Fat: Friend or Foe for Multiple Sclerosis Patients?

For the person with multiple sclerosis (MS) knowing which foods are best and which should be avoided can be confusing.

The best answers come from studies that combine all the reported randomized controlled diet studies with MS patients that had fatigue or quality of life as an outcome. The consistent finding is that adopting certain diets lead to reduced fatigue and improved quality of life ^[1-3] and that eating more added sugars and highly processed foods lead to worse mental health outcomes ^[4]. Dr. Linda Snetselaar conducted a network meta-analysis of 12 diet studies in people with MS, comparing 8 diets with 608 total study participants.

The 8 diets were low-fat, Paleolithic, Mediterranean, ketogenic, intermittent fasting, anti-inflammatory, calorie restriction, and control or usual diet ^[2]. A network meta-analysis allows researchers to rank the effectiveness of the various interventions for improving the outcomes, in this case fatigue and quality of life.

If the mean improvement and the 95% confidence intervals were entirely on the side of benefit, the diet was considered effective. Dr. Snetselaar found three diets to be effective for reducing fatigue: Paleolithic, Mediterranean and low-fat, with Paleolithic being approximately 40% more effective than either Mediterranean or low-fat diet. For improving quality of life, two diets were effective: Paleolithic and Mediterranean. Notably, Paleolithic was twice as effective as Mediterranean. Although the standardized mean improvement for fatigue and quality of life favored the ketogenic diet, the 95% confidence interval for the ketogenic diet crossed over the midline slightly for both fatigue and quality of life. Thus, the ketogenic diet was not found to be as effective at reducing fatigue or improving quality of life. It is possible that larger ketogenic diet studies would allow the 95% confidence interval to be entirely on the side that favors the diet. I am conducting a ketogenic diet study in the setting of relapsing-remitting MS to test if adopting a ketogenic diet leads to improved quality of life. I will have more about that study later in this blog.

Scientists are now studying the impact of ketogenic diets in the setting of MS.

These diets are high-fat, moderate protein, low carbohydrate diets. The mitochondria normally use glucose to generate adenosine triphosphate (ATP). ATP is what the cells in the brain and body use to power the biochemistry of life. It is the currency of biology. Not enough ATP leads to severe fatigue, low mood, and declining quality of life. There is evidence that people with brain-related and or mood-related symptoms have less efficient mitochondria and are less effective at using glucose in the brain. However, the brain can still use fat or ketone bodies to power the mitochondria. This is one of the reasons some scientists believe ketogenic diets may be particularly helpful for people with neurologic or psychiatric symptoms. There is growing evidence that people with psychiatric disorders and neurologic disorders do not utilize glucose in the brain as effectively as people who do not have a psychiatric or neurologic disorder ^[5-9].

The ketogenic diet has been studied in animal models of MS, demonstrating that adopting a ketogenic diet reduces the severity of symptoms and/or leads to an improvement in function ^{[10, 11]}. A single-arm study using a modified Atkins diet that was low in carbohydrates and high in fat in the setting of relapsing-remitting MS was conducted ^[12].

The intervention lasted 6 months and 65 people completed all study visits.

• People could sustain diet as 83% were consistently in ketosis throughout the study period.
• Notably, there was a nearly 50% reduction in fatigue severity and Beck depression index scores (measures of fatigue and depression) at the end of 6 months compared to the baseline visit.
• In addition, there were significant improvements in walking endurance as measured by how far one can walk in 6 minutes and in hand function measured by moving small pegs by hand.

As exciting as these findings are, it was a single-arm study. That means that there was no comparison group. The strongest evidence for whether an intervention is helpful or harmful comes from doing randomized controlled studies. There are only a handful of small, randomized controlled ketogenic diet studies in the setting of MS that were included in a network meta-analysis of diet studies.^[2] The ketogenic diet was not able to show that the 95% confidence interval for the reduction in fatigue or improvement in quality of life was entirely on the side of the ketogenic diet. The 95% confidence interval crossed slightly over to favor the control diet. We need larger and longer studies to show that ketogenic diets can lead to reduced fatigue and improved quality of life in people with MS. I am doing just such a study. I’ll tell you how to sign up below.

I have been conducting clinical research testing the effects of diet in people with MS since 2010. Our studies have included the modified Paleolithic diet, ketogenic diet, and the low saturated fat diet ^[13-19]. We have consistently observed that following one of these diets leads to reductions in fatigue ^{[13, 14, 18-20]}, anxiety ^{[16, 21]}, depression ^{[16, 21]}, and improved quality of life ^{[13, 14, 16, 18, 19]}. We are recruiting people for a new study: Efficacy of Diet on Quality of Life in Multiple Sclerosis. In this study, we help people improve their nutrition to investigate the impact of diet on fatigue and quality of life. We’d love to include you in this study!

What diet to follow if you have MS

More research about the ketogenic diet is needed before it can be recommended as an effective diet for addressing fatigue or improving quality of life. The current research shows that the best diets for reducing fatigue and improving quality of life are the Mediterranean and Paleolithic diets:

Mediterranean

• Encourages more vegetables and fruits, whole grains, legumes, fish, nuts, and seeds
• Reduces or eliminates added sugars, processed foods, fast foods, white breads, and white rice.

Modified Paleolithic

• Encourages more vegetables (target is 6 to 9 servings), 6 to 12 ounces of meat or fish, fermented foods, nuts, and seeds.
• Excludes gluten containing grains, dairy, and eggs.
• Reduces or eliminates added sugars, processed foods, fast foods, and grains.

Next steps for improving your diet

I encourage my patients to make diet changes as a family. Decide as a family which foods you will emphasize and which food items you wish to reduce or eliminate. Consider taking a cooking class to acquire more cooking skills. It is not easy to stop eating sugar or processed foods.

Participate in a ketogenic and Paleolithic diet study

We are currently conducting a two-year study comparing the modified Paleolithic elimination diet and the time-restricted ketogenic diet to usual diet (control) (NCT05007483). We are looking for people with relapsing-remitting MS between ages 18 and 70 who live in the United Stated, Canada, or Mexico. Learn more about the study here. People must be willing to be randomized to one of three diets: the modified Paleolithic, also known as the Wahls™ diet, the time-restricted olive oil ketogenic diet, or usual diet. People in the usual diet arm will get education on how to improve their diet, but they can elect to continue to eat their usual foods. Screen to see if you are eligible for the study here.

Participate in other studies

Even if you do not qualify for this study, we encourage you become part of our participant registry. If you have optic neuritis, radiologically isolated syndrome, clinically isolated syndrome or MS (both relapsing-remitting and progressive MS), I encourage to complete this short survey and become part of our registry so we can inform you about future studies. We periodically conduct survey-only studies that recruit people from anywhere in the world.

I tell my students and postdoctoral research scholars that changing the standard of care takes 30 years. I am 15 years into this journey. It is my goal to have it become the standard of care that everyone who has MS is told that diet matters and is encouraged to improve their diet to both improve their lives today and better manage their disease course. For that to happen we need more published, peer-reviewed scientific studies. I am doing that research. I need people like you to come to Iowa and be part of our clinical trials! Let’s change the world together! Join our research registry today by completing short survey.

Citations

1. Parks, N.E., et al., Dietary interventions for multiple sclerosis-related outcomes. Cochrane Database Syst Rev, 2020. 5(5): p. CD004192.

2. Snetselaar, L.G., et al., Efficacy of Diet on Fatigue and Quality of Life in Multiple Sclerosis: A Systematic Review and Network Meta-analysis of Randomized Trials. Neurology, 2023. 100(4): p. e357-e366.

3. Zielinska, M. and I. Michonska, Effectiveness of various diet patterns among patients with multiple sclerosis. Postep Psychiatr Neurol, 2023. 32(1): p. 49-58.

4. Lane, M.M., et al., Ultra-Processed Food Consumption and Mental Health: A Systematic Review and Meta-Analysis of Observational Studies. Nutrients, 2022. 14(13).

5. Jiang, Z., et al., Effects of Ketogenic Diet on Neuroinflammation in Neurodegenerative Diseases. Aging Dis, 2022. 13(4): p. 1146-1165.

6. Kurowska, A., et al., The Role of Diet as a Modulator of the Inflammatory Process in the Neurological Diseases. Nutrients, 2023. 15(6).

7. Bostock, E.C., K.C. Kirkby, and B.V. Taylor, The Current Status of the Ketogenic Diet in Psychiatry. Front Psychiatry, 2017. 8: p. 43.

8. Norwitz, N.G., S. Sethi, and C.M. Palmer, Ketogenic diet as a metabolic treatment for mental illness. Curr Opin Endocrinol Diabetes Obes, 2020. 27(5): p. 269-274.

9. Dietch, D.M., et al., Efficacy of low carbohydrate and ketogenic diets in treating mood and anxiety disorders: systematic review and implications for clinical practice. BJPsych Open, 2023. 9(3): p. e70.

10. Lin, W.S., et al., Role of Ketogenic Diets in Multiple Sclerosis and Related Animal Models: An Updated Review. Adv Nutr, 2022. 13(5): p. 2002-2014.

11. Sun, W., et al., Ketogenic diet attenuates neuroinflammation and induces conversion of M1 microglia to M2 in an EAE model of multiple sclerosis by regulating the NF-kappaB/NLRP3 pathway and inhibiting HDAC3 and P2X7R activation. Food Funct, 2023. 14(15): p. 7247-7269.

12. Brenton, J.N., et al., Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits. J Neurol Neurosurg Psychiatry, 2022. 93(6): p. 637-644.

13. Bisht, B., et al., A multimodal intervention for patients with secondary progressive multiple sclerosis: feasibility and effect on fatigue. J Altern Complement Med, 2014. 20(5): p. 347-55.

14. Bisht, B., et al., Multimodal intervention improves fatigue and quality of life in subjects with progressive multiple sclerosis: a pilot study. Degener Neurol Neuromuscul Dis, 2015. 5: p. 19-35.