Ketogenic Diet Safe, Feasible in MS

May 02, 2019

A ketogenic diet is safe, feasible, and well tolerated in subjects with relapsing multiple sclerosis (MS) and is associated with improved fatigue and depression while also promoting weight loss and reducing serologic proinflammatory adipokines, a new study suggests.  

"We wanted to study a ketogenic diet in MS, as it has been associated with anti-inflammatory and antioxidant effects — both of which may be of benefit in MS — and it has been linked to quality-of-life benefits such as improvements in fatigue, which is a major issue for MS patients," lead author J. Nicholas Brenton, MD, University of Virginia, Charlottesville, told Medscape Medical News.

Brenton noted that ketogenic diets are high-fat, low-carbohydrate diets that mimic a fasting state and promote more efficient use of energy. "The body uses fat rather than carbohydrates for energy and fat is a much more efficient energy source," he said. "The MS brain is undergoing attack and the death of nerve cells could be caused by an energy shortage."

The diet, which has been linked to reduced seizures, has been used for many years in the treatment of epilepsy.  

The current study was published online April 12 in Neurology Neuroimmunology & Neuroinflammation

The open label, uncontrolled study included 20 patients with relapsing MS who followed a ketogenic diet for 6 months with adherence monitored by daily urine ketone testing.

Fatigue and depression scores and fasting adipokines were obtained at baseline and after 6 months on the diet. Patients also underwent brain MRI before and after following the diet.

Results showed that 19 (95%) of the 20 patients adhered to the diet for 3 months and 15 (75%) adhered for 6 months.

The diet was associated with reductions in body mass index (BMI) and total fat mass (P < .0001), and fatigue (P = .002) and depression scores (P = .003) were improved. Serologic leptin was significantly lower at 3 months (P < .0001) and there was a nonsignificant trend for increasing serologic adiponectin levels on the diet.

Fasting insulin and hemoglobin A1c levels were significantly decreased at both 3 and 6 months on the diet. But lipid profiles showed a significant increase in LDL and cholesterol at 3 months, although this increase declined at 6 months and was no longer significant.

Although the study was not designed nor powered to evaluate the effect of diet on MS, no patient experienced worsening MS disease on the diet, and there was a significant decrease in Expanded Disability Status Scale scores at 6 months secondary to improved sensory and bowel/bladder symptoms.

"Our primary goal was to show that following the ketogenic diet for several months was safe and feasible for stable MS patients, and we have shown this," Brenton commented. "The diet does not seem to be detrimental for stable MS patients — it does not exacerbate the disease."

"A small study like this for just a few months is not going to show a benefit in terms of slowing disease in a stable MS population," he noted. "There were, however, some quality of life benefits. We saw a meaningful reduction in fatigue. Many MS patients complain of fatigue and the fatigue scores were quite high at baseline in our cohort and were significantly reduced with the ketogenic diet." 

The researchers also saw a reduction in depression scores, Brenton added. "The majority of our patients had mild levels of depression and the depression scores were reduced with the ketogenic diet."

A supplementary analysis showed that fatigue and depression were reduced more in patients who were compliant with the diet vs those who were not.  

"Fatigue and depression are very common in MS patients, so anything that reduces this will be very helpful. However, the reduction in fatigue and depression could have been due to the loss of weight in these patients," Brenton said.

A strength of the study, Brenton pointed out, was the objective measurement of compliance. "Most diet studies rely on patient recall of their food intake, which can be unreliable, but we asked the patients to measure their urine ketone levels every day," he said. "They did this with strips marked with the day's date which they had to photograph and email to us every day, so we felt confident that the adherence measures were correct."

The criteria for compliance required patients to have detectable levels of ketones in the urine on 85% of the days.

"Although we had a small sample size, we achieved an adherence of 75% at 6 months, which is relatively good for a ketogenic diet study," Brenton noted. 

Brenton believes the daily urine testing was helpful in maintaining compliance with the diet. "Patients liked having a goal of detecting ketones every day. They were excited when they achieved higher values — this acted as a marker for how well they were eating."

He cautioned that many of the patients were overweight or obese and for some of them their primary objective was to lose weight — which they did, with BMI reduced by 3 points on average. This could have led to the improvement in fatigue and depression.

"This was a highly motivated population. There was a real interest in enrolling in the study. We recruited very quickly and we had to turn away many patients," Brenton reported.

His team is now conducting a larger-scale study of the ketogenic diet in about 60 MS patients. That larger study will investigate whether the diet affects immune cells and the gut microbiome, which is believed to interact with the immune system in MS.

Needs Medical Supervision

Although this study suggests ketogenic diet is safe for a few months in MS patients, and it represents an intriguing new approach, Brenton warns against MS patients trying the diet without medical supervision.

"Our patients were closely monitored by a dietitian. I would recommend that if patients wanted to follow this diet they should have their family doctor involved," he said.

"This diet raises LDL cholesterol levels and so may not be appropriate for patients with cardiovascular disease," he cautioned. "A professional should be intermittently following pertinent lab values. We excluded patients at high risk of heart disease from this study. Another side effect can be kidney stones — particularly at risk are those patients who have suffered from kidney stones prior to the diet."

However, Brenton said a less restrictive, low carbohydrate diet does make sense for many people. "One benefit of this study is that we trained our patients to restrict carbohydrates, look at labels, and calculate carbohydrate content of foods. And even those who didn't stay on the ketogenic diet cut down their carbohydrate intake quite substantially. Most of us eat far too much carbohydrate."

"Right now, my advice to patients is follow a well-balanced, healthy diet, which often involves reducing baseline carbohydrate intake," he added.

A ketogenic diet is not going to be the one diet that is right for everyone, Brenton concluded.

"There are many different diets being researched in MS," he noted. "With diet studies for MS, as with and other conditions, it is probably going to be a case of identifying specific diets for specific patients."  

This study was funded through private foundational funding provided by the ziMS Foundation. Brenton has served as a consultant for Novartis.

Neurol Neuroimmunol Neuroinflamm. Published online April 12, 2019. Full text

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