The strongest evidence that an intervention is helpful (or harmful) is when multiple studies are combined and analyzed together. This type of analysis is called a meta-analysis. A network meta-analysis combines all known studies and compares them to identify which treatments are the most effective.
In January 2023, there was an editorial in Neurology, the most widely read journal by neuroscientists and practicing neurologists, stating there is now evidence that diet can reduce fatigue and improve the quality of life for people with MS. This is huge.
In this editorial, Efficacy of Diet on Fatigue and Quality of Life in Multiple Sclerosis: A Systemic Review and Network Meta-analysis of Randomized Trials1, Linda Snetselaar, Ph.D. and her team at the University of Iowa 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.
The study team found published papers of 12 dietary intervention studies and eight diets. The diets studied included Mediterranean, Paleolithic, ketogenic, anti-inflammatory, low-fat, fasting, calorie restriction, and control diet (the participant’s usual diet). A total of 608 participants were enrolled in these 12 studies.
The standardized mean difference (SMD) was calculated for improvements in the measures of fatigue, mental health quality of life, and physical health quality of life for the intervention diet and the control diet.
In analyses like this, the 95% confidence interval (CI) is calculated for the intervention diet and the control diet. If the improvements and the 95% CI are entirely on the side of the intervention, then scientists can safely state the intervention is effective for reducing fatigue or improving quality of life.
When comparing each dietary intervention to control diet, three diets had confidence intervals that were entirely on the side of reducing fatigue. (The other five diets were not significantly better than the control diet.) The magnitude of change for reducing fatigue severity in descending order, was Paleolithic2 (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).
We should not be surprised the largest effect size was with the Paleolithic diet. The three most common food antigens that cause excessive activation of the immune system (gluten, casein, and egg albumin) are removed in the modified Paleolithic diet.
So, why does diet seem to make a difference? From animal models of MS, we know that the bacteria, yeasts, and viruses that live in the microbiome influence how reactive the immune cells are in the brain and in the bloodstream. I expect the foods we eat help determine the makeup of our microbiome, which in turn influences how reactive our immune system is.
In addition, in animal models of MS, diet changes gene expression. So the foods we eat likely change our gene expression too. The more added sugars and highly processed foods we consume, the more likely we are to have a microbiome that drives up inflammation. And the more likely we are to have genes expressed that worsen inflammation.