Food Coma or Postprandial Hypersomnolence

Gavin Giovannoni

1. Food Coma Or Postprandial H ypersomnolence MS TRUST CONFERENCE 2020 Gavin Giovannoni

2. Disclosures No relevant conflicts of interest in relation to this specific presentation. Over the last 5 years I have received personal compensation for participating in advisory boards in relation to clinical trial design, trial steering committees, and data and safety monitoring committees from: Abbvie, Atar a Bio, Biogen, Canbex, Sanofi- Genzyme, Genentech, GSK, MSD, Merck KGaA, Novartis, Roche, Synthon BV and Teva .

3. Definition

4. Siesta Syndrome The Hammock, by Gustave Courbet (1844)

5. Science

6. “The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” Thomas Huxley 4 May 1825 – 29 June 1895

7. The physiology of food coma Adenosine and hypocretin/orexin Glucose concentration stimulate ventrolateral preoptic nucleus of the hypothalamus via astrocytic release of adenosine Orexin-expressing neurons appear to be hyperpolarized (inhibited) by a glucose-activated potassium channel. This inhibition is hypothesized to then reduce output from orexigenic neurons to aminergic, cholinergic, and glutamatergic arousal pathways of the brain, thus decreasing the activity of those pathways. Parasympathetic activation In response to food in the stomach and small intestine, parasympathetic nervous system is stimulated and the activity of the sympathetic nervous system decreases. This shift in the balance of autonomic tone leads to a subjective state of low energy and a desire to be at rest Insulin, large neutral amino acids, and tryptophan High glycemic index foods raise insulin levels which stimulates the uptake of valine, leucine, and isoleucine into skeletal muscle, but not uptake of tryptophan. Tryptophan becomes preferentially available to the large neutral amino acid transporter at the blood–brain barrier. Tryptophan is converted to serotonin and melatonin, which result in sleepiness. Insulin-induced hypokalemia Insulin increases the activity of Na/K ATPase, causing increased movement of potassium into cells from the extracellular fluid. The effects of hypokalemia can include fatigue. https://en.wikipedia.org/wiki/Postprandial_somnolence

8. Diabetes, December 24, 2014. sugar / glucose / carbohydrates / insulin

9. Per capita sugar consumption (UK & USA) R.J. Johnson, et al.: Am J Clin Nutr 86:899 –906, 2007.

10. Index cases

11. Index case 47 year old women with SPMS My index patient is so affected by PPS that she now only eats one meal a day; her evening meal. She does this quite late so that she can crash and sleep about an hour after eating. She is a professional and needs to be functional during the day and finds if she eats anything substantial in the day she simply can’t work because of her overwhelming desire to sleep. We have tried caffeine, modafinil and amantadine to counteract PPS, but they only had a small effect in counteracting her PPS and allowing her to work productively . She finds carbohydrate-rich foods particularly potent at inducing ‘food coma’ and now avoids them. She weighs 47 kg with BMI of 17

12. Social media

13. https://multiple-sclerosis-research.org/2019/01/food-coma-does-it-affect-you/

14. Blog survey

15. https://multiple-sclerosis-research.org/2019/01/food-coma-does-it-affect-you/

16. No Severe and incapacitating https://multiple-sclerosis-research.org/2019/01/food-coma-does-it-affect-you/

17. https://multiple-sclerosis-research.org/2019/01/food-coma-does-it-affect-you/

18. https://multiple-sclerosis-research.org/2019/01/food-coma-does-it-affect-you/

19. https://multiple-sclerosis-research.org/2019/01/food-coma-does-it-affect-you/

20. https://multiple-sclerosis-research.org/2019/01/food-coma-does-it-affect-you/

21. https://multiple-sclerosis-research.org/2019/01/food-coma-does-it-affect-you/

22. Barts-MS audit

23. Objectives Confirm blog o nline survey that found 85% of pwMS reported suffering from PPS As this phenomenon had not been formally studied before, and is a potentially burdensome symptom for pwMS, we decided to do an audit in order to: Compare whether pwMS suffer from PPS more than people without MS (pw/MS) Examine whether the severity of PPS is correlated to the severity of MS Obtain information on the treatments pwMS are using and how effective these treatments have been Slide courtesy of Tatiana Christmas and Neena Singh

24. Methodology Qualitative research was conducted using an online survey, emailed to 350 pwMS from Barts-MS Their siblings, partners and friends were also asked to complete a similar survey for the general population to allow comparison between the two groups. Participants were asked to complete the survey one hour after eating lunch. Link to the survey for people with MS:  https://forms.gle/xZskX1pCKJwUDFJZ9 ​  Slide courtesy of Tatiana Christmas and Neena Singh

25. Methodology The Stanford Sleepiness Score was used to objectively assess degree of Postprandial Somnolence. Slide courtesy of Tatiana Christmas and Neena Singh

26. Results Frequency of Stanford Sleepiness Score Cohort characteristics The mean SSS for pwMS was 3.46, whilst the mean SSS for pw/MS was 2.52 (p=0.001). The mean SSS for pwMS who didn’t describe having fatigue as a symptom was 2.80. Slide courtesy of Tatiana Christmas and Neena Singh

27. Results From the pwMS, 18% felt their PPS started after anything they ate, 61% after an average meal, 22.4% after a slightly large meal and 18.2% after a very large meal. From the pw/MS, 12.5% started after eating anything, 12.5% after an average sized meal, 50% after a slightly large meal and 25% after a very large meal. 63% of pwMS reported making changes to their diet to help their symptoms, these included reducing the portion size the number of portions eaten in a day reducing the amount of specific food components consumed, specifically carbohydrates and fat. Caffeine and exercise were also commonly used, with 20% and 13% of pwMS reporting having tried these as Solutions to improve their symptoms of PPS Slide courtesy of Tatiana Christmas and Neena Singh

28. Quotable Quotes! Slide courtesy of Tatiana Christmas and Neena Singh

29. Conclusions

30. Discussion PwMS are affected by PPS more than control subjects - more people with MS subjectively felt that they suffered from the phenomenon than the general population, but we have also been demonstrated this objectively using the SSS. It is well established that pwMS suffer from fatigue more than the general population, but it is clinically useful to determine whether PPS is a major factor during their daily routines as tailored advice could be given to help with this. pwMS are adopting self-management strategies to help reduce their symptoms of PPS, the most commonly used intervention was caffeine, however patients are making changes to their diet to improve their symptoms which has had varying effects on their symptoms Smaller portion sizes Intermittent fasting Low carbohydrate diet / low glycaemic index diets Caloric restriction / ketogenic diets Moving forward L arger sample size is needed to make the project more robust W e now plan to study the effect of specific food groups on PPS symptoms via glucose/insulin response curve. #AntiSugar

31. https://medium.com/@gavin_24211/evolutionary-medicine-why-low-fat-diets-are-bad-for-you-95922f2f1999

32. Tatiana Christmas, Gavin Giovannoni and Neena Singh, MS Academy Masterclass 7

33. www.ms-res.org / www.clinicspeak.com / www.msbrainhealth.org Twitter @GavinGiovannoni / www. medium.com/@gavin_24211 Thank You! #ThinkHand #ChariotMS #OratorioHand #OffLabel #ThinkCognition #ThinkSocial #AttackMS #ThinkCombination #PreventMS #Women4MS #Run4MS #DigestingScience #ClinicSpeak

34. Questions