#DietSpeak – Prof G's MS Blog Archive

Lukewarm – lifestyle & wellness

Barts-MS rose-tinted-odometer: ★★

How brain-healthy is your lifestyle?

Someone asked yesterday why did I give George Jelinek’s book ‘Overcoming MS’ a positive review and yet we don’t promote it openly on the blog? Very simple our policy is not to advertise commercial products on this blog and if we promoted OMS then what about the other MS-related lifestyle and wellness programmes? I am still pissed off with myself for not making it clear that I don’t support the OMS diet. Yes, I support the principles of OMS in terms of lifestyle interventions, but I simply can’t support the OMS diet. The diet is simply not evidence-based. In fact, there is no ‘MS diet’ that is evidence-based so anyone who claims their diet needs to be followed to treat MS can’t be doing this from any position of authority.

So why did I give OMS a positive review?

The principles that underpin OMS are scientifically sound, but a lot of them are not evidence-based, i.e. they are not supported by randomised controlled trials. Some of the lifestyle recommendations in OMS are also quite extreme and hence are very difficult to follow. I view George Jelinek as the lifestyle-wellness equivalent of the ‘ultra-distance marathon runner’. You don’t need to run ultra-distance marathons to derive the benefits from running, some people do just fine on subscribing to and running regular 5km park runs. It is horses for courses. I think the important messages in OMS and other lifestyle-wellness programmes are:

Lifestyle-wellness interventions are not alternative medicine, but complementary; i.e. you need to do them in addition to taking for example DMTs.
Lifestyle-wellness interventions need to be personalised. In particular, they need to be affordable, compatible with your culture, your worldview and your belief systems.
Lifestyle-wellness interventions fall on a continuum they are not all or nothing phenomenon. You can engage with some aspects of a programme and not others. In other words, doing something is better than doing nothing.
You need to be self-motivated to stick to a healthy lifestyle and wellness programme. I think herein lies the secret of the success of the programmes. Setting goals and sticking to them is self-rewarding. The rewards centres in the brain make you feel good about yourself and motivate you further. The downside is that when you slip you have a sense of self-loathing and guilt. These emotions are part of the package; they are the regulatory or negative emotional feedback loop. My personal opinion is that slipping occasionally is fine, but you need to earn the off-days.
Lifestyle wellness programmes take a holistic view of the management of the disease. Saying this is easy, but it is very difficult to set up a lifestyle-wellness service in the NHS. What is the evidence and how do we show that the programme will be cost-saving to justify the investment? In addition, adherence rates to lifestyle-wellness interventions are very poor. This is a conundrum that challenges HCPs and behavioural psychologists but is not an insurmountable obstacle. There are examples that when politicians, HCPs and the general public get behind a national lifestyle and wellness programme it can work. A good example of this is what Finland has done at a population level over the last 20 years.
Lifestyle-wellness interventions should be adopted by everyone regardless of whether, or not, you have MS. This is why we set up the Barts-MS Brain Health challenge and why I started the Think Brain Health initiative. Getting HCPs to personally engage with their own Brain Health would make them think about their patients’ health. In addition, patients are more likely to take the advice seriously from a Brain Healthy HCP than from an HCP who is unhealthy. If you smoke, are unfit, overweight and eat badly how can you tell your patients to stop smoking, to start exercising, change their diet and lose weight? Unless you walk the talk you are not credible.
Most lifestyle-wellness interventions are common sense with an evidence base from outside the field of MS. However, like any other field, the lifestyle-wellness space is full of quacks and charlatans so be careful to accept anything at face value. Do your research and ask questions. For example, what is the evidence that you need to follow a gluten-free diet? Plant-based diet? Etc? Unless you have documented gluten sensitivity there is no evidence. Similarly, the war on fats, and saturated fats, is built on a very poor evidence base. It is clear that fats, and saturated fats, are not bad for you if eaten in moderation. I am sure more evidence will emerge around this issue in the next few years. It is clear that at present processed and ultra-processed foods are in the dog house and justifiably so. I am adamant that what you eat needs to be compatible with your culture which is why I wrote a piece on Medium about Diet as a Philosophy.
Please let common sense rule the day and if you find you like, and enjoy, walking or running 1 km or 5 km, who knows you may gradually extend your walks and runs to 10 km, half-marathons, marathons and possibly ultra-marathons. The intensity and distance are not that important it is getting started and staying committed that is important.

So I yes I have gone lukewarm on OMS because it is not the be-all and end-all of MS management. I have also heard from many independent sources that George Jelinek promotes it openly as an alternative option for the management of MS. I have seen many tragic examples of patients under my care who are now very disabled as a result of using lifestyle and wellness programmes as an alternative option to DMTs to manage their MS. OMS should only ever be used as a complementary MS management tool.

Conflicts of Interest

Preventive Neurology

Twitter

Medium

Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the position of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.

#DietSpeak: saturated fats – challenging the dogma

Barts-MS rose-tinted-odometer: ★★★

Since my rather neutral “#DIETSPEAK: IS THERE AN IDEAL MS DIET?” post last week, in which I refuse to support any particular MS diet I have had a torrent of social media abuse about my position. Intriguingly, many people out there have bought into the falsehood that saturated fats are bad for you and some commentators even believe that saturated fats cause MS. The evidence is clearly to the contrary for the former and for the latter the evidence is just not there to draw any causal inferences. In fact, as saturated fat consumption has gone down the incidence and prevalence of MS has increased. This alone indicates that saturated fat consumption cannot be the cause of MS.

John Maynard Keynes, the famous British economist responsible for ‘Keynesian economics’, is often quoted as saying: “When the facts change, I change my mind. What do you do, sir?”.

The claim that saturated fat is bad for health was promoted by the now-discredited physiologist and nutritionist Ancel Keys. His theory was based on his ‘Seven Countries Study’, which has now been discredited with several commentators suggesting that some of the data was made up. There is evidence that of 22 countries that he had data for, he cherry-picked 7 countries so the data would fit and prove his hypothesis. Despite this, he and his collaborators managed to change the dietary guidelines of the world, recommending a low-fat diet to counteract the cardiovascular disease epidemic. Tragically, the rest is history.

Image of Ancel Keys from ‘A decade of diet lies‘ HUFFPOST

The low-fat diet, in particular the low-saturated fat diet, resulted in a caloric switch to carbohydrates, which has seen obesity rates soar and contrary to what was expected cardiovascular disease rates have increased. It is now clear that Ancel Keys was heavily conflicted and was supported by the food industry. Yes, the food industry managed to influence a change in dietary guidelines that have killed tens of millions of people prematurely. I predict that when the dust settles on this issue the food industry will be judged to have behaved much worse than the tobacco industry.

The good news is that the facts have changed and several recent meta-analyses have been unable to find any evidence that saturated fats are bad for you (please see review below). The studies showing saturated fats are associated with poor health outcomes are confounded by other factors for example the consumption of processed carbohydrates.

To address the point that saturated fats cause MS you need to go back to causation theory and apply epidemiological principles. I have addressed this topic several times in the past on this blog, mainly in relation to EBV as a potential cause of MS. To prove or disprove causation you have to satisfy as many of the following nine criteria as possible.

1. CONSISTENCY AND UNBIASEDNESS OF FINDINGS
2. STRENGTH OF ASSOCIATION
3. TEMPORAL SEQUENCE
4. BIOLOGICAL GRADIENT (DOSE-RESPONSE RELATIONSHIP)
5. SPECIFICITY
6. COHERENCE WITH BIOLOGICAL BACKGROUND AND PREVIOUS KNOWLEDGE
7. BIOLOGICAL PLAUSIBILITY
8. REASONING BY ANALOGY
9. EXPERIMENTAL EVIDENCE

When you apply these nine criteria to saturated fat consumption none of them is fulfilled. I, therefore, can conclude that saturated fat consumption is not the cause of MS. On other words, the data disproves the hypothesis.

Another perspective that you can use to tackle this problem is an evolutionary medicine perspective and to look at how our ancestors evolved and what diets they ate. It is clear that our ancestor’s diets were high in saturated fats and as the history of MS suggests it is a relatively new disease it cannot be caused by saturated fat. In fact, if you want to finger a dietary factor you would point at sugar and processed carbohydrates rather than saturated fats.

I wrote a piece on Medium to explain why low-fat diets are potentially bad for you. You may find the evolutionary medicine approach to diet of interest; I think it may prove to be very relevant to MS.

Astrup et al. Saturated Fats and Health: A Reassessment and Proposal for Food-Based. J Am Coll Cardiol 2020 Aug 18;76(7):844-857. doi: 10.1016/j.jacc.2020.05.077. Epub 2020 Jun 17.Recommendations: JACC

The recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against stroke. Although SFAs increase low-density lipoprotein (LDL) cholesterol, in most individuals, this is not due to increasing levels of small, dense LDL particles, but rather larger LDL particles, which are much less strongly related to CVD risk. It is also apparent that the health effects of foods cannot be predicted by their content in any nutrient group without considering the overall macronutrient distribution. Whole-fat dairy, unprocessed meat, and dark chocolate are SFA-rich foods with a complex matrix that are not associated with increased risk of CVD. The totality of available evidence does not support further limiting the intake of such foods.

CoI: multiple

Twitter: @gavinGiovannoni Medium: @gavin_24211

Could diet be the new add-on DMT?

Barts-MS rose-tinted-odometer ★ ★★ ★ ★

I gave my first on using diet as a potential symptomatic and disease-modifying treatment for MS and as a preventative therapeutic strategy in MS, last night.

The symptomatic part of my talk was about food coma and using diet to prevent or reduce the impact of food coma. We are still studying why pwMS are so susceptible to food coma. I suspect it is because they have less cognitive reserve and food coma may interact with other medications to make it such a problem.

The really interesting part of my talk was using caloric restriction (CR), intermittent fasting (IF) or ketogenic (K) diet as a DMT. I suspect the mode of action of all these diets is via ketosis and inducing high levels of circulating β-hydroxybutyrate one of the ketone bodies. Ketone bodies are the source of energy the body uses when we have depleted our sugar stores (glycogen) and are fasting or not absorbing sugar from the gut.

Interestingly, β-hydroxybutyrate works via the hydroxycarboxylic acid receptor 2 (HCA₂), which is also known as niacin receptor 1 (NIACR1) and GPR109A. Why is this so important? This is the same receptor that fumaric acid works on. Yes, ketosis works at a cellular level in the same way that dimethyl fumarate (DMF) and diroximel fumarate work, i.e licensed MS DMTs.

Yes, CR/IF/K diet may induce a metabolic pathway that is known to be disease-modifying in MS.

There is an extensive literature, which I discovered about two years ago, showing that β-hydroxybutyrate works via NRF2 and downregulates NFKappa-B, the master inflammatory transcription factor. In other words ketosis, in particular β-hydroxybutyrate promotes programmed cell survival via the NRF2 two pathway and is also anti-inflammatory. β-hydroxybutyrate may even be better than the fumarates as a treatment for MS because it is likely to penetrate the CNS better than oral fumarates.

The corollary of the above could also explain why a processed and ultra-processed high carbohydrate diet is pro-inflammatory. Most people put it down to the pro-inflammatory signals from adipose tissue, but it could be related to the fact that carbohydrates, via insulin, inhibit ketosis and suppress β-hydroxybutyrate levels in the body.

Another nugget of information I found is that metformin also works via NRF2, but not via the HCA2 receptor. This may explain why metformin promotes rejuvenation of oligodendrocyte precursors and is being explored as a potential remyelination therapy in MS.

I have also discovered whilst reading the NRF2 literature that some statins, including simvastatin, activate NRF2. Could this be a potential mode of action of simvastatin in MS?

I didn’t have time to discuss MS prevention last night. However, we think that about 10-20% of the increase in MS incidence may be caused by childhood and adolescent obesity. This is why we are pushing for policy on sugar and a national campaign to tackle this problem.

So when I say I have declared war on sugar, I mean it in more ways than you realise.

Despite observational evidence showing that pwMS do well on CR/IF/K diets, the studies show that they are generally safe. However, we need controlled evidence before promoting these pwMS as a potential adjunctive treatment for MS. The good news is that there are ongoing studies looking into this. The one below is actually using MRI to see if a ketogenic diet has an impact on MRI activity, i.e. the inflammatory component of MS.

Are you up for biohacking your metabolism as a treatment for your MS?

Bahr et al. Ketogenic Diet and Fasting Diet as Nutritional Approaches in Multiple Sclerosis (NAMS): Protocol of a Randomized Controlled Study. Trials, 21 (1), 3 2020 Jan 2.

Background: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KDs and FDs on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate whether a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression.

Methods: This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing-remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions: a KD with a restricted carbohydrate intake of 20-40 g/day; a FD with a 7-day fast every 6 months and 14-h daily intermittent fasting in between; and a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed.

Discussion: Preclinical data suggest that a KD and a FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and a FD on disease progression of MS.

Trial registration: ClinicalTrials.gov, NCT03508414.

CoI: multiple

Sugar crash

My recent blog post on food coma (14-Jan-2019) not only uncovered another hidden symptom in MSers but has led us to start exploring this phenomenon in our patients and, hopefully, to some evidence-based advice on how to manage the problem.

In our short web survey on food coma, I was surprised to find that 86% of MSers report this phenomenon with 28 of the 81 respondents (35%) reporting their food coma as being severe or severe-and-incapacitating. When exploring the science I was surprised to uncover that insulin, the hormone that the pancreas releases in response to carbohydrates or sugar, is one of the main mediators of food coma. How could this be when my mother always used to accuse me of having a sugar rush as a child? A sugar rush is a so-called period of hyperactivity that occurs after ingesting too much sugar in a short period of time.

I was therefore not surprised to read the following well-done metanalysis debunking this piece of dogma. On the contrary, sugar does not cause a sugar rush, but a sugar crash, another term for food coma.

This and other evidence keeps mounting against sugar and the sugar industry. There seems to be very little reason for anyone to consume sugar or processed carbohydrates in any form. This is why nutritionists have started to refer to processed carbohydrates as empty calories.

So I am going to repeat myself again if you want to select a diet that is healthy for you can I suggest a real-food diet low in carbohydrates, i.e. free of all processed carbohydrates. This means you may need to get most of your calories from fats and proteins. The carbohydrates you eat on the real-food diet will be unprocessed with a low glycaemic index. As a result of this diet, you will keep your insulin levels low and hence you will reduce your postprandial hypersomnolence or ‘food coma’.

Keeping your insulin levels low will have other positive effects on your health; i.e. it will help you maintain a healthy weight, counteract insulin resistance and hence your chances of developing the metabolic syndrome (insulin resistance, diabetes, hypertension, hyperlipidaemia and obesity) and it should reduce your risk of developing common cancers.

What is there to lose? How easy is it to stick to the real-food diet? You tell me.

Mantantzis et al. Sugar rush or sugar crash? A meta-analysis of carbohydrate effects on mood. Neurosci Biobehav Rev. 2019 Jun;101:45-67.

The effect of carbohydrate (CHO) consumption on mood is much debated, with researchers reporting both mood improvements and decrements following CHO ingestion. As global consumption of sugar-sweetened products has sharply increased in recent years, examining the validity of claims of an association between CHOs and mood is of high importance. We conducted a systematic review and meta-analysis to evaluate the relationship between acute CHO ingestion and mood. We examined the time-course of CHO-mood interactions and considered the role of moderator variables potentially affecting the CHO-mood relationship. Analysis of 176 effect sizes (31 studies, 1259 participants) revealed no positive effect of CHOs on any aspect of mood at any time-point following their consumption. However, CHO administration was associated with higher levels of fatigue and less alertness compared with placebo within the first-hour post-ingestion. These findings challenge the idea that CHOs can improve mood, and might be used to increase the public’s awareness that the ‘sugar rush’ is a myth, inform health policies to decrease sugar consumption, and promote healthier alternatives.

Calling all vegans

As a vegan what supplements do I need to take?

I am in the process of researching the dietary landscape for people with MS and will not be ready to make any firm recommendations for some time, but I can make a recommendation of what diets to avoid. The first is a strict vegan diet without supplements.

My index patient was an Asian woman, in her mid-20s, with RRMS who referred for a second opinion about worsening MS symptoms and escalation therapy. She was on glatiramer acetate and was complaining of progressive visual disturbance and painful pins and needles in her hands and feet. When I saw her there was little doubt she had RRMS, but it was clear to me she had superimposed vitamin B12 deficiency as well. She had bilateral visual failure (6/60 vision) with large central blind spots and when I looked into the back of her eyes her optic nerve was very pale indicating she had lost a lot of nerve fibres in the eyes (optic atrophy). The clue to the diagnosis was that she was pale and had a smooth red tongue (atrophic glossitis) and she had lost sensation in her feet and her tendon reflexes were depressed (neuropathy). Other problems included excessive fatigue, shortness of breath with minimal exertion, memory loss, poor concentration and attention, irregular periods and patchy hair loss. When I asked her about her diet she volunteered to be a vegetarian for most of her life and had become a strict vegan in the last 5 years. Apart from the intermittent use of iron supplements for anaemia, she was not taking any supplements. When I checked her blood results she had very low vB12 levels and mild anaemia with a mixed pattern due to a combination of being iron and vB12 deficient. Tragically this patient’s visual function did not recover on vB12 supplements and her peripheral neuropathy became very painful presumably as the nerve fibres started to recover in her feet they started to fire aberrantly causing pain. She is now registered legally blind; a tragedy as her visual loss was preventable.

In addition, to this patient in my 5-years of doing the physician’s clinic at Moorfields eye hospital under Professor W. Ian McDonald’s mentorship, I must have diagnosed subacute combined degeneration of the spinal cord due to dietary vB12 deficiency in at least 5 other patients who were vegans. I have also seen a remarkable case of a lady, who was a vegan, who presented with pins and needles around the mouth and a numb tongue. She was not vB12 deficient as she was taking vB12 supplements, but when I did her peripheral metabolic profile she was profoundly zinc deficient and also had low levels of selenium. Within a week of going onto zinc and selenium supplements, her symptoms resolved.

From an evolutionary medicine, perspective veganism is not natural. We evolved as omnivores, i.e. vegetable and meat eaters; our metabolism tells us this and hence a strict vegan diet is unnatural and unbalanced. If you are vegan you need to make sure you supplement your diet with the following essential nutrients and minerals:

Vitamin B12
Iron
Zinc
Iodine
Calcium
Essential fatty acids, in particular, omega-3 fatty acids

The following may need supplementing:

Vitamin D (you can get sufficient from sunlight exposure at the correct time of the year). At Barts-MS we recommend that all our patients and first- and second-degree relatives take vD supplements according to the vD Council’s recommendations.
Selenium (you can get sufficient selenium from some vegan food sources, e.g. brazil nuts, mushrooms, sunflower seeds and beans)
Protein (adults can get enough protein from a vegan diet, but children and people in a catabolic state, for example with certain diseases, may need additional protein sources)

If you have children on a vegan diet you should be careful about making sure they get enough protein and the above supplements. If not they may become stunted.

The bottom line; strict veganism is not natural in health and/or disease and is deficient in several key nutrients and minerals that need to be supplemented. This is a problem for people who are on the breadline; supplements are relatively expensive and hence vegan diets put poorer people at greater risk of the health consequences of an inadequate diet.

Please note that vB12 is essential for myelin metabolism and is the reason why when you are vB12 deficient you get a mixed demyelinating and axonal nerve loss picture in the optic nerves, spinal cord and peripheral nerves. There is a body of literature showing that pwMS tend to have low vB12 levels and this may be an indication of them needing more vB12 that the average person as it is consumed as part of myelin turnover. I therefore suspect that pwMS are even more senstive to vegan diets than people without MS.

Baroni et al. Vegan Nutrition for Mothers and Children: Practical Tools for Healthcare Providers. Nutrients. 2019 Jan; 11(1): 5.

As the number of subjects choosing vegan diets increases, healthcare providers must be prepared to give the best advice to vegan patients during all stages of life. A completely plant-based diet is suitable during pregnancy, lactation, infancy, and childhood, provided that it is well-planned. Balanced vegan diets meet energy requirements on a wide variety of plant foods and pay attention to some nutrients that may be critical, such as protein, fibre, omega-3 fatty acids, iron, zinc, iodine, calcium, vitamin D, and vitamin B12. This paper contains recommendations made by a panel of experts from the Scientific Society for Vegetarian Nutrition (SSNV) after examining the available literature concerning vegan diets during pregnancy, breastfeeding, infancy, and childhood. All healthcare professionals should follow an approach based on the available evidence in regard to the issue of vegan diets, as failing to do so may compromise the nutritional status of vegan patients in these delicate periods of life.