Originally published April 30 2008
Folate and Vitamin B-12: Two Nutrients Critical for Brain Health
by Barbara L. Minton
(NaturalNews) Recent research documents the critical nature of two nutrients, vitamin B-12 and folate, in brain health and the maintenance of cognitive functioning, including memory. Deficiencies of these key nutrients are markers of the neuropathology leading to cognitive decline, Alzheimer's Disease, and stroke.
Studies and Results
In the past decade, researchers have increasingly focused on an amino acid found in the blood stream called homocysteine, as a factor playing a role in poor memory and brain health.
The January, 2008 edition of Neurobiology and Aging reports a study of the changes of plasma amyloid beta protein, homocysteine, and medical temporal lobe atrophy (MTI) in the transition from cognitive health to mild cognitive impairment and to Alzheimer's disease in a cohort of 75 year-old individuals. Results indicate that whether persons with mild cognitive impairment develop Alzheimer's Disease may depend on an accumulation of toxic metabolites such as homocysteine.
A study in the January, 2008 edition of Prostaglandins, Leukotrienes and Essential Fatty Acids, concluded that low blood folate and elevated homocysteine levels are associated with poor brain function. They found that folic acid enhances blood levels of DHA and EPA (essential omega-3 fatty acids), nutrients which also appear to have some beneficial effects for promoting healthy brain functioning.
In the November, 2007 edition of Stroke, researchers report investigating the individual and combined effects of plasma folate, vitamin B12, and pyridoxal 5-phosphate levels on the risk of ischemic stroke and transient ischemic attack in a large German cohort. (Ischemic stroke is death to an area of the brain resulting from an inadequate supply of blood and oxygen to the brain as a result of blockage of an artery). They concluded that low vitamin B12 plasma levels, particularly in combination with low folate levels, increase the risk of cerebral ischemia.
And as reported in the June, 2007 edition of the Journal of American College of Nutrition, researchers investigated serum levels of folate, B12 and total homocysteine in elderly post-stroke patients, and the possible correlations with radiological markers of neuropathology. The data showed that folate deficiency and hyperhomocysteinemia are prevalent in elderly post stroke patients. These two conditions are strongly and independently associated with the development of brain atrophy.
Folate and Folic Acid
The terms folate and folic acid are used interchangeably to describe this member of the B-vitamins. Folate is found in food as well as in metabolically active forms in the human body. Folic acid is the form more frequently used in supplements.
The role of folate in the body is to act as acceptor and donor of one-carbon units in a variety of reactions critical to the metabolism of nucleic acids and amino acids. It plays a vital role in DNA metabolism from its precursors, thymidine and purines, and is required for the synthesis of methionine, which is required for the synthesis of S-adenosylmethionine (SAM-e). SAM-e is a methyl donor used in many biological methylation reactions, including the methylation of sites within DNA and RNA. Methylation of DNA is seen as playing an important role in cancer prevention.
The synthesis of the amino acid methionine requires folate as well as a vitamin B-12 dependent enzyme. So deficiency of folate can result in decreased synthesis of methionine and buildup of homocysteine, which may be a risk factor for heart disease as well as neuropathology. The amount of homocysteine in the blood is regulated by vitamin B-12, and vitamin B-6 as well as folate.
Folate Deficiency
Folate deficiency is usually caused by dietary insufficiency although it can occur in other situations. Several medications may be contributory.
Folate deficiency is usually initially signaled by rising homocysteine levels. Rapidly dividing cells are particularly vulnerable to folate deficiency and may result in anemia and the hypersegmentation of neutrophils. Progression of such anemia leads to a decreased capacity of the blood to carry oxygen and may ultimately result in symptoms of fatigue, weakness, and shortness of breath. This type of anemia may also result from vitamin B-12 deficiency.
Disease Prevention
Adequate levels of folate at time of conception have been shown to prevent spina bifida, a devastating birth defect, and may prevent the occurrence of other types of birth defects including certain heart defects and limb malformation. Low levels of folate has been associated with increased incidence of miscarriage as well as preeclampsia on placental abruption, the separation of the placenta from the uterus.
More than 80 studies have shown that even moderately elevated levels of homocysteine in the blood increase the risk of cardiovascular diseases, while folate-rich diets have been associated with a decreased risk of cardiovascular disease. 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 no deficiency of vitamin B-12 or vitamin B-6 is present.
Since cancer is thought to arise from DNA damage in excess of ongoing DNA repair and/or the inappropriate expression of critical genes, it is possible for folate intake to affect both DNA repair and gene expression because of the important roles played by folate in DNA and RNA synthesis and methylation. Consuming at least five servings of fruits and vegetables daily has been shown to decrease incidence of cancer. Fruits and vegetables are excellent sources of folate, which may play a role in their anti-carcinogenic effect. Folate from foods and folic acid supplements have been shown to be inversely associated with colorectal cancer risk. Studies of folate and breast cancer have yielded mixed results.
As the noted studies indicate, folate in nucleic acid synthesis and methylation is essential for normal brain function. Several studies have documented the associations between decreased folate levels and cognitive impairment in the elderly. Individuals with low serum folate levels were more likely to have dementia, be institutionalized, and be depressed. Low folate levels were also associated with increased likelihood of short-term memory problems in the elderly.
Food Sources and Supplements
Green leafy vegetables are rich in folate as well as fruit juices, legumes, barley, beef, bran, brewer's yeast, brown rice, cheese, chicken, dates, lamb, lentils, salmon, tuna, liver, pork, wheat germ, whole grains, and whole wheat.
The supplemental form of folate is primarily folic acid. It is available in single ingredient and combination products such as B-complex vitamins. The typical dose is 400 mcg.
Vitamin B-12
Vitamin B-12 is unique in having the largest and most complex structure of all the vitamins, and in containing a metal ion, cobalt. Methylcobalamin and 5-deoxyadenosyl cobalamin are the forms of vitamin B-12 used in the body. Another form, cyanocobalamin, is converted in the body.
Methylcobalamin, along with folate, is required for methionine synthase to function properly as discussed above.
Vitamin B-12 Deficiency
Absorption of vitamin B-12 from food requires normal function of the stomach, pancreas, and small intestine. The most common causes of deficiency are the autoimmune disorders, pernicious anemia, and malabsorption from food sources.
Vitamin B-12 deficiency results in impairment of the activities of B-12 requiring enzymes, and may result in impaired activity of methionine synthase.
The neurologic symptoms of a vitamin B-12 deficiency include tingling of the legs or arms, numbness, difficulty walking, memory loss, disorientation, and dementia. Tongue soreness, appetite loss, and constipation are also associated with vitamin B-12 deficiency.
Disease Prevention
A study of 195 women later diagnosed with breast cancer and 195 age-matched women who were not diagnosed with breast cancer concluded that among women who were postmenopausal, the association between blood levels of vitamin B-12 and breast cancer suggested a threshold effect. The risk of breast cancer was more than doubled in women with serum vitamin B-12 levels in the lowest quintile compared to women in the four highest quintiles. Another study reported that breast cancer risk for women in the highest quartile of vitamin B-12 intake was 68% lower than those in the lowest quartile.
As the studies have shown, people with Alzheimer's disease often have low blood levels of vitamin B-12. One study found lower B-12 levels in the cerebrospinal fluid of Alzheimer's patients than in patients with other types of dementia.
Observational studies have documented as many as 30% of patients hospitalized for depression were deficient in vitamin B-12. A cross sectional study of 700 women over the age of 65 found that B-12 deficient women were twice as likely to be severely depressed as non-deficient women.
Food Sources and Supplements
Only bacteria in the mouth and gut can synthesize vitamin B-12. Food sources are animal products. Individuals over the age of 50 should obtain their B-12 from supplements because of the increased likelihood of food-bound B-12 malabsorption.
Over-the-counter supplements are usually made of cyanocobalamin, but methylcobalamin is also available and is considered the better choice. Available forms are B-12 alone, or as part of a B vitamin complex.
Sources:
Linus Pauling Institute at Oregon State: (http://lpi.oregonstate.edu/infocenter/vitami...)
Linus Pauling Institute at Oregon State: (http://lpi.oregonstate.edu/infocenter/vitami...)
March of Dimes Pregnancy and Newborns: (http://www.marchofdimes.com/pnhec/887.asp)
About the author
Barbara is a school psychologist, a published author in the area of personal finance, a breast cancer survivor using "alternative" treatments, a born existentialist, and a student of nature and all things natural.
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