REVIEW ARTICLE Year : 2021  |  Volume : 13  |  Issue : 3  |  Page : 102-121

Ramadan fasting in health and disease (2020): A narrative review

Khadija Hafidh1, Khawla F Ali2, Salem A Beshyah3
1 Department of Medicine, Dubai Medical College; Department of Diabetes and Endocrinology, Rashid Hospital, DHA, Dubai, United Arab Emirates
2 Department of Medicine, Royal College of Surgeons in Ireland Medical University of Bahrain, Adliya, Bahrain
3 Department of Medicine, Dubai Medical College, DHA, Dubai, United Arab Emirates

Date of Submission30-May-2021Date of Decision06-Jun-2021Date of Acceptance07-Jun-2021Date of Web Publication27-Sep-2021

Correspondence Address:
Dr. Khadija Hafidh
Department of Medicine, Dubai Medical College, Dubai
United Arab Emirates

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ijmbs.ijmbs_35_21

The medical literature on health aspects of Ramadan fasting (RF) is widely spread in many journals of varying access, making it less readily available to those interested in the subject. We performed a nonsystematic review of the international literature from a major online database (PubMed in 1 year [2020]). The search term “Ramadan fasting” was used, and relevant literature was narrated in a concise thematic account excluding diabetes. The publications spanned fundamental, clinical, ethical, professional, cultural, and advocacy facets. The publications predictably crossed the conventional disciplinary lines and geographical locations and appeared in journals with different access systems. The contents are presented under the emerged themes depending on the retrieved literature. This year, the basic coverage included changes in physiology, nutrition during Ramadan. However, the clinical issues included a more comprehensive range such as the impact of RF on the liver and gut, and endocrine conditions such as hypothyroidism and adrenal insufficiency. Coverage also included chronic kidney disease, maternal health and fetal well-being, cardiovascular medicine, nature and function of eyes, and neurological conditions, especially epilepsy. Sports medicine and athletes' well-being received somewhat prominent coverage. Other researchers focused on documenting patients' and health-care professionals' perceptions, attitudes, and practices during Ramadan. Health aspects of RF received a sustained academic interest with a broad spectrum in 2020. This narrative provides a scoping overview to help researchers and clinicians catch up quickly with state-of-the-art science today.

Keywords: Cardiovascular, endocrine, literature, metabolism, nutrition, patients' perceptions, physiology, pregnancy, professional, Ramadan, renal, research, sports medicine

How to cite this article:
Hafidh K, Ali KF, Beshyah SA. Ramadan fasting in health and disease (2020): A narrative review. Ibnosina J Med Biomed Sci 2021;13:102-21
How to cite this URL:
Hafidh K, Ali KF, Beshyah SA. Ramadan fasting in health and disease (2020): A narrative review. Ibnosina J Med Biomed Sci [serial online] 2021 [cited 2021 Sep 27];13:102-21. Available from: http://www.ijmbs.org/text.asp?2021/13/3/102/326773   Introduction 

The impact on health and disease results from the direct biological effects of the fasting itself and the associated social changes. Recently, health-care providers have shown increased interest regarding possible health-related risks due to Ramadan fasting (RF) practiced by adult Muslims. It includes that the individuals abstain from eating and drinking from dawn to sunset.

The medical profession and religious scholars got closer to patients' advice based on objective risk assessment in common conditions.[1] Although Muslim patients with acute or chronic medical conditions may be exempted from fasting, many observe the fast, even against the physicians' advice. This may adversely affect their health if not appropriately addressed by implementing evidence-based recommendations.[2],[3]

Keeping up with developments in RF research may prove difficult, and hence, a narrative overview under a single cover may help present a digest of the research and expert opinion published in the year. The literature published in 2017–2019 has been reviewed previously.[4],[5],[6] The present article aims to provide a thematic overview of the global research work in 2020. For practical reasons, the narrations of the diabetes-related literature of 2019 and 2020 were published separately.[7],[8] The present review aims allow researchers to catch up with the year's aims to allow researchers directions and highlight the evidence base that may direct practice for clinicians.

  Materials and Methods 

This is a narrative, nonsystematic review of the literature retrieved from two online databases over a full calendar year (2020). The search term “Ramadan fasting” was used to identify the relevant records from PubMed. Due to the extensive number, articles on diabetes were submitted separately elsewhere and were excluded from the present manuscript.[6] The selected articles were reviewed and narrated thematically to provide reasonably concise but adequate representative reading material. Only full-text research articles and systematic reviews-meta analyses in English were included.

  Results 

Physiology and nutrition

Five original studies and two systematic reviews addressed various physiological and nutritional issues during Ramadan.[9],[10],[11],[12],[13],[14],[15] Zouhal et al.[9] studied the effects of RF on gut hormones in thirty sedentary males randomly allocated to either an experimental or a control group. The experimental group completed their RF rituals. There were significant pre-to-post improvements for leptin, GLP-1, peptide YY, and cholecystokinin in the experimental group with no interaction effect for ghrelin. No significant changes occurred in plasma volume variations after RF in either groups. Based on these findings, the authors concluded that RF may be an effective strategy to modify appetite-regulating hormones, leading to improved body composition (BC) indices and reduced obesity. Nugraha et al.[10] determined the effect of RF on fatigue in young individuals. Sleepiness, mood-related symptoms (MRS), and BC were determined as well. Thirty-four young males and females were assessed before, during, and after Ramadan. This study illustrates how prolonged fasting, like RF, benefits the youth, particularly by decreasing fatigue, improving MRS, and positively impacting BC. Miladi et al.[11] compared the 6-min walk test (6MWT) data of a group of 22 healthy fasting boys with an age-matched nonfasting group. The 6MWTs were performed during three experimental conditions: pre-Ramadan (PR), mid-Ramadan, and post-Ramadan. The findings suggest that, in boys, RF does not impact the 6MW distance, heart rate, or oxygen saturation but has minimal impact on the blood pressure (BP). Akın et al.[12] estimated the physiological effects of RF on muscle function and muscle mass in older people. A random sample was recruited from healthy older Muslim people aged 60 years and older who intended to fast for 30 days during Ramadan. Dietary data of the patients during Ramadan were obtained by a 43-item Food Frequency Questionnaire. The mean age of the older people was 66.7 years of age, and 50% were females. There were no significant changes in body weight, muscle function, and muscle mass before and after RF. They consumed adequate milk and yogurt before and after RF. Restriction in meal timing has emerged as a promising dietary approach for managing obesity and dysmetabolic diseases. Levels of cortisol, melatonin, ghrelin, and leptin are highly correlated with circadian rhythmicity. The levels of these hormones are affected by sleep, feeding, and general behaviors and fluctuate with light and dark cycles. Al-Rawi et al.[13] examined the effect of RF on daytime levels of ghrelin, leptin, melatonin, and cortisol in a group of overweight and obese subjects, to determine how anthropometric, dietary, and lifestyle changes during Ramadan correlate with these hormonal changes. Fifty-seven overweight and obese male and female subjects were enrolled. At the end of Ramadan, serum levels of ghrelin, melatonin, and leptin significantly decreased, while salivary cortisol did not change compared to the levels assessed in the prefasting state. Thus, RF significantly altered serum levels of ghrelin, melatonin, and serum leptin. Further, male sex and anthropometric variables were the most impacting factors on the tested four hormones.

A systematic review and meta-analysis by Pellegrini et al.[14] summarized the evidence on the effect of time-restricted feeding (TRF) on weight-loss and cardiometabolic variables compared to unrestricted-time regimens. Studies involving TRF regimen were systematically searched up to January 2019. A total of 11 studies, 5 randomized controlled trials and 6 observational, were included. All studies had a control group without time restriction; hours of fasting ranged from 12 h to 20 h and study duration from 4 to 8 weeks. Most studies involved RF. TRF determined a greater weight loss than control regimens. The subgroup analysis showed an inverse association between TRF and fat-free mass in observational studies. An overall significant reduction in fasting glucose concentrations was observed with TRF regimens. No between-group differences in the other variables were found. TRF regimens achieved a superior effect in promoting weight loss and reducing fasting glucose compared to free time in meal consumption. However, long-term and well-designed trials are needed to draw definitive conclusions. In another systematic review and meta-analysis, Jahrami et al.[15] estimated the effect size of body weight changes in healthy, nonathletic practicing RF, Several databases were searched and 85 studies conducted in 25 countries were identified. Fasting may confer a significant slight reduction in body weight in nonathletic healthy people aged 16 years and above, directly associated with fasting time and variably correlated with the season and country.

  Kidneys 

Impact of Ramadan fasting on renal function in chronic kidney disease

There is no clear information about whether there is an obstacle to fasting in patients with chronic kidney diseases (CKD). Baloglu et al.[16] investigated the effects of RF on the kidney and the factors affecting this relationship in patients with CKD. They involved 117 patients (36 females, mean age 60 years) with stage 2–3 CKD observing RF. Patients were evaluated for acute kidney injury (AKI) during Ramadan. Of that cohort, 27 patients developed AKI. While patients without AKI fasted for more days, urea levels, and frequency of hypertension were higher in the group with AKI. They found a significant relationship between hypertension, the number of fasting days, and AKI. Patients with chronic kidney damage and hypertension should be evaluated more carefully, informed about the importance of hydration after fasting, and should be followed frequently for AKI. Studies investigating the health effects of prolonged intermittent fasting during Ramadan among patients on hemodialysis (HD) are limited and report heterogeneous findings. Adanan et al.[17] evaluated the effects of RF patients' nutritional and functional status on maintenance HD in a 12-week, multicenter, prospective observational study. Nutritional and functional status assessments were carried out 2 weeks before, at the 4th week of Ramadan, and 4 weeks after Ramadan. Nutritional status parameters included anthropometry (body mass index [BMI], interdialytic weight gain, and waist circumference), body composition (mid-arm circumference, triceps skinfold, and body fat percentage), blood biochemistry (albumin, renal profile, lipid profile, and inflammatory markers), BP, dietary intake, and handgrip strength. A total of 87 patients completed the study, with 68 patients (78.2%) reporting fasting for ≥20 days. RF led to significant reductions in BMI, interdialytic weight gain, waist circumference, mid-arm circumference, fat tissue mass, and body fat percentage, but these were not accompanied by any significant change in lean tissue mass. Significant improvement was observed in serum phosphate levels, but serum albumin, urea, and creatinine (Cr) were reduced significantly during Ramadan. There were no significant changes in lipid profile and inflammatory markers. Interestingly, energy and protein intake remained unchanged during Ramadan. Eldeeb et al.[18] evaluated the effect of RF on arterial stiffness parameters, augmentation index (AIx), and pulse wave velocity (PWV) in hypertensive patients with and without CKD. The cohort included 71 patients including 34 with CKD. All patients had hypertension, and 25 patients had diabetes mellitus. In patients without CKD, brachial systolic pressure (BSP). brachial diastolic pressure (BDP), central systolic pressure (CSP), and central diastolic pressure (CDP) significantly decreased. In patients with CKD, BSP and CSP significantly decreased, whereas BDP and CDP decreased, but the change was not significant. AIx significantly decreased in patients without CKD but did not significantly change in patients with CKD. PWV decreased in both groups, but the change was not significant. Serum Cr significantly increased, but estimated glomerular filtration rate (eGFR) did not significantly decrease in patients without CKD. Serum Cr significantly decreased, and eGFR significantly increased in patients with CKD.

Clinical practice and patients' advocacy

Alsughayer et al.[19] explored nephrologists' concerns and recommendations when counseling patients with advanced CKD on RF. An electronic survey was completed by 48 nephrologists practicing in Saudi Arabia. Most respondents were senior nephrologists (75%), practicing for over 10 years (68.8%). The majority of responding nephrologists (85.4%) were concerned about eGFR, diabetes (68.8%), patient age (64.6%), use of diuretics (62.5%), body fluid volume (60.4%), and BP (60.4%). This research in another study, El-Kannishy et al.[20] investigated patients' and medical professionals' opinions toward fasting in four HD centers in Egypt and the impact of physicians' attitude on patient behavior. Patients and physicians were interviewed and asked about their opinion toward fasting in HD patients and any experienced complications during fasting. Eighty-one (50.3%) of the studied HD patients practiced fasting in Ramadan. No significant difference was observed between fasting and nonfasting groups regarding age, sex, and HD duration. Eighty percent of patients reported no complications. Fifteen (65.2%) physicians support the opinion that HD patients are capable of fasting with precautions. There was a significant variation in fasting frequency among HD patients in the studied centers, with a significantly low fasting frequency observed in one center (10.5%). Most physicians from this center adopted that HD patients should not fast. HD patients were keen to practice fasting in Ramadan and were to a considerable extent capable of doing so. Also, the patient's decision seems to be affected by the physician's opinion. Arabi et al.[21] studied what nephrologists would advise transplant recipients on lifestyles and religious duties. Fifty-eight nephrologists responded, of whom, 77% routinely follow-up posttransplant patients; Fifty-four percent of the respondents would let patients with stable graft function fast during Ramadan, whereas 20% would not recommend fasting at any time following transplantation. This response did not change much if the patient had diabetes, although in these patients, not recommending fasting at any time increased to 32%. For kidney donors, fasting would be allowed by 58% of the respondents once the kidney function stabilizes. Finally, The same group[22] presented evidence-based education materials for medical providers (in the English language) and patients and donors (in the Arabic language). These educational materials were prepared to be easy to print or adopt by patients, providers, and centers.

Renal stone formation

There is a concern that RF may be a risk factor for the development of renal stones. Two systematic reviews addressed the question of the association of RF with renal stone formation. Amjadi et al.[23] evaluated the available comparative information through a systematic review. They included all studies comparing fasting and nonfasting conditions, studies evaluating stone formation, and clinical manifestations of kidney stone disease. All the English studies published from January 1980 to the end of 2019 were included. They excluded studies that had fasting out of Ramadan, noncomparative studies, animal studies, patients with bladder stones, and studies evaluating conditions that are only indirectly related to the stone formation or clinical manifestations. Only five studies remained after exclusion. Meta-analysis was not applicable due to the diversity in methods and evaluated population. Kirubarajan et al.[24] conducted a systematic review. Ten observational studies with a total of 9906 participants were included. Nine of the studies were conducted in the context of Islamic fasting during Ramadan, with the majority (7/9) finding that renal colic incidence was unaffected by the month of fasting. In contrast, two studies noted an increased incidence among fasting populations. Two other studies noted that urine metabolites and density were altered with fasting but did not translate into clinical outcomes. The primary trend of the included studies is toward showing no difference between fasting and nonfasting conditions in terms of renal stone formation.

  Cardiovascular Disease 

Cardiac function and risk factors

Hammoud et al.[25] evaluated the effect of RF on the heart rate variation (HRV), an indirect measure of cardiac sympathetic stress in 80 healthy Lebanese females. They were monitored for 24 h when following a normal routine; 38 and 42 females were enrolled before and during Ramadan, respectively. The results reveal no effect of fasting on HRV; there was an insignificant change in HRV between the first and last weeks of Ramadan. Morning fasting was significantly the least stressful period, with lower HR compared with nonfasting day. Therefore, RF does not alter the autonomic nervous activity of the heart nor HRV levels. This may imply that RF is a risk-free practice, which does not interfere with healthy individuals' cardiac autonomic nervous system function. Furthermore, Aslan et al.[26] examined the effect of long RF on BP with ambulatory BP monitoring in hypertensive patients using diuretics. In a prospective observational study involving 129 hypertensive patients (73 in the diuretic group, and 56 in the nondiuretic group. Twenty-four-hour ambulatory BP monitoring was performed during and after Ramadan. In the diuretic group, 24-h systolic BP (SBP) and diastolic BP (DBP) decreased significantly during Ramadan by 8.9 and 4.1 units, respectively. On the other hand, SBP and DBP were lower but insignificantly in the nondiuretic group. The reduction in SBP was significantly higher in the diuretic group. Thiazide-like diuretics tended to lower BP more, thus suggesting that RF might cause significant reductions in mean SBP and DBP measurements in patients using diuretics. Despite decreasing BP, diuretics are generally well tolerated and can be safe in well-controlled hypertensive patients during RF. Furthermore, Bener et al.[27] investigated the effect of RF on BP, fatigue, sleeping, and physical activity among hypertensive patients in a cross-sectional study conducted in 2019. Out of 1118 subjects, 47.6% were males. There were statistically significant differences for the biochemistry parameters regarding Vitamin D, blood glucose, hemoglobin A1c level, Cr, bilirubin, albumin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, uric acid, and SBP for both males and females after Ramadan compared to before Ramadan (BR). Furthermore, BMI was significantly lower during and after the month of Ramadan as compared to BR. Fewer hours of sleeping, SBP, DBP, family size, obesity BMI, fatigue, and smoking cigarettes were significant predictors of hypertensive patients with RF contributing to higher risk. Khorshid et al.[28] assessed the effect of RF on biochemical and exercise parameters among patients undergoing a 12-week exercise-based cardiac rehabilitation (CR) program. Fifty-three patients joining the CR program in a university hospital were included in the study. There were 32 fasting patients and 21 nonfasting patients. All patients underwent supervised exercise-based CR during the month of Ramadan. The two groups were similar in baseline characteristics. After the program, both groups showed significant improvement in ejection fraction, TC, LDL, and HDL levels. Furthermore, an improvement in exercise duration reached and achieved metabolic equivalents before and after the CR program in both groups. An important observation was that fasting did not significantly influence plasma osmolality in either group. Therefore appears to be safe to undergo exercise-based CR during Ramadan, even in the summer season. Farag et al.[29] assessed the effects of RF among a representative sample of hypertensive patients (both sex, aged 25–50 years, on common antihypertensive drugs), during Ramadan of 2020. A total of 120 hypertensive patients were included in the study, with a mean age of 37.5 years. There was a significant decrease in BP, body weight, BMI, and waist circumference after RF. However, lipid profile changes were not statistically significant except for TG which decreased after RF.

Acute coronary syndrome in Ramadan

Patients with acute coronary syndrome (ACS) may face several health issues during Ramadan. Raffee et al.[30] investigated the influence of fasting during Ramadan on ACS occurrence. It was a retrospective observational stufy of 226 patients aged between 20 and 80 years with a principal diagnosis of ACS. The study's findings indicated that RF was not significantly related to ACS occurrence since no difference was found in the incidence of hypertension, diabetes, unstable angina, and coronary artery disease findings during and after Ramadan. Similar findings were obtained for patients' final diagnosis, which had normal kidney function tests, platelets, and ejection fraction. Furthermore, no significant difference was found in patients' smoking status, hospital stay, and discharge rate.

Furthermore, Amin and Alaarag[31] assessed the safety of RF following Percutaneous Coronary Intervention (PCI) in 303 patients who had successful PCI before the 1st day of Ramadan. Although patients were advised that recent PCI could be a valid excuse for not fulfilling RF, many patients insisted on fasting, and they were included in the fasting group. The controls are patients who decided not to fast. All the patients were followed up during and for 6 months after Ramadan. The fasting group (n = 153) showed a significant difference in the incidence of Major Adverse Cardiac Events (MACE) compared to Group II with a P (0.005). MACE's in Group I occurred mainly during RF, with 19 patients having MACE's during Ramadan and four patients during the remainder of the follow-up period. The Receiver Operating Characteristic curve analysis showed the decline of the incidence of MACEs after 90 days from PCI till the start of RF with sensitivity and specificity (90% and 65%), respectively. The authors suggested that low-risk patients with a normal systolic function who underwent PCI may safely fast. Nonetheless, RF during the first 3 months following the PCI may not be safe.

On a different note, AlSheef et al.[32] identified the epidemiologic profile of cerebral vein thrombosis (CVT) among fasting women using oral contraceptive pills (OCPs) during Ramadan in a retrospective study conducted on all patients diagnosed with CVT. The study participants were categorized into two groups RF group and a nonfasting group). Out of 108 female patients with CVT, 36.1% were secondary to OCP, of whom 41% participants were fasting. The most affected site was the transverse sinus. Dehydration among the fasting and protein S deficiency in the nonfasting group was identified as the two prominent risk factors. This study suggests that the adverse effects of OCPs use might outweigh its benefits; thus, it should be prescribed with caution, more so in fasting patients.

  Endocrinology 

Thyroid

Or Koca et al.[33] compared the thyroid-stimulating hormone (TSH) values of hypothyroid patients, before and after Ramadan. Ninety-seven patients, ranging from 18 to 65 years old, diagnosed with hypothyroidism, who fasted during Ramadan, and who had no change of LT4 dose for at least 6 months were included. The median serum TSH level of patients before fasting was 2.19 mIU/L and after fasting was 2.73 mIU/L (P = 0.004). The study demonstrated no significant change in serum free thyroxine (fT4) levels. It may be appropriate to take precautions by making a small increase in LT4 dose BR in some hypothyroid patients wishing to fast. Dellal et al.[34] compared late evening and pre-dawn use of levothyroxine in patients with hypothyroidism in a cross-sectional study in Turkey during 2018. Patients who were on levothyroxine treatment and having normal thyroid functions were recruited for the study last week BR. Patients were offered to take levothyroxine at 10.30–11.00 p.m. before sleep or between 01:30 and 03:00 a.m. at least 30 min pre-sohour. There were 53 (85.5%) females. Basal TSH was 2.02 μIU/mL and insignificantly increased at the end of Ramadan (2.18 μIU/mL). Free triiodothyronine (fT3) decreased while free thyroxine (fT4) increased (P < 0.001 for both). Eighteen patients preferred to take levothyroxine in the late evening, and 44 preferred to take it before dawm. There were insignificant increases in TSH in both groups. At the end of Ramadan, TSH increased in 63.9%, decreased in 36.1% of the participants, Zaboon et al.[35] determined the best time of L-thyroxine intake during Ramadan. Fifty patients taking L-thyroxine treatment for primary hypothyroidism were involved in a prospective study for 3 months including the fasting and prefasting months. The patients were divided into three groups with different times of L-thyroxine intake. In the first group (pre-iftar), the patients were asked to take L-thyroxine at the time of iftar (the sunset meal) and delay any oral intake for at least 30 min. In the second group (post-iftar), the patients were asked to take L-thyroxine 2 h after iftar. The patients in the last group (pre-dawn) were asked not to eat in the last 2 h before suhoor (the predawn meal) and take L-thyroxine tablets 1 h before suhoor. There were no significant differences neither within each group nor among all the study groups. Moreover, the frequencies of the TSH control after Ramadan showed no significant differences within each of the study groups). Similarly, comparison among the study groups showed no significant differences regardless of whether the patients had controlled or uncontrolled TSH BR. In the patients with controlled TSH BR, 8/10 (presuhoor), 8/12 (preiftar), and 4/6 (postiftar) maintained control after Ramadan. While in the patients with uncontrolled TSH BR, 7/10 (presuhoor), 6/8 (preiftar), and 2/4 (postiftar) achieved controlled TSH after Ramadan.

Adrenals

The risks of RF on BP in patients with adrenal insufficiency are unknown. This study aimed to evaluate the levels of BP and particularly the risk for hypotension during a fasting day compared with a nonfasting day in patients with corticotrope deficiency. Chihaoui et al.[36] reported a prospective case-crossover study on 28 patients with known and treated adrenal deficiency who were fasting the month of Ramadan. Clinical and paraclinical data were collected. Patients had a 24 h ambulatory BP monitoring during an RF day then again during a nonfasting day. The data of 25 patients were analyzed; 20 women, median age: 40 years, median duration of the disease: 6 years. The prevalence of hypotension did not differ between the fasting day and the nonfasting day. Hour-by-hour BP levels comparison showed that both systolic and diastolic BP were significantly lower at 2.00 p.m. during fasting. BP variability was significantly lower during the fasting period compared with the same period during the nonfasting day. The same groupm Chihaoui et al.[37] compared hydrocortisone and prednisolone as treatments. In a randomized, double-blind crossover clinical trial conducted during Ramadan 2018 on 53 patients with known adrenal inefficiency treated with hydrocortisone 20 mg/day and who wished to fast during Ramadan. Patients were randomized into two groups; AB received hydrocortisone twice daily for 14 days, then prednisolone once daily with a placebo for 14 days, and BA received the two treatments in the reverse order. Patients had to complete a daily follow-up sheet about their eating and sleeping habits, the occurrence of complications, and blood glucose monitoring and also to respond to the AddiQoL questionnaire at the end of each treatment period. Fifty patients' data were analyzed; 29 men, mean age: 42.4 years, mean duration of the disease: 8.1 years. The frequency of complications, mean blood glucose levels, and the quality of life did not differ on hydrocortisone compared to prednisolone after adjusting the treatment sequence. Chihaoui et al.[38] assessed the daily cortisol profile in hydrocortisone-treated patients with secondary adrenal insufficiency (SAI) and healthy controls during a fasting day. A cross-sectional matched case–control study on fifty hydrocortisone-treated SAI patients and 69 controls who are used to fasting. Clinical and therapeutic data were collected. Five salivary samples for cortisol measurement were collected throughout a fasting day of the 3rd week of Ramadan 2019.

Salivary cortisol levels were significantly higher on awakening, at midnight, and before the predawn meal in patients compared with controls. The circadian cortisol rhythm was disrupted in patients. The area under the salivary cortisol level versus time curve was lower than the 2.5th percentile of the controls in one patient (2.5%) and higher than the 97.5th percentile in 23 patients (59%) who were considered overtreated. Age ≥35 was independently associated with overtreatment. Seven patients broke their fasting for a complication compared with no one of the controls. No factor was associated with this risk.

Hussain et al.[39] guided health-care professionals to educate, discuss, and manage patients with artificial intelligence (AI) during RF. Risk stratification for patients with AI and optimal strategies for management, including steroid dosing, are detailed. Before the commencement of Ramadan, all patients must receive up-to-date education on sick day rules, instructions on when to terminate their fast or abstain from fasting, carry steroid warning information, and must have a valid intramuscular HC pack and know how to administer this. Switching AI patients desiring to fast from multiple daily HC replacement to prednisolone 5 mg once daily at dawn is recommended. Patients on fludrocortisone for AI should be advised to take their total dose at dawn. Beshyah et al.[40] surveyed 145 physicians, two-thirds of whom were adult endocrinologists. Respondents recognized RF as having potential consequences in AI patients. Almost half of the respondents thought that RF has some probable or definite impact on glucocorticoid therapy that certainly warrants specific concern and possible action. The survey revealed a remarkable variation in the physicians' perceptions and practices regarding AI management during Ramadan.

Lipids

Akhtar et al.[41] included 100 healthy adult male volunteers from different mosques in and around Jammu. The study showed a reduction in TC and TG and a rise in HDL-C levels, which had beneficial effects on lipid profile post-RF period in healthy volunteers.

Bariatric surgery

In many practices, bariatric surgery is delayed until after Ramadan in order to avoid postoperative complications. However, there are no studies that have evaluated this practice. Tat et al.[42] evaluated the perioperative outcomes between bariatric surgeries performed before/during Ramadan and at times distant to Ramadan. All patients who underwent primary bariatric surgery at Cleveland Clinic Abu Dhabi between September 2015 and July 2019 were retrospectively reviewed. The PR cohort included patients that underwent surgery during the month of Ramadan and up to 3 months BR. The non-Ramadan (NR) cohort included patients from the remaining 8 months. The study included 542 patients: 185 patients in the PR cohort and 357 patients in the NR cohort. Baseline characteristics were similar. There were no statistically significant differences in perioperative outcomes including emergency department (ED) visits, readmission rates, reoperation, and complications within 30 days. Based on these data, there does not appear to be an increased risk of performing bariatric surgery before or during Ramadan in a comprehensive, multi-disciplinary program.

  Neurology 

Ismail et al.[43] examined the association of RF with clinical outcomes in 131 patients with myasthenia gravis (MG) and used clinical characteristics to estimate outcome risk in a prospective cohort study conducted in a tertiary neurology center in Kuwait (Ramadan 2019). Patients with MG who were willing to fast were evaluated through three clinical visits before, during, and after Ramadan. Disease severity was classified from Class I to Class V. Outcomes were classified as stable, worsened, or improved. The outcomes were stable disease in 91 patients (80.5%) and worsened disease in 17 patients (15.0%) including two patients who developed severe weakness of limb and axial muscles; five patients (4.4%) had improved disease. Of the patients whose conditions worsened during Ramadan, 15 (94.1%) returned to PR status during the follow-up period. Therefore, RF appears to be safe and well tolerated for most patients with MG in this cohort. Only 15.0% showed worsening of their symptoms; however, no patient developed respiratory involvement or myasthenic crisis, and only two patients developed severe weakness of limb and axial muscles. A favorable outcome was observed in patients with ocular MG, those with generalized MG of class IIb or lower BR, those taking pyridostigmine with a dose of 240 mg or less per day at a frequency of 3 times or less per day, those taking prednisolone, and those who needed only one immunosuppressant to control their symptoms. Moreover, most patients whose conditions worsened during Ramadan returned to PR status during the follow-up period. The ability of patients with MG to observe a total or partial fasting during Ramadan can be attributed to the diurnal variation of weakness, which is a characteristic feature of MG. Other possible reasons might be decreased physical exertion, reversed sleep patterns, and shortened working hours during Ramadan.

Transcranial direct current stimulation (tDCS) is a neuromodulation tool used to modify cognitive function in subjects. There is a paucity of data on tDCS' effect on cognitive function during RF. AlSultan et al.[44] assessed the effect of tDCS on three brain areas including the right dorsolateral prefrontal cortex (DLPFC), posterior parietal cortex (PPC), and cerebellum on cognitive function and obtained safety data in healthy adults during RF. Forty-two healthy, right-handed participants were randomly assigned to one of the six stimulation groups. An improvement in performance time in attention tasks was observed; however, it did not reach a significant level after anodal stimulation of the DLPFC, PPC, and cerebellum. Overall, there were no statistically significant differences between the active and sham tDCS groups in cognitive function. There were no significant side effects of tDCS during fasting for any group.

RF represents a challenge for both patients with epilepsy (MPWE) and their treating neurologists who aim to minimize the risk of fasting-related seizures. Several factors may contribute to the risk of fasting-related seizures, such as the half-life of antiepileptic drugs (AEDs), seizure control BR, and sleep fragmentation. Magdy et al.[45] investigated these factors. A prospective observational study included all MPWE who completed RF in 2019, about 16 h per day for 30 days. They were assessed regarding seizure control, AEDs, and sleep alterations using The Pittsburgh Sleep Quality Index. The study included 430 MPWE. The majority of patients (75.58%) completed RF without breakthrough seizures. Patients who achieved successful RF were significantly younger, had shorter disease duration, extended periods of seizure freedom BR, more efficient and longer sleep hours. There was no significant difference between patients receiving monotherapy regimens with short versus intermediate long t½. Maximum seizure freedom BR and sleep hours were identified as independent predictors of successful RF, using multivariate analysis. Every extra week of being seizure-free BR and every extra hour of sleep was associated with an increase in the probability of successful RF by 10% and 30%, respectively. Neurologists should guide MPWE who wish to fast Ramadan about the risks and precautions. Proper seizure control and ensuring adequate sleep duration can increase the probability of a successful RF. Fasting is the basis for the ketogenic diet, and intermittent fasting is emerging as a treatment for epilepsy. There is no available data about the role of Islamic fasting on seizure control. The same group assessed the effect of RF on the frequency of different seizure types.[46] A prospective observational study on Muslim patients with active epilepsy intending to fast during Ramadan of 2019, with an average of 16 fasting hours per day. Seizure frequency for each seizure type was followed over 3 months, 1 month before (Shaaban), during Ramadan, and 1 month after (Shawwal), after ensuring drug compliance. Three hundred and twenty-one Muslim patients with active epilepsy with a median age of 33 years were included (some patients had more than one type of seizure). In Ramadan, 86 out of 224 patients with focal seizures, 17 out of 38 patients with myoclonic seizures, and 6 out of 10 patients with absence seizures showed ≥ a 50% reduction. In Shawaal, such improvement continued to include 83, 13, and 4 patients with focal, myoclonic, and absence seizures. Focal and myoclonic seizures were significantly improved in the months of Ramadan and Shawaal compared to Shaaban. However, absence seizures were significantly improved only in Ramadan compared with Shaaban. The frequency of generalized tonic–clonic seizures did not significantly differ between the 3 months. The authors concluded that RF might indeed have an improving effect, as well as a postfasting effect, on active focal, myoclonic, and absence seizures.

Alqadi et al.[47] aimed to investigate the effect of fasting during Ramadan on seizure control and quality of life in adult patients with epilepsy. A prospective observational study over 3 months (1 month before fasting, the fasting month, and 1 month after fasting). They recruited adult patients with active epilepsy who were able to fast during the month of Ramadan. The primary outcome measures were as follows: (1) seizure control and (2) quality of life score using the Arabic version of the Ferrans and Powers Quality of Life Index (QLI). Changes in anticonvulsant medications were not allowed during the study period. They used a seizure log provided to participants to record the number of seizures during the 3 months. Quality of life was scored at the end of each month of the study period. Thirty-seven patients were studied (59% males). The mean age was 30 years, and the mean age at epilepsy onset was 13 years. On average, patients were on three antiepileptic medications at baseline. A total of 1576 seizures were reported during the 3-month follow-up, where seizures before fasting represented 35.5% of all seizures. Multilinear regression analysis revealed a significant decline of seizures by 21% during the fasting month compared with baseline and by 29% during post fasting compared with baseline. No significant change was found in the QLI scores calculated during the 3 months of the study period.

Effects of fasting on stress responses, mood, and withdrawal symptoms among khat users have not been examined. Nakajima and al'Absi[48] enrolled eighty individuals to complete an ambulatory monitoring period and a laboratory assessment session. Results indicated that withdrawal symptoms were lower during evening hours in the fasting group than in the nonfasting group. Stress-related changes were flattened in the fasting group relative to the nonfasting group. Khat users reported reduced BP responses relative to nonusers. These preliminary results demonstrate that fasting is associated with reduced adverse effects and withdrawal symptoms in khat users.

  Blood and Coagulation 

The changes in the therapeutic effect of warfarin during RF are controversial. Hence, Sridharan et al.[49] carried out a study to assess any alterations in the anticoagulation response to warfarin and identify the associated risk factors. Patients receiving warfarin for at least 1 year were included. Demographic details, warfarin doses, prothrombin time-international normalized ratio (PT-INR) values, and concomitant diseases/drugs were retrieved. Ramadan periods for the calendar years were obtained, and these periods were considered as Ramadan periods. One month before the start dates of Ramadan was considered as PR, and 1 month later than the last dates was considered as post-Ramadan periods. Warfarin sensitivity index (WSI), PT-INR category, and time spent in therapeutic range (TTR) were assessed. National Institute of Clinical Health Excellence (NICE) criteria for anticoagulation status were adhered to where TTR (%) <65 was considered as insufficient anticoagulation. One hundred and eighty-three patients were recruited. No significant differences were observed in warfarin doses between the study participants between PR, Ramadan, and post-Ramadan. Significantly more numbers of PT-INR tests were carried out during Ramadan compared with pre-and post-Ramadan periods. A higher WSI was akin to PT-INR, and lower intra-individual variability was observed in middle-aged and older adults in the post-Ramadan period. Significantly fewer patients had our PT-INR in the therapeutic range and more in the subtherapeutic range during Ramadan. A greater proportion of patients had PT-INR in the supratherapeutic range during the post-Ramadan periods, particularly the elderly. Although 38.3% had poor anticoagulation status overall, 92.4% met the NICE criteria for poor anticoagulation during the 3 months (PR, Ramadan, and post-Ramadan periods). RF influences warfarin's therapeutic effect in lowered TTR (%), reduced proportion of patients achieving therapeutic PT-INR, and increased risk of poor anticoagulation control. Greater caution is required during the post-Ramadan period, particularly in the elderly category, as they are more prone to over-anticoagulation and consequently the risk of bleeding. Batarfi et al.[50] determined patient-guided modifications of OAC medication regimen during Ramadan and to evaluate its consequences. Through a multicenter cross-sectional study conducted in Saudi Arabia. Data were collected shortly after Ramadan 2019. Participants were patients who fasted Ramadan and who were on long-term anticoagulation. Patient-guided medication changes during Ramadan in comparison to the regular intake schedule BR were recorded. Modification behavior was compared between twice daily (BID) and once daily (QD) treatment regimens. Rates of hospital admission during Ramadan were determined. They included 808 patients. During Ramadan, 53.1% modified our intake schedule (31.1% adjusted intake time, 13.2% skipped intakes, and 2.2% took double dosing). A higher frequency of patient-guided modification was observed in patients on the BID regimen than in the QD regimen. During Ramadan, 11.3% of patients were admitted to the hospital. The patient-guided modification was a strong predictor for the hospital admission. Patient-guided modification of OAC intake during Ramadan is common, particularly in patients on BID regimen. It increases the risk of hospital admission during Ramadan. Planning of OAC intake during Ramadan and patient education on the risk of low adherence is advisable.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm classically described as a triphasic disease: chronic, accelerated, and blast crisis. There are many unmet needs and unanswered questions about CML. Intermittent fasting in patients with CML on tyrosine kinase inhibitors is among these unmet needs. Al-Dubai et al.[51] report on the effects of intermittent fasting on response to nilotinib in a 49-year-old female Muslim who fasted during Ramadan and took her medication once instead of twice daily and remained in major molecular response. This is, however, a single case report and therefore cannot be generalized to all patients with CML. Individualization of risk and close follow-up are mandatory for those who choose to fast.

  Skeletal Medicine 

Rheumatoid arthritis (RA) is a common inflammatory disorder affected by various factors including fasting. Siddique et al.[52] the effect of RF on DAS 28 in RA patients in an observational cohort study. Two hundred and forty participants (74 males) were recruited and then divided into fasting (n = 120) and nonfasting cohorts (n = 120) based on their own choice. Mean DAS-28 scores before and after Ramadan were compared in both cohorts with appropriate statistical analyses. The baseline DAS of the fasting group was significantly low as compared to the nonfasting group. Statistically significant improvement in fasting and nonfasting groups in total and in both sexes was evident. Mean improvement in DAS was numerically more remarkable and statistically significant in the nonfasting group than fasting ones. Post-Ramadan DAS was, however, significantly low in the fasting group versus the nonfasting group. RA patients with moderate disease activity who want to observe fasting can do so without any fear of disease worsening.

Ben Nessib et al.[53] reviewed data that assessed the relationship of RF with rheumatic diseases. Recent evidence indicates that RF may attenuate the inflammatory state by suppressing pro-inflammatory cytokine expression and reducing the body fat and the circulating levels of leukocytes. Therefore, it may be a promising nonpharmacological approach for managing the course of rheumatic inflammatory diseases. Despite differences between studies in daily fasting duration and dietary norms, there appears to be a consensus that most patients with RA or spondyloarthritis (SpA) who fasted Ramadan experienced relief of their symptoms. Nevertheless, further clinical trials are required to assess the effect of RF on other musculoskeletal and bone disorders. In addition, the authors evaluated the impact of RF on chronic medication intake. Although a few studies on this issue are available, the primary outcomes indicate that RF does not significantly impair compliance or tolerance to chronic medications. These findings may give some reassurance to patients with a specific fear of drug intake during this month. The critical points generated from the observations include (a) RF can modulate the inflammatory status through the downregulation of metabolic syndrome, the reduction of pro-inflammatory cytokines, and the reduction of circulating levels of leukocytes; (b) RF can effectively improve the activity of rheumatic inflammatory diseases; (c) although further studies are still required, there seems no harm for patients with gout to participate in RF; and (d) primary outcomes indicate that RF may be a promising nonpharmacological intervention for managing patients with osteoarthritis and osteoporosis.

Ben Nessib et al.[54] specifically assessed the impact of RF on RA and SpA activity and assessed its impact on chronic medication intake in patients with rheumatic diseases. In a prospective study that included patients with RA or SpA who fasted during Ramadan of 2019. The disease activity and the management of chronic medications were assessed and compared between two visits: the first one six months before starting RF and the second after fasting at least 7 days. Fifty-six patients were included: 36 with RA and 20 with SpA. Fasting did not significantly affect either compliance with chronic medications or tolerance. Fasting can be a possible way to induce the rapid improvement of rheumatic disease activity. In addition, patients with a specific fear of drug intake during this period can be reassured, which will enhance treatment adherence. In this set of patients, beneficial effects of intermittent fasting were demonstrated on RA activity but were less evident in patients with SpA despite a general trend towards improvement.

Pehlivan et al.[55] identified rheumatology patients' attitudes toward RF in a descriptive, cross-sectional study involving 374 patients. Using a questionnaire form, It was determined that 56.1% fasted during Ramadan. When asked about the effect of fasting on the disease, 88.4% of those who fasted answered “it did not affect,” and 80.1% of those that did not fast said “it affected negatively.” They observed that more than half of the rheumatology patients fasted, the majority of patients thought it would not affect their disease, and the rate of request for information from the doctor was low. The authors conclude that a drug program could be helpful for individuals who are willing to fast, in which drugs are taken between the İftar and Suhoor times, to help patients fast safely without any additional risk of worsening disease.

  Eyes 

Beyoğlu et al.[56] evaluated the effect of fasting on anterior chamber depth (ACD), anterior chamber volume (ACV), and corneal and lens density (LD) by Scheimpflug technology and measured intraocular pressure (IOP) changes. Fifty healthy fasting individuals in Ramadan (study group) and 50 healthy nonfasting subjects (control group) were included. Central corneal thickness (CCT), ACD, ACV, corneal density (CD), and LD were evaluated. Although there was a statistically significant difference between the ACV, CD, and IOP values on the left side, no statistical significance was found for the ACV value on the left side. While fasting did not lead to any change in LD and CCT, the results demonstrated that it caused a slight decrease in ACD and ACV and a significant decrease in CD and IOP values. Gokmen and Ozgur[57] investigated the effect of religious fasting and dehydration during Ramadan on the choroidal thickness and vessel density in the superficial and deep vascular plexuses with optical coherence tomography angiography (OCTA) of 70 eyes of 35 healthy subjects with a mean age of 43 years. The measured choroidal thickness, superficial vessel density index, and deep vessel density index were 288.89 μm, 40.6%, and 41.4%, respectively, compared to 284.62 μm, 40.41%, and 41.41%, respectively when measured in the nonfasting period. The choroidal thickness under the fovea center was significantly higher in the fasting period than in the nonfasting period. The mean total choroidal thickness was reduced in the nonfasting period, although not to a statistically significant degree. An analysis of the mean total superficial and deep vascular plexuses revealed no statistically significant difference. Although a significant increase was noted in central choroidal thickness in the fasting period, no significant change due to fasting was observed in the superficial and deep capillary plexuses. The choroidal layer may vary in thickness due to fasting-related metabolic factors, while retinal vessels are more stable against such effects.

Demirtaş et al.[58] investigated the effects of RF on diurnal superficial-deep parafoveal vessel density (pfVD) and nerve head (NH)-radial peripapillary capillary (RPC) peripapillary vessel density (ppVD) using OCTA, as well as other related ocular dynamic and hemodynamic parameters and compared these findings with those in the nonfasting period in healthy individuals. A total of 105 healthy individuals, 42 women and 63 men were included in this prospective study. OCTA was used to examine the superficial-deep pfVD and NH-RPC ppVD. In the 3rd week of Ramadan, OCTA readings were obtained twice daily at 08:00 and 16:00 h under fasting conditions and compared with nonfasting values 2 weeks after Ramadan. Compared with the 08:00 h values, the 16:00 h IOPs, superficial-deep pfVDs, and RPC ppVDs were substantially reduced during fasting and nonfasting periods. No differences were found in the diurnal change of superficial-deep pfVDs, NH-RPC ppVDs, IOPs, and mean ocular perfusion pressures between fastin