By Ulrike W. Kaunzner, MD
Assistant Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: This study evaluated the use of dietary conjugated linoleic acid (CLA) supplementation to modulate the disease outcome in a spontaneous mouse model of central nervous system autoimmunity and also studied patients with relapsing-remitting multiple sclerosis receiving CLA supplementation. CLA may act as a modulator of the gut-brain axis by targeting immune cells in the gut, with a subsequent effect in the brain.
SOURCE: Fleck AK, Hucke S, Teipel F, et al. Dietary conjugated linoleic acid links reduced intestinal inflammation to amelioration of CNS autoimmunity. Brain 2021;144:1152-1166.
The etiology of multiple sclerosis (MS), a chronic inflammatory and demyelinating disorder of the central nervous system (CNS), is largely unknown, and a combination of genetic and environmental factors is thought to play a role. As more focus is put on the gut-brain axis, several influences, such as the type of diet, microbiome composite, vitamin D status, or nutrients, such as fatty acids, are discussed. So far, only a few clinical studies have been conducted with
the aim to influence the diet or microbiome of MS patients. Study design, adherence to certain diets, and ethical aspects can make these types of studies difficult. Fleck et al designed a study supplementing conjugated linoleic acid (CLA) to assess the potential modification of the gut and immune cells in a spontaneous mouse model of MS, as well as in a pilot study in relapsing-remitting MS patients.
CLA is a naturally occurring fatty acid in the meat and dairy products of ruminants, which has a beneficial effect on inflammatory bowel disease when studied in animal models. This mechanism is thought to interact with the nuclear peroxisome proliferator-activated receptor (PPAR) family that can be found in various tissues, such as PPARα in kidney and gut tissue or PPARδ in brain and adipose tissue. The anti-inflammatory properties of CLA also can ameliorate certain immune pathways, such as the anti-inflammatory cytokine interleukin 10 (IL-10), which can be low in MS patients.
In their study, Fleck et al show that CLA-enriched chow has a strong protective effect in a spontaneous mouse model of CNS autoimmunity. A reduction of intestinal inflammation was noticed, as well as a shift within the intestinal myeloid cells accompanied by an attenuation of intestinal barrier dysfunction. Furthermore, the researchers noticed enhanced production of anti-inflammatory IL-10 as well as suppression of T-cell proliferation. This suggests a major local innate immune response, with a subsequent beneficial effect on CNS autoimmunity. In addition, a proof-of-concept study was conducted on first-line disease-modifying treatment in 15 MS patients, who received dietary CLA for six months. A down-regulation of pro-inflammatory cell subsets and an increase in anti-inflammatory subsets was seen in the study.
COMMENTARY
This is a very important publication, since CLA seems to have a regulating effect on the intestinal barrier function and a concomitant ameliorating effect on CNS autoimmunity. These effects were not influenced by changes in the microbiome, indicating that the CLA effects are beyond a pure effect on the composite of the microbiota and might be associated with changes of immune cells in the intestinal wall itself.
Given the positive objective findings in this study and the observed positive effect in other diseases (e.g., atherosclerosis and Crohn’s disease), a potential anti-inflammatory effect needs to be evaluated in a larger, randomized, placebo-controlled trial, examining levels of inflammation within MS patients, as well as investigating classical clinical and imaging endpoints. This potential study design also should investigate the confounding effect of disease-modifying treatments. Since this study focused on a small cohort of relapsing-remitting MS, and since the effect of CLA is thought to be the result of peripheral immune regulation, it also will be interesting to see if there is any effect in progressive MS patients, where inflammation is considered to be compartmentalized to the CNS itself.
The various pathways of communication between the gut and the brain immune system, altered by CLA, also will need further investigation to identify a potential target for better intervention. Moreover, the correct dosing of CLA and potential long-term side effects need to be established, since, as the authors pointed out, increased liver enzymes, triglycerides, and steatosis have been observed in other trials.
In conclusion, this is an important study, since dietary supplements, nutrients, or special diets are a frequent topic in the management of patients with MS. This study will widen the scope of discussion on the treatment of neurological disorders. Traditional medications can have a benefit on overall well-being and on the disease outcome. Nutritional supplements need to be discussed with caution until clear recommendations can be given based on clinical trials and other strong evidence of efficacy without significant side effects.
