Fat composition in ketogenic diet may influence outcomes in MS
Diet failed to reduce optic nerve damage in mouse model
A ketogenic diet — a very low-carbohydrate, high-fat diet — rich in long-chain, saturated fatty acids like those in butter and fatty red meat didn’t reduce optic nerve damage in a mouse model of multiple sclerosis (MS), a study shows.
Instead, feeding mice this type of diet before the onset of their disease modestly worsened certain visual impairments.
While ketogenic diets have been proposed to offer anti-inflammatory benefits to people with MS, the findings suggest the type of fat used may be a critical factor when considering such diets as a treatment strategy.
“We present new data that the use of [the ketogenic diet] in the treatment of MS should take the composition of the [the ketogenic diet] into consideration,” the researchers wrote in the study, “A high-saturated, long-chain fatty acid ketogenic diet negatively impacts visual and motor-sensory function in a pre-clinical model of multiple sclerosis,” which was published in Frontiers in Immunology.
MS is caused by immune-mediated damage to the brain and spinal cord, which gives rise to various neurological manifestations. One of the first signs of MS is optic neuritis, or inflammation of the optic nerve that carries signals from the eyes to the brain. This can lead to vision problems, including blurred vision, and impaired color vision and depth perception.
The ketogenic (keto) diet is a very low-carbohydrate, high-fat regimen originally developed to manage seizure disorders, but that may also have anti-inflammatory effects. The diet forces the body to rely on fat rather than sugar for energy.
Some studies suggest a keto diet may help ease fatigue and improve exercise capacity, cognition, and hand dexterity in people with MS. However, research in mouse models of MS has yielded mixed results, possibly because some studies used medium-chain fatty acids and others used long-chain fatty acids, the researchers said.
“These studies suggest the need for further analysis of the [keto diets] utilized in [MS] studies and exploration of how the chain length and saturation effects outcomes,” they wrote.
Keto diet’s effects on MS mouse model
Scientists at the University of Iowa examined the effects of a keto diet made up of long-chain, saturated fatty acids on optic neuritis using mice with experimental autoimmune encephalomyelitis (EAE), an induced disease that’s often used to model MS.
Long-chain, saturated fatty acids are those typically found in red meats (beef, lamb, pork), dairy products (full-fat milk, cream, cheese, butter), and coconut and palm oil.
Mice were fed either the keto or standard diet starting before their disease induction, at the time of induction, or at symptom onset. Along with disease severity, optic neuritis was assessed by measuring visual acuity and electrical impulses along the optic nerve, and by imaging and tissue analysis.
Mice that began the keto diet before EAE induction showed significantly worse disease severity than those on a standard diet. No significant differences were seen when the diet was introduced at disease induction or symptom onset.
Visual acuity also declined more severely in mice pretreated with the keto diet, but again, no differences were seen in the groups that started the diet later.
“We propose that pretreatment with a long-chain, saturated [ketogenic diet] … leads to an initial priming of the immune system that results in a more robust immune response and inflammatory cascade when disease induction occurs,” the researchers wrote.
Despite this, some aspects of optic nerve health weren’t affected by diet. Imaging of the retina, a light-sensitive layer of tissue at the back of the eye, showed similar thinning of nerve layers across all EAE groups, regardless of diet.
Likewise, the strength and speed of visual signals along the optic nerve were impaired in EAE mice compared with healthy mice, but these impairments didn’t differ between the diet groups. Tissue analyses also showed similar levels of optic nerve damage in EAE mice across all the diet groups.
“Our results demonstrate that irrespective of the timing of its implementation, a long-chain, saturated fatty acid [ketogenic diet] does not significantly improve visual outcomes in EAE mice,” wrote the researchers, who noted the findings underscore the importance of considering fat composition, and not just the amount of specific macronutrients, when evaluating the potential use of ketogenic diets in managing MS.
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