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Ramadan Diet Restrictions Modify the Circadian Time Structure in Humans. A Study on Plasma Gastrin, Insulin, Glucose, and Calcium and on Gastric pH¹

Hassan II Foundation for Scientific and Medical Research on Ramadan (L.I., F.H.), Faculté de Médecine et de Pharmacie, Casablanca, Morocco; Service de Biochimie (A.B., Y.T.), Faculté de Médecine Pitié-Salpêtrière, 75013 Paris, France; Service d’Exploration Fonctionnelle Digestive (N.A.), Hôpital Ibn Sina, Souissi, Rabat, Morocco; and Hôpital Bnou Rochd (A.A.), Service de P3, Casablanca, Morocco

Address all correspondence and requests for reprints to: Pr Yvan Touitou, Department of Biochemistry, Faculty of Medicine Pitié-Salpêtrière, 91 Bd de l’Hôpital, 75013 Paris, France.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The rule of Ramadan (1 month of food and water intakes re-stricted to night hours) is followed by the majority of the Moslem fraction of the human population, but the possible consequences of this long-lasting modification of food intake schedule on public health have not yet been extensively documented. Therefore, a group of healthy control subjects and a group of healed duodenal ulcer patients were studied before (controls), during (both groups), and after (both groups) the month of Ramadan. The time-restricted food and water intakes were associated with variations of gastric pH, plasma gastrin, insulin, glucose, and calcium documented on a circadian basis. All of the studied biological variables, except insulin, underwent changes in their 24-h mean concentration (e.g. decrease in gastric pH, increase in plasma gastrin), some of which were still present 1 month after the end of Ramadan. The circadian patterns of all the studied variables were altered during the month of Ramadan. Some differences between the group of healthy control subjects and the group of healed duodenal ulcer patients may suggest a greater susceptibility of the latter to the modifications of feeding and sleeping schedule, which could possibly be a risk factor for the disease.

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
RAMADAN is the month during which Moslems must refrain from eating and drinking from sunrise to sunset. Behavioral modifications are thus concerned with meal scheduling (three at night within a short span of time) and shortening of time allowed to sleep.

Synchronizers are environmental factors able to modify one or several parameters of the circadian rhythm of a biologic variable (1, 2). In humans, socioecological factors, including the rest-activity cycle, play a role in the synchronization of individuals (3). Meal timing also serves as a synchronizer for humans; however, this influence is overestimated by some authors (4, 5, 6) and underestimated by others (7, 8).

The purpose of the present study was to investigate the possible influence of the simultaneous modification of feeding time (meals at night only) and sleeping time (2 h delayed and shortened) on the circadian rhythm of intragastric pH, plasma insulin, gastrin, glucose, and calcium in healthy male volunteers and in patients with healed duodenal ulcers (HDU), during the month of Ramadan.

	Subjects and Methods

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Volunteers meeting the inclusion criteria participated in the study, and each gave written and informed consent. The protocol was approved by the Ethical Committee of the Faculté de Médecine of Casablanca and by the religious board of the Hassan II Foundation for Scientific and Medical Research on Ramadan.

Healthy subjects

Nine healthy male volunteers were included in this study after routine clinical and laboratory examination and upper gastrointestinal fibroscopy. They were 25.0 ± 1.2 yr old (mean ± SD; range 20–32 yr) and had a mean BW (±SEM) of 73.3 ± 4.0 kg (range 60–95 kg). None of them took any medication either before or during the study, and they were all free from any chronic or acute somatic or psychiatric disorder.

HDU patients

Six HDU male patients were included in this study after routine clinical and laboratory examination and fibroscopy. They were 39 ± 2 yr old (range 33–43 yr) and had a BW of 64 ± 4 kg (range 50–74 kg). They were all healed from a duodenal ulcer for more than 3 months (range 4 months–3 yr).

Protocol

The healthy volunteers were studied four times during a 24-h span: once before Ramadan (P1), on the 10th day (P2) and on the 24th day (P3) of Ramadan, and last, 1 month after the end of Ramadan (P4). HDU patients were studied twice: on the 17th day of Ramadan (U1) and 6 weeks after the end of Ramadan (U2).

During each test day, the following variables were documented: intragastric pH data were continuously recorded over 24 hours; plasma gastrin, insulin, glucose, and calcium were determined on 11 blood samples (10 mL, lithium heparinate) drawn from the antecubital vein through an indwelling catheter at the following clock hours: 1700 h, 1930 h, 2100 h, 2230 h, 0100 h, 0230 h, 0800 h, 0930 h, 1300 h, 1430 h, and 1700 h.

Before the month of Ramadan, the subjects were synchronized with a nocturnal rest from 2300 h ± 1 h to 0800 h and a diurnal activity, but during test days, they were awakened for the 0100 h and 0230 h blood samplings. During the month of Ramadan, except for test days, the subjects slept from 0130 h to 0800 h uninterrupted and followed their usual activities during daytime. Thus, the average sleep time of the subjects was 2 h shorter during the month of Ramadan.

On test days, the volunteers stayed in the laboratory from 1630 h to 1730 h the following day. On arrival, an indwelling nasogastric pH probe (Ingold M3) was inserted; the pH probes were calibrated at pH = 4 and 7 with a SOLAL pH-meter (Prolabo, Paris, France) before use. The 24-h records of intragastric pH were performed on a PC-compatible computer with the Sandhill^TM software.

All the meals were qualitatively and quantitatively standardized by a nutritionist, were taken at fixed hours, and lasted 15–20 min.

Meal timing and composition before and after the month of Ramadan: 0800 h: bread, jam, butter, coffee, and milk (total 730 kcal); 1100 h: coffee with sugar (total 40 kcal); 1300 h: chicken, vegetables, bread, banana, tea (total 1370 kcal); 1700 h: milk and bread (total 350 kcal); 2100 h: vegetable soup, giblets omelette, noodles, bread, yogurt (total 960 kcal).

Meal timing and composition during the month of Ramadan: 1800 h: milk, vegetable soup, dates, honey cake, egg, bread, coffee with sugar (total 1270 kcal); 2100 h: chicken, vegetables, bread, banana, tea (total 1370 kcal); 0100 h: milk, pancake with sugar, bread and butter, apple, tea (total 800 kcal).

Biochemical assays

Plasma insulin was determined by RIA with first and second antibodies provided by Dr. Sodoyez and according to Sodoyez-Goffaux et al. (9) technique. This method has a sensitivity threshold of 1.5 µU/mL; the intra- and interassay coefficients of variation were, respectively, 6.3% and 6.0%. Plasma gastrin was determined by RIA (10) with a commercial kit (GASK-PH, CIS Biointernational, Gif-sur-Yvette, France). The sensitivity of the test was 10 pg/mL; the intra- and interassay coefficients of variation were, respectively, 14.5% and 4.5%. Blood glucose was determined enzymatically through a NADH/glucose dehydrogenase-mutarotase reaction (11) with spectrophotometrical readings at 340 nm and 380 nm. The interassay coefficient of variation was between 1.7% and 2.5%. Plasma calcium was measured with a colorimetric method using O-cresolphtalein-complexon as chromogenic agent in the presence of 8-hydroxyquinolein to prevent magnesium interferences (12). The interassay coefficient of variation was between 1.8% and 2.4%.

Statistical analysis

Intragastric pH data were integrated and averaged over 15 min (96 points per 24 h). The data for pH, insulin, gastrin, glucose, and calcium were plotted vs. time as means ± SEM for the control group and the HDU group. Data were analyzed with a repeated-measures ANOVA (2 within, 0 between) with the SuperAnova^TM software (Abacus Concepts, Inc. Berkeley, CA) to look for the circadian variations (effect of time), the influence of Ramadan upon the 24-h mean concentrations (e.g. P1 vs. P2, and U1 vs. U2) and the possible interaction of Ramadan upon the circadian variations (e.g. P1-P2¹time interaction).

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
pH

The circadian profiles of gastric pH in healthy control subjects are shown in Fig. 1. The 24-h mean pH values were P1: 2.84 ± 0.06, P2: 2.35 ± 0.06, P3: 2.25 ± 0.05, and P4: 2.32 ± 0.05. The values for mean pH on P3 and P4 were found significantly lower than that of P1 (Table 1). An effect of time (circadian variation) was validated in the four study periods. A significant interaction between test day and time was observed with the P1 vs. P2 and P3 comparisons.

View larger version (37K): [in this window] [in a new window]   Figure 1. Circadian pattern of gastric pH in healthy control subjects documented before (P1) Ramadan, on the 10th day (P2) and on the 24th day (P3) of Ramadan, and 1 month after the end of Ramadan (P4). The black horizontal bar shows the time of sleep and the gray columns show the times of meal Each point is the mean and SEM of eight subjects. Significance of the effect of time of day upon measures, differences in 24-h mean levels (e.g. P1 vs. P2, etc.), and influence of test day upon effect of time (e.g. P1-P2*time interaction, etc.) are given in Table 1.

View larger version (24K): [in this window] [in a new window]   Figure 2. Circadian pattern of gastric pH in HDU patients documented on the 17th day (U1) of Ramadan and 6 weeks after the end of Ramadan (U2). The black horizontal bar shows the time of sleep and the gray columns, the time of meals. Each point is the mean and SEM of five patients. Significance of the effect of time of day upon measures, differences in 24-h mean levels (e.g. P1 vs. P2, etc.), and influence of test day upon effect of time (e.g. P1-P2*time interaction, etc.) are given in Table 2.

The 24-h patterns of plasma gastrin in healthy controls are shown in Fig. 3. The effect of time could be validated in the four study periods (Table 1). The 24-h mean concentrations were P1: 64.3 ± 2.3 pg/mL, P2: 76.0 ± 2.4 pg/mL, P3: 56.5 ± 2.3 pg/mL, and P4: 62.7 ± 2.4 pg/mL. A significant difference was observed only with the P2 vs. P3 comparison. The interaction between test day and time was validated for the P1 vs. P2 and P1 vs. P3 comparisons.

View larger version (25K): [in this window] [in a new window]   Figure 3. Circadian pattern of plasma gastrin in healthy control subjects documented before (P1) Ramadan, on the 10th day (P2) and on the 24th day (P3) of Ramadan, and 1 month after the end of Ramadan (P4). The black horizontal bar shows the time of sleep and the gray columns, the time of meals. Each point is the mean and SEM of seven subjects. Significance of the effect of time of day upon measures, differences in 24-h mean levels (e.g. P1 vs. P2, etc.), and influence of test day upon effect of time (e.g. P1-P2*time interaction, etc.) are given in Table 1.

View larger version (14K): [in this window] [in a new window]   Figure 4. Circadian pattern of plasma gastrin in HDU patients documented on the 17th day (U1) of Ramadan and 6 weeks after the end of Ramadan (U2). The black horizontal bar shows the time of sleep and the gray columns, the time of meals. Each point is the mean and SEM of five patients. Significance of the effect of time of day upon measures, differences in 24-h mean levels (e.g. P1 vs. P2, etc.), and influence of test day upon effect of time (e.g. P1-P2*time interaction, etc.) are given in Table 2.

A circadian variation was validated in the four study periods (Table 1). Whereas no difference was found in the 24-h mean concentrations (P1: 23.9 ± 3.0 µU/mL, P2: 23.4 ± 2.5 µU/mL, P3: 21.3 ± 2.3 µU/mL, P4: 21.9 ± 1.7 µU/mL), an obvious change in the circadian pattern was observed during Ramadan (Fig. 5), and the interaction between test day and time was validated except for the P2 vs. P3 comparison.

View larger version (25K): [in this window] [in a new window]   Figure 5. Circadian pattern of plasma insulin in healthy control subjects documented before (P1) Ramadan, on the 10th day (P2) and on the 24th day (P3) of Ramadan, and 1 month after the end of Ramadan (P4). The black horizontal bar shows the time of sleep and the gray columns, the time of meals. Each point is the mean and SEM of seven subjects. Significance of the effect of time of day upon measures, differences in 24-h mean levels (e.g. P1 vs. P2, etc.), and influence of test day upon effect of time (e.g. P1-P2*time interaction, etc.) are given in Table 1.

View larger version (14K): [in this window] [in a new window]   Figure 6. Circadian pattern of plasma insulin in HDU patients documented on the 17th day (U1) of Ramadan and 6 weeks after the end of Ramadan (U2). The black horizontal bar shows the time of sleep and the gray columns, the time of meals. Each point is the mean and SEM of six patients. Significance of the effect of time of day upon measures, differences in 24-h mean levels (e.g. P1 vs. P2, etc.), and influence of test day upon effect of time (e.g. P1-P2*time interaction, etc.) are given in Table 2.

The 24-h patterns of blood glucose in healthy controls (Fig. 7; Table 1) showed significant modifications both in concentration and timing. The effect of time was validated before, twice during, and after Ramadan. The 24-h mean ± SEM concentrations of blood glucose were P1: 5.16 ± 0.06 mmol/L, P2: 4.33 ± 0.06 mmol/L, P3: 5.22 ± 0.06 mmol/L, and P4: 5.33 ± 0.06 mmol/L. It has to be noted that in terms of overall concentration, the only significant differences were found when comparing P1 with P2 and P2 with P3. The interaction between test day and time was validated for the comparisons before vs. during (P1 vs. P2 and P3). It has to be noted that no significant interaction was observed with the before vs. after and with the 10th day vs. 24th day during Ramadan comparisons.

View larger version (24K): [in this window] [in a new window]   Figure 7. Circadian pattern of plasma glucose in healthy control subjects documented before (P1) Ramadan, on the 10th day (P2) and on the 24th day (P3) of Ramadan, and 1 month after the end of Ramadan (P4). The black horizontal bar shows the time of sleep and the gray columns, the time of meals. Each point is the mean and SEM of nine subjects. Significance of the effect of time of day upon measures, differences in 24-h mean levels (e.g. P1 vs. P2, etc.), and influence of test day upon effect of time (e.g. P1-P2*time interaction, etc.) are given in Table 1.

View larger version (16K): [in this window] [in a new window]   Figure 8. Circadian pattern of plasma glucose in HDU patients documented on the 17th day (U1) of Ramadan and 6 weeks after the end of Ramadan (U2). The black horizontal bar shows the time of sleep and the gray columns, the time of meals. Each point is the mean and SEM of six patients. Significances of the effect of time of day upon measures, differences in 24-h mean levels (e.g. P1 vs. P2, etc.), and influence of test day upon effect of time (e.g. P1-P2*time interaction, etc.) are given in Table 2.

Circadian variations of blood calcium in healthy controls were validated in the four study periods (Fig. 9; Table 1). The 24-h mean concentrations were P1: 2.54 ± 0.01 mmol/L, P2: 2.52 ± 0.01 mmol/L, P3: 2.39 ± 0.01 mmol/L, and P4: 2.51 ± 0.02 mmol/L. A decrease in the 24-h mean concentration was significant only when P3 was compared with P1 or P2. Significant interactions between test day and time were observed for the P3 vs. P1 and P2 comparisons.

View larger version (26K): [in this window] [in a new window]   Figure 9. Circadian pattern of plasma calcium in healthy control subjects documented before (P1) Ramadan, on the 10th day (P2) and on the 24th day (P3) of Ramadan and 1 month after the end of Ramadan (P4). The black horizontal bar shows the time of sleep and the gray columns the time of meals. Each point is the mean and SEM of nine subjects. Significance of the effect of time of day upon measures, differences in 24-h mean levels (e.g. P1 vs. P2, etc.), influence of test day upon effect of time (e.g. P1-P2*time interaction, etc.) are given in Table 1.

View larger version (14K): [in this window] [in a new window]   Figure 10. Circadian pattern of plasma calcium in HDU patients documented on the 17th day (U1) of Ramadan and 6 weeks after the end of Ramadan (U2). The black horizontal bar shows the time of sleep and the gray columns the time of meals. Each point is the mean and SEM of six patients. Significance of the effect of time of day upon measures, differences in 24-h mean levels (e.g. P1 vs. P2, etc.), influence of test day upon effect of time (e.g. P1-P2*time interaction, etc.) are given in Table 2.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

A number of studies have reported the existence of circadian variations in the basal acid gastric secretion (16, 17, 18, 19, 20, 21). A study with 24 h continuous pH recording (21) compared the intragastric acidity in nine healthy volunteers after a 28-h fast and after 3 meals and 3 snacks and showed that a circadian variation of gastric pH existed during both fasting and feeding. Although most studies agree with a minimum in gastric pH in the nocturnal span (2000 h to 2400 h) and a maximum in gastric pH in the morning hours (0800 h to 1000 h), no clear consensus was found about the effects of the timing of food intakes upon this circadian variation. Indeed, some authors (4, 5, 6) support the hypothesis that the timing of meals would modulate some circadian rhythms in humans, whereas others (7, 8) deny it. This controversy prompted us to look for the possible incidence of prolonged diet restriction as seen during the month of Ramadan upon the circadian rhythmicity of gastric pH, plasma gastrin, insulin, glucose, and calcium both in healthy controls and in HDU patients. The observance of Ramadan being one of the five major rules of Islam, its effects, if any, on public health concern a noticeable fraction of the human population.

The timing of the peaks and troughs of basal gastric pH observed in this study are in good agreement with those reported in the literature (16, 17, 18, 19, 20, 21). The profiles of gastric pH here obtained in healthy control subjects show that a circadian variation existed both before, during, and 1 month after the end of Ramadan. From our data, it can be concluded that it took more than 10 days of diet restriction to decrease the 24-h mean gastric pH, because a significant difference in mean concentrations was evident when comparing P1 with P3 but not with P2. It also has to be noted that the mean gastric pH values 1 month after Ramadan were still significantly lower than on the basal day. Our results also show that Ramadan resulted in significant modifications in the number and time-location of gastric pH peaks and troughs, which were validated on P2 and persisted on P3. Contrary to the 24-h mean pH values, the circadian pattern observed 1 month after the end of Ramadan was very similar to that seen on basal day. In HDU patients, the profile of gastric pH observed 6 weeks after Ramadan was very similar to that seen in control subjects studied at a similar time. On the other hand, the pattern of gastric acidity during Ramadan was apparently more modified by diet restriction than were those of healthy controls. During Ramadan, HDU patients exhibited about 8 h (0800 h to 1600 h, ie. fasting hours) of continuously low gastric pH, which could be a factor increasing the risk of relapse.

Plasma gastrin has been studied by many authors (21, 22, 23, 24, 25, 26) reporting the presence of a circadian rhythm during fasting of more than 24-h, as well as under standardized food intakes. Nevertheless, plasma gastrin concentrations are believed to be closely related to the qualitative and quantitative composition of food intakes (21, 27, 28). In both HDU patients and healthy controls in our study, significant circadian variations were observed in all situations. In healthy control subjects, Ramadan induced a modification of these variations as soon as study day P2, which persisted during study day P3 but was corrected on study day P4. In HDU patients, a clear difference was observed between the patterns of plasma gastrin on the 17th day of diet restriction and 1 month after Ramadan. In addition, HDU patients showed unexpectedly high plasma gastrin concentrations during the fasting span of the day. This is, to our knowledge, the first time that such a difference between healthy and duodenal ulcer patients in relation with food intake frequency has been shown.

Several reports showed the circadian rhythmicity of plasma insulin (29, 30) after three major meals (breakfast, lunch, and dinner). It is now understood (30, 31) that plasma insulin levels display a circadian rhythm with a major peak in the middle of the day and three or four other peaks induced by food intake. In our study, circadian variations of plasma insulin were validated in both groups of subjects and all study days. In healthy control subjects, the circadian pattern was modified as soon as the 10th day of Ramadan and remained the same on the 24th day. During Ramadan, plasma insulin concentrations in healthy control subjects markedly increased after the first meal and stayed at high levels, probably because the two other meals occurred at short intervals. The plasma insulin concentrations then decreased continuously until the next day’s first meal. It has to be noted that the profile 1 month after Ramadan was still found significantly different (higher night values) from that seen in basal conditions and that, thus, a particular sensitivity of the insulin regulation mechanism to the evening meal cannot be ruled out and might be a remnant effect of temporal reorganization imposed by Ramadan. In HDU patients, during Ramadan, the concentration markedly increased after the first meal but decreased rapidly, despite the two subsequent meals that resulted in a flattened profile from zero h to 1800 h, when compared with that in healthy controls. This difference is likely related to the group origin (healthy subjects vs. healed ulcer patients).

Previous studies have shown in healthy subjects a morning peak in plasma glucose concentration called the dawn phenomenon (32, 33), which would be a consequence of the rise of plasma cortisol, resulting in an enhanced availability of glucose at the time of awakening (31). In both groups of this study, a circadian variation in plasma glucose was validated in all situations. The pattern observed in healthy control subjects before Ramadan showed a rise in the hours preceding awakening and a peak after breakfast, and a rapid decrease until lunch, which resulted in a plateau. The afternoon snack was followed by a rise enhanced by dinner. This pattern was altered during Ramadan with decreased concentrations in the first part of the night. No significant difference in pattern was evident between the day before and 1 month after Ramadan. The 24-h mean concentration of plasma glucose was lower on the 10th day of Ramadan when compared with other study days, which would indicate that more than 10 days were necessary for healthy control subjects to recover from the change in feeding and sleeping habits. In HDU patients, no significant difference in the 24-h mean concentrations or circadian pattern could be observed between the day during and after Ramadan. It has to be noted that neither profile was similar to those seen in healthy control subjects. In HDU patients, both seemed to be more closely related to meal frequency than did those observed in healthy control subjects.

Several studies have described a circadian rhythm of plasma calcium (34, 35, 36) with a trough around 1600 h and an early-morning peak. Both in healthy control subjects and in HDU patients, a circadian variation of plasma calcium was evident during all study days. In healthy control subjects, both before and one month after Ramadan, the peak of plasma calcium was located around 1030 h to 1300 h and the trough, at 0500 h, although secondary peaks were observed around meal times. Both a significant decrease in 24-h mean plasma calcium concentration of healthy control subjects and a modification of the circadian pattern were validated on the 24th day of Ramadan, resulting in a flattened pattern much like that observed in HDU patients during Ramadan. Contrary to healthy control subjects, the pattern seen in HDU patients after the end of Ramadan was still significantly altered, with a peak of plasma calcium concentration located at the beginning of the night and a trough in the early morning hours (0230).

Last, the question arises of whether the HDU patients lost more or less weight than the control subjects during Ramadan. Unfortunately, the baseline weight of the HDU group is not available, and this point cannot be discussed properly here. We can only give here a piece of information (unpublished data): in controls, the paired t test found no difference between weights P1/P4 (t = 0.686; P = 0.5121); in controls, the paired t test found no difference between weights P3/P4 (t = 1.139; P = 0.2875); in HDU, the paired ^t test found no difference between weights U1/U2 (t = 0.107; P = 0.9190).

Because, both in control and HDU groups, no difference could be validated between weights during and after Ramadan, it might be reasonable to assume that the above results could be the same for the HDU group, before and after Ramadan, as those found for the controls.

The prominent modifications in living habits occurring during the month of Ramadan are those dealing with meal timing, because food and water intakes are allowed only between sunset and sunrise, i.e. for year 1995 in Morocco, between 1800 h and 0500 h from February 1 til March 2. The activity-rest cycle is less modified, because in Morocco, most professional activities take place between 0900 h and 1500 h. The effects described here, caused by the prolonged and profound modifications in feeding habits during the month of Ramadan, might support the hypothesis by other authors (4, 5, 6, 37) that food intakes could act as synchronizing agents for some biological variables, but further studies documenting the effects of sleep and feeding schedule modifications will be required to ascertain their respective roles and strength. Studies performed during the month of Ramadan will be a new field of investigation for chronobiology (38). It should be kept in mind that Ramadan is based upon a lunar calendar, and therefore, the beginning of Ramadan may occur at any time in the year, and hence, the duration of the daily fasting span undergoes large variations in relation to the season and latitude. This phenomenon, together with seasonal variations in the studied variables, may result in differences in the observed effects, according to the time of the year these studies are performed.

In conclusion, these data show that the modifications concerning meal scheduling, and possibly sleep duration and onset, play an important role on the circadian variations of the studied biological variables. In healthy control subjects: 1) all the studied biological variables (gastric pH, plasma gastrin, insulin, glucose, and calcium) had their circadian profile modified during Ramadan, either as soon as the 10th day (pH, gastrin, insulin, glucose) or later, on the 24th day (calcium); 2) one circadian profile (insulin) was still altered one month after the end of Ramadan; and 3) all the biological variables, except plasma insulin, had a change in their 24-h mean concentrations during the month of Ramadan, and mean gastric pH was still modified 1 month after its end. Similar modifications also were observed in HDU patients but with characteristics that suggested a possible increased risk factor for relapse.

A point deserves to be emphasized: despite lower mean calcium and gastrin levels, both during and after Ramadan, in the HDU group when compared with the healthy control group, gastric acidity was higher, supporting an abundance of evidence of a hypersensitivity of the parietal cell to gastrin stimulation in the HDU population. In addition, during Ramadan, when comparing study day U1 and study days P2 or P3, one can see a clear elevation in plasma gastrin levels during daytime on U1, but not during P2 or P3, suggesting, once again, a disturbance in the the circadian pattern of plasma gastrin in the HDU population when compared with healthy controls.

These results should be taken into account when adapting specific therapeutic schemes to patients during Ramadan. Indeed, increased gastric acidity observed during the day (i.e. fasting) hours suggests giving antiulcer drugs as late as possible at night during Ramadan.

In addition, the observed modifications in plasma concentrations of glucose and calcium (e.g. precocious decrease with blood glucose and late increase with blood calcium) prompts the practitioner to a special consideration in interpreting the results of biological tests performed during and after the month of Ramadan.

	Acknowledgments

 
We wish to thank, for their useful discussion and comments, Professor E. Haus (St. Paul, MN) and A. Reinberg (Paris, France). The authors wish to thank Pr. Plombeux (Service de Toxicologie Clinique, Centre Hospitalier Universitaire, Liêge), Mr. Renaud (Usines Solal), Pr. Cherkaoui (Service de Gastro-Entérologie, Centre Hospitalier Universitaire Ibn Rochd, Casablanca), Mr. Touzani (El Fida Laboratory, Casablanca), Ms. Hadj R. Khalifa, and K. Jellouli for their help in this study.

	Footnotes

 
¹ This work was supported by the Hassan II Foundation for Scientific and Medical Research on Ramadan and the Conseil Scientifique de l’Université Pierre et Marie Curie (équipe D.R.E.D. EA 1538).

Received April 12, 1996.

Revised July 1, 1996.

Revised October 28, 1996.

Accepted December 9, 1996.

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