1. Ramadan; “unique metabolic model.” Usama Ragab Youssif (Msc.) Assistant Lecturer of Internal Medicine Tuesday, 16 May 2017

2. Agenda Introduction and facts. Physiological effects of Ramadan Fasting. Fasting in Health. Fasting in disease. Fasting and thyroid. Fasting and kidneys Fasting and heart. Fasting and GIT. Fasting and medicines. Final bottom line and take home message.

3. بسم الله الرحمن الرحيم يَا أَيُّهَا الَّذِينَ آمَنُوا كُتِبَ عَلَيْكُمُ الصِّيَامُ كَمَا كُتِبَ عَلَى الَّذِينَ مِن قَبْلِكُمْ لَعَلَّكُمْ تَتَّقُونَ (183) أَيَّامًا مَّعْدُودَاتٍ ۚ فَمَن كَانَ مِنكُم مَّرِيضًا أَوْ عَلَىٰ سَفَرٍ فَعِدَّةٌ مِّنْ أَيَّامٍ أُخَرَ ۚ وَعَلَى الَّذِينَ يُطِيقُونَهُ فِدْيَةٌ طَعَامُ مِسْكِينٍ ۖ فَمَن تَطَوَّعَ خَيْرًا فَهُوَ خَيْرٌ لَّهُ ۚ وَأَن تَصُومُوا خَيْرٌ لَّكُمْ ۖ إِن كُنتُمْ تَعْلَمُونَ (184) شَهْرُ رَمَضَانَ الَّذِي أُنزِلَ فِيهِ الْقُرْآنُ هُدًى لِّلنَّاسِ وَبَيِّنَاتٍ مِّنَ الْهُدَىٰ وَالْفُرْقَانِ ۚ فَمَن شَهِدَ مِنكُمُ الشَّهْرَ فَلْيَصُمْهُ ۖ وَمَن كَانَ مَرِيضًا أَوْ عَلَىٰ سَفَرٍ فَعِدَّةٌ مِّنْ أَيَّامٍ أُخَرَ ۗ يُرِيدُ اللَّهُ بِكُمُ الْيُسْرَ وَلَا يُرِيدُ بِكُمُ الْعُسْرَ وَلِتُكْمِلُوا الْعِدَّةَ وَلِتُكَبِّرُوا اللَّهَ عَلَىٰ مَا هَدَاكُمْ وَلَعَلَّكُمْ تَشْكُرُونَ (185) سورة البقرة

4. Who must fast? صوم رمضان فرضه الله تعالى على كل : 1- مسلم. 2- بالغ، فلا يجب على الصبي. 3- عاقل، فلا يجب على المجنون. 4- قادر على الصوم، فلا يجب على المريض الذي يزيد الصوم مرضه، أو يؤخر بُرؤه. 5- مقيم، غير مسافر. 6- سالم من الموانع، أي من الحيض والنفاس.

5. In 2009, Islam making up 23% of the world population of 6.8 billion, and is growing by ∼ 3% per year

6. Fast Facts Ramadan in the Islamic calendar is 9 th lunar months and the start of the islamic year advances 11 days each year compared with the seasonal year. Ramadan occurs at different times of the seasonal year. Ramadan occurs in a different season every 9 years.

7. Fast Facts (cont.) What is different? Eating pattern. Amount of food. Night time eating. Day time sedentary life. Abstinence of what? is it selective fasting? Food. Water. Smoking. Oral medication. IV fluids & nutrients.

8. Fasting means abstinence X To stop eating, drinking and sexual activity from dawn until dusk X Smoking is also prohibited during fasting ! X

9. Exemption Upon reaching puberty, all healthy Muslims are required to partake in the fast. Individuals who are sick, traveling, pregnant, breast-feeding, menstruating, or debilitated are exempt from fasting. However, many Muslims who are eligible for exemption choose to fast nonetheless. Trepanowski and Bloomer Nutrition Journal 2010, 9:57

10. The truth Muslims consume a greater variety of foods during Ramadan compared with the rest of the year. Also, sugary foods and drinks are consumed more frequently during Ramadan. Am J Clin Nutr 1988, 48:1197-1210. Am J Clin Nutr 1982, 36:350-353.

11. Introduction and facts. Physiological effects of Ramadan Fasting. Fasting in Health. Fasting in disease. Fasting and thyroid. Fasting and kidneys Fasting and heart. Fasting and GIT. Fasting and medicines. Final bottom line and take home message.

12. 1- On Calorie intake Regarding diet, energy intake during Ramadan has been reported to increase in Saudi Muslims and decrease in Indian Muslims ; these discrepant findings are believed to be due to the differences in food choices between the groups. Am J Clin Nutr 1995, 62:302-307.

13. 1- Calorie intake (cont.) Trepanowski and Bloomer Nutrition Journal 2010, 9:57

15. Counterregulatory hormones (stress) will increase thus stimulating both gluconeogenesis and ketogenesis Reduced insulin levels

16. Response of the body to fasting Reduced insulin level enhances glycogenolysis and prevents hypoglycemia. Moreover, this process is followed by elevated levels of glucagon, growth hormone, and catecholamines, which are involved in the stimulation of gluconeogenesis and ketogenesis.

17. 2- Effects of Fasting on Carbohydrate Metabolism 1. Slight fall in serum Glucose (to 60 mg) 2. Serum Insulin decreases due to 1 3. Serum Glucagon and Growth Hormone increases due to 1 4. Increase in sympathetic activity

18. 3- Fasting and plasma lipids Trepanowski and Bloomer Nutrition Journal 2010, 9:57

19. 4- Other Effects of Fasting Weight loss of 1.7-3.8 Kg (obese lost more weight than non obese) Decrease in appetite due to ketosis and increase in Beta-endorphins

20. Many Confounders?? To summarize, little consensus exists regarding the effects of Ramadan fasting on the majority of health related outcomes. Many of the discrepancies regarding findings are likely due to: Differences between studies in daily fasting time Smoking in non fasting time Drug consumption Eating habits. Trepanowski and Bloomer Nutrition Journal 2010, 9:57

21. Introduction and facts. Physiological effects of Ramadan Fasting. Fasting in Health. Fasting in disease. Fasting and thyroid. Fasting and kidneys Fasting and heart. Fasting and GIT. Fasting and medicines. Final bottom line and take home message.

22. Thyroid disease and Fasting

24. Optimal timing for the ingestion of thyroid hormone during Ramadan There are many factor to be in mind: gastric motility greatly impaired with excess fast. heavy meals circadian rhythms alteration, and effect of deiodinase activity. So, it is better to take levothyroxin an hour before Sohor or at bed time away from any medication.

25. Optimal timing for the ingestion of anit-thyroid drugs during Ramadan Propylthiouracil has a limitation during Ramadan due to its required dosing of every 4–6 h. The other most commonly used anti-thyroid drug “methimazole” has a fairly long duration of action, and can be taken at any time of the day in a single or divided doses.

26. Thyroid Final Bottom line Hypothyroid patients can take their thyroxine at bedtime easily (but there should be an interval of minimum 2 hours since the last meal). Hyperthyroid patients, the preferred oral antithyroid treatment is methimazole, which can be taken once or twice daily in Ramadan easily. Patients with mild to moderate symptoms of hyperthyroidism can fast safely.

27. Introduction and facts. Physiological effects of Ramadan Fasting. Fasting in Health. Fasting in disease. Fasting and thyroid. Fasting and kidneys Fasting and heart. Fasting and GIT. Fasting and medicines. Final bottom line and take home message.

28. Renal Function in Fasting Urinary volume, osmolality, solute and electrolyte excretion remain normal Slight increase in BUN (insignificant) Increase in Uric acid (less in Ramadan fasting than in prolonged fasting) Ibnosina Journal of Medicine and Biomedical Sciences2.5 (2010): 240-257

29. Kidney disease & Risk of hypoglycemia

30. J Res Med Sci 2014;19:665-76.

31. RecommendationIssue -concentration of immunosuppressive drugs tends to remain stable -No kidney loss has been documented. -One author: cyclosporine toxicity, acute rejection episodes, and urinary infections. Ramadan and kidney transplant (463 patients) -does not seem to deteriorate health. -any renal changes are fully reversible after 10 days from the end of the fasting. Ramadan and urolithiasis (1,262 subjects) -Existing data in the literature are scarce and give inconclusive results. -No severe adverse effects have been recorded, apart from one study (Al- Muhanna). -Fasting on non-dialysis days is probably safe and that dietary advice in fasting patients assumes increasing importance*. Ramadan and chronic kidney disease (140 subjects) 40 on hemodialysis, 18 on peritoneal dialysis (PD), 15 on predialysis, 67 on pharmacological treatment. *Ibnosina Journal of Medicine and Biomedical Sciences2.5 (2010): 240-257

32. Patients suffering from acute tubular necrosis, polyuria (urine volume ≥2.5 L/day), uncontrolled or poorly controlled diabetes mellitus and insipidus or other dysmetabolic disorders, hypertension, angina, postural hypotension, acute infections, significant co-morbidities (such as cardiovascular disorders and chronic liver disease) leading to marked limitations and amendments of daily activities History of noncompliance and adherence to therapy, dietary and drugs modifications. Who should not fast??

33. Clinical recommendations for patients willing to fast Patients should attend regular follow-up every 1-2 weeks, before, during and after Ramadan. Patients should take regularly their treatment twice daily (with suhoor and Iftar respectively); if not possible shouldn’t fast.

34. Clinical recommendations for patients willing to fast (cont.) They should break the fasting if the plasma creatinine increases by the 30% above the baseline values and/or if you observe clinical symptoms due to changes in serum potassium and sodium. Body weight, blood pressure, biochemical parameters such as fluid and electrolytes should be regularly checked

35. Clinical recommendations for patients willing to fast (cont.) They should avoid high potassium and phosphorous diet (such as dates, apricots, fried food, nuts, cheese, soft juices and drinks, tea, coffee). If they have a tendency to hyperkalemia, they should take some calcium resonium powder (30 g/die with lactulose once a day). Rehydrate vs. dehydrate vs. overhydrate.

36. Introduction and facts. Physiological effects of Ramadan Fasting. Fasting in Health. Fasting in disease. Fasting and thyroid. Fasting and kidneys Fasting and GIT. Fasting and heart. Fasting and medicines. Final bottom line and take home message.

37. Fasting not eating??!! Under normal circumstances, fasting (not eating) is the normal state of feeding and the postprandial state is the temporary state. There is a reduction in the secretions and slowing in the GIT motility. Ibnosina Journal of Medicine and Biomedical Sciences2.5 (2010): 240-257

38. Fasting and common GI disorders (cont.) J Fasting Health. 2017; 5(1): 20-23.

39. 1- Gastro-Esophageal Reflux Disease Gastro-esophageal Reflux disease is higher during Ramadan fasting. Eating too fast without chewing or chewing with mouth open, smoking at Iftar and Sohar, drinking too much of carbonated and caffeinated beverages, such as cola, coffee and tea and eating fatty and spicy food. Ibnosina Journal of Medicine and Biomedical Sciences2.5 (2010): 240-257

40. 1- Gastro-Esophageal Reflux Disease (cont.) Diet should contain a lower fat content and the meals are made smaller in size. If erosive disease is evident by endoscopy, treatment should be given in the form of proton pump inhibitors (PPI’s) at iftar and suhour. (NERD) or GERD diagnosed by symptoms only, a single daily dose of PPI should be adequate before Iftar. Ibnosina Journal of Medicine and Biomedical Sciences2.5 (2010): 240-257

41. 2- Bowel diseases IBD?? Which phase determine your response: Active = full nutrition support. Quiescent = fast and divide drugs at Iftar and suhor. Fasting will be helpful for IBS. Ibnosina Journal of Medicine and Biomedical Sciences2.5 (2010): 240-257

42. Changes in liver function tests during Ramadan fasting Liver glycogen content is decreased by glycogenolysis. Fasting hyperbilirubinemia: occurs in healthy individuals but remember Gilbert’s syndrome. No significant changes in ALT, AST, protein, albumin in any of the studies in normal Ibnosina Journal of Medicine and Biomedical Sciences2.5 (2010): 240-257

43. Fasting in chronic liver diseases Patients suffering from cirrhosis should be assessed individually. Patients with decompensated cirrhosis should be advised against fasting. Ibnosina Journal of Medicine and Biomedical Sciences2.5 (2010): 240-257 X X

44. Drugs for GIT

45. Final bottom line for liver & GI disorder in Ramadan Most mild and stable GI conditions do not constitute a reasonable cause for avoiding fasting. 1 Avoidance of over-eating, 2 eating low fat food, 3 drinking plenty of water, and 4 adjusting previous medications to once or twice daily regimes to meet the timing of Iftar & Suhoor.

46. Introduction and facts. Physiological effects of Ramadan Fasting. Fasting in Health. Fasting in disease. Fasting and thyroid. Fasting and kidneys Fasting and GIT. Fasting and heart. Fasting and medicines. Final bottom line and take home message.

47. Fasting and heart No clear scientific consensus on its effects on cardiovascular disease. Risk factors are modified (improved). Stable remain stable* Previous controlled attacks. Predictable stable angina. Early stage of heart failure. Properly controlled heart rhythms Hypertension is probably more better controlled (possibly due to lack of fluid).

48. Modification of CV risk? Studies have shown improvement in LDL and 30- 40% increase in HDL Cholesterol levels. Triglyceride level is variable depending on dietary habits of the local population. (This is not a trend) There is improvement in blood glucose and ? HbA1C On an average there is 1.7 to 3.8 kgs of weight reduction for those who are overweight or obese.

49. Fasting and Cardiovascular Health 465 outpatients with stable heart disease had no increase in hospitalization in Ramadan. Hospitalization for heart failure, stroke, acute coronary events did not increase in Ramadan. A change in circadian variation of cardiac events: Less at 5 – 8 am, 11% vs 19% More at 5 – 6 pm, 11% vs 6% More at 3 – 4 am, 11% vs 7% More strokes between noon - 6 pm vs 6 am to noon. Ozkan et al. J Int Med Res. 37:1988, 2009 Chong VH. Singapore Med J. 50:619, 2009

50. Unstable CVD Recent ‘Heart Attack’ Unstable Angina Decompensated Heart Failure Uncontrolled severe Hypertension Active and symptomatic Heart Rhythm problem requiring active teatment.

51. Hypertension

52. Hypertension (cont.)

55. Medications During Ramadan (Cardio)

56. Selected drugs with circadian variation in pharmaco- kinetics and pharmaco-dynamics

57. Commonly encountered drug-food interactions and recommendations

58. DIET Complex carbohydrate : whole grain Avoid food with High Glycemic Index (GI) Proteins are essential. Some amount of fat is essential Vitamins from vegetables and fruits. Drink plenty of water. Avoid carbonated and caffeinated drinks.

59. Final Bottom Line

60. People who are exempted from fasting Aged*Sick** Pregnant Women** Suckling Women** Menstruating Women** * فدية طعام مسكين * * قضاء ما عليه يوم مقابل يوم قبل مجئ رمضان التالي Minors Traveler** Mentally Impaired فَمَن كَانَ مِنكُم مَّرِيضًا أَوْ عَلَىٰ سَفَرٍ فَعِدَّةٌ مِّنْ أَيَّامٍ أُخَرَ ۚ وَعَلَى الَّذِينَ يُطِيقُونَهُ فِدْيَةٌ طَعَامُ مِسْكِينٍ ۖ

61. In spite of fasting in Ramadan is practised by many many Muslims worldwide, there is yet no clear scientific consensus on its effects many health issue Even in diabetes all are Expert opinion rather than strong evidence based practice.

62. Mark Ramadan on your office calendar, and prepare to be the one that brings up the topic for discussion. Patients are unlikely to initiate the discussion. Inquire about past experiences during Ramadan fasts, and plans for the upcoming Ramadan.

63. Consider a switch to slow-release or once- daily medications for the month of Ramadan. Recommend dosing schedules coincident with pre-dawn (Suhoor) and sunset (Iftar) meals.

64. وَمَا جَعَلَ عَلَيْكُمْ فِي الدِّينِ مِنْ حَرَجٍ سورة الحج الآية 78 فقال عليّ بن عبد الله : الحرج : الضيق, فجعل الله الكفارات مخرجا من ذلك, سمعت ابن عباس يقول ذلك.

65. عن أبي هريرة رضي الله عنه ، قال : سمعت رسول الله صلى الله عليه وسلم يقول : ( ما نهيتكم عنه فاجتنبوه ، وما أمرتكم به فأتوا منه ما استطعتم ؛ فإنما أهلك الذين من قبلكم كثرة مسائلهم ، واختلافهم على أنبيائهم ) رواه البخاري ومسلم.

66. حدثنا قتيبة بن سعيد ، حدثنا عبد العزيز بن محمد ، عن عمارة بن غزية ، عن نافع ، عن ابن عمر قال : قال رسول الله صلى الله عليه وسلم : ” إن الله يحب أن تؤتى رخصه ، كما يكره أن تؤتى معصيته “ صححه الالباني رحمه الله مسند أحمد بن حنبل - ومن مسند بني هاشم مسند عبد الله بن عمر رضي الله عنهما - حديث :‏5703‏