Multiple sclerosis shows a "striking" association with obesity at age 20 years that strongly interacts with genetic susceptibility, according to an analysis of data from two case-control studies that examined environmental and genetic risk factors for MS.
This relationship between adolescent obesity and MS is of the same magnitude as the separate associations between MS and carriage of the high-risk HLA-DRB1*15 allele, absence of the protective HLA-A*02 allele, and smoking, said Dr. Anna Karin Hedström of the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, and her associates.
"The biological explanations for these interactions are far from clear, but the data open [the way] for mechanistically oriented studies," they said.
Three previous studies have suggested that obesity in early life may be linked to increased risk of developing MS later. Dr. Hedström and her colleagues examined this association using data from a Swedish population-based, case-control study and from a separate American case-control study.
In the Swedish study, 1,510 adults with incident MS who were treated at 40 clinics across the country during a 7-year period and 2,017 control subjects completed detailed questionnaires concerning environmental exposures and other factors. The controls were matched for age, sex, and area of residence, and all the participants gave blood samples for HLA typing.
The American study involved 937 white adults with prevalent MS who were members of a single large health maintenance organization covering northern California and 609 white control subjects matched for age, sex, and area of residence. All the participants completed computer-assisted telephone interviews regarding environmental exposures and lifestyle factors.
All the subjects in both studies reported what their heights and weights had been at age 20 years, from which the investigators calculated body mass index (BMI).
In both studies, participants whose BMI at age 20 years was 27 kg/m2 or greater showed an increased risk of developing MS later in life, compared with those whose BMI was 18.5-21 kg/m2. The odds ratios (ORs) were 2.2 for subjects in the Swedish study and 1.8 for those in the American study, Dr. Hedström and her associates said (Neurology 2014 [doi:10.1212/WNL.0000000000000203]).
Similarly, participants with a slightly lower but still above-normal BMI of 25-27 kg/m2 showed a modestly increased risk of developing MS later in life: The ORs were 1.4 in the Swedish study and 1.3 in the American study.
These ORs were unchanged when a sensitivity analysis was performed, including only the study subjects who had been genotyped.
Participants who carried the high-risk HLA-DRB1*15 gene, did not carry the protective HLA-A*02 gene, and had a BMI of 27 kg/ m2 or greater at age 20 years had an OR of 16.2 for developing later MS, compared with those who had none of those risk factors. In contrast, subjects who had the same HLA profile but had not been obese at age 20 years had an OR of only 5.1.
The investigators proposed that the low-grade chronic inflammation associated with obesity, together with obesity’s adverse effects on autoimmunity, may raise the risk of HLA-related activation of T cells that attack the CNS.
Both the Swedish and the American study were limited in that they were retrospective and relied on participants’ self-reports. In addition, Dr. Hedström and her associates modified the usual definition of obesity for the purposes of their study. The typical standard for obesity is a BMI of greater than 30 kg/m2, not greater than 27 kg/m2. However, the number of subjects at this level of BMI was too small in the Swedish cohort to allow accurate analysis, so the researchers combined the top two categories of BMI into one designation of "obese."
This study was supported by several private nonprofit foundations, the Swedish Research Council for Health, Working Life and Welfare, and the U.S. National Institute of Neurological Disorders and Stroke. Dr. Hedström and five of the other seven authors reported no financial conflicts of interest. One coauthor reported ties to numerous industry sources and one reported receiving research support from Swedish government agencies.
Causality not yet established
This study and other research linking obesity early in life with the later development of MS are observational and cannot establish causality, so we don’t yet know whether decreasing obesity with diet and exercise will lead to a decrease in the incidence of MS.
Nevertheless, these findings are concerning. “It is time to begin developing a targeted approach to prevent MS by improving common health behaviors, including body weight and smoking,” Dr. Marrie and Dr. Beck said.
People who are at high genetic risk can be readily identified by focusing HLA genotyping on the first-degree relatives of known MS patients, they added.
Dr. Marrie is in the departments of internal medicine and community health sciences at the University of Manitoba, Winnipeg. She has received funding from Sanofi-Aventis and Canadian governmental agencies and nonprofit organizations, including the MS Society of Canada and the MS Scientific Foundation. Dr. Beck is in the department of biostatistics and computational biology at the University of Rochester (N.Y.) Medical Center. Dr. Beck has received support from a variety of healthcare companies as well the U.S. Food and Drug Administration and the U.S. National Institutes of Health.
These remarks were taken from their editorial accompanying Dr. Hedström’s report (Neurology 2014 [doi:10.1212/WNL.0000000000000195]).
Source: Clinical Endocrinology New Copyright © 2014 Frontline Medical Communications LLC (12/02/14)
Drinking alcohol appears to have a dose-dependent inverse (opposite) association with the risk of developing multiple sclerosis (MS) and researchers suggest their findings give no support to advising patients with MS to completely refrain from alcohol, according to a study by Anna Karin Hedstrom, M.D., of the Karolinska Institutet, Sweden, and colleagues.
The results of previous studies have been inconsistent about the impact of alcohol and the risk of developing MS.
Researchers investigated the association using two population studies in Sweden with participants between the ages of 16 and 70 years: 745 cases of MS plus 1,761 controls in the Epidemiological Investigation of Multiple Sclerosis (EIMS) study and 5,874 cases of MS with 5,246 controls in the Genes and Environment in Multiple Sclerosis (GEMS) study.
In EIMS, women who reported high alcohol consumption had an odds ratio (OR) of 0.6 of developing MS compared with nondrinking women, and men with high alcohol consumption had an OR of 0.5 compared with nondrinking men, according to the results. The corresponding OR comparison in GEMS was 0.7 for both women and men. Alcohol consumption also appeared to be associated with the attenuation (lessening) of the effect of smoking, the results also indicate.
"Although the effect of alcohol on already established MS has not been studied herein, the data may have relevance for clinical practice since they give no support for advising persons with MS to completely refrain from alcohol," the authors conclude.
Source: MedicalXpress © Medical Xpress 2011-2014 (07/01/14)
Exposure to cigarette smoke is emerging as an environmental risk factor for multiple sclerosis (MS).
We investigated the possible association between environmental tobacco smoke, its cumulative exposure, and MS risk.
We used data from the Iranian Multiple Sclerosis Registry to identify a case-control of 662 patients who had MS and a comparison group of 394 patients. Information regarding current smoking status, including the number of cigarettes smoked per day, duration, and smoking pack-years indicative of cumulative dose of tobacco smoked was obtained.
We analyzed the incidence of MS among ever-smokers who had been smokers during their disease course and prior to disease onset in comparison with never-smokers who had never been exposed by calculating the odds ratio (OR) with a 95% confidence interval (CI) employing logistic regression. Of the 662 MS patients, there were 523 women (79.0%) and 139 men (21.0%), with a mean age of 31±10.0years at disease onset.
The risk for MS was increased among ever-smokers (OR=1.78, 95% CI=1.22-2.59, p=0.03) compared to never-smokers. As compared with never smokers, the OR for patients with 6-10 pack years was 2.91 for men (95% CI=1.11-9.47, p=0.03) and 1.69 for women (95% CI=1.02-6.45, p=0.04).
Our results demonstrate that cigarette smoking is significantly associated with an increased risk for MS. The risk effects of smoking were more noticeable in male patients and at higher tobacco doses.
Asadollahi S, Fakhri M, Heidari K, Zandieh A, Vafaee R, Mansouri B.
School of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran.
Sources: J Clin Neurosci. 2013 Aug 20. pii: S0967-5868(13)00182-3. doi: 10.1016/j.jocn.2013.01.018. Copyright © 2013 Elsevier Ltd & Pubmed PMID: 23972559 (03/09/13)
Is MS in the Milk?(26/06/13)
Scientists still don't know what causes multiple sclerosis (MS). It could be viruses, genetics or environmental factors, or a combination of all three. One new study suggests it could be the kind of work people do.
The results of that study showed that dairy workers in a certain Danish population had higher rates of MS than people in other lines of work.
This research is the first to show an increased risk of MS in dairy workers.
While the researchers could not explain what caused this increased risk, they did mention previous studies that have linked cow's milk to MS.
This study, led by Henrik Horwitz, MD, of Bispebjerg Hospital at the University of Copenhagen in Denmark, was sparked by a finding that Dr. Horwitz and colleagues made some years back.
In 2006, while looking at critical illness insurance claims from a Danish pension fund, these researchers noted a high number of claims made by patients diagnosed with MS who worked in agriculture.
Critical illness insurance is an insurance plan that pays policyholders in a lump sum when they are diagnosed with a critical illness.
According to the researchers, these agricultural workers — made up of dairy workers, gardeners and agricultural assistants — had the lowest rates of critical illness in general. So why did MS seem to pop up so often?
Previous research has suggested that vitamin D, which most people get from being exposed to the sun's UV light, may protect against MS. Other research has shown an association between cow's milk and risk of MS.
For this current study, Dr. Horwitz and colleagues set out to see if gardeners or dairy workers had a higher risk of developing MS compared to other workers in PensionDenmark, a pension fund that insures more than 300,000 Danish workers.
Over the course of 10 years, 389 people were diagnosed with MS. The rate of MS among men was 10.2 per 100,000 men. Among women, that rate was 16.1 per 100,000.
The highest rate of MS was found among agricultural workers.
After looking a little deeper, the researchers found that this high rate of MS among agricultural workers could be tracked more specifically to dairy workers, who were two times more likely to develop MS than any of the other workers.
"Interestingly, dairy operators had the highest risk of developing MS, and the tendency was found both among men and women," the study authors wrote. "We were puzzled by the finding of an increased risk of MS among members of the agricultural segment of the pension fund, because this would seem to go against the vitamin D and sun exposure hypothesis. However, it became clear that dairy operators constituted one-third of this cohort, and this seemed to explain our findings."
Simply put, the researchers were surprised at first to find the increased risk of MS in agricultural workers, since many of these workers are typically outside getting that protective vitamin D from the sun. But then they saw that so many of the agricultural workers in this pension fund worked in the dairy sector, which doesn't require as much outdoor activity.
"No previous research has identified an increased risk of MS in dairy operators, so is this a coincidence? Or is it a clue to etiology (the origin or causes of disease)?" the researchers asked.
They went on to cite past research that has linked cow's milk to MS risk but concluded that this question should be studied further.
This study was published June 25 in BMJ Open.
The research did not receive any specific funding. The authors declared no competing interests.
Source: Daily Rx Copyright © 2013 dailyRx, Inc (26/06/13)
This interesting article investigated the effects of smoking on disability progression and disease severity in 895 people with MS with mean disease duration of 17 years. 49% of participants were regular smokers at the time of diagnosis or disease onset (ever smokers).
They found that the average disease severity as measured by the MS severity scale was greater in ever-smokers, by 0.68. The risk of reaching EDSS scores of 4 and 6 in ever-smokers compared to never-smokers was 1.34 and 1.25 respectively. Current smokers showed 1.64 and 1.49 times higher risk of reaching EDSS scores 4 and 6 compared with non-smokers. Those that stopped smoking either before or after the onset of disease (ex-smokers) had a significantly lower risk of reaching EDSS scores 4 and 6 than current smokers. They did not find any significant difference between ex-smokers and non-smokers in relation to EDSS scores 4 and 6.
Therefore this study demonstrates that regular smoking is associated with more severe disease, in addition to faster progression to disability. A slower progression of disability is seen in smoking cessation whether before or after disease onset.
Abstract Tobacco smoking has been linked to an increased risk of multiple sclerosis. However, to date, results from the few studies on the impact of smoking on the progression of disability are conflicting. The aim of this study was to investigate the effects of smoking on disability progression and disease severity in a cohort of patients with clinically definite multiple sclerosis.
We analysed data from 895 patients (270 male, 625 female), mean age 49 years with mean disease duration 17 years. Forty-nine per cent of the patients were regular smokers at the time of disease onset or at diagnosis (ever-smokers).
Average disease severity as measured by multiple sclerosis severity score was greater in ever-smokers, by 0.68 (95% confidence interval: 0.36-1.01). The risk of reaching Expanded Disability Status Scale score milestones of 4 and 6 in ever-smokers compared to never-smokers was 1.34 (95% confidence interval: 1.12-1.60) and 1.25 (95% confidence interval: 1.02-1.51) respectively.
Current smokers showed 1.64 (95% confidence interval: 1.33-2.02) and 1.49 (95% confidence interval: 1.18-1.86) times higher risk of reaching Expanded Disability Status Scale scores 4 and 6 compared with non-smokers.
Ex-smokers who stopped smoking either before or after the onset of the disease had a significantly lower risk of reaching Expanded Disability Status Scale scores 4 (hazard ratio: 0.65, confidence interval: 0.50-0.83) and 6 (hazard ratio: 0.69, confidence interval: 0.53-0.90) than current smokers, and there was no significant difference between ex-smokers and non-smokers in terms of time to Expanded Disability Status Scale scores 4 or 6.
Our data suggest that regular smoking is associated with more severe disease and faster disability progression. In addition, smoking cessation, whether before or after onset of the disease, is associated with a slower progression of disability.
Manouchehrinia A, Tench CR, Maxted J, Bibani RH, Britton J, Constantinescu CS.
Source: Multiple Sclerosis International Federation & Pubmed PMID: 23757766 (19/06/13)
MS birth month link dismissed(12/06/13)
Statistics boffins have dismissed the theory that a person’s month of birth influences their risk of developing multiple sclerosis.
The Cambridge researchers slated previous studies that suggested the risk of MS is higher for babies born in spring and lower in babies born in winter, arguing that their findings probably suffered from false positives.
The researchers said the previous studies had probably been confounded by extraneous variables such as year and place of birth. They said the number of babies born in certain months differs greatly in different countries and year-on-year, but that the studies had used homogenous, average population statistics as controls.
This had likely skewed the results, they said. “In the absence of adequate control for confounding factors, such as year and place of birth, our analyses indicate that the previous claims for association of MS with month of birth are probably false positives.
“Risk factors that are easy to determine and seemingly homogenous, such as date of birth, may yet be heterogeneous within the general population and therefore generate false positive signals if cases and controls are not adequately matched for the relevant extraneous variables,” they said.
Reporting in the Annals of Neurology, the authors called for studies of environmental risk factors to be held to the same statistical standards as studies of complex genetics.
Source: Neurology Update (12/06/13)
Having higher exposure to infant siblings during the first six years of life is linked to a lower risk of multiple sclerosis, according to a study.
There has been much interest in the ‘hygiene hypothesis’ of disease. That is, those who are not exposed to common infections in childhood are more likely to develop allergic or autoimmune disorders like asthma.
Having brothers and sisters increases the likelihood of exposure to infection. A team at the Menzies Research Institute, Hobart, Australia, have studied a group of 136 people with multiple sclerosis (MS) – a disease thought to have a strong auto-immune component. They compared them with a group of healthy controls, with respect to their exposure to siblings in early life.
Increasing duration of contact with a younger sibling aged less than two years in the first six years of life led to decreased risk of MS. One to three years of contact reduced the risk by 43 per cent, three to five years reduced it by 60 per cent. And if the contact was more than five years, the risk was reduced 88 per cent. Tests also showed altered immune responses with exposure to infant siblings. Further work is now needed to determine how childhood exposure to infection and its effect on the immune system govern the risk of MS.
Source: NewsFix Copyright 2013 NewsFix.ca (03/06/13)
Much of the early mortality seen in multiple sclerosis patients is related to their smoking habits, a researcher said here.
In a prospectively followed cohort of nearly 900 MS patients, 68% of those who died in a 40-year period were current or former smokers, compared with 50% of surviving patients, according to Ali Manouchehrinia of the University of Nottingham in England.
After adjusting for sex, age of MS onset, initial diagnosis (relapsing versus progressive MS), and use of disease-modifying drugs, the hazard ratio for death among ever-smokers versus lifetime nonsmokers was 2.13 (95% CI 1.26 to 3.61, P=0.005), he told attendees at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.
The mortality rate in ever-smokers was 5.48 per 1,000 person-years, compared with 2.30 per 1,000 person-years among the lifetime nonsmokers in the cohort.
Of the 66 patients in the cohort who died, 45 (68%) were smokers; 49% of the entire cohort were smokers.
Manouchehrinia noted that deaths among never-smokers in the cohort still tended to be premature relative to the general population. But the difference was less than half that seen among patients with a smoking history.
He also indicated that age of onset of significant disability was slightly younger in the ever- versus never-smokers, but the net result was that the never-smokers lived longer with disability, on average.
Overall life expectancy among MS patients is about 5 years less than in other people, for reasons that are unclear. Smoking, however, is a strong epidemiological risk factor for development of MS, which also means that smokers are overrepresented in MS patients relative to the general population.
Because smoking is itself associated with a substantial reduction in life expectancy, Manouchehrinia said, he and his colleagues sought to determine how much it may contribute to early mortality in MS patients.
They examined data on 895 MS patients registered at Nottingham University Hospital who had been followed for up to 40 years after diagnosis. Smoking status was recorded in the data. A total of 66 patients in this cohort had died as of December 2011.
Average age at death was 65, whereas the mean age of survivors as of December 2011 was 52. Decedents were also largely male (58%), whereas 72% of survivors were women.
The distribution of diagnoses also differed significantly between decedents and survivors. Half the survivors had relapsing forms of the disease, compared with only 12% of patients who had died. Two-thirds of the decedents had secondary progressive disease at last follow-up, compared with 38% of the survivors.
The differences largely reflected the older age of decedents, although Manouchehrinia noted that other research has suggested that disease progression is faster in smokers.
Another difference between decedents and survivors was that 44% of the latter had received at least a year of disease-modifying therapy, compared with only 13% of those who died.
Such disparities necessitated a multivariate analysis to assess the role of smoking in mortality. After adjusting for these factors, it remained the case that smoking approximately doubled the risk of death in the cohort, Manouchehrinia said.
A Kaplan-Meier curve showed that, with disease duration of 45 years, the survival rate among ever-smokers was 50% compared with about 75% in lifetime nonsmokers.
The researchers also calculated that, compared with life expectancy in the general population, a total of 1,779 years of life were lost prematurely in the cohort -- 62% of which were in ever-smokers.
The study had no external funding.
All authors declared they had no relevant financial interests.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis
Source reference: Manouchehrinia A, et al "Smoking is a potentially modifiable risk factor for all causes of mortality in patients with multiple sclerosis" ECTRIMS 2012; Abstract 65.
Source: Medpage Today © 2012 MedPage Today, LLC (15/10/12)