Multiple Sclerosis Diet Research: Past, present and the future with Dr. Terry Wahls
The world is changing. Neurology and MS care are changing. It’s been a long journey to this point, and not an easy one. Let me tell you how we got here.
New ideas never take hold easily. When I began speaking about diet and MS 15 years ago, many scientists and physicians condemned me. I tell my students and post-doctoral fellows that it typically takes 30 years to change the standard of clinical care. I am halfway there.
In that time, I have gone from being banned as a speaker, my ideas perceived as dangerous, to being recognized as a leading dietary intervention researcher in the setting of multiple sclerosis (MS). I am not so crazy anymore.
More neurologists agree with me that diet matters. It is much less hard these days to get our papers accepted by top tier scientific journals. A very exciting thing recently happened at the journal Neurology, one of the highest impact journals covering MS clinical care and research. They published an editorial stating that there is sufficient evidence that diet matters a great deal for people with MS. I have been saying this for years and am heartened that one of the leading journals finally agrees with me.
For me, this is personal. After experiencing my own personal healing journey, I felt morally compelled to share my story and give hope to others with severe disability caused by chronic health problem(s).
But new ideas like mine are usually met enormous resistance and I was no exception. I was labeled as dangerous, accused of faking MS. Some claimed I sat in wheelchair for 4 years while at work but worked out at home every day, which is why I was able to recover. Others said the MS specialists who treated me must have been incompetent, misdiagnosing my disease.
I gave lots of interviews. Mostly people wanted to introduce their audience to my story of healing and thoughts on what is possible for people with complex chronic disease. Sometimes the interviews were quite hostile. When that happened, I reminded the host I was simply sharing my experience, theories, and the research I believed needed to happen.
In 2010, I published my first book Minding Your Mitochondria. In 2009 and 20101,2 , I published care reports and case studies of people with multiple sclerosis who experienced significant improvement in function using diet, exercise, and electrical stimulation of muscles as part of their MS treatments. Our first clinical trial (NCT01381354) tested the same interventions I had used in my clinical recovery in others with progressive multiple sclerosis. It took us several tries, but in 2014, we published our first paper on the study results, which showed that people with progressive MS could implement my program and experience remarkable reductions in fatigue and improvement in quality of life.3
I gave talks wherever I was invited, including a TEDx talk I gave in 2011 that would eventually be seen by nearly 4 million people.
My next book, The Wahls Protocol®, was published in 2014. The National MS Society (NMSS) monitors social media to know what their constituents are saying about MS treatments. After my book came out, there was a sudden and dramatic uptick in the conversation about diet, exercise, and the Wahls Protocol® that exceeded the mentions about all the disease-modifying drug treatments combined.4 The NMSS then decided to have a Wellness Conference, inviting researchers, patient advocates, and me. At that conference I saw the dramatic graphs depicting the social media mentions,4 explaining why the NMSS held the conference, and why I was there. NMSS made Wellness Research a priority for 2015. I helped them find researchers who conducted dietary intervention studies, which are very different from drug development studies.
In 2016, the NMSS society began funding pilot Dietary Intervention studies. I submitted a research proposal to conduct a study comparing the effect of the Swank and Wahls diets on fatigue and quality of life. Our project was funded by the National Multiple Sclerosis Society, allowing us to launch our 4th clinical trial. The results demonstrated that adopting both the Swank and Wahls diets was associated with significant reductions in fatigue and improvements in quality of life. We have 3 more studies whose data we are analyzing and will present at the spring meeting of the Consortium of MS Centers.
We now have several meta-analyses of these dietary intervention studies.
A meta-analysis, which combines several studies, provides the strongest evidence that an intervention is helpful (or harmful). A network meta-analysis combines the studies and compares them to identify which treatments are the most effective. To be included in a meta-analysis, a study must be randomized and conducted on humans with MS.
Meta-analyses drive change in the standard of care, but they take time. Most studies take 3 to 5 years to complete, and a meta-analysis needs multiple studies that show the benefit of the intervention, which is why it takes 20 to 30 years for practice patterns to change. Research is an endurance sport. You must be in it for the long haul.
The first meta-analysis examined the role of fish in the diet5 and included six studies. The analysis found that including fish in the diet decreased the odds ratio or risk of developing MS (P=0.004). Having at least ½ serving of fish per day during adolescence may reduce the risk of developing MS later in life. According to the analysis, the consumption of fish decreases the risk of MS [OR (95% CIs): 0.77 (0.64, 0.92); p-value = 0.004; I2 = 54.7%] compared with controls. Eating at least a half serving of fish per week during adolescence and as an adult may reduce the risk MS.
The next paper was a meta-analysis of the health benefits of green leafy vegetables and multiple health outcomes6. They found 24 meta-analyses and 29 health outcomes to include in the review. Researchers found that per 100 grams/day of green leafy vegetables was associated with 25% decreased risk of cancer, heart disease, stroke, all cause death, macular degeneration, metabolic syndrome, and ALS. Green leafy vegetables are rich sources of vitamin K, lutein, zeaxanthin and other carotenoids that protect the retina from the harmful effects of ultraviolet light and are associated with lower risk of cognitive decline.
The next paper was a meta-analysis of dietary intervention studies in the setting of MS.7 They found 8 studies with 515 patients. They combined all dietary interventions into one intervention labeled “diet.” Five studies analyzed the effect on disability as measured by the expanded disability status scale (EDSS), 3 examined fatigue severity as measured by the modified fatigue impact scale (MFIS), and 2 examined quality of life (QoL). They found evidence of a trend in reduction in fatigue (308 patients). The difference between the means of the control group and diet intervention group was -2,033, 95%-IC (-3,195, -0,152), a p-value of 0.0341)-. There was an increase in QoL (77 patients studied), but no significant effect on EDSS (337 patients studied) and no severe adverse events. The authors concluded that diet improvement is beneficial and should be recommended based on the patient’s and family’s preferences, according to what they can adopt and sustain as a family. That is remarkably close to my message.
The last paper was published on January 24, 2023 in Neurology, the most widely read journal among practicing neurologists. Dr. Linda Snetselaar conducted a network meta-analysis of randomized dietary intervention studies in MS that lasted at least 12 weeks and had either fatigue or quality of life as an outcome.8 A network meta-analysis allows the researcher to compare the various interventions with each other through comparisons to control arms, which is how researchers can compare the efficacy of various drug treatments for MS. The study team found 12 dietary intervention studies and 8 dietary interventions. Dr. Snetselaar used the study team’s classification to assign studies to 8 different dietary interventions: Mediterranean, Paleolithic, ketogenic, anti-inflammatory, low-fat, fasting, calorie restriction, and control diet, which was the participant’s usual diet. A total of 608 participants were enrolled in the 12 studies. When comparing each dietary intervention to the control diet, three diets were associated with significant reduction in fatigue. The other 5 dietary patterns had smaller effect sizes that were not significantly better than the control diets. The magnitude of change for reducing fatigue severity in descending order was: Paleolithic (SMD: -1.27; 95% CI: -1.81, -0.74), low-fat diet (SMD: -0.90; 95% CI: -1.39, -0.42), and Mediterranean (SMD: -0.89; 95% CI: -1.15, -0.64). When comparing each diet to usual diet for improving quality of life, there were two diets associated with significant improvement in quality of life: Paleolithic (SMD: 1.01; 95% CI 0.40, 1.63) and Mediterranean (SMD: 0.47; 95% CI 0.08, 0.86).
I am not surprised that the diet with the largest effect size is the Paleolithic diet since that diet removes the three most common food antigens (gluten, casein, and egg albumin) that cause excessive activation of the immune system.
The Paleolithic Diet and Mediterranean diets have many common features: less added sugar, less ultra-processed foods, and more non-starchy vegetables. The authors acknowledge that the studies were small pilot studies of relatively brief duration (a year or less) and that larger, longer (ideally 2 years or longer) studies are needed to develop stronger evidence of the benefits of improving diet.
The same issue of Neurology included an editorial entitled The Role of Diet in Multiple Sclerosis: Food for Thought. The authors discussed the network meta-analysis and found that there is sufficient evidence to recommend a healthy diet as an adjunct to treating MS. They discussed the common features of the Paleolithic and Mediterranean diets and said that neurologists should talk to their MS patients about the importance of a healthy diet but not feel compelled to say there is one best diet for MS. Rather, they encourage neurologists to have their patients choose the most appealing diet based on their individual tastes, culture, and background. They also suggest neurologists consider referring patients to registered dietitians for guidance and support on diet improvement, referrals that would likely be covered by many health insurance plans. Finally, they called for more research that includes MRI findings and follows people for two years. I agree that larger, longer studies are needed.
We are currently conducting our 8th clinical trial, a two-year study comparing modified Paleolithic elimination diet and time-restricted ketogenic diet to usual diet control (NCT05007483). We are also recruiting participants for future trials as well as our MS disease registry. Complete the screening here to see if you are eligible to participate in our study, Efficacy of Diet on Quality of Life in Multiple Sclerosis. If you have optic neuritis, radiologically isolated syndrome, clinically isolated syndrome or multiple, I encourage you to complete this short survey and join our patient registry.
We have made so much progress. This year we are presenting our research at the Consortium of MS Centers’ annual meeting, the largest meeting of medical teams who care for MS patients and conduct research on MS. This year, for the first time, the meeting will include a full track on nutrition. My team is scheduled to give six presentations about nutrition and nutrition-related research. In addition, we have submitted four research abstracts about our current studies.
The world is changing. We will continue to do research and learn more about the impact of diet on disease states. And we will continue to tell our patients and the world what we already we know: that improving your diet improves your health.
The low fat, Paleolithic, and Mediterranean diets all encourage more vegetables and fruits, fiber, nuts, and seeds as well as a reduction in added sugars, fast food, and ultra-processed foods. For most people, these dietary choices result in better health. If you want to improve your health, consider adopting one of these diets. Keep in mind that the modified Paleo diet has the largest effect size for reducing fatigue and improving quality of life.
