAMUS, NEW JERSEY. 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.
Bendich, Adrianne, et al. Potential health economic benefits of vitamin supplementation. Western Journal of Medicine, Vol. 166, May 1997, pp. 306-12

Broccoli is not enough
COLERAINE, NORTHERN IRELAND. 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.
Cuskelly, Geraldine J., et al. Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects. The Lancet, Vol. 347, March 9, 1996, pp. 657-59

Supplementation urged
BERKELEY, CALIFORNIA. 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.
Block, Gladys Micronutrients and cancer: time for action? Journal of the National Cancer Institute, Vol. 85, No. 11, June 2, 1993, pp. 846-47

Women urged to supplement with folic acid
ATLANTA, GEORGIA. 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.
Science, September 25, 1992, p. 1857

Vitamin C supplementation may increase vitamin E and folate stores in elderly people
BOSTON, MASSACHUSETTS. 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.
Jacob, Robert A. Vitamin C status and nutrient interactions in a healthy elderly population. American Journal of Clinical Nutrition, Vol. 48, No. 6, December 1988, pp. 1436-42