~ 020508 Declining Folate Levels Linked with Dementia

In an article published online ahead of print in the Journal of Neurology, Neurosurgery and Psychiatry, researchers from Chonnam National University Medical School in Kwanju, Korea report that older individuals who were deficient in folate had triple the risk of developing dementia compared to those with higher levels of the vitamin.

The study included 625 men and women aged 65 and older who were free of dementia in 2001. Upon enrollment, blood samples were collected and analyzed for serum folate and vitamin B12, as well as plasma homocysteine, and assessments for dementia were conducted. These tests were repeated at follow-up examinations which took place an average of 2.4 years later.

Folate deficiency was present in 3.5 of the participants at the beginning of the study, and B12 deficiency in 17.4 percent. Twenty percent had elevated homocysteine levels, which were associated with having lower folate and B12. Five hundred eighteen participants completed the study, of which 34 went on to develop Alzheimer's disease, seven acquired vascular dementia, and four developed dementia of other origin.

Over the course of the study, folate levels decreased and vitamin B12 levels rose. Dementia was significantly associated with having lower folate levels upon enrollment as well as with showing a decline in the vitamin at follow-up . Those whose folate levels were deficient at the beginning of the study experienced 3.43 times the risk of dementia than those who whose folate levels were considered adequate. Having comparatively lower levels of B12 and increased homocysteine concentrations were also associated with dementia.

The drop in folate, but not B12 levels may reflect vitamin supplementation, since most Korean supplements provide B12 but not folic acid. The authors note the possibility that the differences associated with dementia in this study may reflect supplement use; however they do not believe that this is the only explanation for the finding.

The researchers suggest that alterations in nutrient levels may be associated with other indicators of impending dementia, including weight loss, which can indicate changes in dietary quality. "Attention needs to be paid to the nutritional status of people with dementia from the time of diagnosis onwards, regardless of whether this is a cause or effect of their condition," the authors observe. "In addition, there may be good arguments for focusing interventions for the prevention of dementia on nutritionally deficient frail populations," they conclude.

Related Health Concern: Homocysteine Reduction

Since its discovery in 1932, homocysteine's journey into mainstream medicine has been rocky. For the first 36 years after its discovery, little was understood about it. Then in 1968 a Harvard researcher named Dr. Kilmer McCully noticed that children with genetically elevated homocysteine levels experienced heart disease similar to the heart disease found in middle-aged patients.

Scientists have worked hard to understand why our homocysteine level increases throughout life, and how that impacts our health. Homocysteine level is affected by a number of influences, including lifestyle, dietary choices, and genetics. As we age, our ability to absorb nutrients decreases. As a result, less of the important B vitamins are available to help metabolize homocysteine. Homocysteine level is also increased by certain pharmaceuticals, an aging metabolism, smoking, drinking too much alcohol or coffee, lack of exercise, obesity, and stress.

Management of hyperhomocysteinemia begins with folic acid, vitamin B6, and vitamin B12. To varying degrees, folic acid and vitamin B12 increase the remethylation of homocysteine back into SAMe. Vitamin B6 is necessary for the conversion of homocysteine into glutathione along the transsulfuration pathway. The following studies have shown a rapid and dramatic decrease in homocysteine levels caused by folic acid and some B vitamins:

  • In 1996, the Food and Drug Administration (FDA) mandated that cereal-grain flour products be fortified with folic acid. Modest but significant decreases in homocysteine levels followed (Jacques PF et al 1999; Anderson JL et al 2004).

  • One set of patients with a history of myocardial infarction or unstable angina was given 2000 mcg of folic acid daily. Another group of patients with the same conditions received only 200 mcg. The higher dosage significantly reduced total homocysteine levels (Neal B et al 2002).

  • Daily supplementation with 350 mcg of folic acid for 17 weeks reduced serum homocysteine levels by nearly 20 percent, enough to reduce the risk of vascular disease (Venn BJ et al 2002).



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