Fish Oil May Guard Against Alcohol-Related Brain Damage

(Upated July 28, 2014) An omega-3 compound found in fish oil may lower the risk for brain damage caused by long-term alcohol use, new research suggests.

A study of rat brain cultures exposed to alcohol levels equivalent to 4 times the legal driving limit showed that animals also exposed to omega-3 docosahexanenoic acid (DHA) had 90% less "neuronal death" and 90% less neuroinflammation than those not exposed to DHA.

"We wanted to try and find out what the underlying mechanisms are for the brain damage that occurs in the binge-drinking rat model and if it's connected to the process of neuroinflammation," principal investigator Michael A. Collins, PhD, professor in the Department of Molecular Pharmacology and Therapeutics at the Stritch School of Medicine at Loyola University, Chicago, Illinois, told Medscape Medical News.

"Too much release of arachidonic acid is going to cause oxidative stress and what we term neuroinflammation processes. Because levels of DHA are depleted by too much alcohol, we looked at replenishing it and saw that that may be protective," added Dr. Collins.

The study was published online July 16 in PLoS One.

Suppresses Cell Death

In September 2013, Dr. Collins presented initial results of this study at the Congress of the European Society for Biomedical Research on Alcohol in Warsaw, Poland.

"We hypothesized that omega-3 fatty acids, specifically DHA...would suppress or prevent the neuronal degeneration due to binge alcohol exposure," he told Medscape Medical News at the time.

"And basically, that is what we found."

He added that this animal study was not specifically focused on dementia. However, "since brain degeneration underlies persistent or permanent dementia, the results were extrapolated to what might happen in humans."

The researchers assessed brain samples from adult male rats exposed during a period of several days to repetitive ethanol intoxication. Half of the brain samples were further exposed to omega-3 DHA and the other half were not.

Results showed higher levels of phospholipase A2 (PLA2) resulting from the excessive alcohol exposure, which led to increased neuroinflammation, or astroglial aquaporin-4 (AQP4), and increased brain edema.

Compared with rats who had not been exposed to alcohol, those that had been exposed had significantly higher levels of cPLA2 and phospho-CPLA2 in the hippocampus, entorhinal cortex, and olfactory bulb (all, P < .05). They also had significantly increased levels of sPLA2 in all 3 areas (P < .05 for the first 2, P < .01 for the latter).

More Research Needed

All 3 brain areas also showed significantly higher levels of AQP4 and ADP-ribose polymerase-1 (PARP1; all, P < .05).

"Aquaporin-4 is the big one. It's the water channel," said Dr. Collins. "And PARP is the nucleus of all brain cells. It's a repair enzyme, but overactivity of this in the brain can actually lead to the neurons dying."

There was also a significant increase in levels of "oxidative stress footprint, 4-hydroxynonenal (4HNE)-adducted proteins," in the hippocampus and entorhinal cortex in the rats that had been exposed to binge alcohol vs those that had not been exposed (P < .01).

However, the addition of DHA to brain slice cultures decreased elevation in the oxidative footprint and decreased the elevated levels of PLA2, AQPA, and PARP1. It was also found to decrease neurodamage caused by excessive alcohol consumption.

"It's an animal study, but it's very interesting," said Dr. Collins. "I'd say the number 1 take-away is that oxidative stress–related neuroinflammation is linked to neurodegeneration/neuronal cell death in alcohol bingeing. And omega-3 fatty acid has the potential to suppress and prevent these things."

However, he noted that more research is needed, and the investigators hope to soon begin examining whether the DHA compound can protect against alcohol-related neurodegeneration in intact male and female rats.

For now, Dr. Collins added that heavy drinkers should cut back on their drinking ― or consider quitting entirely ― because the study is not saying it is okay to take a few capsules and then continue abusing alcohol.

"Provides Further Evidence"

"Despite the fact that this is a preclinical study, it provides further evidence that omega-3, in particular DHA, has neuroprotective and anti-inflammatory properties," Gregor Berger, MD, psychiatrist and clinical and translational researcher in Zurich, Switzerland, told Medscape Medical News.

"It also provides interesting ideas around the underlying mechanism of alcohol-related brain damage (parthanatos), in particular, using a binge drinking model," he added.

Dr. Berger, who was not involved with the research, has been involved in numerous trials assessing omega-3 fatty acid supplementation, particularly in early psychosis.

He added that binge drinking continues to increase among youth ― and that a lot of adolescents underestimate the potential long-term effects of their drinking habits. He also noted that the current results, if replicated in larger studies, could be practice changing.

"The use of omega-3 fatty acid supplementation, in particular DHA, in alcohol-intoxicated patients or withdrawal regimes may be one potential clinical implication of this preclinical study and should be investigated in controlled clinical trials," said Dr. Berger.

The study was funded by grants from the National Institutes of Health, including the National Institute of Alcohol Abuse and Alcoholism (NIAAA). Although the study authors have reported no relevant financial relationships, 1 is from the NIAAA.

PLoS One. Published online July 16, 2014. Full text

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Cite this: Fish Oil May Guard Against Alcohol-Related Brain Damage - Medscape - Jul 25, 2014.