Folates are vitamins essential to the development of the central nervous system. Insufficient folate activity at the time of conception and early pregnancy can result in congenital neural tube defects. In adult life folate deficiency has been known for decades to produce a characteristic form of anaemia ("megaloblastic"). More recently degrees of folate inadequacy, not severe enough to produce anaemia, have been found to be associated with high blood levels of the amino acid homocysteine. Elevated blood levels of homocysteine have been linked with the risk of arterial disease, dementia and Alzheimer's disease. Such degrees of folate inadequacy can arise because of insufficient folates in the diet or because of inefficient absorption or metabolic utilization of folates due to genetic variations. Conventional criteria for diagnosing folate deficiency may be inadequate for identifying people capable of benefiting from dietary supplementation. There is therefore interest in whether dietary supplements of folic acid (an artificial chemical analogue of naturally occurring folates) can improve cognitive function of people at risk of cognitive decline associated with ageing or dementia, whether by affecting homocysteine metabolism or through other mechanisms.
There is a risk that if folic acid is given to people who have undiagnosed deficiency of vitamin B12 it may lead to neurological damage. Vitamin B12 deficiency produces an anaemia identical to that of folate deficiency but also causes irreversible damage to the central and peripheral nervous systems. Folic acid will correct the anaemia of vitamin B12 deficiency and so delay diagnosis but will not prevent progression to neurological damage. For this reason trials of folic acid supplements may involve simultaneous administration of vitamin B12. Apparent benefit from folic acid given in the combination would therefore need to be "corrected" for any effect of vitamin B12 alone. A separate Cochrane review of vitamin B12 and cognitive function has been published (Malouf 2003).