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 Table of Contents  
Year : 2019  |  Volume : 10  |  Issue : 1  |  Page : 7

Effects of intermittent fasting during ramadan on insulin-like growth factor-1, interleukin 2, and lipid profile in healthy muslims

1 Department of Nutrition, Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, I.R. Iran
2 Department of Laboratory Technology, Paramedical Faculty, Bushehr University of Medical Sciences, Bushehr, I.R. Iran
3 Department of Nutrition,Student Research Committee, Bushehr University of Medical Sciences, Bushehr, I.R. Iran

Date of Submission09-Jun-2017
Date of Acceptance21-May-2018
Date of Web Publication15-Jan-2019

Correspondence Address:
Dr. Ali R Rahbar
Department of Nutrition, Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr
I.R. Iran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2008-7802.250289

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Background: Insulin-like growth factor-1 (IGF-1) and interleukin-2 (IL-2) play an essential role in pathophysiology of several chronic diseases. As a stressor, fasting in Ramadan may increase inflammatory markers such as IGF-1 and IL-2 in Muslims. The aim of this before–after study was to investigate the effects of fasting in Ramadan on IGF-1 and IL-2 levels in individuals. Methods: In all, 34 men age 16–64 years were selected out of the overall number of individuals who were ready for fasting entirely throughout Ramadan. A sample of blood was drawn from the contributors before and after Ramadan, and plasma IGF-1, IL-2, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined. To identify differences between the initial and final values of test results of the study for plasma IGF-1, IL-2, and lipid parameters, we used paired sample T-test. Results: Paired sample T-test illustrated a significant decrease in IGF-1 and IL-2 levels after Ramadan fasting compared to before Ramadan. The concentration of TG, cholesterol, and LDL-C levels underwent significant decreases over the period of the study. HDL-C levels did not change significantly during the study. A significant decrease in weight, waist circumferences, calorie, carbohydrate, and fat intake were observed in participants during Ramadan fasting. Conclusions: It is concluded that fasting in Ramadan independent of anthropometric measures attenuates inflammation and is beneficiary to health.

Keywords: Fasting, insulin-like growth factor-1, lipids

How to cite this article:
Rahbar AR, Safavi E, Rooholamini M, Jaafari F, Darvishi S, Rahbar A. Effects of intermittent fasting during ramadan on insulin-like growth factor-1, interleukin 2, and lipid profile in healthy muslims. Int J Prev Med 2019;10:7

How to cite this URL:
Rahbar AR, Safavi E, Rooholamini M, Jaafari F, Darvishi S, Rahbar A. Effects of intermittent fasting during ramadan on insulin-like growth factor-1, interleukin 2, and lipid profile in healthy muslims. Int J Prev Med [serial online] 2019 [cited 2021 Nov 30];10:7. Available from: https://www.ijpvmjournal.net/text.asp?2019/10/1/7/250289

  Introduction Top

Insulin-like growth factor-1 (IGF-1) plays an essential role in growth and development in humans. This factor directly activates IGF-1 receptor (IGF-1R) and regulates various intracellular signaling pathways. It has been noted that distortion of IGF-1R signaling cascades contributes to a variety of health-threatening diseases such as diabetic retinopathy,[1] age-related macular degeneration,[2] cardiovascular disease, and cancers.[2] The biological activities of IGF-1 have been of strong concern in tumorigenesis.[3],[4] In addition, the role of IGF-I in the pathophysiology of vascular complications has been supported by experimental findings.[5]

It has been reported that fasting decreases IGF-1 levels in animals.[6] To stay alive during famine and starvation, one should direct energy expenditure from growth and reproduction toward survival.[7] Therefore, despite elevated GH secretion, starvation and malnutrition lower circulating IGF-I levels.[6]

Among Muslim population, fasting during Ramadan differs from formal fasting. In fact, two whole meals are consumed immediately after sunset and just before sunrise which could be assigned as intermittent fasting,[8] and therefore, it could be assumed the changes in physiology during Ramadan differ from experimental fasting.[9] In addition, in Ramadan the time of serving and the content of the meals, pattern of sleep and being awake, activity, and circadian rhythm are interrupted.[10] In fact, people in Ramadan cope with fasting as a stressor which causes stress response.[11] And inflammatory mediators such as interleukin-2 (IL-2) are produced following this psychological and physiological stress induction.[12] Although some studies indicated positive effect of intermittent fasting on inflammatory markers,[13] it might attenuate the benefits of fasting. To the best of our knowledge, so far, there is no published study on the effects of intermittent fasting on IGF-1 and very scarce surveys have reported the changes in serum IL-2 levels during Ramadan in Muslim population.

Therefore, we conducted this study to investigate the impact of fasting in Ramadan on IGF-1 and IL-2 levels in humans. In addition, we measured the changes in lipid profiles during Ramadan.

  Methods Top

Study design and participants

This project was a before–after study. In all, 34 men age 16–64 years were selected out of the overall number of people who were willing to fast in Ramadan. The participants were invited to come to the Persian Gulf Tropical Medicine Research Center in Bushehr University of Medical Sciences between 1 and 30 of July in fasting state through a letter delivered to their homes by the research team. The objectives of the study were explained in the letter. The criteria for inclusion in the study were as follows: willing to fast during Ramadan, being of male gender, and a minimum age of 15 years (cut point for male Muslims to execute their religious duty). Volunteers were excluded if they were smokers, took thyroid drugs, estrogen or medications for hypertension, or showed any clinical signs of dyslipidemia, diabetes mellitus, or hypothyroidism. Potential participants were interviewed and examined by expert physicians and dietitians. At the beginning of the study, a written, signed informed consent was obtained from each participant.

The experimental protocol of the study was approved by the research deputy (DP/8703277/176,14/4/2013). The ethical aspects of the study were also approved by the ethics committee (bpums.res, 2015,32), and the research reported here was carried out in accordance with the principles of the Declaration of Helsinki as revised in 2000.

Variable assessment

With a calibrated scale and stadiometer, the weight and height of participants were determined. Heavy outer garments and shoes were removed before height and weight were measured. Body mass index was calculated as weight in kilograms divided by the square of the height in meters (kg/m2). Waist circumference was measured with a nonstretchable measuring tape at the midpoint between the lower edge of the rib cage and iliac crests. Waist-to-hip ratio (WHR) was determined as waist circumference divided by hip circumference. For this parameter, waist circumference was defined as the smallest circumference measured at the navel, and hip circumference was defined as the largest circumference measured at the hips and buttocks.

A validated questionnaire (International Physical Activity Questionnaire, Epic-Norfolk) was used to estimate physical activity of participants.[14]

A 24-h dietary recall for 3 nonconsecutive days before Ramadan and during Ramadan was recorded in an interview conducted by trained dietitians. Each food and beverage were analyzed for the content of energy and other nutrients with Nutritionist III software (version 7.0; NSquared Computing, Salem, OR, USA), which was adapted for Iranian foods.

A blood sample was obtained from each participant before and at the end of the month of Ramadan and was transferred to the laboratory of Persian Gulf Tropical Medicine Research Center. Plasma's total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low0density lipoprotein cholesterol (LDL-C), IGF-1, and IL-2 were determined. Venous blood samples were drawn between 8.00 and 9.00 hours and centrifuged at 3000 g for 15 min at 4°C. Immediately after centrifugation, the serum samples were frozen and stored at –80°C for a period no longer than 6 weeks. Plasma's IGF-1 levels were measured with a commercially available ELISA kit (Mediagnost, Reutlingen/Germany; Catalog No. E20 d/e 100212). The assay range was 42–1050 ng/mL, and the intra- and inter-assay coefficients of variance were less than 6.7% and 6.8%, respectively.

IL-2 levels in serum were measured with an ELISA kit (Bioassay Technology Laboratory, Shanghai Crystal day Biotech Co., Ltd., Shanghai, China; Catalog No. E0094Hu). The range of assess was 5–2000 ng/L. The intra-assay coefficient of variance was less than 10%. Moreover, a value of less than 12% for inter-assay coefficient was reported.

Serum TG was measured with an enzymatic technique for oxidation by glycerol-3 phosphate and detection with phenol aminoantipyrine in an automated Technicon Axon Analyzer. The HDL-C concentration (after precipitation with magnesium chloride) was measured with enzymatic techniques (Pars Azmoon Co., Tehran, Iran). LDL-C concentration was calculated with Friedewald formula.[15]

Statistical analysis

Normality was evaluated using probability plots and Shapiro–Wilk's test. To identify differences between continuous variables at the beginning and at the end of the study, we used paired sample T-test. Chi-square McNemar was used to analyze the differences between categorical variables before and after the study. The relationship between the variables was determined by calculating Pearson's correlation coefficient. A value of P < 0.05 was accepted as significant.

All statistical analyses were done with an IBM computer and SPSS v. 15 statistical software packages (SPSS Inc., Chicago, IL, USA).

  Results Top

Anthropometric indices and biochemical parameters of the participants are shown in [Table 1]. Changes in serum IGF-1 and IL-2 levels correlate significantly with change in weight, waist circumference, WHR, and body mass index or calorie intake [Table 2].
Table 1: Characteristics of the individuals (n = 34); means±SD

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Table 2: Correlation between changes in anthropometric measures and calorie intake with changes in serum IGF-1 and IL-2 in fasted individuals

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Paired sample T test illustrated a significant decrease in IGF-1 levels during the month of Ramadan. IL-2 decreased significantly after Ramadan fasting compared to before Ramadan [Table 3].
Table 3: Change in variables before and after Ramadan unadjusted and adjusted for age

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The concentration of TG, cholesterol, and LDL-C levels underwent significant decreases over the period of the study. HDL-C levels did not change significantly during the study [Table 3].

Paired sample T-test showed a significant decrease in weight and waist circumferences during Ramadan fasting [Table 3].

Calorie, carbohydrate, and fat intake underwent significant decreases during the study [Table 3].

Physical activity levels in study population decreased significantly during Ramadan in comparison with the periods prior to the month of Ramadan [Table 3].

  Discussion Top

The findings of this study were indicative of significant reduction in IGF-1 levels over the course of intermittent fasting in Ramadan. It seems that short periods of starvation, even less than 12 h, influence hormonal responses in the human body. In accordance, Azizi reported significant changes in physiologic hormones during Ramadan.[9] Observations indicate that food shortage in various organisms, starting from yeasts and culminating in humans, mediates its impacts through the changes it induce in IGF-1 circulating hormone levels. In this regard, many of the mutations that extend life span act by reduction in IGF-1 levels which springs from suppressed nourishing-signaling pathways.[16] One study which was conducted on mice demonstrated that short-term fasting induces beneficiary effects by reducing circulating IGF-1.[6] In fact, fasting causes the human body to prefer to perform activities for the purpose of survival in comparison with activities such as energy consumption for growth. Therefore, growth hormone–IGF-1 axis adapts with new endocrine situation and IGF-I levels decrease regardless of raised GH secretion.[17] And it might explain the desired impact of intermittent fasting on health-threatening diseases,[18] especially when the role of IGF-1 in human diseases has been clarified.[1],[2],[3],[4],[5] However, Bouhle et al. found no changes in IGF-1 level in trained athlete men during submaximal exercise during Ramadan fasting.[19] It should be mentioned that the participants in Bouhle et al. study were trained athletes with daily exercise schedule. Therefore, it could be concluded that exercise intervenes with the effect of intermittent fasting on IGF-1 level.

Moreover, it is well known that calorie restriction decreases insulin levels.[20] The relationship between insulin level and IGF-1 may explain the association between calorie restriction and reduced IGF-1 production. Edge et al. reported that insulin deficiency leads to impaired hepatic IGF-1 synthesis.[21] Insulin regulates the growth hormone receptor (GHR) production and decrement in insulin secretion following fasting which leads to reduction in GHR expression in liver which consequently decreases synthesis of IGF-1.[22],[23]

Collectively, we hypothesize that intermittent fasting by above mechanisms, independent of weight reduction, synergistically decreases circulating IGF-1 levels during Ramadan in the Muslim population.

In Ramadan in addition to fasting, several lifestyle changes, including changes in physical activity, time and regularity of feeding, content and calorie of diet, pattern of sleep and being awake, and circadian rhythm[10] which all in all as stressors induce stress response in subjects.[11] However, in this study, Ramadan fasting could decrease IL-2. In accordance with our findings, some studies reported significant decrease in IL-2 level following fasting.[24] In this regard, decrease in cytokine levels during Ramadan is due to down-regulation of nuclear factor κB (NF-κB) signaling.[25] Another explanation might be the effect of psychological and physiological stress, in stimulating the secretion of endorphin which could compensate the undesired impact of stress.[26] Mohajeri et al. depicted a significant decrease in CXC chemokines concentration during Ramadan[27] which might explain the reason for suppression of inflammatory chemokines during Ramadan.[25]

In this study, the lipid profile including TG, cholesterol, and LDL-cholesterol decreased in the study's participants during Ramadan. Nematy et al. reported a significant improvement in coronary heart disease risk factors after Ramadan fasting. They found a significant lowered plasma cholesterol, TGs, and LDL-C levels following the month of Ramadan.[28] Marbut et al. in agreement with our study observed a significant decrease in serum cholesterol, serum TGs, and LDL-C levels in addition to a significant increase in serum HDL-C levels at the end of Ramadan.[29] Some studies have indicated an increase in TG level, which attributed to lipolytic effect of prolonged fasting.[30] Moreover, other lines of research have pointed to changes in metabolism of some appoliproteins, which in turn might influence LDL-C metabolism.[31] Furthermore, findings of several studies have been indicative of increases in TG.[32],[33],[34] The discrepancies in the finding of various studies concerning the impact of Ramadan fasting on lipid profiles relate to fluctuations in activity levels and feeding patterns as well as different cultural factors between diverse nations during Ramadan. In fact, increased TG concentration reported by some studies in Ramadan could be attributed to consumption of rich carbohydrate meals along with reduced physical activity in this month. Repeatedly, it is reported a trend for consumption of high-sugar meals in Ramadan.[32],[33],[34] Accordingly, the association between increased sucrose intake and raised TG level was demonstrated and reported by Albrink and Ullrich.[35] In contrast, based on the findings of this study, the carbohydrate intake in parallel with TG was significantly decreased in Ramadan in comparison to before Ramadan.

In this study, despite significant reductions in dietary energy intake, no significant changes were observed in anthropometric measures and this might be due to the decline in physical activity during the course of the study. Based on our findings, the physical activity levels decreased during Ramadan in comparison to the periods prior to the month of Ramadan [Table 3].

Limitations and strengths

The limitation of this study was that because of the avoidance of participants, the dietary intake analysis was obtained by 24-h dietary recall for 3 nonconsecutive days and not by food weighing record. Dietary intake analysis by food weighing record would validate the finding of this study to a higher degree. The strength of this study was that we measured all variables including dietary intake analysis and physical activity which might influence the serum IGF-1 and IL-2 level, and if they were correlated with serum IGF-1 and IL-2 we used them as covariates in statistical analysis.

  Conclusions Top

It is concluded that fasting in Ramadan independent of anthropometric measures decreases IGF-1, IL-2, and serum lipid levels.


The authors thank K. Shashok (AuthorAID in the Eastern Mediterranean) and F. Soleimani for improving English language in this article.

Financial support and sponsorship

This study was supported, in part, by a grant from Bushehr University of Medical Sciences, Bushehr, I.R. Iran [DP/20/18/3/2316,1/1/2015].

Conflicts of interest

There are no conflicts of interest.

  References Top

Smith LE, Shen W, Perruzzi C, Soker S, Kinose F, Xu X, et al. Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Nat Med 1999;5:1390-5.  Back to cited text no. 1
Slomiany MG, Rosenzweig SA. IGF-1–induced VEGF and IGFBP-3 secretion correlates with increased HIF-1α expression and activity in retinal pigment epithelial cell line D407. Invest Ophthalmol Vis Sci 2004;45:2838-47.  Back to cited text no. 2
Baserga R, Hongo A, Rubini M, Prisco M, Valentinis B. The IGF-I receptor in cell growth, transformation and apoptosis. Biochimica Et Biophysica Acta 1997;1332:F105-26.  Back to cited text no. 3
LeRoith D, Werner H, Beitner-Johnson D, Roberts CT, Jr. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 1995;16:143-63.  Back to cited text no. 4
Goke B, Fehmann HC. Insulin and insulin-like growth factor-I: Their role as risk factors in the development of diabetic cardiovascular disease. Diabetes Res Clin Pract 1996;30(Suppl):93-106.  Back to cited text no. 5
Lee C, Safdie FM, Raffaghello L, Wei M, Madia F, Parrella E, et al. Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index. Cancer Res 2010;70:1564-72.  Back to cited text no. 6
Schneider JE. Energy balance and reproduction. Physiol Behav 2004;81:289-317.  Back to cited text no. 7
Azizi F. Islamic fasting and thyroid hormones. Int J Endocrinol Metab 2015;13:e29248.  Back to cited text no. 8
Azizi F. Islamic fasting and health. Ann Nutr Metab 2010;56:273-82.  Back to cited text no. 9
Bahammam A. Does Ramadan fasting affect sleep? Int J Clin Pract 2006;60:1631-7.  Back to cited text no. 10
Lahdimawan A, Handono K, Indra MR, Prawiro SR. Effect of Ramadan fasting on endorphin and endocannabinoid level in serum, PBMC and macrophage. Int J Pharm Sci Invent 2013;2:46-54.  Back to cited text no. 11
Lin J, Shen Y, Gao Y, Li L. beta-Endorphin enhances IL-2 and IFN-gamma gene expression in human blood mononuclear cells. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 1997;19:353-6.  Back to cited text no. 12
Faris MA, Kacimi S, Al-Kurd RA, Fararjeh MA, Bustanji YK, Mohammad MK, et al. Intermittent fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects. Nutr Res [New York, NY] 2012;32:947-55.  Back to cited text no. 13
Craig CL, Marshall AL, Sjorstrom M, Bauman AE, Booth ML, Ainsworth BE, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003;35:1381-95.  Back to cited text no. 14
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.  Back to cited text no. 15
Fontana L, Partridge L, Longo VD. Extending healthy life span—From yeast to humans. Science (New York, NY) 2010;328:321-6.  Back to cited text no. 16
Lee C, Safdie FM, Raffaghello L, Wei M, Madia F, Parrella, E et al. Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index. Cancer Res 2010;70:1564-72.  Back to cited text no. 17
Nugraha B, Ghashang SK, Hamdan I, Gutenbrunner C. Effect of Ramadan fasting on fatigue, mood, sleepiness, and health-related quality of life of healthy young men in summer time in Germany: A prospective controlled study. Appetite 2017;111:38-45.  Back to cited text no. 18
Bouhlel E, Zaouali M, Miled A, Tabka Z, Bigard X, Shephard R. Ramadan fasting and the GH/IGF-1 axis of trained men during submaximal exercise. Ann Nutr Metab 2008;52:261-6.  Back to cited text no. 19
Johnston CS, Sears B, Perry M, Knurick JR. Use of novel high-protein functional food products as part of a calorie-restricted diet to reduce insulin resistance and increase lean body mass in adults: A randomized controlled trial. Nutrients 2017;9.  Back to cited text no. 20
Edge JA, Dunger DB, Matthews DR, Gilbert JP, Smith CP. Increased overnight growth hormone concentrations in diabetic compared with normal adolescents. J Clin Endocrinol Metab 1990;71:1356-62.  Back to cited text no. 21
Baxter RC, Bryson JM, Turtle JR. Somatogenic receptors of rat liver: Regulation by insulin. Endocrinology 1980;107:1176-81.  Back to cited text no. 22
Leung K-C, Doyle N, Ballesteros M, Waters MJ, Ho KK. Insulin regulation of human hepatic growth hormone receptors: Divergent effects on biosynthesis and surface translocation 1. J Clin Endocrinol Metab 2000;85:4712-20.  Back to cited text no. 23
Ünalacak M, Kara IH, Baltaci D, Erdem O, Bucaktepe PG. Effects of Ramadan fasting on biochemical and hematological parameters and cytokines in healthy and obese individuals. Metab Syndr Relat Disord 2011;9:157-61.  Back to cited text no. 24
Arumugam TV, Phillips TM, Cheng A, Morrell CH, Mattson MP, Wan R. Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann Neuro 2010;67:41-52.  Back to cited text no. 25
Carrasco L, Villaverde C, Oltras C. Endorphin responses to stress induced by competitive swimming event. J Sports Med Phys Fitness 2007;47:239.  Back to cited text no. 26
Mohajeri FA, Ahmadi Z, Hassanshahi G, Akrami Mohajeri E, Ravari A, Ghalebi SR. Dose Ramadan fasting affects inflammatory responses: Evidences for modulatory roles of this unique nutritional status via chemokine network. Iran J Basic Med Sci 2013;16:1217.  Back to cited text no. 27
Nematy M, Alinezhad-Namaghi M, Rashed MM, Mozhdehifard M, Sajjadi SS, Akhlaghi S, et al. Effects of Ramadan fasting on cardiovascular risk factors: A prospective observational study. Nutr J 2012;11:1.  Back to cited text no. 28
Marbut MM, Hahsm A-N, Abdulrahman M. Effect of Ramadan fasting on some physiological parameters. Tikrit Med J 2005;11:6-8.  Back to cited text no. 29
Laajam M. Ramadan fasting and non-insulin-dependent diabetes: Effect on metabolic control. East Afr Med J 1990;67:732-6.  Back to cited text no. 30
Nomani M. Dietary fat, blood cholesterol and uric acid levels during Ramadan fasting. Int J Ramadan Fasting Res 1997;1:1-6.  Back to cited text no. 31
Elhazmi M, Alfaleh F, Almofleh I. Effect of Ramadan fasting on the values of hematological and biochemical parameters. Saudi Med J 1987;8:171-6.  Back to cited text no. 32
Gumma K, Mustafa K, Mahmood N, Cadet A. The effect of fasting in Ramadan: 1—Serum uric acid and lipid concentration. Br J Nutr 1978;40:573-81.  Back to cited text no. 33
Hallak MH, Nomani M. Body weight loss and changes in blood lipid levels in normal men on hypocaloric diets during Ramadan fasting. Am J Clin Nutr 1988;48:1197-210.  Back to cited text no. 34
Albrink MJ, Ullrich IH. Interaction of dietary sucrose and fiber on serum lipids in healthy young men fed high carbohydrate diets. Am J Clin Nutr 1986;43:419-28.  Back to cited text no. 35


  [Table 1], [Table 2], [Table 3]


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