INTRODUCTION:

Coronary Heart Disease (CHD) is ranked seventh for Non-Communicable Diseases (NCD) in Indonesia, with a prevalence of 63% of all deaths^1,2. Basic Health Research (Riskesdas) 2007 and 2013 showed an increase in NCD including heart disease. CHD is one of the major cardiovascular diseases affecting the world's population³. The cardiovascular disease mortality rate due to CHD is 45% of the 9.4 million deaths⁴. The 2014 sample registration system survey found 12.9% mortality at all ages due to CHD. Identification of risk factors will facilitate the planning of CHD prevention interventions. Several risk factors for CHD, including hypertension, DM, dyslipidemia, lack of physical activity, stress, and an unhealthy diet are modifiable CHD risk factors^1,2.

Riskesdas 2017 states that the prevalence of CHD increases with risk factors, one of which is an unbalanced diet. The control program for NCD is more emphasized on prevention efforts². One of the CHD that often causes death is CAD⁵. CAD is one of the most important causes of mortality and morbidity in the country⁶. The underlying pathological condition for CAD is atherosclerosis. Coronary artery diseases (CAD) represent a condition in which the blood supply to the heart muscle is partially or completely blocked⁵. The principle mechanism of atherosclerosis is a chronic, inflammatory and progressive disease with early manifestations that occur even at a young age⁷. Experimental data suggest that sustained elevations of heart rate may play a role in the pathogenesis of coronary atherosclerosis⁸. The plaque get builder up over many years and when the plaque which gets formed in the arteries, the condition is called atherosclerosis⁹. Although there are several causes of CVD progression, atherosclerosis is the most prevalent one among these disease conditions¹⁰.

Intermittent fasting (IF) can increase life span, reduce the incidence of diseases due to aging, such as diabetes, obesity, and cardiovascular disease¹¹. The strongest risk factor for cardiovascular disease is age because increasing age with all parameters other than normal age will increase the risk of cardiovascular disease⁷. Research by Ahmet et al (2010) using rats treated with alternate day fasting (ADF) for six months which was monitored by echocardiogram concluded that heart muscle tolerance increased to ischemic damage¹².

Another study on two-week-old Drosophila flies that were fasted 12 hours per day (time-restricted feeding = TRF) without reducing their daily calorie intake showed no increase in body weight from three to seven weeks of age, while free-feeding flies experienced an aging process in their hearts with signs of increased diastolic and systolic intervals and arrhythmias¹³.

Dawood’s fasting is one of the sunnah fasts that can be done at any time except at times when fasting is forbidden. This fasting is a combination model of TRF and ADF (modified ADF = MADF). The way to do this is not to eat from sunrise to sunset, alternate one day fasting and one day not fasting. Izzaturrahmi et al (2017) found that there were significant differences in BMI and abdominal circumference of respondents in the Dawood’s fasting and non-fasting groups¹⁴. Research on female students of Ponpes Al-Fithroh Yogyakarta found that the perpetrators of Dawood’s fasting tend to have a high level of emotional control so that they can withstand anger and lust, which can prevent the occurrence of emotional mental disorders which are one of the risk factors for CHD¹⁵. Yatindra et al. (2019) proved that there was a significant decrease in white blood cells in the group of rats undergoing Dawood’s fasting model with intermittent fasting of 10 hours a day, after being induced by acetaminophen¹⁶.

Atherosclerosis generally occurs when the fatty, yellow-colored plaques i.e. (atheroma’s) build up on the artery walls, narrowing the arteries and restricting the flow of blood. It also known as arteriosclerosis, in which plaque of cholesterol is developed within walls of artery and result’s in the restriction of blood flow¹⁷. The main pathophysiological mechanisms of atherogenesis, which is thought to underlie all cardiovascular diseases, include activation and dysfunction of the endothelium, induction of a proinflammatory and procoagulative state and induction of proatherogenic serum lipid profiles and lipid oxidation products¹⁸. Plaque formation during atherogenesis in arterial walls is a complex process involving lipid accumulation, cellular activation that induces and differentiates monocytes into foam cells, and various immune reactions involving T and B sets, neutrophils, granulocytes (neutrophils), and dendritic cells¹⁹. Monocytes contribute to atherogenesis by triggering leukocyte recruitment into plaque, moving towards the damaged endothelium that overexpresses monocyte chemotactic protein-1 (MCP-1) ligands and adhesion molecules (VCAM-1, ICAM-1, endothelin) on their cell surfaces, then diapedesis across the surface of the endothelium, then in the subendothelial space will differentiate into macrophages and will digest oxidized low-density lipoprotein (LDL-Ox) to form "foam cells". Foam cells will undergo apoptosis and die, but the lipids will accumulate in the intima and form plaques^20,21.

Blood total cholesterol (TC) is one of the early markers used to determine CHD risk²². Dyslipidemia is well recognized and modifiable risk factor that should be identified early to institute aggressive cardiovascular preventive management²³. A person who eats a lot of fatty foods and is high in carbohydrates will increase levels of fat in the blood, including small dense LDL (sd-LDL). Small dense LDL (sd-LDL) is LDL whose particles are small and dense so it has greater atherogenic potential because it is more easily oxidized²⁴. Risk factors have an important relationship with the mechanism of atherogenesis. Clinical studies show that the appearance of inflammation in atherosclerosis occurs also in humans⁷. Studies on the effect of voluntary fastings such as the Dawood’s fasting (MADF), which is a combination of alternate day fasting (ADF) and mealtime restriction (TRF) methods in inhibiting the formation of atherogenic sd-LDL during a predetermined fasting time and its implications for the incidence of atherosclerosis have not yet been studied. Dawood’s fasting (MADF) is expected to be an alternative to prevent the formation of atherogenic sd-LDL, especially in people with risk factors for cardiovascular disease, by looking at the differences caused by Dawood’s fasting treatment. This study was designed to fulfill the research objective of knowing the effect of Dawood's fasting (MADF) in preventing atherosclerosis.

MATERIALS AND METHODS:

Participants:

Thirty-eight healthy and young men were recruited for this study (±18-30 years) from Hidayatullah Islamic Boarding School in Surabaya through registration and selected according to inclusion criteria. At the commencement of this study, the participants were chosen allocated in to control (17 participants) and treatment (22 participants) group based on purposive sampling. The inclusion criteria included: male; age (18-30 years); Moslem; used to perform fasting at least 2x per month, healthy (no history of high blood pressure, diabetes mellitus and heart diseases). Prior to the study, participants were screened by questionnaires related to atherosclerosis risk factors, physical examination (blood pressure (BP), body temperature and heart rate (HR)) and laboratory testing (current blood glucose (CBG) and electrocardiography (ECG)). If the participants were not able to complete six consecutive weeks of Dawood fasting or experienced any illnesses or have any medical concerns, the participants will be withdrawn from this study. At the end of the study, three participants from the participants in the treatment group were withdrawn from this study because of unable to complete the MADF for six consecutive weeks, experienced illness, and heavy campus activities.

Baseline participant characteristics are provided in Table 1. This study was approved by Faculty of Medicine-Universitas Airlangga Research Ethics Committee and conformed to the standards outlined in Declaration of Helsinki (reference number 163/EC/KEPK/ FKUA/2019). All subjects provided written informed consent prior to their involvement in this study.

Study design:

Prior to study commencement, participants visited the laboratory for familiarization with the study protocol, motivated by resource person and completed a medical history, physical examination and pre-intervention laboratory testing. The blood samples (10 ml) were taken from participants at the same time of day (7 A.M) in a quiet and temperature-controlled room (23°C) and subsequently were analysed for serum sdLDL levels in the Research and Development section of the Clinical Pathology Laboratory, RSUD Dr. Soetomo, Surabaya.

Following preliminary assessment, the participants in the control group were asked to maintain their daily diet, while participants in the training group underwent Dawood fasting for six consecutive weeks, as described below. Dawood fast is a type of fasting that alternates a day which is preceded by eating sahur before sunrise and ends at sunset (Maghrib time). During the treatment, participants were tightly observed. All preliminary assessments were repeated following 3- and 6-weeks of intervention, at least three days after the last fasting to eliminate any acute fasting effects.

Diet intervention:

Initial examination of research variables on research subjects who meet the requirements as research respondents were carried out after previously receiving spiritual motivation from the resource person regarding the motivation for participation in this study. The study started two days after this initial examination, namely with Dawood’s fasting treatment (MADF) in the treatment group. All research respondents were advised to eat twice a day during the study and get the same menu for sahoor and breakfast, as well as the same iftar menu and lunch provided by the researcher. The MADF treatment schedule was given to the treatment group respondents with one respondent coordinator waking up at dawn. The researcher also reminded respondents about the treatment schedule through the WhatsApp group. This research was carried out for six weeks (42 days) with a varied daily food intake menu from caterers who collaborated with researchers. with a varied daily food intake menu from caterers who collaborated with researchers and included a menu for takjil (sweet food eaten upon breaking the fast) in the form of dates and hot tea for all groups. Researchers remind this schedule through WhatsApp groups.

Assessment of blood sLDL:

Prior to the blood sampling, participants were asked to fast for at least 8 hours (start at 10 P.M. at the previous night), and abstain from alcohol, tea, caffeine and chocolate 12-hours prior to test. They were also asked to avoid exercise or vigorous activity for 24-hours before each test.

Ten ml of blood were taken from cubital vein. The required volume of 5 milliliters was then put into a yellow capped SST vacutainer tube for ELISA examination of variable sdLDL levels. The examination was carried out on the day when the fasting group respondents were not fasting, with previously required not to eat and only allowed to drink water since 10 o'clock the night before. Blood sampling started at 7 A.M. Examination of serum sdLDL levels using the enzyme-linked immunosorbent assay (ELISA) method (using the Elabscience human sdLDL ELISA kit code E-EL-H5105).

This ELISA kit uses the Sandwich-ELISA principle. Elabscience Human sdLDL ELISA kit Code E-EL-H5105 with sensitivity 0.19 nmol/mL and detection range: 0.31 – 20 nmol/mL. Sample preparation was carried out by collecting in a serum separator tube and left for two hours at room temperature or overnight at 4^oC. Centrifugation was carried out after the formation of lumps for 15 minutes at a speed of 1000 × g at a temperature of 2 – 8^oC. The supernatant formed was immediately taken and stored at -80^oC. All reagents were removed at room temperature (18~25℃) before use, then followed the Microplate reader manual for setting and preheat for 15 minutes before OD measurement. 100 L of standard or sample was added to each well, then incubated for 90 minutes at 37°C. The liquid was discarded after completion, and 100 L of the biotinylation detection antibody was added and continued for 1 h at 37°C. Aspiration was carried out and washed 3 times. 100 L HRP Conjugate was added and incubated for 30 minutes at 37°C. Aspiration was repeated and washed 5 times. 90 L of reagent substrate was added and again incubated for 15 minutes at 37°C. Stop solution was added as much as 50 L and read immediately at 450 nm, followed by calculation of the results.

Statistical analysis:

The calculation of sample size was determined based on the published data of Setyawan, 1996, which reported “Effect of aerobic and anaerobic physical exercise on the body's resistance response - A psychoneuroimmunological approach”²⁵. Based on the effect size in that experiment, and assuming α=0.05 and β=0.8, the minimum number of subjects required to establish a significant change in this research was determined at 13 per group. Considering 30% of dropouts, the minimum total number of subjects was 17 people per group.

Statistical analysis was performed using SPSS version 20.0. The results are reported as means and standard deviations (SD), unless stated otherwise. Statistical analysis was performed using 2-way analysis of variance (ANOVA) to calculate differences between groups, with a repeated measure pre- mid- vs post-dietary intervention. When ANOVA tests were significant, post-hoc analysis using Fischer's least significant differences were used to assess changes. Results are statistically significant if p < 0.05. A stepwise regression test with a path analysis model were performed to determine the causal relationship between research variables and the strength of the relationship between one variable and another. The positive correlation results indicate that if the influencing variable is increased, the affected variable will increase. The result of a negative correlation is that if the influencing variable is increased, the affected variable will decrease.

RESULTS:

This research went through several stages, namely (1) research socialization to male students at Hidayatullah Islamic Boarding School, totaling 134 people; (2) Recruitment of research subjects who are willing to participate in research as evidenced by informed consent after being given information for consent, a total of 44 people with details of the control group as many as 20 people and the treatment group as many as 24 people; (3) examination of the health screening of research subjects for prospective respondents which include questionnaires related to atherosclerosis risk factors, examination of blood pressure, body temperature and heart rate, examination of CBG and ECG; (4) the determination of research subjects based on the results of health screening obtained 17 people from the control group and 21 people from the treatment group who met the predetermined inclusion criteria.

Participants characteristics:

Participant characteristics pre (week 0), mid (week 4) and post (week 7) intervention are presented in Table 1. Age, resting blood pressure, resting heart rate, body weight, waist circumference, hip circumference, waist-hip circumference ratio and BMI did not differ between groups at baseline (Table 1, week 0).

Table 1. Subjects’ characteristics

	CON (n = 17, male)	TR (n = 22, male)	Anova P Value
Age, yr	20.5 ± 1.3	20.7 ± 1.4	0.728
BMI, kg/m²	19.5 ± 1.4	19.7 ± 3.4	0.851
Blood pressure, mmHg
Systolic	114,7 ± 6.2	113.2 ± 9.9	0.584
Diastolic	87.6 ± 4.4	85.5 ± 9.1	0.368
Mean	101.2 ± 2.8	99.3 ± 9.2	0.426
Resting heart rate, beats/ min	72.9 ± 9.9	69.1 ± 10.2	0.243
Waist circumference	21.5 ± 1.9	21.9 ± 2.7	0.618
Hip circumference	26.4 ± 1.7	26.8 ± 1.8	0.470
Waist-hip circumference ratio (WHR)	0.8 ± 0.1	0.8 ± 0.1	0.984

Data are presented in means ± SD. CON, control; TR, treatment; ANOVA P Value at 0.05.

The characteristics of the research subjects can be seen in table 1. The mean age in the control group (20.5 ± 1.3) was lower than the treatment group (20.7 ± 1.4). BMI in the control group (19.5 ± 1.4) was also lower than the treatment group (19.7 ± 3.4). Systolic blood pressure (114.7 ± 6.2), diastolic blood pressure (87.6 ± 4.4), mean blood pressure (101.2 ± 2.8), and resting heart rate (72.9 ± 9.9) in the control group were higher than the treatment group (113.2 ± 9.9; 85.5 ± 9.1; 99.3 ± 9.2; 69.1 ± 10.2). Waist circumference (21.5 ± 1.9) and hip circumference (26.4 ± 1.7) in the control group were lower than the treatment group (21.9 ± 2.7; 26.8 ± 1.8). The waist-hip circumference ratio in the control group (0.8 ± 0.1) was the same as in the treatment group (0.8 ± 0.1), where both have low cardiovascular risk (<0.95).

Impact of Dawood fasting on sdLDL

The table below shows the results of the research on sdLDL variables.

Table 2: Descriptive test data from the results of the sdLDL variable research (nmol/mL)

	Group	WEEK 0	WEEK 4	WEEK 7
sdLDL	Control	8.87± 5.62	18.35 ± 16.52	16.20 ± 12.63
	Treatment	20.05 ± 5.17	12.65 ± 12.25	16.22 ± 8.66

Data are presented in means ± SD. CON, control; TR, treatment

Table 2 above shows descriptive data in the form of mean sdLDL at the beginning, middle, and end of the study for each group. These results can be illustrated in Figures 1 and 2 below.

Figure 1. Graph of mean sdLDL at the beginning, middle, and end of the study for each group.

Figure 2. Graph of pre-test and post-test mean sdLDL trends for each group.

The mean sdLDL graph in Figure 1 shows that the post-test mean sdLDL level in the treatment group is slight higher than the control group, while Figure 2 shows that the pre-test and post-test mean sdLDL trend in treatment groups is decreased while the trend mean sdLDL levels in control groups is increased.

The data from the normality test for the distribution of sdLDL variables showed that all data were normally distributed (p > 0.05), except for the middle sdLDL data in the treatment and control groups and the final sdLDL in the control group. This causes the test to be continued for the non-parametric test. The Wilcoxon signed-rank test to distinguish the sdLDL data at the beginning and end of the treatment and control groups, the results are as shown in table 3 below.

Table 3. Non-parametric Wilcoxon signed-rank test results for initial and final sdLDL variables

sd-LDL 3 – sd-LDL 1	Control	Treatment
Z	-1.40	-2.20
p	0.16	0.03

Description: significantly different, if p < 0.05

The results of the non-parametric Wilcoxon signed-rank test for the initial and final sdLDL variables in the treatment and control groups showed that in both groups the Z value was negative, namely -2.20 in the treatment group and -1.40 in the control group. The p-value in the treatment group showed a significant difference (p < 0.05) of 0.03, while the control group showed p = 0.16, which means there was no difference.

Path Analysis Test Results

Meaningful results from path analysis and the complete strength of the relationship can be seen in Table 4 below.

Table 4. Regression values and significance between variables

No.	Variable	Beta (β)	r²	p-value
1	SBP à sdLDL	-0.559**	0.363	0.01*
2	DBP à SBP	0.843	0.711	0.01*
3	Fasting à DBP	0.374	0.354	0.02*

Description:

Beta (β) : regression coefficient, shows the relationship of the independent variable to the dependent variable (increase or decrease).

r² : coefficient of determination, the contribution of the independent variable to the variation (increase or decrease) of the dependent variable.

p-value : significance probability value, declared significant or meaningful if p value < 0.05

Sign * : significant or meaningful

Sign ** : negative relationship

Based on the data in the table above, it can be seen that the significant relationship between variables is SBP with sdLDL; DBP with TDS; and fasting with DBP. The relationship that has a positive direction is the provision of fasting treatment with DBP and DBP with SBP. The relationship that has a negative direction is SBP with sdLDL.

Based on the path analysis carried out, there was a significant path between fasting treatment and DBP. DBP has a significant pathway with SBP, and SBP has a significant pathway with sdLDL. The results of the path analysis between the dependent and independent variables are presented in the schematic below.

0.374 0.843 -0.559

Fasting------- Diastole --------- systole --- sdLDL

Figure 3. Path analysis test results

The results of the path analysis above show that the administration of MADF (Dawood fasting) for 6 consecutive weeks can affect sdLDL through the DBP and SBP pathways. The effect of MADF (Dawood's fast) on sdLDL can be determined by multiplying the beta value (β) on each path to the dependent variable as follows:

Effect of MADF (Dawood’s fasting) on sdLDL levels:

fasting x DBP x SBP = 0.374 x 0.843 x - 0.559 =

- 0.1762 = - 17.62%

Based on the description above, it is found that MADF (Dawood’s fasting) for 6 consecutive weeks reduced sdLDL levels by 17.62%.

DISCUSSION:

Overview of Research Subjects:

Table 1 shows the distribution of age, BMI, SBP, DBP, MBP, rHR, WC, HC and WHR of research subjects. The age of the research subjects all met the inclusion criteria which ranged from 18-30 years indicates that the mean age in the control group is relatively younger than the treatment group. BMI is calculated based on the weight and height of the subject with the formula BW (kg) / BH² (m). The mean BMI of both groups was normal. The control group had a lower mean than the treatment group. BMI can be used to assess nutritional status so that in general the subjects in the treatment group showed better nutritional status than the control group. WHR is calculated based on the ratio of waist circumference to hip circumference (in cm). In both groups, the mean WHR showed the same value (0.8±0.1). WHR value < 0.95 indicates a small cardiovascular risk, while a value > 0.95 indicates a major cardiovascular risk. Based on the general description of the research subjects, it was found that all research subjects in a state of nutritional status were not obese and indicates a small cardiovascular risk.

The Effect of Fasting Dawood (MADF) for Six Weeks in a row on Small Dense Low-Density Lipoprotein (sdLDL) Levels in Peripheral Blood Circulation:

The purpose of this study was to compare the levels of small dense LDL (sdLDL) of individuals who fasted Dawood for six consecutive weeks with controls. The results of this study found that the post-test mean sdLDL was slightly higher in the treatment group than the control group (figure 1), but the increase (delta mean pre and post-test) in the treatment group was smaller than that in the control group (figure 2). The different test on the mean sdLDL levels pre-test and post-test as shown in table 3 shows a significant difference between pre and post-test in the treatment group (p=0.03), while in the control group there is no difference (p=0.16). This means that in young adults with normal BMI or underweight, there was no statistically significant change in blood sdLDL levels due to the effect of MADF (Dawood’s fasting) for 6 consecutive weeks.

This result is not in line with the results of the path analysis test which found that Dawood’s fasting (MADF) hurt sdLDL levels (figure 3). This is because sdLDL as a risk factor for atherosclerosis is influenced by multiple pathways, where the accumulated influence of other pathways on sdLDL levels is stronger than the negative effect of Dawood’s fasting (MADF) alone, increasing sdLDL levels in the blood at the end of treatment. Other pathways that affect sdLDL levels include food intake, physical activity/sports, and others.

During the transition from a period of eating to a period of fasting, hunger-like mechanisms can arise involving extreme hunger, the release of stress hormones, and changes in metabolism. This can result in side effects, one of which is an imbalance between the hormones hunger and satiety, thus making the body unresponsive to signals that the body is full at the time of breaking the fast. This shift in hormonal balance may or may not occur depending on the length of time fasting, food, or dietary intake when breaking the fast during fasting, and physical activity while fasting. The composition of food intake when breaking the fast is important to maintain the balance of these hormones.

Someone who eats a lot of fatty foods and is high in carbohydrates will increase fat levels in the blood, including small dense LDL (sdLDL). Small dense LDL (sdLDL) is LDL whose particles are small and dense so it has greater atherogenic potential because it is more easily oxidized²⁴. Fasting can increase GH secretion from the anterior pituitary and will indirectly affect insulin through IGF-1 so that it will increase post-test OGTT levels. Stimuli that can increase GH secretion are divided into 3 categories, namely (1) hypoglycemic or fasting conditions in which there is a marked decrease in the substrate used for energy production, (2) conditions in which the number of amino acids is increased in plasma and (3) stimuli from stress. GH secretion is also increased in subjects who experience rapid eye movement (REM) sleep disturbances and is inhibited in normal REM sleep states. Sex hormones induce GH secretion, increase GH response to triggering stimuli such as arginine and insulin, and also act as factors that enable GH action in the periphery. This seems to contribute to the relatively high circulating GH levels and is associated with the accelerated growth spurt at puberty. In contrast, GH secretion is inhibited by cortisol, free fatty acids, and medroxyprogesterone²⁶.

The initial response that occurs in fasting is glycogenolysis, which is the release of glucose from the liver and muscles. The liver begins to synthesize and release de novo glucose at the same time, initially using lactate, which is returned to the liver from the muscles via the Cori cycle. Lipolysis is activated in adipose tissue shortly thereafter, which then releases fatty acids for burning in the muscles and supplies energy to fuel gluconeogenesis in the liver. Liver fatty acid oxidation also produces ketone bodies acetoacetate and -hydroxybutyrate, which can partially replace glucose for energy in the brain and muscles. This entire process is regulated by hormones, primarily through decreased insulin and increased glucagon, which activates gluconeogenesis in the liver, and growth hormone (GH), which stimulates lipolysis in adipose tissue^26,27. This is thought to also contribute to the body's response to sdLDL levels in this study which were not different.

The BMI of the underweight dominant treatment group may also affect the subject's body response in fasting metabolism because it is said that individuals who are thin and very active, have high-stress levels, and have poor eating habits tend to experience appetite regulation disorders, so they can lose control over food intake. when breaking the fast. Emotional control of food, related to appetite regulation in the limbic system may also affect the results of this study.

Sabaka et al. in their 2015 study found that short-term aerobic exercise performed by 10 healthy subjects affected a significant reduction in the atherogenic medium size LDL profile during fasting and after eating²⁸. The composition of fat in food intake also determined the increase in LDL size in 35 obese subjects who were treated with ADF with a low-fat and high-fat diet composition. The results obtained are that ADF with a high-fat diet composition is as effective as ADF with a low-fat diet composition in increasing LDL particle size²⁹. These results indicate that sdLDL levels are not only influenced by the state of IF/ADF but can also be influenced by physical activity/exercise and the regulation of diet composition which was not carried out in this study.

The Effect of Fasting Dawood (MADF) for Six Weeks in a row on Small Dense Low-Density Lipoprotein (sd-LDL) Levels as a Risk for Atherosclerosis in Peripheral Blood Circulation:

The risk of atherosclerosis is defined by researchers as the possibility of inflammation due to the hardening and progressive narrowing of the arteries due to fatty deposits. The indicator of this variable is the level of blood sdLDL. The discussion on the effect of Dawood's fasting (MADF) for six weeks in a row lowering sdLDL levels in peripheral blood circulation has been discussed before that MADF (Dawood’s fasting) hurts blood sdLDL levels from the results of statistical tests. MADF (Dawood’s fasting) for six consecutive weeks can inhibit the rate of increase in sdLDL levels due to other factors in peripheral blood circulation as a risk of atherosclerosis. Individuals who undergo MADF (Dawood’s fasting) can experience a reduced risk of atherosclerosis but must be supported by other prevention, for example by regulating the composition of food intake, physical activity/exercise, drugs that prevent other risk factors for atherosclerosis.

The effect of preventing the risk of atherosclerosis in this study appears to be directly related to blood vessels, although many other factors also influence blood LDL levels as risk factors for atherosclerosis. This may be due to the implementation of fasting, which is only six weeks, still requires additional time to determine the effect of significant metabolic and immunological changes.

The Relationship Between the Variables Under Study:

The results of the path analysis that have been carried out in the previous sub-chapter show that Dawood’s fasting (MADF) has a causal relationship to DBP, while DBP has a causal relationship to SBP and SBP has a causal relationship to sdLDL levels. It can be interpreted that Dawood’s fasting (MADF) has an influence on sdLDL levels through the DBP and SBP pathways.

Based on the results of path analysis, it was found that MADF (Dawood’s fasting) for 6 consecutive weeks reduced sdLDL levels by 17.62%. This means that Dawood's fasting can inhibit the rate of increase in sdLDL levels by 17.62%, in healthy young adult men who undergo it.

NEW RESEARCH FINDINGS:

This study obtained several new findings, namely:

1. This study is the first study in Indonesia to prove the negative effect of Dawood’s fasting (MADF) to inhibit the rate of increase in the risk of atherosclerosis.

2. The mechanism of atherosclerosis goes through a process that involves multifactorial and multi-pathways, so it cannot be controlled only by Dawood’s fasting alone.

3. Control of risk factors for atherosclerosis requires support for other prevention, which can change various factors that do not support the mechanism of atherosclerosis.

RESEARCH LIMITATIONS:

This study has several limitations that can be used as input for further research, namely:

1. This study did not control for psychological factors, including sincerity, which influenced the motivation and mood of the research subjects.

2. In this study, the composition of the diet was not adjusted, so it was not possible to calculate the composition of calories consumed by the research subjects.

3. This study did not directly measure oxidized-LDL as a direct risk factor for atherosclerosis, because the examination method is complicated and expensive.

4. There was no blinding and cross intervention in this study, so it is prone to potential bias and data contamination.

CONCLUSION:

1. The sdLDL levels of individuals who fasted Dawood for six consecutive weeks were found to be no different from controls.

2. Atherosclerosis is a process that involves multiple pathways and multiple variables. The accumulation of other effects that increase sdLDL levels was found to be stronger than the effect of Dawood's fasting.

3. Fasting of Dawood (MADF) for six consecutive weeks hurts levels of sdLDL which is an atherogenic lipoprotein as a risk factor for atherosclerosis.

ACKNOWLEDGEMENT:

Indri Ngesti Rahayu is supported by a Doctoral Dissertation Research Scholarship funded by Indonesian Endowment Fund for Education (LPDP), Ministry of Finance, Indonesia with contract number PRJ-27/LPDP.4/2020.

CONFLICT OF INTEREST:

The authors declare that there are no conflict of interest.

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Received on 22.06.2022 Modified on 11.08.2022

Research J. Pharm. and Tech 2023; 16(6):2724-2732.

DOI: 10.52711/0974-360X.2023.00448