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Linus Pauling Institute
Micronutrient Research for Optimum Health

The terms folic acid and folate are often used interchangeably for this water-soluble B-complex vitamin. Folic acid, the more stable form, occurs rarely in foods or the human body but is the form most often used in vitamin supplements and fortified foods. Naturally occurring folates exist in many chemical forms. Folates are found in foods as well as in metabolically active forms in the human body (1). In the following discussion forms found in food or the body will be referred to as "folates", while the form found in supplements or fortified foods will be referred to as "folic acid."

FUNCTION:  One-carbon metabolism

The only function of folate coenzymes in the body appears to be in mediating the transfer of one-carbon units (2). Folate coenzymes act as acceptors and donors of one-carbon units in a variety of reactions critical to the metabolism of nucleic acids and amino acids (3).

Nucleic acid metabolism
Folate coenzymes play a vital role in DNA metabolism through two different pathways. 1) The synthesis of DNA from its precursors (thymidine and purines) is dependent on folate coenzymes. 2) A folate coenzyme is required for the synthesis of methionine, and methionine is required for the synthesis of S-adenosylmethionine (SAM). SAM is a methyl group (one-carbon unit) donor used in many biological methylation reactions, including the methylation of a number of sites within DNA and RNA. Methylation of DNA may be important in cancer prevention (see Disease Prevention).
Amino acid metabolism
Folate coenzymes are required for the metabolism of several important amino acids. The synthesis of methionine from homocysteine requires a folate coenzyme as well as a vitamin B12-dependent enzyme. Thus, folate deficiency can result in decreased synthesis of methionine and a buildup of homocysteine. Increased levels of homocysteine may be a risk factor for heart disease as well as several other chronic diseases (see Disease Prevention).

Nutrient interactions:  Vitamin B12 and vitamin B6

The metabolism of homocysteine, an intermediate in the metabolism of sulfur-containing amino acids, provides an example of the interrelationships among nutrients necessary for optimal physiological function and health. Healthy individuals utilize two different pathways to metabolize homocysteine (see diagram). One pathway (methionine synthase) synthesizes methionine from homocysteine and is dependent on a folate coenzyme and a vitamin B12-dependent enzyme. The other pathway converts homocysteine to another amino acid, cysteine, and requires two vitamin B6-dependent enzymes. Thus, the amount of homocysteine in the blood is regulated by three vitamins: folate, vitamin B12, and vitamin B6 (4).

Deficiency - Causes

Folate deficiency is most often caused by a dietary insufficiency; however, folate deficiency can occur in a number of other situations. For example, alcoholism is associated with low dietary intake and diminished absorption of folate, which can lead to folate deficiency. Additionally, certain conditions such as pregnancy or cancer result in increased rates of cell division and metabolism, causing an increase in the body's demand for folate (5). Several medications may also contribute to deficiency (see Drug interactions).

Symptoms

Individuals in the early stages of folate deficiency may not show obvious symptoms, but blood levels of homocysteine may increase (see Prevention). Rapidly dividing cells are most vulnerable to the effects of folate deficiency; thus, when the folate supply to the rapidly dividing cells of the bone marrow is inadequate, blood cell division becomes abnormal resulting in fewer but larger red blood cells. This type of anemia is called megaloblastic or macrocytic anemia, referring to the enlarged, immature red blood cells. Neutrophils, a type of white blood cell, become hypersegmented, a change which can be found by examining a blood sample microscopically. Because normal red blood cells have a lifetime in the circulation of approximately four months, it can take months for folate deficient individuals to develop the characteristic megaloblastic anemia. Progression of such an anemia leads to a decreased oxygen carrying capacity of the blood and may ultimately result in symptoms of fatigue, weakness, and shortness of breath (1). It is important to point out that megaloblastic anemia resulting from folate deficiency is identical to the megaloblastic anemia resulting from vitamin B12 deficiency, and further clinical testing is required to diagnose the true cause of megaloblastic anemia.

The Recommended Dietary Allowance (RDA)

Determination of the RDA

Traditionally, the dietary folate requirement was defined as the amount needed to prevent a deficiency severe enough to cause symptoms like anemia. The most recent RDA (1998) was based primarily on the adequacy of red blood cell folate concentrations at different levels of folate intake, as judged by the absence of abnormal hematological indicators. Red cell folate has been shown to correlate with liver folate stores. Maintenance of normal blood homocysteine levels, an indicator of one-carbon metabolism, was considered only as an ancillary indicator of adequate folate intake. Because pregnancy is associated with a significant increase in cell division and other metabolic processes that require folate coenzymes, the RDA for pregnant women is considerably higher than for women who are not pregnant (3). However, the prevention of neural tube defects (NTD) was not considered when setting the RDA for pregnant women. Rather, reducing the risk of NTD was considered in a separate recommendation for women capable of becoming pregnant (see Prevention), because the crucial events in the development of the neural tube occur before many women are aware that they are pregnant (6).

Dietary Folate Equivalents (DFE)

When the Food and Nutrition Board of the Institute of Medicine set the new dietary recommendation for folate, they introduced a new unit, the Dietary Folate Equivalent (DFE). Use of the DFE reflects the higher bioavailability of synthetic folic acid found in supplements and fortified foods compared to that of naturally occurring food folates (6).

1 microgram (mcg) of food folate provides 1 mcg of DFE

  • 1 mcg of folic acid taken with meals or as fortified food provides 1.7 mcg of DFE
  • 1 mcg of folic acid (supplement) taken on an empty stomach provides 2 mcg of DFE

For example, a serving of food containing 60 mcg of folate would provide 60 mcg of DFE, while a serving of pasta fortified with 60 mcg of folic acid would provide 1.7 x 60 = 102 mcg DFE due to the higher bioavailability of folic acid. A folic acid supplement of 400 mcg taken on an empty stomach would provide 800 mcg of DFE. It should be noted that DFEs were determined in studies with adults and whether folic acid in infant formula is more bioavailable than folates in mother's milk has not been studied. Use of DFEs to determine a folic acid requirement for the infant would not be desirable.

Recommended Dietary Allowance for Folate in Dietary Folate Equivalents (DFE)
Life StageAgeMales (mcg/day)Females (mcg/day)
Infants0-6 months65 (AI)65 (AI)
Infants7-12 months80 (AI)80 (AI)
Children1-3 years150150
Children4-8 years200200
Children9-13 years300300
Adolescents14-18 years400400
Adults19 years and older400400
Pregnancyall ages-600
Breast-feedingall ages-500

Genetic variation in folate requirements

A common polymorphism or variation in the gene for the enzyme methylene tetrahydrofolate reductase (MTHFR), known as the C677T MTHFR polymorphism, results in a less stable enzyme (7). Depending on the population, 50% of individuals may have inherited one copy (C/T), and 5% to 25% of individuals may have inherited two copies (T/T) of the abnormal MTHFR gene. MTHFR plays an important role in maintaining the specific folate coenzyme required to form methionine from homocysteine (see diagram). When folate intake is low, individuals who are homozygous (T/T) for the abnormal gene have lower levels of the MTHFR enzyme and thus higher levels of homocysteine in their blood (8). Improved folate nutritional status appears to stabilize the MTHFR enzyme, resulting in improved enzyme levels and lower homocysteine levels. An important unanswered question about folate is whether the present RDA is enough to normalize MTHFR enzyme levels in individuals who are homozygous for the C677T polymorphism, or whether those individuals have a higher folate requirement than the RDA (9).

Disease Prevention

Pregnancy complications

Neural tube defects

Fetal growth and development are characterized by widespread cell division. Adequate folate is critical for DNA and RNA synthesis. Neural tube defects (NTD) result in either anencephaly or spina bifida, which are devastating and sometimes fatal birth defects. The defects occur between the 21st and 27th days after conception, a time when many women do not realize they are pregnant (10). The risk of NTD in the United States prior to fortification of foods with folic acid was estimated to be one per 1000 pregnancies (1). Results of randomized trials have demonstrated 60% to 100% reductions in NTD cases when women consumed folic acid supplements in addition to a varied diet during the periconceptional period (about one month before and one month after conception). The results of these and other studies prompted the U.S. Public Health Service to recommend that all women capable of becoming pregnant consume 400 mcg of folic acid daily to prevent NTD. The recommendation was made to all women of childbearing age because adequate folic acid must be available very early in pregnancy, and because many pregnancies in the U.S. are unplanned. Despite the effectiveness of folic acid supplementation, it appears that less than half of women who become pregnant follow the recommendation (11). To decrease the incidence of NTD, the FDA implemented legislation in 1998 requiring the fortification of all enriched grain products with folic acid (see Sources). The required level of folic acid fortification in the U.S. was estimated to provide 100 mcg of additional folic acid in the average person's diet, though it probably provides even more due to overuse of folic acid by food manufacturers (9). The Centers for Disease Control and Prevention reported that the frequency of NTD in the U.S. has decreased 26% since the mandate (12). However, studies in Canada, where fortification is nearly identical to that in the U.S. (1.5 and 1.4 mg of folic acid/kg of grain, respectively), have reported greater reductions in the incidence of NTD. In fact, it was recently proposed that the fortification legislation has prevented approximately 50% of NTD in Canada and the U.S, but improvements in the U.S. have been largely underestimated (13).

Other pregnancy complications

Adequate folate status may also prevent the occurrence of other types of birth defects, including certain heart defects and limb malformations. However, the support for these findings is not as consistent or clear as support for NTD prevention (10). Additionally, low levels of dietary folate during pregnancy have been associated with increased risks of premature delivery and infant low infant birth weights. More recently, elevated blood homocysteine levels, considered an indicator of functional folate deficiency, have been associated with increased incidence of miscarriage as well as pregnancy complications like preeclampsia and placental abruption (14). Thus, it is reasonable to maintain folic acid supplementation throughout pregnancy, even after closure of the neural tube in order to decrease the risk of other problems during pregnancy.

Cardiovascular disease

Homocysteine and cardiovascular disease

The results of more than 80 studies indicate that even moderately elevated levels of homocysteine in the blood increase the risk of cardiovascular diseases (4). An analysis of the observational studies on blood homocysteine and vascular disease indicated that a prolonged decrease in plasma homocysteine level of only 1 micromole/liter resulted in about a 10% risk reduction (15). The mechanism by which homocysteine increases the risk of vascular disease remains the subject of a great deal of research, but it may involve adverse effects of homocysteine on blood clotting, arterial vasodilation, and thickening of arterial walls (16). Although increased homocysteine levels in the blood have been consistently associated with increased risk of cardiovascular diseases, it is not yet clear whether lowering homocysteine levels will reduce cardiovascular disease risk (see below, Folate and homocysteine). Consequently, the American Heart Association recommends screening for elevated total homocysteine levels only in "high risk" individuals, for example those with personal or family history of premature cardiovascular disease, malnutrition or malabsorption syndromes, hypothyroidism, kidney failure, lupus, or individuals taking certain medications (nicotinic acid, theophylline, bile acid-binding resins, methotrexate, and L-dopa). Most research indicates that a plasma homocysteine level of < 10 micromoles/liter is associated with a lower risk of cardiovascular disease and a reasonable treatment goal for individuals at high risk (17).

Folate and homocysteine

Folate-rich diets have been associated with decreased risk of cardiovascular disease. A study that followed 1,980 Finnish men for ten years found that those who consumed the most dietary folate had a 55% lower risk of an acute coronary event when compared with those who consumed the least dietary folate (18). Of the three vitamins that regulate homocysteine levels, folic acid has been shown to have the greatest effect in lowering basal levels of homocysteine in the blood when there is no coexisting deficiency of vitamin B12 or vitamin B6 (see Nutrient interactions). Increasing folate intake through folate-rich foods or supplements has been found to lower homocysteine levels. Moreover, blood homocysteine levels have declined since the FDA mandated folic acid fortification of the grain supply (9). A recent meta-analysis of 25 randomized controlled trials found that supplementation with 0.8 mg folic acid daily maximally reduced plasma homocysteine concentrations; daily doses of 0.2 mg and 0.4 mg of folic acid were associated with 60% and 90% reductions, respectively, in plasma homocysteine (19). A supplement regimen of 400 mcg of folic acid, 2 mg of vitamin B6, and 6 mcg of vitamin B12 has been advocated by the American Heart Association if an initial trial of a folate-rich diet (see Sources) is not successful in adequately lowering homocysteine levels (17). Although increased folic acid intake has been found to decrease homocysteine levels, it is presently not clear whether increasing folic acid intake results in decreased risk of cardiovascular diseases. Several randomized placebo-controlled trials have been conducted or are ongoing to determine whether homocysteine lowering through folic acid and other B vitamin supplementation reduces the incidence of cardiovascular diseases. A preliminary meta-analysis of data from four of the ongoing trials, including about 14,000 subjects, showed that B vitamin supplementation had no significant effect on risk of coronary heart disease or stroke (20). Similarly, another meta-analysis of 12 randomized controlled trials, including data from 16,958 individuals with preexisting cardiovascular or renal disease, found that folic acid supplementation had no effect on coronary heart disease, stroke, or all-cause mortality despite 13%-52% reductions in plasma homocysteine concentrations (21). Consequently, the American Heart Association removed its recommendation for using folic acid to prevent cardiovascular diseases in high-risk women (22). Completion of the ongoing clinical trials should provide a more definitive answer whether folic acid is beneficial for the prevention or treatment of heart disease or stroke.

 

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Cancer

Cancer is thought to arise from DNA damage in excess of ongoing DNA repair and/or the inappropriate expression of critical genes. Because of the important roles played by folate in DNA and RNA synthesis and methylation, it is possible for folate intake to affect both DNA repair and gene expression. The consumption of at least five servings of fruits and vegetables daily has been consistently associated with a decreased incidence of cancer. Fruits and vegetables are excellent sources of folate, which may play a role in their anti-carcinogenic effect. Observational studies have found diminished folate status to be associated with cancers of the cervix, colon and rectum, lung, esophagus, brain, pancreas, and breast. Intervention trials of folic acid supplementation in humans have been conducted mainly with respect to cervical and colorectal (colon and rectal) cancer. While the results in cervical cancer have been inconsistent (2), randomized intervention trials regarding colorectal cancer have been more promising (23, 24).

Colorectal cancer

A recent meta-analysis of seven cohort and nine case-control studies found that folate from foods was inversely associated with colorectal cancer risk; however, total folate from foods and folic acid supplements was not associated with colorectal cancer risk (25). It is important to note that the case-control studies examined in this meta-analysis were highly heterogeneous, and that the authors stated that dietary fiber or other vitamins could have confounded their results. Overall, the role of folate in the possible prevention of colorectal cancer provides an example of the complexity of the interactions between genetics and nutrition. In general, observational studies have found that relatively low folate intake and high alcohol intake are associated with increased incidence of colorectal cancer (1, 26, 27). Alcohol interferes with the absorption and metabolism of folate (5). In a prospective study of more than 45,000 male health professionals, current intake of more than two alcoholic drinks per day doubled the risk of colon cancer. The combination of high alcohol and low folate intake yielded an even greater risk of colon cancer; however, increased alcohol intake in individuals who consumed 650 mcg or more of folate per day was not associated with an increased risk of colon cancer (28). In some studies, individuals who are homozygous for the C677T MTHFR polymorphism (T/T) have been found to be at decreased risk for colon cancer when folate intake is adequate. However, when folate intake is low and/or alcohol intake is high, individuals with the (T/T) genotype have been found to be at increased risk of colorectal cancer (29, 30).

While dietary folate may be protective against colorectal cancer, high doses of supplemental folic acid may actually accelerate tumor growth in cancer patients. A recent chemopreventive trial in patients with a history of colorectal adenoma associated supplementation of 1 mg/day of folic acid (more than twice the RDA) with a statistical trend for advanced colorectal lesions as well as with a significantly increased risk (>2-fold) for the presence of three or more colorectal adenomas (31). However, other trials have not found evidence that folic acid supplementation increases risk of colorectal adenoma recurrence (32, 33). Two trials have associated folic acid supplementation with increased risk of prostate cancer (31, 34). A recent meta-analysis of seven randomized controlled trials found that supplemental folic acid use (800 mcg-40 mg/day [median 2.5 mg/day] for 2.0-7.3 years) did not increase risk for overall cancer incidence or cancer-related mortality (35). Human observational studies as well as animal studies on high-dose folate and cancer have reported mixed results. Thus, more research is needed to determine the role of high-dose folate in cancer progression.

Breast cancer

Studies investigating whether folate intake affects breast cancer risk have reported mixed results (36). The results of two prospective studies suggest that increased folate intake may reduce the risk of breast cancer in women who regularly consume alcohol (37-39); moderate alcohol intake has been associated with increased risk of breast cancer in women in several studies. Interestingly, a very large prospective study in more than 88,000 nurses reported that folic acid intake was not associated with breast cancer in women who consumed less than one alcoholic drink per day. However, in women consuming at least one alcoholic drink per day, folic acid intake of at least 600 mcg daily resulted in about half the risk of breast cancer compared with women who consumed less that 300 mcg of folic acid daily (39).

Alzheimer's disease and cognitive impairment

The role of folate in nucleic acid synthesis and methylation reactions is essential for normal brain function. Over the past decade several investigators have described associations between decreased folate levels and cognitive impairment in the elderly (40). A large cross-sectional study in elderly Canadians found that those individuals with low serum folate levels were more likely to have dementia, be institutionalized, and be depressed. However, these findings could reflect the poorer nutritional status of institutionalized elderly and individuals with dementia. In the same study, low serum folate levels were associated with an increased likelihood of short-term memory problems in elderly individuals who hand no signs of dementia (41). A study in 30 elderly nuns, who lived in the same convent, ate the same diet, and had similar lifestyles, reported a strong association between decreased blood folate levels and the severity of brain atrophy related to Alzheimer's disease (42). More recent studies have reported conflicting results as to whether folate status impacts Alzheimer's disease risk. One study in elderly people of predominantly Hispanic and African-American ethnicity with a high prevalence of vascular risk factors reported that a higher folate intake, from diet and folic acid supplements, was associated with a decreased risk for Alzheimer's disease (43). In contrast, a prospective study in elderly individuals reported that dietary folate is not associated with Alzheimer's disease (44), whereas another prospective study reported that a high folate intake, from foods and from folic acid supplements, was associated with increased rates of cognitive decline in the elderly (45). Moderately increased homocysteine levels, as well as decreased folate and vitamin B12 levels, have been associated with Alzheimer's disease and vascular dementia. One study in 370 elderly men and women, who were followed over three years, associated low serum levels of vitamin B12 (≤ 150 pmol/L) or folate (≤ 10 nmol/L) with a doubling of the risk of developing Alzheimer's disease (46). In a sample of 1,092 men and women without dementia followed for an average of ten years, those with higher plasma homocysteine levels at baseline had a significantly higher risk of developing Alzheimer's disease and other types of dementia (47). Those with plasma homocysteine levels greater than 14 micromoles/liter had nearly twice the risk of developing Alzheimer's disease.

 

Sources -

Food sources

Green leafy vegetables (foliage) are rich sources of folate and provide the basis for its name. Citrus fruit juices, legumes, and fortified cereals are also excellent sources of folate (1). A number of folate-rich foods are listed in the table below along with their folate content in micrograms (mcg). For more information on the nutrient content of specific foods, search the USDA food composition database.

FoodServingFolate (mcg)
Fortified breakfast cereal1 cup200-400
Orange juice (from concentrate)6 ounces83
Spinach (cooked)1/2 cup132
Asparagus (cooked)1/2 cup (~ 6 spears)134
Lentils (cooked)1/2 cup179
Garbanzo beans (cooked)1/2 cup141
Lima beans (cooked)1/2 cup78
Bread1 slice20 (Folic acid)*
Pasta (cooked)1 cup60 (Folic acid)*
Rice (cooked)1 cup60 (Folic acid)*

*To help prevent neural tube defects, the FDA required the addition of 1.4 milligrams (mg) of folic acid per kilogram (kg) of grain to be added to refined grain products, which are already enriched with niacin, thiamin, riboflavin, and iron, as of January 1, 1998. The addition of nutrients to foods in order to prevent a nutritional deficiency or restore nutrients lost in processing is known as fortification. It has been estimated that this level of fortification increases dietary intake by an average of 100 mcg folic acid/day (10). For more information on folic acid fortification, review the FDA fact sheet.

Supplements

The principal form of supplementary folate is folic acid. It is available in single ingredient and combination products such as B-complex vitamins and multivitamins. Doses equal of 1 mg or greater require a prescription (48).

Safety -

Toxicity

No adverse effects have been associated with the consumption of excess folate from foods. Concerns regarding safety are limited to synthetic folic acid intake. Deficiency of vitamin B12, though often undiagnosed, may affect a significant number of people, especially older adults (see Vitamin B12). One symptom of vitamin B12 deficiency is megaloblastic anemia, which is indistinguishable from that associated with folate deficiency (see Deficiency). Large doses of folic acid given to an individual with an undiagnosed vitamin B12 deficiency could correct megaloblastic anemia without correcting the underlying vitamin B12 deficiency, leaving the individual at risk of developing irreversible neurologic damage. Such cases of neurologic progression in vitamin B12 deficiency have been mostly seen at folic acid doses of 5,000 mcg (5 mg) and above. In order to be very sure of preventing irreversible neurological damage in vitamin B12 deficient individuals, the Food and Nutrition Board of the Institute of Medicine advises that all adults limit their intake of folic acid (supplements and fortification) to 1,000 mcg (1 mg daily). The board also noted that vitamin B12 deficiency is very rare in women in their childbearing years, making the consumption of folic acid at or above 1000 mcg/day unlikely to cause problems (1); however, there are limited data on the effects of large doses.

Tolerable Upper Intake Level (UL) for Folic Acid

Age GroupUL (mcg/day)
Infants 0-12 monthsNot possible to establish*
Children 1-3 years300
Children 4-8 years400
Children 9-13 years600
Adolescents 14-18 years800
Adults 19 years and older1,000

*Source of intake should be from food and formula only.

Drug interactions

When nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen, are taken in very large therapeutic dosages (i.e., to treat severe arthritis), they may interfere with folate metabolism. In contrast, routine low dose use of NSAIDs has not been found to adversely affect folate status. The anticonvulsant, phenytoin, has been shown to inhibit the intestinal absorption of folate, and several studies have associated decreased folate status with long-term use of the anticonvulsants, phenytoin, phenobarbital, and primidone (49). However, few studies controlled for differences in dietary folate intake between anticonvulsant users and nonusers. Also, taking folic acid at the same time as the cholesterol-lowering agents, cholestyramine and colestipol, may decrease the absorption of folic acid (48). Methotrexate is a folic acid antagonist used to treat a number of diseases, including rheumatoid arthritis and psoriasis. Some of the side effects of methotrexate are similar to those of severe folate deficiency, and increased dietary folate or supplemental folic acid may decrease side effects without reducing the efficacy of methotrexate. A number of other medications have been shown to have antifolate activity, including trimethoprim (an antibiotic), pyrimethamine (an antimalarial), triamterene (a blood pressure medication), and sulfasalazine (a treatment for ulcerative colitis). Early studies of oral contraceptives (birth control pills) containing high doses of estrogen indicated adverse effects on folate status; however, this finding has not been supported by more recent studies on low dose oral contraceptives that controlled for dietary folate (1).

Linus Pauling Institute Recommendation

The available scientific evidence shows that adequate folate intake prevents neural tube defects and other poor outcomes of pregnancy, is helpful in lowering the risk of some forms of cancer, especially in genetically susceptible individuals, and may lower the risk of cardiovascular diseases. The Linus Pauling Institute recommends that adults take a 400 mcg supplement of folic acid daily, in addition to folate and folic acid consumed in the diet. A daily multivitamin-mineral supplement, containing 100% of the Daily Value (DV) for folic acid provides 400 mcg of folic acid. Even with a larger than average intake of folic acid from fortified foods, it is unlikely that an individual's daily folic acid intake would regularly exceed the tolerable upper intake level of 1,000 mcg/day established by the Food and Nutrition Board (see Safety).

Older adults (65 years and older)

The recommendation for 400 mcg/day of supplemental folic acid as part of a daily multivitamin-multimineral supplement, in addition to a folate-rich diet, is especially important for older adults because blood homocysteine levels tend to increase with age (see Disease Prevention).

References


Written in April 2002 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in September 2007 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in September 2007 by:
Barry Shane, Ph.D., Professor
Department of Nutritional Sciences and Toxicology
University of California, Berkeley

Updated 5/9/11  Copyright 2000-2011  Linus Pauling Institute


Disclaimer

The Linus Pauling Institute Micronutrient Information Center provides scientific information on health aspects of micronutrients and phytochemicals for the general public. The information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. The information should not be used in place of a consultation with a competent health care or nutrition professional.

The information on micronutrients and phytochemicals contained on this Web site does not cover all possible uses, actions, precautions, side effects, and interactions. It is not intended as medical advice for individual problems. Liability for individual actions or omissions based upon the contents of this site is expressly disclaimed.


http://lpi.oregonstate.edu/infocenter/vitamins/fa/
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Background

The prevalence of folic acid deficiency has decreased since the United States and Canada introduced a mandatory folic acid food fortification program in November 1998. People with excessive alcohol intake and malnutrition are still at high risk of folic acid deficiency.

Histologically, the megaloblastosis caused by foliHistologically, the megaloblastosis caused by folic acid deficiency cannot be differentiated from that observed with vitamin B-12 deficiency.

The significance of folic acid deficiency is compounded further by the following attributes:

  • An association of folate deficiency with elevated homocysteine, leading to increased arteriosclerosis risks[1]
  • The reduced incidence of neural tube defects with folate supplementation
  • The role of folate in the occurrence of cancer

Hence, folic acid clearly is of consequence in public health in the United States, especially because heart disease and cancer constitute the number 1 and number 2 causes of mortality in the United States. This article explores the mechanisms and manifestations behind folate deficiency, as well as its ramifications with regard to health and disease at large.

Pathophysiology

Folic acid is composed of a pterin ring connected to p-aminobenzoic acid (PABA) and conjugated with one or more glutamate residues. It is distributed widely in green leafy vegetables, citrus fruits, and animal products. Humans do not generate folate endogenously because they cannot synthesize PABA, nor can they conjugate the first glutamate.

Folates are present in natural foods and tissues as polyglutamates because these forms serve to keep the folates within cells. In plasma and urine, they are found as monoglutamates because this is the only form that can be transported across membranes. Enzymes in the lumen of the small intestine convert the polyglutamate form to the monoglutamate form of the folate, which is absorbed in the proximal jejunum via both active and passive transport.

Within the plasma, folate is present, mostly in the 5-methyltetrahydrofolate (5-methyl THFA) form, and is loosely associated with plasma albumin in circulation. The 5-methyl THFA enters the cell via a diverse range of folate transporters with differing affinities and mechanisms (ie, adenosine triphosphate [ATP]–dependent H+ cotransporter or anion exchanger). Once inside, 5-methyl THFA may be demethylated to THFA, the active form participating in folate-dependent enzymatic reactions. Cobalamin (B-12) is required in this conversion, and in its absence, folate is "trapped" as 5-methyl THFA.

From then on, folate no longer is able to participate in its metabolic pathways, and megaloblastic anemia results. Large doses of supplemental folate can bypass the folate trap, and megaloblastic anemia will not occur. However, the neurologic/psychiatric abnormalities associated with B-12 deficiency ensue progressively.

The biologically active form of folic acid is tetrahydrofolic acid (THFA), which is derived by the 2-step reduction of folate involving dihydrofolate reductase. THFA plays a key role in the transfer of 1-carbon units (such as methyl, methylene, and formyl groups) to the essential substrates involved in the synthesis of DNA, RNA, and proteins. More specifically, THFA is involved with the enzymatic reactions necessary to synthesis of purine, thymidine, and amino acid. Manifestations of folate deficiency thereafter, not surprisingly, would involve impairment of cell division, accumulation of possibly toxic metabolites such as homocysteine, and impairment of methylation reactions involved in the regulation of gene expression, thus increasing neoplastic risks.

A healthy individual has about 500-20,000 mcg of folate in body stores. Humans need to absorb approximately 50-100 mcg of folate per day in order to replenish the daily degradation and loss through urine and bile. Otherwise, signs and symptoms of deficiency can manifest after 4 months.

Epidemiology

Frequency

United States

The current standard of practice is that serum folate levels less than 3 ng/mL and a red blood cell (RBC) folate level less than 140 ng/mL puts an individual at high risk of folate deficiency. The RBC folate level generally indicates folate stored in the body, whereas the serum folate level tends to reflect acute changes in folate intake.

Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 indicate the prevalence of low serum folate concentrations (< 6.8 nmol/L) decreased from 16% before folic acid fortification to 0.5% after folic acid fortification.[2] In elderly persons, the prevalence of high serum folate concentrations (>45.3 nmol/L) increased from 7% before fortification to 38% after fortification. The latest results from NHANES are available.[3]

International

Countries that do not have a mandatory folic acid food fortification program have higher rates of folic acid deficiency. For example, a population based study in Iran (where there is no fortification) showed an age-adjusted prevalence of hyperhomocysteinemia (Hcy ³15 micromol/L) of 73.1% in men and 41.07% in women (aged 25-64 y).

Casey et al examined the effects over 1 year of a free weekly iron-folic acid supplementation and deworming program in 52,000 Vietnamese women of childbearing age.[4] The investigators collected demographic data and blood and stool samples at baseline and at 3 and 12 months following the implementation of the program.

Findings included a mean Hb increase of 9.6 g/L (P < 0.001) and a reduction in the presence of anemia from 37.5% of the women at baseline to 19.3% at 12 months.[4] Iron deficiency was also reduced, from 22.8% at baseline to 9.3% by 12 months, as well as hookworm infection (76.2% at baseline to 23.0%) in the same period.

A discussion of selected national Australian policies is presented in Lawrence et al.[5]

Mortality/Morbidity

Hematologic manifestations

Folate deficiency can cause anemia. The presentation typically consists of macrocytosis and hypersegmented polymorphonuclear leucocytes (PMNs). More detailed laboratory findings are discussed in the Workup section.

The anemia usually progresses over several months, and the patient typically does not express symptoms as such until the hematocrit level reaches less than 20%. At that point, symptoms such as weakness, fatigue, difficulty concentrating, irritability, headache, palpitations, and shortness of breath can occur. Furthermore, heart failure can develop in light of high-output cardiac compensation for the decreased tissue oxygenation. Angina pectoris may occur in predisposed individuals due to increased cardiac work demand. Tachycardia, postural hypotension, and lactic acidosis are other common findings. Less commonly, neutropenia and thrombocytopenia also will occur, although it usually will not be as severe as the anemia. In rare cases, the absolute neutrophil count can drop below 1000/mL and the platelet count below 50,000/mL.

Elevated serum homocysteine and atherosclerosis

Folate in the 5-methyl THFA form is a cosubstrate required by methionine synthase when it converts homocysteine to methionine. As a result, in the scenario of folate deficiency, homocysteine accumulates. Several recent clinical studies have indicated that mild-to-moderate hyperhomocystinemia is highly associated with atherosclerotic vascular disease such as coronary artery disease (CAD) and stroke. In this case, mild hyperhomocystinemia is defined as total plasma concentration of 15-25 mmol/L and moderate hyperhomocystinemia is defined as 26-50 mmol/L.

Genest et al found that a group of 170 men with premature coronary artery disease had a significantly higher average level of homocysteine (13.7 ± 6.4).[6] In another study, Coull et al found that among 99 patients with stroke or transient ischemic attacks (TIAs), about one third had elevated homocysteine.[7]

Elevated homocysteine levels might act as an atherogenic factor by converting a stable plaque into an unstable, potentially occlusive, lesion. Wang et al found that in patients with acute coronary syndromes, levels of homocysteine and monocyte chemoattractant protein-1 (MCP-1) were significantly higher.[8] MCP-1 is a chemokine characterized by the ability to induce migration and activation of monocytes and therefore may contribute to the pathogenesis of CAD. Homocysteine is believed to have atherogenic and prothrombotic properties via multiple mechanisms.

Bokhari et al found that among patients with CAD, the homocysteine level correlates independently with left ventricular systolic function.[9] The mechanism is unknown, but it may be due to a direct toxic effect of homocysteine on myocardial function separate from its effect on coronary atherosclerosis.

Although in multiple observational studies elevated plasma homocysteine levels have been positively associated with increased risk of atherosclerosis, randomized trials have not been able to demonstrate the utility of homocysteine-lowering therapy. In the Heart Outcomes Prevention Evaluation (HOPE) 2 trial, supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease.[10] Similarly, in the trial of Bonaa et al treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction.[11]

Pregnancy complications

Possible pregnancy complications secondary to maternal folate status may include spontaneous abortion, abruption placentae, and congenital malformations (eg, neural tube defect). In a literature review, Ray et al examined 8 studies that demonstrated association between hyperhomocystinemia and placental abruption/infarction.[12] Folate deficiency also was a risk factor for placental abruption/infarction, although less statistically significant.[13]

Several observational and controlled trials have shown that neural tube defects can be reduced by 80% or more when folic acid supplementation is started before conception. In countries like the United States and Canada, the policy of widespread fortification of flour with folic acid has proved effective in reducing the number of neural tube defects.[14]

Although the exact mechanism is not understood, a relative folate shortage may exacerbate an underlying genetic predisposition to neural tube defects.

Effects on carcinogens

Diminished folate status is associated with enhanced carcinogenesis. A number of epidemiologic and case-control studies have shown that folic acid intake is inversely related to colon cancer risk.[15] With regard to the underlying mechanism, Blount et al showed that folate deficiency can cause a massive incorporation of uracil into human DNA leading to chromosome breaks.[16] Another study by Kim et al suggested that folate deficiency induces DNA strand breaks and hypomethylation within the p53 gene.[17]

Effects on cognitive function

Several studies have shown that an elevated homocysteine level correlates with cognitive decline. In Herbert's classic study in which a human subject (himself) was in induced folate deficiency from diet restriction, he noted that CNS effects, including irritability, forgetfulness, and progressive sleeplessness, appeared within 4-5 months. Interestingly, all CNS symptoms were reported to disappear within 48 hours after oral folate intake.

Low folate and high homocysteine levels are a risk factor for cognitive decline in high-functioning older adults[18] and high homocysteine level is an independent predictor of cognitive impairment among long-term stay geriatric patients.[19]

Mechanistically speaking, current theory proposes that folate is essential for synthesis of S- adenosylmethionine, which is involved in numerous methylation reactions. This methylation process is central to the biochemical basis of proper neuropsychiatric functioning.

Despite the association of high homocysteine level and poor cognitive function, homocysteine-lowering therapy using supplementation with vitamins B-12 and B-6 was not associated with improved cognitive performance after two years in a double-blind, randomized trial in healthy older adults with elevated homocysteine levels.[20]

Sex

Women who are pregnant are at higher risk of developing folate deficiency because of increased requirements.

Age

Elderly people also may be more susceptible to folate deficiency in light of their predisposition to mental status changes, social isolation, low intake of leafy vegetables and fruits, malnutrition, and comorbid medical conditions. The greatest risk appears to be among low-income populations and institutionalized elderly people and less risk among the free-living elderly population.

EileenDurante

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Reply with quote  #4 
Ah Ella you beat me to it LOL

I wanted to start a thread on the epidemic of canine ovarian  and uterine cysts in mastiffs. Seems like so many breeders I talk to that have done surgical implants,  C-sections and/or pyometra spays where upon exam of their reproductive organs have found them to be cystic.

Every time I hear about a vet popping them it makes me crazy. It horrifies me to think how much valuable irreplaceable semen is wasted when breedings are continued after these popping sprees that often result in pyo, endometriosis and spay.  So often the vets tell  us ' it's ok we have seen some bitches conceive after the cysts are popped ". " SOME " ????  Care to quote statistics here ?

It horrifies me how much of the breeders money is flushed  down the toilet along with their hopes and dreams of that perfect litter.

In human medicine one of the most common treatments for poly cystic ovaries is prescribed folic acid supplementation.  This does not require a prescription. This is an inexpensive supplement. So why don't we do this for  our dogs too ?

For anyone interested my dear friend Ella sent me a gift of this wonderful supplement at a time when I was burning the candle at both ends and exhausted. But as I was taking these and looking at the bottle in my hand a light bulb went off in my head.  I had a flash back to my old career in pharmacy and remembered exactly why I had taken these before. My gyno doctor had given them to me many years ago when I was having infertilty issues myself.

For anyone interested Ella is a naturopathic healer and sells this product called Foliplex with B12
I am now giving this to my own intact bitches,
The only side affect I have seen is they have more energy and are not laying around sleeping all day.
I like it 


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HeatherG

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Reply with quote  #5 
is the Foliplex with B12 vegan ?

 

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Reply with quote  #6 
HERE IS WHAT THE PRODUCT LABEL STATES:

DescriptionIngredientsSpecifications
Foliplex with B-12 Raspb. Flavor 60 tabs

Supplement Facts
Serving Size: 1 Tablet Amount/Serving

Folic Acid USP 800 mcg
Vitamin B-12 (as Cyanocobalamin USP) 2.5 mg

Other Ingredients: Sorbitol, mannitol, raspberry flavor, stearic acid, magnesium stearate, and silicon dioxide.

Contains No: milk, yeast, gluten, corn, soy or animal products.

Notes: Well-tolerated by most highly sensitive individuals.
If pregnant or nursing, consult with your healthcare practitioner prior to use.

Keep this product out of reach of children.
Store in a cool, dry place.

Tamper-evident packaging for your protection.
As with any product, discontinue use if adverse effects occur.

Recommendations: Take 1 tablet daily, dissolve in the mouth before swallowing, or as directed by your healthcare practitioner.
HeatherG

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Reply with quote  #7 

isn't the Methylcobalamin form better as the body can absorb it better (speaking humans)


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Reply with quote  #8 
and thank you
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EileenDurante

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Reply with quote  #9 
Heather : these are raspberry flavor chewables. They are smaller than a  piece of kibble and quickly absorbed

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Reply with quote  #10 
I know for myself about a year ago, I found myself just dragging everyday, and my hair and nails just spitting and cracking.  After alot of reading I put myself on prenantal vitamins that have alot of folic acid, and in addition a super b complex ( has all the b's as well as extra b-12 for energy.)  the result has been my hair and nails have grown alot, and I have alot of energy I found to be lacking.  Its a good thing b/c life isoo very busy any more, it helps me think straight, work hard, and the improvement in my hair and nails is great.
at age 50 I do not want to conceive, and get some eyeballs when I buy refills, but it has been worth it.

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HeatherG

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Reply with quote  #11 
Hi Eileen, I understand,  I get the Methylcobalamin tabs... cherry flavor

The body can process the M better then the C.... or so that is what I have read

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Reply with quote  #12 

For the pharmalogically disadvantaged.....what are you talking about pls...."process the M better then the C"????  TIA


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Reply with quote  #13 
the body converts it. . .

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The Way Up Newsletter
Vol. 33, 04-15-02



VITAMIN B12 / FOLIC ACID / HOMOCYSTEINE


NAMASTE & WELCOME TO THE WAY UP NEWSLETTER!

Every day I come across someone who is taking supplements, & expecting improved health. Yet they are choosing a supplement program in a hit & miss fashion based upon articles read about this or that item. They read about beta-carotene, & buy a bottle. They read about Selenium, & buy a bottle, then Calcium, & so forth.
 
Because of the confusion & misinformation, one of this months topics is:
WHAT IS AN OPTIMUM SUPPLEMENT PROGRAM?

The other topics are:
THE IMPORTANCE OF VITAMIN B12, and THE IMPORTANCE OF FOLIC ACID.

I recommend one not take any individual nutritional supplement, unless first taking a good multivitamin mineral (which by itself covers many basic nutritional needs). It is impossible to build the walls & roof of a house without first laying a proper foundation.

Most nutrients are dependent upon the presence of other nutrients, as they work together to do their job, just as would happen with a PERFECT diet!!?? Singular supplementing, without a baseline balanced product can actually create deficiencies. For instance, if you are taking one of the single B vitamins without getting the whole complex of B’s you can actually cause a deficiency of those not supplemented. Or if you are taking only Calcium, & no Magnesium, you can add to a Calcium imbalance , & so on. So before you add any individual vitamin, mineral, or amino acid, have your Multi vitamin mineral in place. This rule does not apply for digestive enzymes , hormones, herbs, certain specialty products, & homeopathics which have unique functions not dependent upon a certain balance of nutrients.

WHAT IS A GOOD BASIC SUPPLEMENT PROGRAM FOR A REASONABLY HEALTHY PERSON?
CHILDREN:A good children's multivitamin mineral in the dosage resommended on the label
.An Essential Fatty Acid supplement
.Extra Vitamin C, 250 mg twice daily
..
ADULT MINIMAL:High quality Multivitamin Mineral, as directed on bottle Vitamin C 1000 mg twice daily with meals
.Vitamin B Complex 1 with breakfast (for extra B + what is in multi)
.A sublingual B12/Folic Acid 1-2 under tongue in a.m.
.Fish Oil, or Flax oil caps, 2-3 twice daily with meals, or Essential Fatty Acid Complex 1 dropper full twice daily
..
WOMEN OVER 35 &
THOSE OFF DAIRY :
Add extra Calcium/ Magnesium to total - including Multi
.Calcium 1200-1500 mg & Magnesium 1000-1500 mg daily in divided doses (magnesium dose can be limited by laxative effect in some)
..
VEGETARIANS &
PREGNANCY / NURSING:
Add extra iron
.Use 2-3 of a sublingual B12/folic acid.
WHY ARE B12 & FOLIC ACID SO IMPORTANT?
These nutrients are especially critical for 2 reasons:

1 - There are so many conditions & commonly used drugs which deplete them or interfere with their absorption
2 - The deficiency of either can go undetected to cause great damage & suffering.

These 2 nutrients are addressed together because when supplementing one, the other must also be supplemented, again for 2 reasons:

1 - If there is a B12 deficiency & only folic acid is taken, it can mask some of the blood changes & clues that a B12 deficiency exists. Such masking can allow progressive & irreversible damage to take place in the brain, spinal column, & peripheral nerves. Further, folic acid must be present for the proper use of B12.
2 - Many of the same factors contribute to deficiencies of these 2 nutrients.
WHAT SPECIAL CONDITIONS REQUIRE ASSURED AMOUNTS OF B12 & FOLIC ACID?
The only non meat foods containing B12 are eggs, blue-green algae, & nori seaweed, so vegetarians are at risk for deficiency.
 
Those with low thyroid function have impaired B12 absorption, while those with high thyroid function have excessive loss of B12.
 
Most with stomach /GI disturbances are at risk, whether it be from intestinal malabsorption, inflammatory diseases, chronic diarrhea, parasites, tapeworms, low stomach acid, gastrectomy, or the depletion of a protein called “intrinsic factor”, secreted in the stomach by what are called parietal cells. Intrinsic factor only exists to extract B12 from food. Auto immune illnesses can act in the stomach, to prevent production of or to bind the intrinsic factor preventing B12 absorption. Such people may have anti-parietal cell antibodies which can be easily found on a blood test. As if absorption weren’t a big enough problem, there may be defects in molecules which transport B12 from the blood to the tissue, so though serum levels look normal, the cells are deficient. There are 12 different inherited disorders which affect absorption, transport, or intracellular metabolism of B12.
 
High mercury , lead or other heavy metals which can reduce B12 uptake in the cells. A significant percentage of my patients have metal toxicity. For more see the Metal Toxicity Newsletter.
 
The elderly are at risk, because B12 absorption is known to decrease with age. Also they are more likely to be low in folic acid, iron, calcium, & vitamin B6 which contributes to depleted B12. They are more likely to have low stomach acid, or to be on acid blockers which impair absorption. They use more laxatives which deplete the storage of B12. Research suggests that elderly people with “normal” serum B12 levels are still metabolically deficient in B12 & often respond positively to the addition of B12.
 
Pregnant & nursing women, as well as infants need extra amounts of B12 / folic acid
 
Alcoholics notoriously are deficient, as well as those with anorexia, malnutrition, general illness states, or chronic stress.
 
Those with AIDS, or asymptomatic HIV are often compromised re B12 status. This occurs at an early stage of the infection. Such low levels are associated with acceleration of the disease , while adequate B12 treatment is correlated with increased CDT4 cell counts & improved AIDS index. Studies suggest B12 deficiency may both increase susceptibility to catching the virus in the first place & promote the progression to AIDS. When HIV positive & B12 deficient the progression to AIDS will come 4 years sooner. The “poppers”, an alkyl nitrite inhalant “recreational” drug can inactivate B12. The use of “poppers” has long been associated with susceptibility to HIV infection. It is believed there is a B12 deficiency in about 50% of all AIDS cases.
 
Those with mental, or emotional illness, or retardation may also be vulnerable to low levels. Besides helping to maintain the structural integrity of the brain & nerves, B12 & folic acid are needed for the synthesis of the essential neurotransmitters serotonin, norepinephrine, & dopamine. These are critical regulators for mood, sleep, appetite, drive, motivation, movement, cognition & numerous brain functions. Studies have shown certain people with “treatment resistant” depression responded well to folic acid treatment, which also potentiated the effect of Prozac & helped to protect against side effects.

 
 
WHAT DRUGS/SUBSTANCES CAN CAUSE LOW B12 AND FOLIC ACID?
Besides antacids & laxatives, other drugs they which deplete B12 are Aspirin, & the other salicylates, Tricosal, Trilisate, Arthropan; diuretics such as Bumetanide, Ethacrynic Acid, Furosemide, & Torsemide; & steroid medications. ( Be sure to check generic names on your drugs)
 
High dose vitamin C supplementation without the addition of B12/folic acid can contribute to deficiency.
 
Birth control pills decrease both B12 & folic acid. This is of particular significance if a woman then decides she wants to get pregnant & stops birth control pills without starting supplements. It is well know that the birth defects of spina bifida, cleft palate & lip are caused by low folic acid levels in the mother, especially in the first 6 weeks of pregnancy. A B12 deficient infant will suffer severe developmental abnormalities.
 
Many of the same conditions which deplete B12 also decrease folic acid. The drugs which contribute to folic acid deficiency are many of those used to treat seizure disorders, such as: barbiturates, Tegretol, Depakote, Zarontin, Celontin, Primidone, Dilantin, & Fosphenytoin; many of which are also used in the psychiatric population. The whole class of non-steroidal anti-inflammatory meds such as Ibuprofen, Anaprox, Motrin, Naprosyn, Naprelan, Pamprin, Voltaren, etc deplete folic acid.
 
Other culprits are drugs used for stomach problems & esophageal reflux, such as Pepcid, Axid, Tritec, Cimetidine & Zantec; the immune suppressants Methotrexate , Azulfidine, & steroids; Indomethacin; Viox; Aspirin & the other salicylates; Colestid;
 
WHAT ARE THE ACTIONS & DEFICIENCY SYMPTOMS OF B12 & FOLIC ACID?
  • Depression
  • Mental lethargy
  • Withdrawal
  • Irritability
  • Poor memory
  • Confusion
  • Dementia
  • Psychosis-paranoia
  • Insomnia
  • Digestive disturbances
  • Diarrhea
  • Weakness
  • Numbness
  • Stiffness/spasticity
  • Headaches
  • Restless legs
  • Burning feet
  • Increased sensitivity to pain
  • Sore tongue
  • Lesions at corners of mouth
  • Anemia (megaloblastic)
  • Shortness of breath
  • Low white blood cell count
  • Lowered resistance to infection, decreased antibody formation
  • Graying hair
  • Toxemia of pregnancy
  • Premature births
  • Increased risk of certain birth defects
  • Sprue
  • Weight loss
  • Anorexia (appetite loss)
 
WHAT IS THE HOMOCYSTEINE CONNECTION?
Those who read health articles in the general press have likely come across information about homocysteine. Homocysteine is a normal necessary substance in the body produced from the metabolism of an essential amino acid called methionine. (All amino acids are components of protein). The homocysteine, in turn, converts to a detoxifying amino acid called cysteine, a substance called ATP which is critical in producing energy in the cells, SAMe & also back to methionine. This occurs when all is working as it should be. But these conversions do not take place properly if adequate amounts of B12, Folic acid, & Pyridoxal 5 phosphate (B6) , are not present. When the homocysteine does not metabolize properly , it then accumulates to unhealthy high levels & becomes a silent formidable enemy.
 
Elevated levels of homocysteine are associated with a greater risk for cardiovascular diseases such as heart attacks, peripheral arterial disease, strokes, venous thrombosis, & carotid artery stenosis. In fact, the homocysteine level is the strongest predictor of both overall mortality from any cause & mortality from cardiovascular causes. Cardiovascular disease accounts for 43% of all deaths in the U.S.
 
Excess homocysteine is directly toxic & damaging to the walls of the blood vessels which helps lead to atherosclerosis. It also stimulates an inflammatory substance in the platelets called thromboxane which helps cause clots. It may also contribute to the oxidation of LDL. (Imagine how much good could be done if all cardiologists included a multivitamin mineral, B12, folic acid, extra B6, co-enzyme Q10, & policosonal in their treatment plans!)
 
Excess homocysteine also contributes to the development of Alzheimer’s, arthritis, & diabetes. A new study in the New England Journal of Medicine involving 1092 subjects over the course of 8 years found that for every 5 micromoles /l increase of homocsyteine the risk of dementia or Alzheimer’s was increased by 40%. Homocysteine levels over 14 nearly doubled the risk of Alzheimer’s. Clearly homocysteine is not the only contributing factor to these illnesses, but plays its deadly part.
 
Interesting other studies have shown high levels to be associated with miscarriage, which was corrected when the women were supplemented with folic acid 15mg daily & B6 750 mg daily, which are quite large doses. Another study showed levels greater than 6.3 were associated with an increased risk for cervical cancer.
 
WHAT TESTS CAN BE DONE TO SEE IF THERE ARE DEFICIENCIES?
One can get a homocysteine blood test by itself, or a panel such as the Comprehensive Cardiovascular Assessment, which contains this test as well as numerous other evaluations for cardiovascular risk. The optimal safe range for homocysteine is less than 6, the lower the better.
 
The most exciting & informative new test which has just become available,is the Cardio Genomic Profile http://www.genovations.com. This test identifies gene variations which foretell the increased likelihood of developing cardiovascular disease. It can identify if you are at risk for the development of high homocysteine so you can really act preventatively. The test identifies your genetic risk for increased blood clotting, increased blood pressure, cholesterol imbalance, & inflammatory cardiovascular disease. It is also useful if you already know you have these problems, because it tells you how to change your genetic predisposition! You can then retest in several months to make sure mission accomplished. The test can be done at home by collecting mouth wash samples & sending in the kit. The DNA in buccal cells is analyzed. You would have to ask your Dr to order the kit. Because it is so new, insurance does not yet cover it, so if that is an issue, you might use some of the other tests mentioned here-but this is my current preference.
 
Many Drs only order a serum B12 & serum folic acid test. If these are normal, they consider all to be fine in this arena. This is simply not true. These tests are only useful when they are low, which then indicates a substantial deficiency. Numerous studies have shown a positive response to treatment with B12/folic acid, when the blood levels were normal. The amount in the blood tells nothing about transport to, uptake, or utilization by the cells.
 
A useful indirect measurement of B12 deficiency is the urine or blood methyl malonic acid test. When this substance is elevated, there is a B12 deficiency.
 
A complete blood count (CBC) can be useful in those people who manifest blood changes, but not all do. In fact, one can be sufficiently low to exhibit neurological damage without showing any blood cell changes. Again, when there is overt anemia of what is called the megaloblastic or macrocytic type, there is likely a B12/folic acid problem. But it is useful to look for more subtle signs such as low normal total number of red blood cells, large red blood cells(high normal MCV) , low normal total number of white blood cells, low normal platelets, or low normal neutrophils ( a type of white blood cell).
 
There is a good blood test called the Functional Intracellular Analysis.
 
WHAT FORMS OF B12/FOLIC ACID ARE BEST TO TAKE?
Vitamin B12 comes in several chemical forms & folic acid in two forms. The most common & least expensive B12 is cyanocobalamin. This is fine to use for basic supplementation. And plain folic acid is fine for a basic program. There are also the methyl-, hydroxy-, & adenosyl- cobalamin forms of B12 which are more expensive & previously have been less available.
 
Dietary or supplemental cyanocobalamin converts in the body to the other forms listed here, especially Methylcobalamin (MeCb). Folic acid must be present for this conversion to take place. The folic acid must be in the coenzyme form called L- 5 methyl tetrahydrofolate. A properly functioning body would have converted regular dietary or supplemental folic acid to this coenzyme form. When there are diseases, sometimes the folic acid does not convert properly, & one would have to supplement with the L-5 methyl tetrahydrofolate instead.
 
The methyl cobalamin (MeCb) is the most active form of B12 in the body, especially in the brain & nervous system. There is the belief the MeCb has some therapeutic applications not as well achieved by other forms of B12. MeCb is also utilized more efficiently & has better tissue retention. For this reason much of the recent research has been done using this MeCb. Some of the research uses the injectable, some the sublingual form. When possible, I suggest a combination of the 2 when one is treating a significant health problem.
 
At the risk of going on interminably, can’t help but think some would like examples of when to use these supplements in higher doses, so
WHAT ARE EXAMPLES OF WHEN YOU WOULD USE HIGHER THERAPEUTIC DOSES?
.Those with: Pernicious anemia, an inherited defect in the absorption of B12, or with any anemia associated with large red blood cells.
 High levels of MeCb are needed to regenerate nerve cells & the covering of the long nerves, called myelin sheath. MeCb also protects against neurotoxicity. Thus those with a variety of neurological disorders may respond well.
 In studies on Bells Palsy (a painful condition the facial nerve), patients treated with 1.5-6 mg MeCb daily recovered in an average time of 1.95 weeks. Those treated with the usually prescribed steroids took an average of 9.6 weeks to recover.
 Parkinson’s patients. Oral MeCb helped to delay the progression of Parkinson’s & to maintain a longer benefit from Sinemet (a drug for Parkinson’s)
 Those with ALS (Lou Gehrigs Disease), Multiple Sclerosis(doses up to 60 mg/d for this) Muscular Dystrophy, Peripheral Neuropathy, restless legs, neurological aging, dementia, depression, psychosis, mood swings.
 Infertile men treated with 1.5-6mg daily experienced a 38 % increase in sperm count & 50% increase in sperm motility.
 Those with chronic fatigue, fibromyalgia, burstitis.
 Those with immune disorders of any kind.
 Those with asthma.
 Those with liver disorders.
 Women with abnormal PAP smears.
 Those with sleep/wake cycle disorders, or those with excessive sleepiness.
 Those with a family history of colon cancer.
 Those with vitiligo.
 Those with chronic myelogenous leukemia have overall increased cobalamin levels, but a decreased proportion of methylcobalamin compared to normals. The lower the proportion of MeCb, the worse the prognosis, the higher the proportion the better the prognosis. ( Also MeCb improved the survival time in leukemic mice).
 The form used in the above research varied between injectable & sublingual, but all was with methylcobalamin. All was in the dose range of 1-6 mg daily. Remember these vitamins are usually listed as micrograms, so would take 1000 mcg to make 1 mg. Research doses of folic acid have ranged from 1-20 mg/daily.
 


until next time,
Peace, Love & Health...
Priscilla Slagle M.D.
 
“May the thread of my song be not cut before my life merges in the sea of love”
    --from God Makes The Rivers To Flow
 
 
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HeatherG

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Reply with quote  #14 
HI Cindy
 
you can get a B12 vitamin as Cyanocobalamin or Methylcobalamin.  It is my understanding from reading and talking with the folks at the health food store that the body has to convert the C into the M to use it.
 
I have been vegan for 15 years or so, I take b12 Methylcobalamin

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Reply with quote  #15 

I've taken folic acid daily for 15 years and my periods have been regular with no cramping!


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"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well. Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything"...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
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Reply with quote  #16 
Quote:
Originally Posted by SteveOifer

I've taken folic acid daily for 15 years and my periods have been regular with no cramping!


I'm very proud of you, Steve, that you have been able to address your feminine side and share openly. 
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I enjoy being sunny & share!


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For the betterment of the breed!

"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well. Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything"...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
"I can live with doubt, or not knowing, rather than to have answers that might be wrong"...Richard Feynman
TEST YOUR DOGS!
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Reply with quote  #18 
Quote:
I've taken folic acid daily for 15 years and my periods have been regular with no cramping!


This explains so much Steve. I have often suspected there were times you suffered from PMS


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Quote:
Originally Posted by EileenDurante
Quote:
I've taken folic acid daily for 15 years and my periods have been regular with no cramping!


This explains so much Steve. I have often suspected there were times you suffered from PMS



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Reply with quote  #20 
PMS= Post Mastiff Syndrome!
 
Yes! I admit to that!!!

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For the betterment of the breed!

"Above all, a uniform type should be aimed at by breeders and uniformity of type can only exist in a proportionate ratio in the purity and distinctiveness in any breed"!.........M. Moore
"If breeds did not adhere to a specific shape, form, and colour range, or if breeders disregarded this blueprint, the breed would degenerate to the point that it would hardly resemble the breed at all. Selective breeding does not just create breeds- it preserves them as well. Breeding purebred dogs inherently means accepting limitations on your freedom to just breed anything"...Catherine McMillan
" A reinforced consolidation of the American and British standards could be the basis for restoring our breed to the gladiatorial glory of its ancient past, in capability if not in usage".....Norman Howard Carp-Gordon
"I can live with doubt, or not knowing, rather than to have answers that might be wrong"...Richard Feynman
TEST YOUR DOGS!
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Reply with quote  #21 
Quote:
I've taken folic acid daily for 15 years and my periods have been regular with no cramping!


Steve....thank you for the chuckle this morning....now I have to go clean the coffee off my monitor!!

Heather, Ella....tks for explaining the difference!

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Reply with quote  #22 
When my wife was pregnant with our first baby in 1989, the elderly doctor we had then prescribed folic acid, but when we were having our second baby in 1992 after he had retired, the younger doctor didn't. Since then I believe it is popular for pregnancy again.
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Reply with quote  #23 

The majority of the products I use are practitioner products of which this is one of those. . .

I had been using this product for a couple of years (and, boy it helped during puppy-ville) . . and was talking to Eileen (the nocturnal machine) one day and found that it may be helpful. . .well, of course, Eileen being Eileen thinking if it's good for me, "here, doggie, doggie". . .and the rest is history.

Anyway, if you would like further information or to order please feel free to contact me at my e-mail address:  healthyspiritnaturally@yahoo.com


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Reply with quote  #24 
Wow - this was very helpful to me!  Thanks Dr Ella

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Reply with quote  #25 

Quote:
Originally Posted by HeatherG
Hi Eileen, I understand,  I get the Methylcobalamin tabs... cherry flavor

The body can process the M better then the C.... or so that is what I have read


btw - synergy is critical wherein the sum of the parts exceeds the simple addition of the two . . .
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Reply with quote  #26 

Quote:
Originally Posted by TexunNYC
Wow - this was very helpful to me!  Thanks Dr Ella


you are certainly welcome!
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Reply with quote  #27 
Excerpt from above for the impatient among us.

Quote:
WHAT FORMS OF B12/FOLIC ACID ARE BEST TO TAKE?
Vitamin B12 comes in several chemical forms & folic acid in two forms. The most common & least expensive B12 is cyanocobalamin. This is fine to use for basic supplementation. And plain folic acid is fine for a basic program. There are also the methyl-, hydroxy-, & adenosyl- cobalamin forms of B12 which are more expensive & previously have been less available.
 
Dietary or supplemental cyanocobalamin converts in the body to the other forms listed here, especially Methylcobalamin (MeCb). Folic acid must be present for this conversion to take place. The folic acid must be in the coenzyme form called L- 5 methyl tetrahydrofolate. A properly functioning body would have converted regular dietary or supplemental folic acid to this coenzyme form. When there are diseases, sometimes the folic acid does not convert properly, & one would have to supplement with the L-5 methyl tetrahydrofolate instead.
 
The methyl cobalamin (MeCb) is the most active form of B12 in the body, especially in the brain & nervous system. There is the belief the MeCb has some therapeutic applications not as well achieved by other forms of B12. MeCb is also utilized more efficiently & has better tissue retention. For this reason much of the recent research has been done using this MeCb. Some of the research uses the injectable, some the sublingual form. When possible, I suggest a combination of the 2 when one is treating a significant health problem.
 

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Reply with quote  #28 
Quote:
Originally Posted by erikam
Excerpt from above for the impatient among us.

Quote:
WHAT FORMS OF B12/FOLIC ACID ARE BEST TO TAKE?
Vitamin B12 comes in several chemical forms & folic acid in two forms. The most common & least expensive B12 is cyanocobalamin. This is fine to use for basic supplementation. And plain folic acid is fine for a basic program. There are also the methyl-, hydroxy-, & adenosyl- cobalamin forms of B12 which are more expensive & previously have been less available.
 
Dietary or supplemental cyanocobalamin converts in the body to the other forms listed here, especially Methylcobalamin (MeCb). Folic acid must be present for this conversion to take place. The folic acid must be in the coenzyme form called L- 5 methyl tetrahydrofolate. A properly functioning body would have converted regular dietary or supplemental folic acid to this coenzyme form. When there are diseases, sometimes the folic acid does not convert properly, & one would have to supplement with the L-5 methyl tetrahydrofolate instead.
 
The methyl cobalamin (MeCb) is the most active form of B12 in the body, especially in the brain & nervous system. There is the belief the MeCb has some therapeutic applications not as well achieved by other forms of B12. MeCb is also utilized more efficiently & has better tissue retention. For this reason much of the recent research has been done using this MeCb. Some of the research uses the injectable, some the sublingual form. When possible, I suggest a combination of the 2 when one is treating a significant health problem.
 

 

ERIKA - you are funny  :-)   o' impatient one ,, yes, excerpt from my post.

Perhaps injectable if severely depleted would be best but I for one am not into the needles . . .

Again, regardless of Meth- or cyo - . . .synergy. . .

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Reply with quote  #29 
Quote:
.well, of course, Eileen being Eileen thinking if it's good for me, "here, doggie, doggie". . .and the rest is history.


ROFL You know me so well Ella


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Reply with quote  #30 

Quote:
Originally Posted by EileenDurante
Quote:
.well, of course, Eileen being Eileen thinking if it's good for me, "here, doggie, doggie". . .and the rest is history.


ROFL You know me so well Ella


. . .gettin' there, ma'am . . .   
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