Multiple sclerosis (MS) is a chronic immune, inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS), characterized by demyelination that damages nerve fibers and myelin sheaths, affecting the brain, spinal cord and the optic nerves.1 The global average prevalence of MS is 33 out of 100,000 people, and it is increasing in both developed and developing countries.2 The prevalence of MS varies widely in different countries, Europe and North America have the highest prevalence (108 and 140 per 100,000 people, respectively), while Asia and sub-Saharan Africa have the lowest prevalence (2.1 and 2.2 per 100,000 population, respectively).3 MS appears mainly after the age of 30,4 and its prevalence is high in women (approximately a 3:1 ratio).5 The cause of MS is unknown, but it is believed to be the result of a complex interaction between genetic predisposition and environmental exposure,6 environmental influences modify the risk and progression of the disease, possibly through epigenetic changes that could positively or negatively regulate the immune response and influence neuronal development.3,7 Environmental factors mainly include smoking, low vitamin D due to inadequate exposure to sunlight, Epstein–Barr virus infection, and a variety of dietary factors.6,8 There is currently no curative treatment for MS, but disease-modifying therapy can stabilize its progression in the early flare phase and possibly delay the transition to a secondarily progressive phase of the disease.9

Nutrition is considered a possible influencing factor in the pathogenesis of MS. Nutritional intervention studies have shown that diet can be regarded as an adjuvant treatment to control disease progression and has the potential to reduce MS-related symptoms.10 A healthy diet, providing adequate amounts of essential nutrients and limiting saturated fat intake, can improve the course of MS,11 which is consistent with a study by Fitzgerald, which suggested that high-quality diets that emphasize the intake of fruits, vegetables, legumes, and whole grains, and low intakes of sugar and red meat are associated with lower levels of disability and fatigue in people with MS.12 The justification for the dietary intervention is based on the effect of these dietary factors in the control of the inflammation process and oxidative stress.13 The process of controlling inflammation is carried out through epigenetic changes in gene expression and changes in the composition of the intestinal microbiome.6 Diet can directly affect the gut microbiota by providing substrates to support the growth of members of the gut community, and it can also directly affect the gut microbiota by inhibiting the growth of gut community germs.14 In addition, diet can indirectly affect intestinal flora by affecting host immunity, intestinal barrier function, and the production of host-derived by-products.14

Currently, many researchers attempt to treat MS through special diets, including the Swank low saturated fat, McDougall low fat plant-based diets, Mediterranean diet, fasting/energy restriction ketogenic diet, and modified Paleolithic diet.6 Since there is currently no consensus on following eating habits to improve the course and/or symptoms of the disease, there is insufficient evidence to recommend a specific diet for MS patients. Different countries have different customs and are in different climates, so the food products are different, which leads to differences in the final food culture. Therefore, we have carried out this questionnaire to evaluate the daily eating habits of MS patients in three different countries: China, Spain, and Cuba, and explore a healthier diet for them. Furthermore, we evaluated whether different diets are risk factors for relapse in patients with MS.

MS is a chronic disease of the central nervous system with inflammatory and neurodegenerative components, most patients initially present a remitting–recurrent course. MS is believed to be the result of a combination of genetic predisposition and environmental influences. Diet is an important source of environmental interaction, and dietary metabolites exert far-reaching systemic effects, making diet an attractive candidate as a potential environmental mediator in MS.15 Diets cannot replace conventional treatment in MS patients, but a healthy nutritional intervention is well accepted and can improve their physical and inflammatory condition.10 A study on this topic revealed that increased fruit and vegetable intake is associated with lower levels of disease activity and disability reported by MS patients.16 Another prospective pediatric MS study points to an increased risk of relapse associated with higher intake of saturated fat, and also noted that as vegetable intake increases, the relapse rate decreases.17 Furthermore, it has been found that patients perceive how the severity of the daily manifestations of their disease symptoms is directly related to the excessive consumption of meat, fatty foods, and processed sugars.9 However, and despite the importance of diet for the disease, eating habits in patients with MS have not been studied in depth so far. With this in mind, the purpose of this study is to compare the daily eating habits of MS patients in three different countries (China, Spain, and Cuba) and to explore healthier diets for them, and to assess the risk factors for relapse of MS patients.

Our study found that in the three countries of China, Spain, and Cuba, MS patients are the most common in women, the incidence rate from women to men is 2-3:1, which usually occurs between 25 and 59 years, which coincides with the epidemiological characteristics of MS.18 Recurrent–remitting type is the most common type of MS in the three different countries, including 70-80% of MS patients have experienced relapse of the disease to varying degrees during the course of their disease. Most MS patients in China and Cuba have a mixed diet, while MS patients in Spain (most are Andalusian) have a typical Mediterranean diet. Mediterranean diets are low in saturated fat, high in polyunsaturated and monounsaturated fats (especially fish and olive oil), high in fruits, vegetables, nuts, and low in processed foods, which implies a low salt content. The Mediterranean diet is proposed to influence inflammation through increased consumption of antioxidants, including polyphenols.19 A recent study showed that adherence to the Mediterranean diet was associated with a reduction in the risk of MS.20 Another study randomly divided women with MS into a Mediterranean diet or a control diet for six months, the result showed that the Expanded Disability Status Scale (EDSS) was reduced and fatigue improved.21 Through logistic regression analysis, we found that the type of diet is an important risk factor for relapse of MS (p = 0.003, OR = 2.628, 95% CI: 1.393-4.968), the risk of relapse of MS by mixed diet is 2.6 times greater than that of the Mediterranean diet; Furthermore, other variables are not risk factors for relapse, such as age, sex, BMI, MS classification, time since MS diagnosis, coffee, and low-salt diet.

Well-designed studies have shown the benefits of the Mediterranean diet in preventing cardiovascular disease. In the 10-year follow-up of a cohort of almost 33,000 women in Sweden, a self-administered questionnaire recorded the food composition of the Mediterranean diet.22 The results showed that among these people who adhere to the Mediterranean diet, the incidence of myocardial infarction, acute ischemic stroke, and heart failure have been reduced.22 Both the American Heart Association and the American Stroke Association recommend a Mediterranean diet to prevent strokes.23 In addition, some studies have also shown that the Mediterranean diet is related to Alzheimer's disease or mild cognitive impairment, such as the degree of longitudinal cognitive impairment.24 The Mediterranean diet is considered a healthy diet, but there is very little work on the Mediterranean diet in MS. In this study we show that the Mediterranean diet can reduce relapse in MS patients, but large-scale multicenter studies are still needed to verify our findings in the future.

To our knowledge, this study is the first study to compare the daily eating habits of MS patients in three different countries and assesses the relationship between the Mediterranean diet and relapse of MS disease. However, we also admit that our study has its limitations, among them that the number of patients is small and the study population is limited to China, Spain, and Cuba. These patients come from different patients from different health systems, and the treatment standards they receive are not uniform. Second, the research is based on Internet questionnaires, which have their own shortcomings. Third, we have not yet considered the impact of disease-modifying treatments on results. Also, there is no healthy control group in this study and selection bias may exist. In the future, research should be conducted to cover patients from other countries, so that the MS eating habits of different ethnic and regional groups can be compared and analyzed.

Diets cannot replace conventional treatment in MS patients, but a healthy nutritional intervention can be beneficial. There are few studies on the eating habits of MS patients in different countries and their effects on the disease. Our study found that the daily diet of MS patients in China and Cuba is based on mixed diet, while MS patients in Spain are based on Mediterranean diet. Our research shows that the Mediterranean diet can reduce the risk of flare-ups in MS patients. In the future, more large-scale, multicenter studies are still needed to verify our findings in the future.

Wen-Ting Zhang and Guo-Xun Zhang conceived and designed the study. Wen-Ting Zhang and Guo-Xun Zhang are responsible for data collection, analysis, and writing of the manuscript. Run-Ze Zhao, Shuai-Shuai Gao help in data collection. Gang Zhao provides advice on the manuscript. Guillermo Izquierdo is responsible for the conceptualization and revision of the manuscript. All authors read and approved the manuscript.