Can you reduce the chances of your children getting MS? #ClinicSpeak #ResearchSpeak #MSBlog
Obesity, in particular adolescent obesity, is a risk factor for developing MS. The study below shows that this risk, not surprisingly, extends into childhood or paediatric MS.
Is obesity simply associated with MS due to another factor or does obesity act in the MS causal pathway? An example of an association would be that its actually low vD levels, or lack of outdoor activity and less sun exposure, that is the causal factor. People who have less outdoor activity tend to be more sedentary and hence more likely to be obese. The risk factor here is less outdoor activity and not the associated obesity.
Obesity could be causal if some part of adipose tissue biology interacts with the MS causal pathway. An example of this is could be one of pro-inflammatory mediators that adipose tissue produces, and there are many such mediators, prime the immune system to develop autoimmunity. In other words if there was less adipose tissue, and as a result less adipose tissue induced systemic inflammation, then the risk of autoimmunity will drop.
Another way adipose tissue may interfere with the causal pathway is actually via vD metabolism. Adipose tissue may lower systemic vD levels by consuming vD as part of its metabolism. The low vitamin D level, and not the obesity, that is the risk factor here.
The only way to answer the association vs. causation question is to do a randomised controlled trial of a dietary, or pharmacological intervention, which reverses or prevents adolescent obesity, and to see if the intervention reduces the risk of developing MS. This type of trial would be very difficult to do and in my opinion is not feasible now. It may become feasible when we have a pharmaceutical that effectively treats obesity; with drugs it is easier to do randomised controlled trials. With lifestyle interventions, particularly weight loss and obesity, this is even more difficult when the outcome needs to be looked at a population level.
A cheaper, and cleverer, way to do randomised-controlled trial to prove causation is to use the Mendelian randomization method and to see if the genetic variants that are linked to obesity are risk factors for developing MS.
An earlier study using people from California registered with the Kaiser Permanente HMO and a replication sample from Sweden showed just this. The investigators constructed a weighted genetic risk score using genetic variants previously established to predict obesity. Subjects with higher genetically-induced obesity scores had a higher risk of developing MS. Although the investigators controlled for birth year, sex, education, smoking status, ancestry, and genetic predictors of MS they clearly couldn’t control for other important con-founders that are very relevant to this analysis, for example dietary factors, exercise – in particular out-door activity – and vD levels. Despite this that study suggested that obesity is probably part of the MS causal pathway and that if we want to reduce the incidence of MS in the population we need to tackle the problem of adolescent obesity.
Tackling adolescent obesity is much easier said than done! However, if you have MS and you children are already at higher risk of developing MS you may want to think about this more seriously.
In high prevalence areas such as Western Europe the lifetime risk of a woman developing MS is ~ 1 in 500 (background population risk). If you are a woman with MS and have children you need o be aware that the chance of your daughter(s) getting the disease is ~ 1 in 40 and your son(s) ~1 in 80. Would you want to do everything you can to lower that risk?
OBJECTIVE: The aim of this study was to examine the relative contributions of body mass index (BMI) and pubertal measures for risk and age of onset of pediatric MS.
METHODS: Case-control study of 254 (63% female) MS cases (onset<18 years of age) and 420 (49% female) controls conducted at 14 U.S. Pediatric MS Centers. Sex- and age-stratified BMI percentiles were calculated using CDC growth charts from height and weight measured at enrollment for controls, and within 1 year of onset for MS cases. Sex-stratified associations between MS risk and age at symptom onset with both BMI and pubertal factors were estimated controlling for race and ethnicity.
RESULTS: Only 11% of girls and 15% of boys were prepubertal (Tanner stage I) at MS onset. 80% of girls had onset of MS after menarche. BMI percentiles were higher in MS cases versus controls (girls: P < 0.001; boys: P = 0.018). BMI was associated with odds of MS in multivariate models in postpubertal girls (OR = 1.60, 95% confidence interval [CI]: 1.12, 2.27, P = 0.009) and boys (OR = 1.43, 95% CI: 1.08, 1.88, P = 0.011). In girls with MS onset after menarche, higher BMI was associated with younger age at first symptoms (P = 0.031). Younger menarche was associated with stronger effects of BMI through mediation and interaction analysis. In pubertal/postpubertal boys, 89% of whom were obese/overweight, earlier sexual maturity was associated with earlier onset of MS (P < 0.001).
INTERPRETATION: Higher BMI in early adolescence is a risk factor for MS in girls and boys. Earlier age at sexual maturity contributes to earlier age at MS onset, particularly in association with obesity.