Fructose found in sweetened drinks, syrups, honey and foods sweetened with corn syrup causes changes to genes in the brain leading to a host of diseases from diabetes, cardiovascular disease, Alzheimer's disease and attention deficit hyperactivity disorder. Luckily an omega-3 fatty acid DHA seems to reverse these changes, but needs to be supplemented in diet.
The UCLA study found 900 genes altered by high fructose diet, of which two genes Bgn and Fmod, were the first genes to be affected. The two then set off a cascade effect altering hundred other genes.
The altered genes in mice are similar to those in humans and are the ones that regulate metabolism, cell communication and inflammation. Their alterations can lead to Parkinson's disease, depression, bipolar disorder, and other brain diseases, said Xia Yang, a senior author of the study and a UCLA assistant professor of integrative biology and physiology.
The team believes that Bgn and Fmod could be potential targets for new drugs to treat many of these ailments.
Fructose removes or adds a biochemical group to cytosine, one of the four nucleotides that make up DNA. This type of modification plays a critical role in turning genes "on" or "off."
On the other hand, the omega-3 fatty acid known as docosahexaenoic acid, or DHA, pushes not a few genes but the entire gene pattern back to normal. DHA that enhances learning and memory is present naturally in the membranes of our brain cells, but not in large quantities to help fight diseases.
"The brain and the body are deficient in the machinery to make DHA; it has to come through our diet," said Fernando Gomez-Pinilla, a UCLA professor of neurosurgery and of integrative biology and physiology, and co-senior author of the paper.
The long chain fatty acid DHA is abundant in wild salmon and, to a lesser extent, in other fish and fish oil, as well as walnuts, flaxseed, and fruits and vegetables. Fructose is also found is in most baby food and in fruit, although the fiber in fruit substantially slows the body's absorption of the sugar, Yang said.
The rat model
The researchers trained rats to escape from a maze, and then randomly divided the animals into three groups. One group drank water with an amount of fructose that would be roughly equivalent to a person drinking a liter of soda per day. The second group was given fructose water and a diet rich in DHA. The third received water without fructose and no DHA.
After the six weeks, the rats were put through the maze again. The animals that had been given only the fructose were slower in navigating than the rats that drank only water, indicating memory impairment. The rats that had been given fructose and DHA, however, showed very similar results to those that only drank water, suggesting that the DHA annulled fructose's harmful effects.
The rats on a high-fructose diet had much higher blood glucose, triglycerides and insulin levels than the other two groups, another reason why fructose should be avoided.
On sequencing more than 20,000 genes in the rats' brains, the team identified more than 700 altered genes in the hypothalamus and more than 200 altered genes in the hippocampus (which helps regulate learning and memory).
The research is published online in EBioMedicine, a journal published jointly by Cell and The Lancet.
Previous research led by Gomez-Pinilla found that fructose damages communication between brain cells and increases toxic molecules in the brain; besides diminishing the brain's ability to learn and remember information.
The paper's lead author is Qingying Meng, a postdoctoral scholar in Yang's laboratory.
