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Researchers have long believed that the keto diet could help reduce an overactive immune system and benefit individuals with conditions such as multiple sclerosis.
Now, they have reason to believe it could be true.
Scientists at UC San Francisco have discovered that the diet makes the gut and its microbes produce two factors that attenuated symptoms of MS in mice.
If the study translates to humans, it points toward a new way of treating MS and other autoimmune disorders with supplements.
The keto diet severely restricts carbohydrate-rich foods like bread, pasta, fruit and sugar but allows unlimited fat consumption.
Without carbohydrates to use as fuel, the body breaks down fat instead, producing compounds called ketone bodies. Ketone bodies provide energy for cells to burn and can change the immune system.
Working with a mouse model of MS, the researchers found that mice who produced more of a particular ketone body, called β-hydroxybutyrate (βHB), had less severe disease.
The additional βHB also prompted the gut bacterium Lactobacillus murinus to produce an indole lactic acid (ILA) metabolite. This blocked the activation of T helper 17 immune cells involved in MS and other autoimmune disorders.
“What was exciting was discovering that we could protect these mice from inflammatory diseases simply by putting them on a diet supplemented with these compounds,” said Peter Turnbaugh, PhD, of the Benioff Center for Microbiome Medicine.
Earlier, Turnbaugh had shown that when secreted by the gut, βHB counteracts immune activation. This prompted a postdoctoral scholar working in his lab, Margaret Alexander, PhD, to see if the compound could ease the symptoms of MS in mice.
In the new study, which appears Nov. 4 in Cell Reports, the team examined how the ketone body-rich diet affected mice unable to produce βHB in their intestines and found that their inflammation was more severe.
However, when the researchers supplemented their diets with βHB, the mice got better.
To find out how βHB affects the gut microbiome, the team isolated bacteria from the guts of three mice fed either the keto diet, a high-fat diet, or the βHB supplemented high-fat diet.
Then, they screened the metabolic products of each group’s distinct microbes in an immune assay and determined that the diet’s positive effects were coming from a member of the Lactobacillus genus: L. murinus.
Two other techniques, genome sequencing and mass spectrometry, confirmed that the L. murinus they found produced indole lactic acid, which is known to affect the immune system.
Finally, the researchers treated the MS mice with either ILA or L. murinus, improving their symptoms.
Turnbaugh cautioned that the supplement approach still needs to be tested in people with autoimmune disorders.
“The big question now is how much of this will translate into actual patients,” he said. “But I think these results provide hope for the development of a more tolerable alternative to helping those people than asking them to stick to a challenging restrictive diet.”
Recent research published in the journal *Glia* has uncovered important connections between dietary choices and the progression of multiple sclerosis (MS). The study, led by Patrizia Casaccia, the founding director of the Advanced Science Research Center at the CUNY Graduate Center’s Neuroscience Initiative and an Einstein Professor of Biology and Biochemistry at the same institution, investigated the role of enzymes known as ceramide synthase 5 and 6. These enzymes are linked to the harmful effects of a diet high in palm oil on neurons in the central nervous system, which may lead to an increase in the severity of MS symptoms.
Multiple sclerosis (MS) is an inflammatory autoimmune disease characterized by significant damage to the myelin sheath, which protects nerves throughout the body. Current treatments aim to control the immune system’s response, but the exact mechanisms leading to neurodegeneration in MS are still not well understood. Previous research from the Casaccia lab and others has indicated that a high-fat diet can exacerbate the severity of MS symptoms. In their study, researchers investigated potential mechanisms by which a diet high in palm oil may negatively affect neuronal health.
Neuroprotection From Palm Oil-Induced Toxicity
In the experimental autoimmune encephalomyelitis (EAE) model of inflammatory demyelination, researchers discovered that mice with diets high in palm oil had a more severe disease course.
“We hypothesized that within neuronal cells, palm oil is transformed into a toxic substance known as C16 ceramide by specific enzymes called CerS5 and CerS6,” explained principal investigator Casaccia. “This ceramide causes damage to mitochondria, depriving neurons of the energy they require to combat inflammation in the brain. Consequently, we investigated whether inactivating these enzymes could provide neuroprotection.”
The researchers found that genetically deleting the enzymes CerS6 and CerS5 in neurons could prevent neurodegeneration in an experimental model of MS.
“This was true even when mice were given a diet high in palmitic acid,” said Damien Marechal, a research associate with the Casaccia Lab and co-first author of the paper. “This new information highlights a specific metabolic pathway that shows how dietary fats can exacerbate MS symptoms.”
Significance for MS Patients and Clinicians
The paper’s findings have significant implications for individuals diagnosed with MS, clinicians treating patients, and neuroscientists researching the disease. The work reinforces that lifestyle choices, such as diet, can profoundly impact the course of the disease. The study’s results build on previous concepts about careful dietary decisions in managing the symptoms of MS. The findings also identify potential molecules that could help slow diet-induced symptom severity.
“Our research provides a molecular explanation for how to protect neurons from the palm-oil-dependent creation of molecules that harm them,” said Casaccia. “We hope this information can empower patients to make informed dietary decisions that could positively impact the course of the disease while identifying strategies to counteract the effect of cerS5 and cerS6 in a neuron-specific fashion.”
The costs that individuals pay out-of-pocket for branded medications to treat neurological diseases such as multiple sclerosis (MS), Alzheimer’s disease, and Parkinson’s disease continue to rise, particularly for MS drugs. According to a study published in the online issue of Neurology®, the medical journal of the American Academy of Neurology, on October 30, 2024, the average out-of-pocket expenses for MS medications increased by 217% over a nine-year period.
Costs have dropped for medications where generic versions have been introduced.
“In some instances, the out-of-pocket costs for patients have risen significantly more than the total cost of the drug itself, indicating that patients are bearing an unfair share of these cost increases,” said Amanda V. Gusovsky, MPH, PhD, from The Ohio State University in Columbus. “In other cases, when generic drugs were introduced and overall costs decreased, the out-of-pocket expenses for patients did not fall, meaning they did not benefit from these reductions.”
For the study, researchers used a large private healthcare claims database to analyse the costs of medications for five common neurological diseases from 2012 to 2021. The study included 186,144 individuals with epilepsy, 169,127 with peripheral neuropathy, 60,861 with Alzheimer’s disease or other forms of dementia, 54,676 with multiple sclerosis (MS), and 45,909 with Parkinson’s disease.
MS drugs had the largest cost increase, with the average out-of-pocket drug cost increasing from $750 per year in 2012 to $2,378 per year in 2021. All MS drugs had increasing out-of-pocket costs.
“MS medications costs remain exceptionally high and pose a substantial financial burden to people with this devastating disease,” Gusovsky said. “It’s imperative that we develop policy solutions such as caps on costs, value-based pricing and encouraging production of generic drugs to address this issue.”
The study found that the cost of several drugs for these diseases decreased by 48% to 80% in the years after introducing a generic version.
Gusovsky said both neurologists and patients should consider using generic or biosimilar drugs where available to control costs. She noted that previous studies have shown that high costs can create burdens such as medical debt, skipping food or other essentials, or not taking drugs as often as prescribed, which can possibly lead to complications and higher costs later.