Nature and nurture both probably influence the likelihood of developing MS and its clinical course.1,2
For instance, researchers have linked a multitude of genetic variants to MS but the number of MS cases is rising more rapidly than genetic drift can explain. Disease prevalence increased by around 2.4 per cent annually between 1990 and 2010 in the UK,3 leading to the conclusion that drivers of the increase are probably environmental. Indeed, studies associate a growing number of environmental risk factors with MS, including vitamin D, Epstein-Barr virus, cigarette smoking, obesity and the Western diet.1,2
The emerging link between MS and the Western lifestyle could partly account for reports that co-morbidities are “more common than expected in MS, even at the time of diagnosis”.3
A Canadian study compared 23,382 people with newly diagnosed MS and 116,638 controls. Depression (relative risk [RR] 2.04), chronic lung disease (RR 1.34), epilepsy (RR 2.18), fibromyalgia (RR 2.87), inflammatory bowel disease (IBD; RR 1.68), anxiety (RR 1.61), bipolar disorder (RR 1.86) and schizophrenia (RR 1.32) were commoner in people with MS at diagnosis.
The study also linked several lifestyle-related co-morbidities to MS, including diabetes (RR 1.17), hypertension (RR 1.17) and ischaemic heart disease (RR 1.30).4
The risk of hypertension was 48 per cent higher in men with MS than male controls and 16 per cent higher in women. Men also had a disproportionately higher prevalence compared to women for diabetes (31 and 10 per cent respectively), epilepsy (184 and 125 per cent), depression (82 and 59 per cent) and anxiety (78 and 57 per cent).4
Further studies need to confirm these findings and examine the causes of the sexspecific differences4, but several factors potentially link MS and the co-morbidities. For example, doctors may be more likely to diagnose a comorbidity because of increased surveillance or more frequent contacts.
Multiple sclerosis and the co-morbidity may share risk factors – for instance, some of the same genes contribute to MS and IBD. Low levels of vitamin D seem to increase the likelihood of developing MS, ischaemic heart disease and diabetes.4
The autoimmune reaction underlying MS seems to be largely mediated by Th1 and Th17 lymphocytes. Several adipokines – chemical messengers released by fat cells – seem to regulate immunity and inflammation. Leptin, for example, modulates food intake and energy expenditure, increases secretion of the inflammatory mediators interleukin (IL)-1 and tumour necrosis factor (TNF), and enriches numbers of Th1 cells. Obese people show high levels of leptin and low levels of adiponectin, which is antiinflammatory. 5
Against this background, MS patients taking metformin and pioglitazone showed a decrease in the number of MRI changes that indicate inflammation and an increase in the number of regulatory T-cells. These cells suppress pro-inflammatory Tlymphocytes’ effects. Patients receiving metformin showed fewer cells secreting the inflammatory mediators interferon and IL-17, while pioglitazone seemed to reduce the number of cells secreting IL-6 and TNF (both involved in inflammation).
Despite between 75 and 80 per cent of patients receiving disease-modifying therapy, they presented with highly active MS, suggesting that metabolic syndrome can affect the course of MS. The authors suggest that the results warrant further study to see if they can help improve treatment.5
In other words, MS seems set to join the growing number of conditions – alongside diabetes, heart disease and some cancers – linked to obesity and diet. A salt-rich diet, for example, may contribute to autoimmune responses in the central nervous system as well as being an important risk factor for hypertension. Certain fatty acids and the composition of the gut microbiome may also influence MS risk. As such, dietary measures might become an adjuvant treatment to established MS therapies.2
Multiple sclerosis will probably remain a neurological sphinx for some time to come since numerous questions remain, such as how diet, the microbiome and the immune system interact to cause the disease.2 Clearly we’re still some way from fully understanding this fascinating, but enigmatic, condition.
The study linked several lifestyle-related co-morbidities to MS