Rheumatologists have long known that obesity exacerbates arthritis symptoms. For that reason, an Oklahoma Medical Research Foundation physician-scientist was among the many clinicians who recommended a ketogenic diet for weight loss to patients.
Not anymore.
Matlock Jeffries, M.D., said he was stunned by the results of his recent study testing the effects of a keto diet on mice with osteoarthritis, the most common form of the disease. Jeffries discovered that while a keto diet helped the mice lose weight, it worsened the arthritis and the related pain in their knees.
“I had hypothesized that a keto diet would improve their symptoms because of the accompanying weight loss,” said Jeffries, a rheumatologist who directs OMRF’s Arthritis Research Center and supervises OA treatment at OMRF and the Veterans Affairs Medical Center in Oklahoma City. “What we found was the exact opposite.”
Developed about 100 years ago to control epileptic seizures, the keto diet restricts intake of carbohydrates like breads, rice and other starches while requiring consumption of high-fat sources like meat, eggs, nuts and low-carb vegetables. This switch tricks the metabolism into believing the person is fasting.
The advent of anti-seizure medication ended the diet’s popularity for epilepsy, but it made a comeback over the past two decades, primarily for its weight-loss benefits. Many physicians favor the keto approach, especially to control type 2 diabetes. However, others say the diet’s strict regimen often causes their patients to give up and then quickly regain the lost weight.
In Jeffries’ study, mice with a meniscus tear – a common knee injury found in humans – were divided into two groups: those fed a high-fat diet and those fed a keto diet.
After eight weeks, he found that those on the keto diet had worse knee damage and more pain than the other mice. Additionally, the keto diet increased chemicals in the blood linked to inflammation.
Following this study, Jeffries will still advise his OA patients to manage their weight. However, he will now suggest other alternatives to a keto diet, such as weight-loss drugs like Wegovy and Zepbound, or a Mediterranean diet, which emphasizes vegetables, fruits, nuts, whole grains and unprocessed foods.
“This is the first time the results of an experiment have made me change the advice I give patients,” he said.
To make sense of his lab’s surprising results, Jeffries is considering several new avenues, such as extending the study period or conducting it in another experimental model.
Judith James, M.D., Ph.D., OMRF’s executive vice president and chief medical officer, sees this new work as key to finding new ways to help patients with osteoarthritis, a disease that affects more than 30 million Americans. Approved treatments relieve inflammation and some pain but do not slow disease progression.
“Each new discovery brings us closer to fully understanding the complexities of osteoarthritis,” James said. “Little is known about the impact of various diets on arthritis and arthritis pain. So, experiments like these are critical as we move toward human studies and comprehensive care plans.”
Jeffries’ discovery was published in a journal of the American College of Rheumatology. His research was supported by grant No. PR191652 from the Congressionally Directed Medical Research Program, plus the following National Institutes of Health grants: K08AR070891, R33AR078075, R61AR078075 and R01AR076440 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and P20-GM-125528 from the National Institute of General Medical Sciences.
This news release is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
