Are you sick and tired of hearing about COVID-19 and MS? How about something completely different; the destigmatization of obesity?
Finally, the medical community or at least a part of it are making amends for the half-century or more of treating obesity as a disorder of self-control. The joint internal consensus statement for ending the stigma of obesity is long overdue (see article and box below).
Even when I have done factual posts about childhood and adolescent obesity as a risk factor for developing MS I have been criticised by commentators for fat-shaming. I am not. All I am doing is quoting the evidence that childhood/adolescent obesity is associated with an increased risk of developing MS and may in fact be in the causal pathway that leads to developing MS.
What the consensus statement below is finally acknowledging is the irrefutable evidence that obesity is a disorder of metabolism; an endocrine disorder that leads to patients increasing the amount of energy they store as fat. Finally, the dogma that obesity is due to the excess consumption of calories and/or the reduced expenditure of calories is finally being put to rest as not being the root cause of obesity.
A simplified way of explaining the mechanisms that lead to obesity is that your metabolism gets hijacked by a hormonal imbalance that results in energy be hoarded away in your adipose tissue and it not being released for consumption by the remainder of the body. This triggers the brain to think that you are starving and sets off a behavioural response to seek more food or calories. In other words, the metabolic state associated with obesity causes hunger and the food-seeking behaviour associated with it and not the other way around.
The sad thing is that we the medical profession have known about this insight for centuries, but we decided to forget or ignore the metabolic research underpinning obesity being a metabolic disease in the 70’s and 80’s when we were hoodwinked by dodgy science and fake news. Yes, the high saturated-fat heart hypothesis of cardiovascular disease is to blame. The conspiracy underpinning the change in the dietary guidelines that have caused the global obesity pandemic has been well highlighted by investigative journalists in several extremely well-crafted exposes. The tragedy is as the population replaced saturated fat in our diets with polyunsaturated fats and carbohydrates, in particular, processed and ultra-processed carbohydrates, we created a metabolic storm that has resulted in an epidemic of obesity, diabetes, hypertension, fatty liver and the other ills associated the metabolic syndrome.
Shifting the focus sway from obesity as a result of an individual’s lack of self-discipline to it being a metabolic disease driven primarily by diet will allow us to tackle the epidemic, i.e. to flatten the curve and hopefully chop off its tail to steal a COVID-19 analogy.
The metabolic cause of obesity is rather quite simple; it is driven predominantly by raised insulin levels or hyperinsulinaemia. High blood sugar or glucose levels stimulate the pancreas to produce insulin. The insulin works to reduce blood glucose levels by signalling to the liver and muscles to make glycogen (short-term glucose storage) and to the liver and adipose tissues to make fat. Whilst insulin levels are high the adipose tissue is unable to release fat as an energy source and so the adipose tissue continues to take-up glucose to convert into fat. As glucose levels drop it triggers a counter-regulatory hormonal response that causes you to become hungry and you then seek out sugary foods. This then starts a vicious cycle that results in insulin levels being raised most of the day, instead of only being raised for a few hours after a meal. This hyperinsulinaemia eventually causes the liver and muscles to become resistant to insulin’s action, but less so in adipocytes particularly the adipocytes around the abdomen and internal organs. The latter causes the so-called centripetal and visceral obesity that is typical of insulin resistance.
The only way to break this vicious metabolic cycle is to try and lower your insulin levels as much as possible. This is why low carbohydrate or ketogenic diets work so well at correcting the metabolic syndrome (hyperinsulinaemia) and result in loss of weight. The good thing about keeping insulin levels low is that the body gets used to a new normal or steady-state glucose level that is driven by another metabolic process called gluconeogenesis (glucose from protein), which does not trigger the counter-regulatory hormonal response that makes you feel hungry. In addition, the ketones your body produce, particularly β-hydroxybutyrate, is known to suppress appetite and explains why people on ketogenic diets don’t feel the same levels of hunger as people on high carbohydrate diets.
If you have MS having high levels of circulating β-hydroxybutyrate maybe be good for your MS. β-hydroxybutyrate activates the hydroxycarboxylic acid receptor 2 (HCA2), which is also known as niacin receptor 1 (NIACR1) and GPR109A. This is the same receptor that fumaric acid works on. I suspect that ketosis works at a cellular level in the same way that dimethyl fumarate (DMF) and diroximel fumarate work, which are both licensed MS disease-modifying therapies (DMTs). By binding to the HCA2 receptor β-hydroxybutyrate stimulates a transcription factor called NRF2 and downregulates NFKappa-B the master regulator of inflammation. The NRF2 mechanism of ketosis almost certainly overlaps with what has been described in animals with intermittent fasting and the drug metformin to promote the rejuvenation of oligodendrocyte precursors, remyelination and recovery of function.
Despite criticism from dietary zealots the evidence that low-carbohydrate/ketogenic diets are bad for you is very weak. In fact, I would argue that from an evolutionary perspective man was first a low-carbohydrate species and only acquired the sophisticated carbohydrate metabolic response to fatten up for winter when fruits and grains are plentiful at the end of summer. We were never meant to metabolise carbohydrates 24/7 365 days a year. Feast and famine was the norm, which is how our primate cousins live in the wild.
Although we need controlled evidence before promoting low-carbohydrate/ketogenic diets as a treatment for MS and for MS prevention there is no reason why pwMS can’t try these dites improve their metabolic health. If I had MS I would not hesitate to hack my metabolism with either a low-carbohydrate/ketogenic diet or intermittent fasting, but not caloric restriction. The scientific case for using these former diets as an adjunct to other MS therapies is simply too compelling to ignore.
Rubino et al. Joint International Consensus Statement for Ending Stigma of Obesity. Nat Med 2020 Apr;26(4):485-497.
People with obesity commonly face a pervasive, resilient form of social stigma. They are often subject to discrimination in the workplace as well as in educational and healthcare settings. Research indicates that weight stigma can cause physical and psychological harm, and that affected individuals are less likely to receive adequate care. For these reasons, weight stigma damages health, undermines human and social rights, and is unacceptable in modern societies. To inform healthcare professionals, policymakers, and the public about this issue, a multidisciplinary group of international experts, including representatives of scientific organizations, reviewed available evidence on the causes and harms of weight stigma and, using a modified Delphi process, developed a joint consensus statement with recommendations to eliminate weight bias. Academic institutions, professional organizations, media, public-health authorities, and governments should encourage education about weight stigma to facilitate a new public narrative about obesity, coherent with modern scientific knowledge.