Our study, involving 397 participants, provided a comprehensive analysis of the factors influencing the chance of MS. Notably, MS patients demonstrated a higher total body fat percentage and smoking prevalence, while the healthy group exhibited a higher fat-free mass. Despite similar macronutrient distributions across groups, MS patients had a significantly higher energy intake. Furthermore, our study found that MS patients had a lower DPI score but higher scores in the NEAP and PRAL. Our study also identified several factors that significantly influence the chance of developing MS, including sex, smoking habits, waist circumference, body fat percentage, fat-free mass percentage, and energy intake.
The findings reported in the current study align with previous investigations that have established a strong association between obesity and increased chance of MS. Several studies, as discussed in the review by Gianfrancesco and Barcellos [28], have consistently demonstrated a two-fold increased risk of developing MS in individuals with a BMI during adolescence and young adulthood. Specifically, the review highlighted findings from the Nurses’ Health Study [29], where women with a BMI ≥ 30 kg/m2 at age 18 had a 2.25-fold increased risk of MS compared to those with a normal BMI. Similar observations were reported in population-based studies from Sweden [30], Norway, and Italy [31], further corroborating the link between elevated BMI and MS susceptibility.
In line with these previous reports, the current study found that individuals with a larger waist circumference had a 5.9% higher likelihood of developing MS, and the chance of MS increased by 10.4% with a one percent increase in body fat percentage. Conversely, a higher lean body mass percentage was associated with a reduced chance of MS 22.9% per one percent increase. These findings support the protective role of a lower body fat composition and higher lean mass against MS development, potentially attributed to the significantly higher energy intake observed in MS patients in the current study.
There are several links between adipose tissue and the immune system [32]. MS is characterized by inflammation and demyelination accompanied by axonal transection. An investigation indicates that a genetically elevated BMI is associated with an increased likelihood of developing MS, providing evidence for the causal involvement of obesity in the etiology of MS [33]. Furthermore, being overweight can worsen the severity of MS symptoms, make them harder to manage, increase the frequency of relapses, and speed up the progression of MS toward escalating disability.
Our study indicated gender as a significant factor that affected the chance of MS, and male sex was associated with a 90.2% reduction in the chance of developing MS. According to recent studies, MS is more prevalent in females than males [34]. In this regard, Greer and McCombe [34] demonstrated that MS is more prevalent in females than males. They suggest that the increased prevalence of MS in females could be attributed to several factors, including intrinsic differences between the male and female immune systems, genetic and epigenetic factors, effects of gonadal hormones, and environmental exposures.
In line with Hedström’s study [35], our study revealed that smoking cigarettes increased the chance of MS by 210.1%. Cigarette smoking can cause oxidative stress and pro-inflammatory responses in lung tissue. Additionally, smoking can lead to posttranslational modifications of proteins in the lungs, which may affect their antigenicity and trigger autoimmunity against CNS antigens. So, the link between smoking and getting MS might be due to immune system responses against changed proteins that cross-react with antigens in the CNS [35].
In our study, we utilized DPI to measure dietary phytochemical content. We found that patients with MS had a lower DPI score than healthy participants. Our study showed that DPI was a protective factor that could be related to a reduced chance of MS. Phytochemicals and their derivatives can potentially protect the nervous system by regulating chronic inflammation, oxidative stress, and downstream signaling [15]. Studies have shown that phytochemicals can reduce mitochondrial dysfunction and inhibit the formation of α-synuclein accumulation-induced oxidative stress and inflammatory responses [16]. It is evident from various research studies that the Mediterranean Diet and Vegetarian Diet are dietary patterns characterized by a significant consumption of phytochemicals [36]. Several investigations have demonstrated that plant-based dietary patterns (whole grains, vegetables, legumes, nuts, and fruit) are highly adequate in augmenting the levels of phytochemicals in the bloodstream while concurrently diminishing the overall acid load of the diet [11, 12].
Although the NEAP and PRAL scores were significantly higher among MS patients compared to the healthy group, there was no relationship between NEAP and PRAL and MS incidence. This could be due to changes in dietary intake among MS patients after their disease diagnosis, which may include increased consumption of fruits and vegetables, reduced amounts of saturated fat and sugar, and increased intake of dietary supplements. This result is contradictory to the study by Saeedirad et al. [37] in which higher DAL, as indicated by higher NEAP or PRAL scores, was associated with increased odds of MS.
According to several studies, a dietary pattern that increases the dietary acid load while low in phytochemicals leads to increased excretion of calcium and magnesium and cortisol secretion, ultimately resulting in decreased citrate excretion. These physiological changes are believed to contribute to elevated blood pressure and insulin resistance [19, 20]. Several articles highlight that insulin resistance and metabolic syndrome are more prevalent among MS patients [38], and this may be caused by the activation of microglia and elevated proinflammatory cytokines, which are known to be elevated in people with MS [18].
Additionally, consuming more phytochemical-rich plant foods such as fruits, vegetables, legumes, whole grains, nuts, seeds, and olive oil and reducing consumption of foods high in animal protein may help lower the risk of developing multiple sclerosis (MS). Other potential dietary and lifestyle recommendations that may help reduce the risk of MS include avoiding smoking, adopting a plant-based dietary pattern like the Mediterranean diet, and achieving a healthy body weight and body composition through balanced energy intake and physical activity levels. Optimizing the consumption of phytochemicals and acid–base balance through these dietary and lifestyle alterations may act as an additional preventive strategy in addition to traditional MS treatment options, while further study on dietary interventions is still needed.
There are limitations requiring mention. The study results could be impacted by recall bias, confounding variables, and the challenge of establishing causal relationships. Misclassification of dietary components may occur due to recall bias. At the same time, confounding factors such as genetic predisposition or environmental factors may obscure the underlying link between these items and chance of MS. Selection bias due to the specific locations the controls and cases were recruited from might limit the generalizability of the findings to other populations or geographic areas. Furthermore, the limited external validity, as the study was conducted on a specific Iranian population, might not apply to other ethnic or demographic groups due to differences in dietary habits, genetic backgrounds, and environmental exposures. Hence, it is imperative to interpret the study’s findings in light of these potential biases and limitations. These limitations, however, underscore the need for further research in this area, building upon the foundation laid by this study.
