Pupils at 36 schools will be asked to take the supplements
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About 5,000 secondary school pupils are to be offered daily doses of fish oil supplements in the hope it will have a direct impact on exam results.
All Year 11 pupils in County Durham will be encouraged to take the omega-3 "eye q" pills until their GCSE examinations in summer 2007.
The initiative is the brainchild of the county council's chief schools inspector Dave Ford.
But charity Food and Behaviour Research said more research was needed.
Mr Ford is convinced the fatty oils can improve concentration and learning.
He said: "We are able to track pupils' progress and we can measure whether their attainments are better than their predicted scores."
A first indication of the supplement's effectiveness will be when the children sit their mock GCSEs in December.
'Improved concentration'
The initiative has won the backing of county councillors, who said they were committed to improving children's life chances.
Four years ago the county council ran a trial for younger pupils, which saw 12 schools offer the eye q supplement to pupils aged six to 12 as part of a controlled study.
Significant improvements were seen in attention, hyperactivity and short-term memory. Achievements in reading and spelling were also highly significant.
Claire Vasey, cabinet member for children and young people's services, said: "We have been leading the way in researching the effects of omega-3 supplementation on children's behaviour and learning.
"If we can improve the concentration of some of our children with this initiative, then they will benefit even more from the opportunities presented to them in our schools.
"These are the valuable experiences that will have a great impact on determining their future."
But Dr Alex Richardson of Food and Behaviour Research said some pupils should take dummy pills to determine whether supplements improved performance generally.
She said: "Proper trials of omega-3 have shown benefits for some children. However, the real burning question is whether they will help children in general.
"The Durham project is taking for granted that fish oils will help. There is no control and there must be a placebo.
"You cannot give omega-3 to every child and then say that the supplements have made a difference."