In late June, a group of children from the city of Ribeirão Preto, in inner-state São Paulo, started being given daily doses of fish oil as a supplement to medication they took to control epilepsy. Regarded as the world’s most common chronic neurological disease – it affects 1% of the population of the United States and Europe, and 2% of the population of Brazil – epilepsy is characterized by abrupt changes in the functioning of the neurons, a type of brain cell. During crises, which last for minutes, specific groups of these cells release stronger and more frequent electrical discharges to other neurons, causing behavioral changes, violent involuntary muscle contractions, or becoming unconscious.
The 52 children that are currently taking part in the experiment – the physicians plan to include another 38 – have a severe form of epilepsy in which the centers that originate the electrical discharges typical of the crises are spread throughout the brain and cannot be surgically removed. “They have epileptic crises almost every day,” explains Vera Cristina Terra, a neurologist at the University of São Paulo in Ribeirão Preto (USP-RP), who is in charge of this clinical trial. It is expected that the consumption of fish oil, which is rich in omega 3 fatty acids (fat molecules that are part of the composition of cells, but that are not produced by the human body) may generate among the children the same benefits observed in trials with lab animals and adults: less frequent crises and neuron preservation.
It is believed that using these supplements can replace another type of treatment that can help ease epilepsy: a ketogenic diet, in which dietary carbohydrates are replaced by fats – this diet is stricter and can change the level of blood cholesterol. “We tried a compound that is fat rich and that can be used for long time spans with no significant side effects,?” says Vera.
The plans to test omega 3 against epilepsy arose in 2008, when she started her postdoctoral studies at the Federal University of São Paulo (Unifesp), with Esper Cavalheiro. At the time, the team of neuroscientist Fulvio Scorza, from Unifesp, and of Roberta Cysneiros, from Mackenzie University, were completing tests on rats, showing the protective effects of omega 3, which is classified as a food supplement, not a drug. For two months, Danuza Ferrari had given rodents with and without epilepsy a daily dose of fish oil equal to the content of three supplement capsules. Carried out jointly with Ricardo Arida, from Unifesp, and Antonio Carlos de Almeida, from the Federal University of São João Del Rei, in the state of Minas Gerais, the brain analysis revealed that the rats treated with omega 3 had lost fewer neurons in the hippocampus – an area that is damaged in certain forms of epilepsy and that is connected with learning and the acquisition of memory. “We gave the rodents fish oil orally, to simulate what happens to people who take omega 3 capsules,” says Scorza, who described the results of the study in 2008 in Epilepsy & Behavior.
Excitement and death
It is unclear how omega 3 avoids neuron death. One likely mechanism might be that it blocks the entry of calcium into these cells, given that during epileptic crises, the chemical messenger glutamate is released; this promotes the entry of calcium in the neurons, making its concentration within the cell ten times greater than outside. In excess, however, calcium, which is fundamental for cell communication, kills them.
In his experiments, Scorza observed in the animals treated with omega 3 an increase in the production of calretinin and parvalbumin, two proteins that keep calcium from entering the neurons. In other recently completed tests, his team also demonstrated the formation of new neurons and the reduction of the level of inflammatory proteins that, according to some theories, might lead to epilepsy. “An ideal diet for both epileptics and for healthy people should include three portions of cold-water fish a week, or a capsule a day of fish oil,” says Scorza. During the course of the last century, the human population brutally reduced their consumption of omega 3, replaced by omega 6, found in meat and industrialized products, but less beneficial. The fish indicated for consumption are salmon and sardines. “Tuna is rich in omega 3, but it has high levels of mercury, which is toxic for the neurons,” he tells us.
In the Ribeirão Preto trial, the children will be given fish oil capsules free of charge for six months. One group will get 2 grams and another 3 grams, besides their epilepsy drugs. “We chose capsules to avoid the risk of the children not adapting to eating sardines,” Vera tells us. At the end of this period, the results will be compared to those of a third group, treated only with epilepsy drugs. If everything runs well, the test will be extended for a further six months.Republish