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A team of Trinity College researchers has found that three weeks on a low carbohydrate "ketogenic" diet can lower pain and inflammation in juvenile and adult animals, offering hope that metabolic, diet-based therapies could have broad implications for helping people. The study is published in the open-access journal PLoS ONE.
A ketogenic diet is not unlike a strict version of the popular Atkins diet, where low carbohydrate content results in low glucose and forces the body to burn ketones for cell metabolism. People who adhere to such diets are restricted from eating foods such as bread, pasta, fruit and candy, but are allowed to eat green leafy vegetables, meat, fish and some dairy products.
Clinically, ketogenic diets have proven effective in treating pediatric epilepsy and type II diabetes, and recent studies provide evidence that ketogenic strategies could reduce brain injury. Ketones are used by the body during fasting, and the diet was developed initially based on the observation that people with epilepsy experienced a reduction in their seizures when they did not eat.
The Trinity research, which took almost a year to complete, focused on the pain sensitivity and anti-inflammatory effects of a ketogenic diet on juvenile and adult rats. The work was performed in the laboratory of Susan A. Masino, Charles A. Dana Research Associate Professor of Psychology and Neuroscience and Director of the Neuroscience Program, along with David N. Ruskin, Research Assistant Professor, and Masahito Kawamura, a visiting researcher from Jikei University in Japan.
Ruskin, the lead author, noted that the effect of the diet did not depend on any special feeding schedule or limits, and pain and inflammation were reduced significantly in both young and adult rats.
"All the animals ate as much as they wanted," said Ruskin. "The younger animals gained less weight on the ketogenic diet, but the adults were not different."
The rats' response to pain was measured by placing them on a warm surface and removing them immediately when they lifted up their hind paw, similar to a person walking barefoot on warm pavement. A control group of rats was fed standard rodent chow. Each rat was tested for six consecutive days at one temperature between 46 and 51 degrees Centigrade. How long each rat tolerated the warm surface on each day was the measure of his response to pain.
"The ketogenic diet seemed to have reduced their sensitivity to pain," said Masino.
In a separate series of experiments, an irritating substance was injected into the rats' paws. The research team found that the swelling and thus the inflammation were reduced significantly in rats fed the ketogenic diet regardless of age.
One reason why the findings are hugely important is that pain and inflammation are hallmarks of diverse acute and chronic diseases. Indeed, chronic pain is one of the most common health-related factors leading to poor quality of life. Across all cultures, patients with chronic pain experience among the lowest reported quality-of-life scores of any medical condition.
Moreover, dietary therapy has long been coveted as a strategy to treat a variety of clinical conditions, including pain and inflammation.
The researchers cautioned that the diet formulation used in this initial study was more restrictive than the ketogenic diet used by people under medical supervision.
A next step would be to identify the key mechanisms underlying the reduced pain and inflammation. Understanding these specific mechanisms could also help people with epilepsy by leading to the development of medications that address all of these conditions. Without question, said the researchers, a great unmet public health need exists for safe, effective and non-addictive strategies to reduce pain and inflammation.
"Our goal is to understand this at the cellular level, which could yield new pharmacological treatments and/or less restrictive diet-based strategies," said Masino. "This is a first exciting step, as effective and non-addictive new therapies for pain and inflammation are urgently needed and could help so many people."
In conclusion, the research team said, the data suggest that ketogenic diets offer promising therapeutic potential for diverse inflammatory or painful conditions across age groups without the added difficulty of maintaining caloric restriction. Based on these results and clinical experience with diet-based therapies for pediatric epilepsy, a novel anti-inflammatory and analgesic application of ketogenic diet therapy would be effective, non-addictive and relatively free of major side effects.
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