Not COVID-19: obesity and MS

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. Nat Med 2020 Apr;26(4):485-497.

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.

CoI: multiple

34 thoughts on “Not COVID-19: obesity and MS”

  1. Very interesting and yet, probably known to MS researchers and doctors.

    The question is this – is there a way to retrospectively examine those who develop MS in adult life (say in their second decade) and trace their BMIs, vitamin D levels, ethnicity, smoking history and history of mononucleosis (all in one shot, and via their pediatric physicians’ records) to isolate, if at all possible, the individual causal factors associated with development of MS in later life ? Sure, it would be a retrospective snapshot but these types of analyses shed light on a ton of information that is sorely lacking…….

    1. In addition to smoking history – lifelong exposure to acrolein. As a non-smoker with extensive workplace exposure to 2-propenal, then acute reactions AND hypersensitivity to second hand smoke, there are ways other than smoking to be exposed to similar chemicals.

  2. Please don’t underestimate genetic factors, nor the body’s innate drive to gain nutrition. Lack of “willpower” can strictly be our brain’s attempts to access enough protein, or a mineral, when eating foods that are not nutrient dense. Hence ”any” nutrient dense diet is best.

    (Pregnancy, chocolate and magnesium. My in to this understanding lol).

    Keto-as-written isn’t a winner for those of us with certain genetic SNPs.

    Plus – for weight and overall health, it’s so important to work with our biochemical pathways.

    If there is a pre-existing pathway in the body to make a hormone, as there is for vitamin D, and yet someone is deficient, what is missing for that pathway to work? Basic chemistry. Don’t just dump lots of the end product into the system.

    In vitamin D (and I suspect Mavenclad by the adverse effects seen!) metabolism – it’s often magnesium. (Aside from the obvious – use of sunscreens, lack of outdoor time, etc.)

    We are currently much better served in the area of tweaking biochemical pathways to better health function by the naturopathic community. The allopathic community tends to use high-dose supplements as medicine. There is always a ripple effect.

    It actually shocked me to discover that my perception of naturopathy was so wrong – that it is my ND and not my doctor pulling out biochemical pathway charts to help me figure out “why”.

    Allopathic and naturopathy are a strong combo for those living with MS. Not only for weight.

    Back to weight shaming. So much of it. And I don’t believe any weight issues are purely psychological. Our biochemistry and genetics dictate so much.

    1. Yes, metabolism sits at the bottom of the -omics, including genomics, and is the integrator of them all (genomics, transcriptomics, proteomics, metagenomics/microbiome and environmentomics*). In summary, life is metabolism.

      *environmentomics is not a word by a neologism (made up or new word). Do you like it?

      1. Well, that’s a mouthful .. therefore perfect lol.

        “Life is metabolism.” Yes, this.

  3. Thank you for this description of the mechanism involved and why eating low-carb might be particularly good for those of us with MS. Encouragement for those of us who feel well eating that way is so valuable. It seems to me likely that change in this area needs to be driven by patients and clinicians together. There is a very great deal of unhelpful established orthodoxy to be unpicked before official guidance on what to eat catches up with the science. We need all hands on deck to achieve that change.

  4. Thanks Prof G. Not really read the paper for simple reason. Does a Metsbolic disorder stop u for putting the fork down?

    1. Yes, it does. Obesity at the levels we see is a relatively new phenomenon. What has happened to the epidemiology of obesity can’t be explained by a lack of will power. What has changed is our food environment and the guidelines that dictate it.

      1. Thanks Prof G. Yesterday there was a article on EBV confirming links to MS. Given this a hypothesis being promoted by barts for at least last 5 to 10 years. Is there a plan of action or road map to bring this to the therapeutic Market? If not what is the point of research in any subject when all findings are ignored unless pharma stand to make billions?

  5. This is a very privileged take on matters. ” The cause of obesity is simple ” Really? Maybe the physical cause but what of the socio-economic, cultural and political issues?

    Low carb is a legitimate strategy for weight loss, as are many others. I think we can agree that refined carbs are not an ideal food to be eating huge amounts of but the idea that carb restriction is necessary for weight loss is clearly false.

    “Dietary zealots” ? The Prof lives in an echo chamber full of such individuals. They claim to follow the science but in fact are only interested in science that reinforces their existing positions. Any evidence to the contrary is always ignored or blamed on bad studies or conspiracies.

    1. Re: “carb restriction is necessary for weight loss is clearly false”

      I think you miss the point and are misquoting me. I am not saying carb restriction is the only way you can lose weight. I am saying that carb restriction is how you correct the metabolic problem of hyperinsulinemia and insulin resistance, which is one of the metabolic switches that drive the accumulation of fat. You can do also do this with calorie restriction, but the downside of this is cyclical insulin levels and counter-regulatory responses that drive hunger and you also don’t get the potential health benefits of metabolic ketosis. An in-between solution, i.e. between calorie restriction and low-carbohydrate/ketogenic diets, is intermittent fasting.

      At a population level, the idea that calorie restriction (dieting) and calorie burn (exercise) works is the real falsehood. Despite decades of public health officials, dieticians, nutrionists, doctors, etc. promoting this message, with low-fat in front, has clearly failed. If it did work we wouldn’t be heading towards a population prevalence of obesity of 50%. At an individual level yes you lose weight with calorie restriction and exercise, but look at how successful it is in the long-term. Ask anyone who is obese and has tried this strategy.

      This is why the implications of the destigmatisation of obesity are so important; it doesn’t blame the individual for getting fat and it doesn’t blame the individual when dieting doesn’t work either. With a new perspective on obesity we are all winners; except maybe the junk food industry and the companies that serve up processed and ultra-processed carbohydrates.

      1. I need to take time to read this again, but this is exactly the sort of information I need.
        I’ve lived with MS for over 25 years and have tried all sorts of dietary approaches. When I’ve hit a stage of ketosis I feel better. Currently I use a little coconut oil (bad fat? Whole new discussion) and show ketones.

        Yes I’m obese, but eat healthily (just rather too much!)
        The MS community (and obese community) could do with some honest and precise medical input!!
        Prof G I would dearly love to invite you to cover a podcast episode on just this post. Would you be open to this? I’m also speaking with Dr Wahls, Best Bet diet and OMS representative. The MS Show would love your input 🙏

      2. Re: little coconut oil (bad fat?)

        No the evidence that saturated fat is bad for you is very weak and even then confounded by other factors. In my opinion, saturated fat is not bad for you. What is bad for you is polyunsaturated fats, particularly the hydrogenated and oxidised forms.

      3. Maybe I am missing your point. What makes you think a ketogenic diet will be any more successful long term than energy balance?
        Of course we must destigmatise obesity but addressing this problem and the wider food environmment will not be achieved by demonising entire food groups.
        On a separate but related point have you read Kevin Hall’s recent preprint on this topic? It doesn’t provide any simple conclusions but certainly raises some interesting points surrounding the carbohydrate-insulin model of obesity versus the passive overconsumption model.

      4. No, but I will read it. I am not sure anyone has a problem with the demonisation of processed and ultra-processed carbohydrates except politicians on the take and the food industry. I have little doubt we will come to view the sugar lobby as being worse than the cigarette lobby in the future.

      5. Yes decreasing added sugar intake (and implementing anti-sugar policies) is a good idea for personal and public health. This is not the full picture though.
        Recent data I have seen shows added sugar intake actually decreasing (in the US). The largest increase in calories in the food system has come from fat–mostly salad and cooking oils

      6. The British Empire and the French Empire for that matter were built on slavery and the sugar trade. At its peak, about 50% of the GDP of France was from sugar.

  6. Hi Prof G, excellent post. Do you think supplementing with butyrate could have a similar effect to ketosis (ie by mimicking beta hydroxy butyrate), is this the link with the gut organisms producing butyrate and it’s anti-inflammatory effects? What’s your take on the TUDCA/butyrate trial- does this look promising?
    Do you think the benefits of the FMD/IF (5 day plan) are driven through ketosis rather than protein restriction and the mtor pathway? Could cycling FMD be more beneficial than ketogenic diet (as it is certainly more realistic and easier to follow)?

      1. It does seem to according to my sources.
        (S Offermanns, SL Colletti, AP IJzerman, TW Lovenberg, G Semple, A Wise, MG Waters. “Hydroxycarboxylic acid receptors”. IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 13 July 2018)
        Seems to be a very interesting link. Will be very curious to see the outcome of the AMX0035 trials for PPMS/ALS. If butyrate is the link then supplementation would be much easier for pwms compared to a ketogenic diet. Also reintroduces the question of gut dysbiosis being treated with faecal transplant to inc butyrate proceeding bacteria. Very interesting stuff.

  7. Hi Prof G, excellent post.
    I was wondering what your take was on a couple of things.
    1) do you think supplementing with butyrate would be as beneficial as ketosis, if the main anti inflammatory effect is driven by Beta hydroxybutyrates anti-inflammatory effect driven by HDAC inhibition. What’s your take on the TUDCA/butyrate trial in PPMS/ALS? Is the link with butyrate producing bacteria also key here?
    2) do you think the fasting mimicking diet /IF benefits would be due to ketosis (therefore ketogenic diet would be more effective) or is the link with mtor due to the low protein diet more key? I would certainly find IF and a cyclical 5 day FMD, say every month, more realistic to follow. As well as not having to worry about high cholesterol.

    1. Re; “.. fasting mimicking diet /IF benefits would be due to ketosis”

      Yes. I think intermittent ketosis is the common denominator of all these diets that trigger the NRF2 pathway.

      Not sure about butyrate, I will look into it and the trial you mention.

  8. Prof G what’s your opinion about a 5 or 6 day caloric restriction followed by normal diet for 20 days? This would be equivalent to alternate day fasting that they had the mice on in the metformin study

    Why shouldn’t people with MS really hack their body? I think 6 consequitive day of really low calorie a month to mimic what happens in mice is quite doable.
    I have been doing it for the past three month. Everytime I lose around 10 % of my body mass just as the mice. My lost weight returns rapidly minus a few kilos within one day upon breaking the fast.

    What do you think?

  9. I have always wanted to ask your opinion around this – what do you think of the 16:8 pseudo-keto diet?

    That is, unrestricted eating (no qualitative or quantitative caloric monitoring) during 8 hours per day.

    Is it worth it the effort from an MS perspective?


      1. Thanks – I am asking because I am a lazy epicurian who lacks the will power and conviction to follow a diet. of any sort.

        I have thought hard all this since G’s “how Healthy is your lifestyle?” post on Jan 13th. Fasting from 7pm to 11am is about the best I can do really…

      2. My partner started to eat like this a few months ago after reading lots about the benefits of intermittent fasting. He was a normal healthy, probably low bmi to start, but he has lost quite a bit of weight. I wouldn’t say he is careful with what he eats in those 8 hours… I’m surprised at the amount of (often unhealthy…) snacks he gets away with.

  10. Fascinating! Thank you for posting about this. I have Polycystic Ovarian Syndrome as well as MS and keeping my weight down is very hard. Luckily, both my MS nurse and the endrocrinologist both say that exercise is good for me. My ‘medical prescription’ includes cycling! I am just waiting for the Covid 19 virus to abate so the swimming pools open again.

  11. I think the problem is not in carbs, but in type of carbs and in their quantity. It’s easy to say cut carbs, but to stay at the same energy intake level, you need to replace them with proteins or fats. Both of which can be problematic if overconsumed. Carbs are simply easiest task for our bodies, and we’re quite well accustomed to them. I think the root cause of obesity is not metabolic or endocrine problem, but our culture. We’re socialized into eating big and jumbo portions, junk food is to be found everywhere, desserts and sweets are the norm, etc. I think mediterranean diet, based on integral grains, fruit and veggies, fish and meat, with some wine and olive oil is the best. However for Multiple Sclerosis, I am definitely not sure. If you have some research that suggests that low carb diet can work in ways similar to dimethyl fumarate, this might indeed be worthy of further research. What I’m afraid that at this point patients might be given a false hope of a certain type of diet being a solution for their disease, and that they might even be worse of in the end due to numerous restrictions that low carb diet entails. Been there, done that… I’ve been following classical Atkins diet, and I know well about ketosis – yes it works great for weight loss, fast weight loss, and completely effortless as you don’t feel hungry. You can even feel more energy… But after a couple of months it’s quite unsustainable… you simply get tired of all meat and veggies based food, your digestion and stool become weird, etc… And you feel on some level that you’re doing something wrong. When you limit carbs, you’re forced to concentrate your food intake among much fewer choices, and the less varied your diet is, the more likely is that you’ll consume too much of something… Be it hormones, antibiotics from meat, or even pesticides from veggies, etc…
    I would certainly limit sugars and refined carbs, like white flour, white rice, etc… choose whole grains instead, fruits instead of sweets, etc… But right now I can’t yet recommend overal carb limitation.
    Regardinng obesity, I agree with you that dieting doesn’t work.
    What I instead recommend, is making a small, unobtrusive, but permanent change in your eating habits. Like cutting your overal caloric intake for just 200 calories, but permanently, would be enough, to cause significant weight loss over long term. Add to this making some tweaks to your diet to make it healthier, and becoming just marginally more physically active, and you get a sustainable solution.

    1. Great post Zlatko but I fear will fall on dear ears with Prof G. He is living in an echo chamber and in thrall to the low carb Gurus. Food writers hold more sway than actual scientists in this world. We ain’t gonna solve the obesity crisis by demonising one food group. If low carb works for you and helps with weight loss, that’s great. I’m all for it. But there’s zero evidence its superior to a calorie/protein equated low fat diet. Nutrition must be tailored each individuals circumstance. One diet does not fit all. That’s before we even begin to tackle the bigger issues around obesity such as the food environment, poverty, socio economics etc. Nothing more privileged than saying cut carbs but it solves nothing on a population level.

      1. Prof G,
        I am not much overweight, but could use 20-30# off. Reading your replies, goes with my blog article just written I wonder if adding Tudca to my pills would work? MS people are low in bile production. goverment studies Links on site. So would Taurine work?
        I have multiple sclerosis, and a rare blood gene, H63d, that caused iron overload (>3%) 17 phlebotomy vein puncture left me anemic for near two years, now a GP says kidneys…

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