Nutrition facts in multiple sclerosis

Abstract

The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness.

Keywords: complementary alternative medicine; gut microbiota; inflammation; lifestyle; multiple sclerosis; nutrition.

Figure 1.

The two routes by which diet can influence our health: (A) the metabolism of our cells and (B) the population of our gut microbiota.

Figure 2.

A schematic and simplified representation of how natural dietary factors can direct cell metabolism toward oxidative metabolism (on the left), biosynthesis (on the right), and NF-kB-induced inflammation (at the bottom of the figure, in red) by their binding to nuclear receptors, transcription factors, and enzymes having transactivating properties. Intermediate receptors and response elements are not indicated. Note. The complete list of agonists (+) and antagonists (−), including some common drugs, of the enzymes, nuclear receptors, and transcription factors, is shown below: • AMPK: (+) calorie restriction, physical exercise, AMP, Ghrelin, alfa-lipoic acid, adiponectin, flavonoids, nonflavonoids, metformin, salicylate; (−) dysbiotic gut microbiota; leptin. • Sirtuins: (+) VDR-D, calorie restriction, alfa-lipoic acid, resveratrol, niacin, TRP, NAD⁺; (−) alcohol, cigarette smoke, nicotinamide. • PPARs alfa/gamma: (+), polyphenols, Sirtuins; coffee component hydroxyl hydroquinone (HHQ), thiazolidinediones, cannabinoid agonists, 15d PGJ2; ibuprofen, statins. • NF-kB: (+) Saturated and trans fatty acids, oncoproteins, ROS, TNF-α, IL-1 b, LPS, viral infections; (−) calorie restriction, polyphenols, n-3 PUFA, butyrate, Sirtuins. • LXRs: (+) n-6 PUFA, oxysterols; glucose; (−) n-3 PUFA. • SREBP-1c: (+) LXRs, gut dysbiosis, alcohol, insulin; (−) n-3 PUFA, metformin, Sirtuins, AMPK • SREBP-2: (−) LXRs, statins • ChREBP (+) glucose; (−) LXRs, statins. PPAR = peroxisome proliferator-activated receptor; LXR = liver X receptor; RXR = retinoid X-receptor; NF-kB = nuclear transcription factor-kB; SREBP = steroid regulatory element-binding protein; ChREBP = carbohydrate responsive element-binding protein; Sirtuins = SIRT-1/2, deacetylating enzymes; AMPK = AMP-activated protein kinase; n-3 PUFA = omega-3 polyunsaturated fatty acids.

Figure 3.

Portion of Figure 2 showing in detail the relationship between diet and inflammation, at the example of the proinflammatory transcription factor NF-kB. Note. The production of some proinflammatory molecules is also shown. MMP = metalloproteinase; VEGF = vascular endothelial growth factor; ROS = reactive oxygen species; ICAM-1 = intercellular adhesion molecule; VCAM-1 = vascular cell adhesion molecule.

Figure 4.

Summary of the relationship between dietary habits, lifestyle, and metabolic balance. The figure emphasizes how, as in a two-dish balance, the molecules that on one hand promote oxidative metabolism and on the other hand downregulate the biosynthetic pathways, including, in particular, the proinflammatory ones. Conversely, the figure shows how Western eating habits and lifestyle have the opposite effect and promote biosynthesis, including the production of proinflammatory molecules.

Figure 5.

The sequence of events representing the influence of low-fiber, hypercaloric, Western diets on the development of gut dysbiosis, intestinal and systemic inflammation, and the subsequent appearance of chronic inflammatory diseases. The figure shows the stages in which it is suggested to apply in sequence nutritional intervention, dietary supplements, and therapy.