As the UK considers whether to fortify flour with folic acid in a bid to improve the health of the nation, not everyone is convinced of the benefits of such a move.
Writing in a letter to the editor of the British Medical Journal, Edward Reynolds, consultant neurologist at the Institute of Epileptology, King's College, London, said that the government's own report on folic acid fortification had understated the potential risks to the nervous system.
"In people with vitamin B-12 deficiency, giving folic acid does much more than mask any anaemia. The response of pernicious anaemia to folic acid is usually suboptimal and temporary and often followed by relapse. The vitamin precipitates not only neurological complications, sometimes after some initial temporary improvement, but also anaemia, although not necessarily to the same degree or in the same time scale," he wrote.
Reynolds then asked whether these problems, which are usually associated with pharmacological doses of folic acid (1-50 mg daily), could be avoided with minimum food fortification, saying that as far as he was aware, there was little scientific data on this matter, although he cited one study of 38 patients with vitamin B-12 deficiency treated with 1 mg folic acid, 30% of whom showed a significant haematological response.
"None of 25 patients treated for seven to 19 days developed nervous system disorder, whereas six of 12 treated for 90-930 days did. Isolated examples of a reticulocyte response and neurological deterioration occurred with doses as low as 0.3-0.5 mg daily. Because of the very active blood-brain barrier for folate the vitamin enters the nervous system slowly and the duration of treatment is just as important as the dose, which is highly relevant to food fortification," he said.
"Folic acid does much more than interfere with the metabolism of antiepileptic drugs. Experimental studies have confirmed that folates are highly convulsant if the blood-brain barrier is circumvented. The risk to patients is small because of the barrier mechanism, but the bigger the dose, the longer the duration, and the greater the damage to the blood-brain barrier then the higher the risk," he wrote in the letter.
He said that the policy of universal fortification was "disproportionate" given the potential risks. "I do not agree that the benefits of fortification are clear. They may be relatively clear with respect to the prevention of neural tube defects, but not all such defects are preventable with folic acid.
"Other, potentially much greater benefits of food fortification exist (including in vascular disease and to mental health), which have yet to be clarified. The possible benefits for mood, cognitive function, and ageing are considerable but have not been evaluated.
"For all these reasons field trials are advisable before the whole population is exposed to a prolonged increase in folate intake," he concluded.