Fructose alters hundreds of brain genes, which can lead to a wide range of diseases

April 22, 2016 by Stuart Wolpert
Syrup contains fructose, which alters brain genes linked to many diseases, UCLA life scientists report.

A range of diseases—from diabetes to cardiovascular disease, and from Alzheimer's disease to attention deficit hyperactivity disorder—are linked to changes to genes in the brain. A new study by UCLA life scientists has found that hundreds of those genes can be damaged by fructose, a sugar that's common in the Western diet, in a way that could lead to those diseases.

However, the researchers discovered good news as well: An omega-3 fatty acid known as docosahexaenoic acid, or DHA, seems to reverse the harmful changes produced by fructose.

"DHA changes not just one or two ; it seems to push the entire gene pattern back to normal, which is remarkable," said Xia Yang, a senior author of the study and a UCLA assistant professor of and physiology. "And we can see why it has such a powerful effect."

DHA occurs naturally in the membranes of our cells, but not in a large enough quantity 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.

DHA strengthens synapses in the brain and enhances learning and memory. It is abundant in wild salmon (but not in farmed salmon) and, to a lesser extent, in other fish and fish oil, as well as walnuts, flaxseed, and fruits and vegetables, said Gomez-Pinilla, who also is a member of UCLA's Brain Injury Research Center.

Americans get most of their fructose in foods that are sweetened with , an inexpensive liquid sweetener made from corn starch, and from sweetened drinks, syrups, honey and desserts. The Department of Agriculture estimates that Americans consumed an average of about 27 pounds of high-fructose corn syrup in 2014. 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—and fruit contains other healthy components that protect the brain and body, Yang said.

To test the effects of fructose and DHA, the researchers trained rats to escape from a maze, and then randomly divided the animals into three groups. For the next six weeks, one group of rats 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 navigated the maze about half as fast than the rats that drank only water—indicating that the fructose diet had impaired their memory. The rats that had been given fructose and DHA, however, showed very similar results to those that only drank water—which strongly suggests that the DHA eliminated fructose's harmful effects.

Other tests on the rats revealed more major differences: The rats receiving a high-fructose diet had much higher blood glucose, triglycerides and insulin levels than the other two groups. Those results are significant because in humans, elevated glucose, triglycerides and insulin are linked to obesity, diabetes and many other diseases.

The research team sequenced more than 20,000 genes in the rats' brains, and identified more than 700 genes in the hypothalamus (the brain's major metabolic control center) and more than 200 genes in the hippocampus (which helps regulate learning and memory) that were altered by the fructose. The altered genes they identified, the vast majority of which are comparable to genes in humans, are among those that interact to regulate metabolism, cell communication and inflammation. Among the conditions that can be caused by alterations to those genes are Parkinson's disease, depression, bipolar disorder, and other brain diseases, said Yang, who also is a member of UCLA's Institute for Quantitative and Computational Biosciences.

Of the 900 genes they identified, the researchers found that two in particular, called Bgn and Fmod, appear to be among the first genes in the brain that are affected by fructose. Once those genes are altered, they can set off a cascade effect that eventually alters hundreds of others, Yang said.

That could mean that Bgn and Fmod would be potential targets for new drugs to treat diseases that are caused by altered genes in the brain, she added.

The research also uncovered new details about the mechanism fructose uses to disrupt genes. The scientists found that fructose removes or adds a biochemical group to cytosine, one of the four nucleotides that make up DNA. (The others are adenine, thymine and guanine.) This type of modification plays a critical role in turning genes "on" or "off."

The research is published online in EBioMedicine, a journal published jointly by Cell and The Lancet. It is the first genomics study of all the genes, pathways and gene networks affected by fructose consumption in the regions of the brain that control metabolism and brain function.

Previous research led by Gomez-Pinilla found that fructose damages communication between brain cells and increases toxic molecules in the brain; and that a long-term high- diet diminishes the brain's ability to learn and remember information.

"Food is like a pharmaceutical compound that affects the brain," said Gomez-Pinilla. He recommends avoiding sugary soft drinks, cutting down on desserts and generally consuming less sugar and saturated fat.

Although DHA appears to be quite beneficial, Yang said it is not a magic bullet for curing diseases. Additional research will be needed to determine the extent of its ability to reverse damage to human genes.

Explore further: High-fructose diet slows recovery from brain injury

More information: Qingying Meng et al. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders, EBioMedicine (2016). DOI: 10.1016/j.ebiom.2016.04.008

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7 comments

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adam_russell_9615
2 / 5 (2) Apr 22, 2016
About that title pic - Does actual 100% maple syrup contain fructose, or just the lousy imitation stuff made from corn syrup?
omatwankr
4 / 5 (2) Apr 22, 2016
100% maple syrup is mainly sucrose, the flavoured stuff would be a good bet it full of corn syrup, fracking fluids and good knows what else
torbjorn_b_g_larsson
not rated yet Apr 23, 2016
"It consists primarily of sucrose and water, with small amounts of the monosaccharides glucose and fructose from the invert sugar created in the boiling process." [ https://en.wikipe...utrition ]

So it contains needless fructose. Here is a Biochem 101 question: where did the fructose come from? Turns out that sucrose is a disaccharide of glucose and fructose. [ https://]/wiki/Sucrose The 50 % fructose is what it is converted to in the stomach (IIRC), but anyway polysacharides are metabolized by being turned into their monosaccharides, which is then used or broken down.

Table sugar should else be the major source of fructose. [ https://en.wikipe...ki/Sugar ]
Shootist
not rated yet Apr 23, 2016
100% maple syrup is mainly sucrose, the flavoured stuff would be a good bet it full of corn syrup, fracking fluids and good knows what else


Fracking fluids: the god given liquid soap that allows our modern lives.

And why is sucrose any different than fructose, as sucrose is composed of 50% glucose and 50% fructose?
SamanthaOrwellSynecdoche
not rated yet Apr 23, 2016
Their description in Section 2.2 is unclear, but a reader might conclude that: 1) All the rats ate mostly an undescribed balanced diet; 2) The Fructose rats had their water changed to 15% fructose water; 3) The fructose-DHA rats had the 15% fructose water and also ~2.3% of their food-mass changed to omega-3 ALA/DHA fats; 4) The control rats ate fully the undescribed balanced diet and pure regular water.
Occams_Razor_Trader
not rated yet Apr 26, 2016
Fructose = Fruit Sugar - all natural and grown by plants.
High Fructose Corn Syrup = Genetically Modified Poison- Made by nature yet "perfected in a laboratory"- to make it sweeter and cheaper- so companies can sell more products for more profit.
Maple syrup also has trace minerals and vitamins (leached from the tree). the garbage on the shelf is cooked cane sugar- stripped of everything.
ValerieDaniele
not rated yet Apr 26, 2016
Why is ADHD in quotation marks in the teaser?

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