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Alterations of Brain-Derived Neurotrophic Factor and Creatinine During Ramadan Fasting: A Prospective, Controlled Clinical Trial

AUTHORS

Samaneh Khoshandam Ghashang 1 , Imad Hamdan 1 , Ralf Lichtinghagen 2 , Christoph Gutenbrunner 1 , Boya Nugraha 1 , *

AUTHORS INFORMATION

1 Rehabilitation Medicine, Hannover Medical School, Hannover, Germany

2 Insitute of Clinical Chemistry, Hannover Medical School, Hannover, Germany

How to Cite: Khoshandam Ghashang S, Hamdan I, Lichtinghagen R, Gutenbrunner C, Nugraha B. Alterations of Brain-Derived Neurotrophic Factor and Creatinine During Ramadan Fasting: A Prospective, Controlled Clinical Trial, Iran Red Crescent Med J. Online ahead of Print ; 21(5):e88324. doi: 10.5812/ircmj.88324.

ARTICLE INFORMATION

Iranian Red Crescent Medical Journal: 21 (5); e88324
Published Online: June 3, 2019
Article Type: Brief Report
Received: December 27, 2018
Revised: May 8, 2019
Accepted: May 9, 2019
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Abstract

Background: Brain-derived neurotrophic factor (BDNF) is associated with mood-related symptoms. Fasting can improve mood. However, there was a lack of information about BDNF during prolonged fasting in Summertime in Germany.

Objectives: This study aimed to determine (1) the effect of Ramadan fasting on BDNF and creatinine during the month of Ramadan in Germany; (2) the correlation of BDNF with body composition parameters and Health-related Quality of Life (HQoL).

Methods: This prospective controlled clinical trial was conducted on a total of fifty healthy adult male during Ramadan 2015 in the Department of Rehabilitation Medicine affiliated to Hannover Medical School, Hannover, Germany. The participants were recruited and divided into two groups, including fasting (FG) and non-fasting groups (NFG). The FG was evaluated at T1: one week before Ramadan, T2: mid of Ramadan, T3: last days of Ramadan, and T4: one week after Ramadan. The NFG was evaluated only at T1 and T3.

Results: No significant differences were found between FG and NFG at T1 or T3 with regard to BDNF and creatinine (P > 0.05). In the FG, significant alterations were demonstrated in terms of BDNF. The BDNF was significantly increased at T3 compared with T2 (P < 0.05). No significant change of creatinine was seen in the FG (P > 0.05).

Conclusions: It seems BDNF plays a role in the Ramadan fasting. Normal range level of creatinine suggested that long-period Ramadan fasting is safe for the kidney of healthy male subjects.

Keywords

Body Composition Brain-Derived Neurotrophic Factor Creatinine Fasting Kidney Mood Ramadan Quality of Life

Copyright © 2019, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited

1. Background

Ramadan fasting (RF) has been known to be of great physical and psychological benefits to healthy people (1-5). Islamic fasting period follows the lunar calendar, which varies according to geographical location. In Germany, the fasting period during Ramadan 2015 was about 18 to 19 hours per day.

Fasting has also an effect on mood-related symptoms (6-8). Mood-related symptoms are associated with the brain-derived neurotrophic factor (BDNF) (1, 9, 10). Moreover, BDNF plays a role in different types of neuronal functions and is shown to be influenced by nutritional intake, fasting, and exercise (11).

However, there is a lack of information about the impact of RF on BDNF and how it correlates with mood. During RF, liquid intake is also forbidden, which can cause serious damage to the kidneys resulting in renal dysfunction.

2. Objectives

Therefore, this study aimed to (1) determine the effects of RF on serum levels of BDNF and creatinine; (2) the correlation of BDNF with mood and health-related quality of life (HQoL). We hypothesized that BDNF would be altered during RF.

3. Methods

This study was a prospective controlled trial. The study was approved by the Ethics Committee of Hannover Medical School, Germany (Ethics No. 6899). This study was performed in accordance with the Ethical Standards laid down in the 1964 Declaration of Helsinki. All patients agreed to participate after informed consent. This study was conducted on Ramadan 2015, June-July 2015. The study center was the Department of Rehabilitation Medicine, Hannover Medical School, Hannover, Germany, and this study has been registered in the German Registry of Clinical Trial with DRKS-ID: DRKS00008181.

3.1. Participants
3.1.1. Inclusion and Exclusion Criteria

Inclusion criteria for fasting group (FG) were (1) healthy (particularly not suffering from any form of chronic disease, pain or psychiatric diagnosis); (2) male; (3) older than 18 years of age, (4) intent on fasting the whole month of Ramadan (5) proficient in German/English. The non-fasting group (NFG) had the same inclusion criteria with the exception that the participants were not fasting.

3.1.2. Assessment Time Points

To assess our endpoints, four time-points were assigned:

T1: one week before the start of Ramadan (June 2015); T2: mid of Ramadan; T3: last days of Ramadan, and T4: one week after Ramadan. In the FG, all participants were assessed at all 4 time points, while the NFG were only assessed at T1 and T3.

3.1.3. Evaluation Parameters

Peripheral venous blood samples were collected from both FG and NFG in serum tubes (Monovette, Sarstedt, Germany) between 08:00 and 10:00 hours. Samples were allowed to clot before being centrifuged at 1500 g for 15 min. Serum samples were stored at -80ºC until analyses.

3.2. BDNF

Serum samples were measured using commercial enzyme immunoassay according to the manufacturer’s instruction kit (Cusabio-CSB-E04501H, Hölzel Diagnostika Handels GmbH, Köln, Germany).

3.3. Creatinine

Serum creatinine levels were analyzed according to the manufacturer’s protocol (Cobas Substrates, Creatinine plus ver.2, Roche Diagnostics GmbH, Mannheim, Germany).

3.4. Questionnaires Related to Mood and HQoL

SF-12 for (HQoL), Beck’s Depression Inventory (BDI)-II, and Hospital and Anxiety Depression Scale (HADS-D) were used for depression score measurement; the fatigue was measured using Visual Analogue Scale (VAS) and Fatigue Severity Scale (FSS); sleep problem was also measured by the Epworth Sleepiness Scale (ESS). We had previously reported on the effect of fasting on HQoL (1). In this article, the correlations between HQoL and BDNF were explored.

3.5. Statistical Analysis

Statistical analysis was performed by using IBM SPSS Software for Windows, version 22.0 (IBM Corp., Armonk, N.Y., USA). The Shapiro-Wilk test was used to check the normality of the data. Friedman test was used to compare significant differences between different time points (followed by post-hoc test with Bonferroni correction). Student’s t-test or Mann-Whitney U test was used to compare baseline levels of FG and NFG at the T1 and T3 time points. The mean imputation method was used for handling missing values. Explorative statistical analyses such as the correlation of biological mediators and body composition parameters, mood, fatigue, sleepiness and health-related QoL of the subjects were performed. Statistical significance was set at P < 0.05.

4. Results

There are no significant differences between FG and NFG at baseline with regard to age, height, body weight, BDNF, and creatinine (Table 1).

Table 1. Characteristics of the FG and NFG at Baselinea, b
GroupP Value
FGNFG
Age and race
Age, y26.12 ± 0.9826.20 ± 0.980.977
White/Asian21/416/90.196c
Body composition
Height, cm177.20 ± 1.41178.16 ± 2.120.884
Body weight, kg77.82 ± 2.4676.16 ± 4.290.739
BMI, kg/m224.78 ± 0.7324.56 ± 0.780.84
Mood and HQoL
Anxiety (HADSA)4.92 ± 3.824.26 ± 3.380.521
Depression (HADS D)4.36 ± 3.883.06 ± 3.470.218
Depression (BDI-II)8.36 ± 8.216.48 ± 5.970.359
Physical health (SF-12)52.60 ± 5.3553.67 ± 3.640.414
Mental health (SF-12)49.48 ± 10.8349.23 ± 11.120.936
Fatigue and sleepiness
Fatigue (VAS)3.01 ± 1.833.08 ± 1.960.893
Fatigue severity scale (FSS)26.92 ± 8.6526.44 ± 10.380.86
Epworth sleepiness scale (ESS)7.96 ± 3.817.16 ± 3.730.457
BDNF, ng/mL47.00 (20.00 - 70.50)51.00 (14.00 - 62.00)0.877
Creatinine, μmol/L84.00 (71.10 - 92.30)88.03 (81.25 - 98.95)0.509

Abbreviations: IQR, iInterquartile range; SEM, standard error of mean; VAS, visual analogue scale.

aValues are expressed as mean ± SEM or median (IQR).

bAge, height and body weight were analysed using the Student’s t-test. The BDNF and creatinine were analysed using the Mann-Whitney U-test.

cFischer’s exact test.

There is no significant difference between the FG and NFG in terms of both BDNF and creatinine levels (Figure 1A and B). Interestingly, the level of BDNF was significantly increased in the FG at T3 as compared to T2 (P < 0.05) and returned to the baseline value at T4. Although the level of creatinine was increased at T2, there was no significant difference between time points in the FG. Significant correlations of BDNF and mood could not be observed at all time-points (P > 0.05).

Effect of Ramadan fasting on serum BDNF (A) and serum creatinine (B) (*P &lt; 0.05).
Figure 1. Effect of Ramadan fasting on serum BDNF (A) and serum creatinine (B) (*P < 0.05).

5. Discussion

The purpose of this study was to determine the alterations of BDNF and creatinine during RF. Our results demonstrate that there are no significant differences between the FG and NFG in both BDNF and creatinine. Interestingly, significant alterations of BDNF occurred in FG during RF.

In this study, BDNF level was decreased at T2 and increased at T3 and returned to the same level as the baseline (T1) at T4. It seems that on T2 and T3, BDNF showed an adaptation process, which led to the alteration of BDNF level. The BDNF has been known to be associated with mood-related disorders (12, 13). The RF could alleviate mood in both healthy subjects and patients (1, 14). However, we could not observe significant correlations between BDNF, mood, and HQoL. This difference can potentially be explained by the inclusion of clinically depressed patients in previous studies, while only healthy subjects were recruited to our study.

Previous studies reported on the association of BDNF with body weight and fat both in animal and human subjects (1, 15). Body weight and fat percentage altered in RF (1); however, this alteration did not correlate with circulating BDNF levels. The reported correlations (15) recruited obese participants, whereas the participants were mostly healthy and non-obese in the current study.

Creatinine is a marker related to glomerular filtration rate function (16). Fasting for long periods of time, particularly during summer months, has previously been postulated to lead to kidney impairment as a result of drastically reduced fluid intake. Our results demonstrate that there is no significant difference in creatinine level between the FG and NFG. In the FG, serum creatinine levels tended to increase at T2, but returned to baseline levels at T3 and T4. It seems the increase at T2 was due to the physiological adaptation of fasting. Therefore, we hypothesize that RF during the summer months is tolerable to the kidney in healthy male subjects, but recommend that patients with specific health conditions (e.g., kidney disease), should undergo monitoring by health professionals (17, 18).

This study has several strengths and limitations. Best to our knowledge, this is the first prospective control study that reports BDNF and creatinine during long-period fasting. Recruiting only male participants increase the homogeneity of the study population. It has also several limitations, as the results could differ in different gender and age populations. Eating habits were not controlled, but this could be also a strength, as it could reflect the real condition of the participants. However, recording eating habits and caloric consumptions should be considered in the future. Two evaluation time points in the NFG were selected as our hypothesis that NFG would not have any changes during T2 and T4. Comparing before fasting (T1) and the last day of the fasting period (T3) was our main focus.

5.1. Conclusions

This study demonstrated no significant differences in terms of BDNF and creatinine between the FG and NFG. The BDNF was altered during RF in the FG. No significant change in creatinine level establishes the tolerable situation for kidney in male healthy subject during a long-period of fasting.

Acknowledgements

Footnotes

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