Mediterranean diet and breastfeeding reduce the risk of gallstone in women

Abstract

OBJECTIVE:

This study aimed to determine the effect of nutrition style and breastfeeding on the formation of gallstone in women.

METHODS:

50 women age from 40 to 69 included in the study. A questionnaire in which the participant’s general information questioned, their anthropometric values recorded, and the Mediterranean diet (MD) adherence scale included, was filled in by the face-to-face interview method.

RESULTS:

Body mass index (BMI), waist circumference (WC), diastolic blood pressure (DBP), fasting blood glucose (FBG), and serum C-reactive protein (CRP) values were higher in those with gallstones than in the control group. The total breastfeeding time and MD adherence scores were higher in the control group. It determined that there was a negative relationship between breastfeeding time with DBP and CRP. It found that an increase in BMI and WC increases the probability of gallstones. It found that an increase in the duration of breastfeeding and MD adherence score decreases the probability of the gallstones.

CONCLUSION:

Breastfeeding and Mediterranean diet reduce the risk of gallstones in women.

Keywords

Body weight breastfeeding C-reactive protein gallstone mediterranean diet

1 Introduction

Gallstones are one of the most common and costly diseases among the digestive system diseases. The incidence of the disease varies according to society and gender. Gallstones reported in about 10–20% of the total population in Europe [1], and about 12% of the people in the United States [2].

Gallstones divided into two groups, which are cholesterol stones and pigment stones, about their contents and causes of occurrence. Cholesterol gallstones are the most common gallstones. Some risk factors thought to play a role in the formation of these stones. Female gender and advanced age are important risk factors for gallstones disease. In a study involving 138 people in India, it found that 36.7% of women and 15.7% of men had gallstones [3]. In Japan, in a study involving 717 people, it was determined that 13.2% of women and 4.25% of men had gallstones [4]. Studies have shown that age 40 represents the limit between low and high cholecystectomy rates. For example, with the Sirmione study, the incidence of gallstones between the ages of 40–69 was approximately four times higher than the young age group [5]. Pregnancy, family history and genetics, obesity, rapid weight loss, diabetes, and western-style nutrition identified as other risk factors that increase the probability of gallstone disease [6 –10].

In recent years, it proved that there is a relationship between nutrition and chronic degenerative diseases that has led researchers to look for the most appropriate nutrition model for maintaining optimal health status. It is well known that nutrition can significantly change the risk profile of the population at both primary and secondary prevention levels. Although there are various diets with different features, one of the most interesting in this regard is the Mediterranean diet [11]. The Mediterranean diet refers to the nutritional characteristics common to the countries around the Mediterranean. High levels of olive oil, fruits and vegetables, cereals, legumes and oilseeds; moderate fish, eggs, poultry, and dairy products, and low levels of red meat and products, and a reasonable amount of wine consumption are primary features of this diet [12]. Studies have shown that diets with high dietary fiber, ascorbic acid, unsaturated fat, vegetables, fruits, nuts, coffee, and medium alcohol intake reduce the risk of gallstone disease. Contrary to Western diets, the Mediterranean diet can reduce gallstone formation due to its rich fiber and antioxidant vitamin content, unsaturated fat content, and many other beneficial nutrients [13].

This study aimed to determine the effect of nutrition style and breastfeeding on the formation of gallstone in women.

2 Methods

This study was conducted with 50 female participants who applied to the T.C. Ministry of Health Ankara Training and Research Hospital General Surgery Polyclinic between 10/06/2019 and 02/12/2019. Ethics Committee Approval numbered 29/2019 and dated 05/11/2019 was obtained from the T.C. Ministry of Health Ankara Training and Research Hospital Clinical Research Ethics Committee for the study. The study was conducted in accordance with the Declaration of Helsinki. All participants provided written informed consent before study enrollment.

Volunteers diagnosed with gallstone disease included the study group; volunteers who not diagnosed with gallstones formed the control group. This study included women aged 40–69 who hospitalized in the general surgery clinic without systemic disease (such as chronic liver disease and diabetes mellitus).

2.1 General features of the participants

A questionnaire prepared in which general information about the participants questioned, anthropometric measurement values recorded, and the scale of adaptation to the Mediterranean diet. This questionnaire was filled in by the researcher through the face-to-face interview method with the participants.

2.2 Adherence to a mediterranean diet

The Mediterranean Diet Adherence Scale with a scoring range of 0–14 points was used to determine the adherence of individuals to the Mediterranean diet [12]. The scale includes 14 questions, 2 for food consumption habits, and 12 for food-frequency. The questions scored as 0 or 1. The Mediterranean diet adherence score classified as ≤5 low adherence, 6–9 moderate adherence,≥9 high adherence. The Turkish version of the scale used in the study was reliable [14].

2.3 Anthropometric measurements and evaluation

Anthropometric measurements of the participants made by the researcher. The heights of the participants measured with their feet adjacent, their heads on in the Frankfurt plane, and without shoes. The body weights of the patients measured with a hospital scale while wearing light clothes. BMI values calculated by dividing body weight by the square of the height (kg/m²). The classification of WHO used in the evaluation of BMI [15]. According to this classification, BMI values evaluated as underweight (<18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²), and obese (≥30 kg/m²). The waist circumference of the participants was measured through their underwear after the individual was standing and exhale. The measurement made from the midpoint between the lowest costa and crista iliaca anterior superior. In the measurement, the non-yawn meter with a sensitivity of 0.1 cm used. Hip circumference was measured from the widest part of the hip, parallel to the ground, while the individual standing. The ratio of waist circumference to hip circumference calculated and values of 0.85 and above were determined as risky in women according to WHO classification [16].

2.4 Biochemical tests and evaluation

In this study, fasting serum blood sugar, urea, creatinine, C-reactive protein (CRP), uric acid, total protein, albumin, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transferase (GGT), total bilirubin, direct bilirubin, and indirect bilirubin tests evaluated. Analysis T.C. It carried out in the Central Laboratories of the Ministry of Health Ankara Training and Research Hospital.

2.5 Statistical analysis

Statistical evaluation of the data done with IBM SPSS (Statistical Package for Social Sciences) version 21 statistical package program [17]. Whether the data are suitable for normal distribution was examined with the Kolmogorow-Smirnov normality test. Descriptive statistics of qualitative and quantitative data given. Qualitative variables (such as performing slimming diet, doing the physical activity) expressed as number (S) and percentage (%), and quantitative variables (age, height, body weight, etc.) expressed as median, minimum and maximum values. Chi-square test used to compare qualitative variables such as a slimming diet, regular exercise, smoking, and alcohol use between the two groups. The “Mann-Whitney U” test used to compare the anthropometric measurement values and biochemical values of the two groups. The correlation coefficient and statistical significance between the quantitative variables calculated with “Correlation analysis”. In all evaluations, situations where p-value is less than 0.05 were considered statistically significant.

3 Results

There was no significant difference between the ages of individuals who had gallstones and who constituted the control group. The bodyweight of those with gallstones was higher than those of the control group. BMI and waist circumference length values were significantly higher in gallstones compared with the control group. While there was no difference in systolic blood pressure (mmHg) between two groups, diastolic blood pressure value was higher in those with gallstones. The total duration of breastfeeding (months) and Mediterranean diet adherence scores were higher in the control group than in the group with gallstones (Table 1).

Table 1
Some basic information of the participants

With Gallstone Without Gallstone Total P

(n = 25) (n = 25) (n = 50) value

Mean±SD Mean±SD Mean±SD

Age (year) 47.4±7.05 48.04±6.27 47.7±6.61 0.736

Weight (kg) 81.56±11.94 69.6±8.91 75.5±12.05 <0.001^*

Height (cm) 160.28±4.0 161.48±4.93 160.88±4.48 0.350

Body mass index (kg/m²) 31.76±4.60 26.74±4.01 29.25±4.97 0.001^*

Waist circumference (cm) 102.72±10.75 93.04±8.31 97.88±10.69 0.001^*

Hip circumference (cm) 116.8±8.76 113.48±6.91 115.14±7.98 0.144

Waist to hip ratio 0.84±0.16 0.81±0.05 0.82±0.12 0.465

Sistoloic blood pressure (mmHg) 130.12±17.66 128.4±16.24 129.26±16.81 0.722

Diastolic blood pressure (mmHg) 74.64±9.74 67.2±9.79 70.92±10.37 0.010^*

Duration of breastfeeding (month) 23.76±13.58 44.32±19.60 34.04±19.65 <0.001^*

Mediterranean diet adherence score 4.1±0.85 8.1±1.49 6.16±2.35 <0.001^*

	With Gallstone	Without Gallstone	Total	P
Age (year)	47.4±7.05	48.04±6.27	47.7±6.61	0.736
Weight (kg)	81.56±11.94	69.6±8.91	75.5±12.05	<0.001^*
Height (cm)	160.28±4.0	161.48±4.93	160.88±4.48	0.350
Body mass index (kg/m²)	31.76±4.60	26.74±4.01	29.25±4.97	0.001^*
Waist circumference (cm)	102.72±10.75	93.04±8.31	97.88±10.69	0.001^*
Hip circumference (cm)	116.8±8.76	113.48±6.91	115.14±7.98	0.144
Waist to hip ratio	0.84±0.16	0.81±0.05	0.82±0.12	0.465
Sistoloic blood pressure (mmHg)	130.12±17.66	128.4±16.24	129.26±16.81	0.722
Diastolic blood pressure (mmHg)	74.64±9.74	67.2±9.79	70.92±10.37	0.010^*
Duration of breastfeeding (month)	23.76±13.58	44.32±19.60	34.04±19.65	<0.001^*
Mediterranean diet adherence score	4.1±0.85	8.1±1.49	6.16±2.35	<0.001^*

SD: Standard deviation, ^*P < 0.05 is significant.

Fasting glucose and C-reactive protein values were higher in the gallstone disease group than in the control group. There was no significant difference in urea, creatinine, uric acid, total bilirubin, direct bilirubin, indirect bilirubin, ALP, AST, ALT, and GGT between the groups (Table 2).

Table 2

Biochemical parameters of the participants

	With Gallstone	Without Gallstone	Total value	P
	(n = 25)	(n = 25)	(n = 50)
	Median (Min-Max)	Median (Min-Max)	Median (Min-Max)
	(mean±SD)	(mean±SD)	(mean±SD)
FBG (mg/dL)	104 (82–121) (100.04±11.66)	95 (77–111) (94.02±7.08)	96.35 (77–121) (97.03±10.02)	0.032^*
Urea (mg/dL)	23 (11–45) (23.44±6.96)	24 (10–47) (26.2±9.18)	24 (10–47) (24.82±8.18)	0.237
Creatinine (mg/dL)	0.70 (0.56–0.83) (0.70±0.07)	0.64 (0.54–0.85) (0.66±0.09)	0.69 (0.54–0.85) (0.68±0.08)	0.070
Uric acid (mg/dL)	4.10 (2.10–6.20) (4.06±0.84)	4.1 (2.60–6.80) (4.25±0.96)	4.1 (2.10–6.80) (4.15±0.90)	0.463
Total bilirubin (mg/dL)	0.49 (0.11–1.33) (0.56±0.27)	0.38 (0.09–1.27) (0.46±0.26)	0.46 (0.09–1.33) (0.51±0.27)	0.209
Direct bilirubin (mg/dL)	0.20 (0.05–0.66) (0.23±0.13)	0.15 (0.05–0.51) (0.18±0.09)	0.18 (0.05–0.66) (0.20±0.11)	0.180
Indirect bilirubin (mg/dL)	0.31 (0.05–0.97) (0.33±0.20)	0.23 (0.04–0.76) (0.27±0.17)	0.25 (0.04–0.97) (0.30±0.19)	0.318
Alkaline phosphatase (U/L)	72 (44–189) (85.36±32.04)	72 (48–149) (79.28±21.78)	72 (44–189) (82.32±27.29)	0.437
Aspartate aminotransferase (U/L)	18 (7–82) (22.52±15.67)	17 (10–60) (18.36±9.35)	17 (7–82) (20.44±12.94)	0.261
Alanine transaminase (U/L)	17 (6–262) (31.72±52.82)	16 (8–122) (20.08±21.75)	15.5 (6–262) (25.9±40.41)	0.313
Gamma-glutamyl transferase (U/L)	24 (8–275) (53.2±75.5)	16 (6.10–180) (26.20±34.99)	21 (6.10–275) (39.70±59.81)	0.111
C-reactive protein (mg/L)	4.3 (0.80–26.10) (7.22±6.13)	1.6 (0.50–5.80) (2.24±1.46)	3.2 (0.50–26.10) (4.73±5.07)	0.001^*

SD: Standard deviation, ^*P < 0.05 is significant.

According to the BMI classification, no weak women found in each group. 8% of gallstones patients and 32% of the control group found as normal weight. The percentage of those who are overweight found to be 20% and 56%, respectively, in the gallstones and the control group. 72% of gallstone group individuals and 12% of the control group individuals were obese. BMI values found to be significantly different between the two groups. In the last six months, the percentage of individuals who had performed a weight loss diet was 20% for gallstones and 4% for the control group. 24% of the gallstones group and 32% of the control group had two pregnancies period. The percentage of those with three or more pregnancies were 68% of the gallstones group and 56% of the control group. The number of pregnancies was not different between the two groups. When groups evaluated according to the Mediterranean diet adherence scale scores, 96% of the gallstone group showed low, and 4% showed moderate compliance. 16% of the control group found to have low, 68% moderate, and 16% high compliance with the Mediterranean diet (Table 3).

Table 3

Descriptive information of the participants

Characteristic	With Gallstone	Without Gallstone	P value
	(n = 25)	(n = 25)
	%	%
Body mass index classification (%)			0.001^*
Underweight	–	–
Normal weight	8	32
Overweight	20	56
Obesity	72	12
Weight loss diet (%)			0.189
Yes	20	4
No	80	96
Pregnancy number (%)			0.654
0	–	–
1	8	12
2	24	32
≥3	68	56
Current smoking (%)			0.123
Yes	40	20
No	60	80
Regular exercise (%)			0.088
Yes	12	32
No	88	68
Adherence to Mediterranean diet (%)			<0.001^*
Low	96	16
Moderate	4	68
High	–	16

^*P < 0.05 is significant.

Logistic regression analysis showed that age was less likely to change the probability of occurrence of gallstone disease (OR 0.98%; 0.905–1.072%; p = 0.173 for each age). Bodyweight found to have an increasing effect on the probability of developing gallstones (OR 1.11; 1.043–1.191; p = 0.001 for each weight). It determined that BMI is also an important factor increasing the risk of disease such as body weight (OR 1.29; 1.109–1.519; p = 0.001). It determined that the increase in waist circumference increased the probability of gallstones (OR 1.11; 1.037–1.204; p = 0.004). Each monthly increase in breastfeeding duration showed a protective effect by reducing the probability of gallstones disease (OR 0.931; 0.892–0.972; p = 0.001). It determined that the number of pregnancies, weight loss diet, smoking, and regular exercise of women did not significantly affect the occurrence of the disease. It observed that each score increase in the Mediterranean diet adherence score reduced the probability of the gallstone (OR 0.10; 0.028–0.418; p = 0.001) (Table 4).

Table 4

Potential risk factors for gallstones disease

Variables	Odds ratio	95% Cl	P
Age (year)	0.98	0.905–1.072	0.173
Weight (kg)	1.11	1.043–1.191	0.001^*
Body mass index (kg/m²)	1.29	1.109–1.519	0.001^*
Waist circumference (cm)	1.11	1.037–1.204	0.004^*
Hip circumference (cm)	1.058	0.980–1.142	0.149
Waist to hip ratio	6.75	0.035–1.289	0.476
Duration of breastfeeding (month)	0.931	0.892–0.972	0.001^*
Pregnancy number	1.21	0.734–2.00	0.453
Weight loss diet (yes)	6.00	0.647–55.66	0.115
Current smoking (yes)	2.66	0.753–9.45	0.129
Regular exercise (yes)	3.45	0.793–15.01	0.099
Mediterranean diet adherence score	0.10	0.028–0.418	0.001^*

^*P<0.05 is significant.

Correlation analysis performed to determine the relationship between breastfeeding duration and some variables. According to the results of the analysis, there was no significant relationship between age, body weight, BMI, waist circumference length, hip circumference length, waist/hip ratio, SBP, glucose, urea, ALP, AST, ALT and GGT. However, there was a negative relationship between breastfeeding duration with DBP (mmHg) (r = –0.413, p = 0.003) and C-reactive protein (mg/L) (r = –0.309, p = 0.029) (Table 5).

Table 5

Relationship between breastfeeding duration and some variables

	Duration of breastfeeding (month)
	R	P
Age (year)	0.134	0.3520.
Weight (kg)	016	0.910
Body mass index (kg/m²)	–0.015	0.920
Waist circumference (cm)	–0.033	0.819
Hip circumference (cm)	0.071	0.257
Waist to hip ratio	–0.175	0.225
Sistoloic blood pressure (mmHg)	0.035	0.807
Diastolic blood pressure (mmHg)	–0.413	0.003^*
Fasting blood glucose (mg/dL)	0.147	0.307
Urea (mg/dL)	–0.018	0.901
Alkaline phosphatase (U/L)	–0.104	0.472
Aspartate aminotransferase (U/L)	–0.029	0.844
Alanine aminotransferase (U/L)	0.038	0.791
Gamma-glutamyl transferase (U/L)	–0.196	0.173
C-reactive protein (mg/L)	–0.309	0.029^*

^*P < 0.05 is significant.

4 Discussion

In our study, possible roles of obesity, breastfeeding, diet, and some serum markers in gallstones investigated. The two most important findings of our study increased breastfeeding time and high compliance with the Mediterranean diet as a protective factor against gallstones.

The Mediterranean diet is considered one of the most effective dietary styles to lead a long and healthy life. It is known to be useful in the treatment of some diseases as well as its role in the prevention of many diseases. Although the pathophysiology of gallstone disease has not exactly clarified, dietary factors have also shown to be effective in the occurrence of the disease [18]. In our study, the mean score of the Mediterranean diet adherence scale found to be significantly lower in the gallstones compared to the control group. Also, in our risk analysis, it was observed that a one-point increase in the Mediterranean diet adherence scale is a factor that reduces the possibility of gallstones. In a cohort study involving 1 033 955 people in France, high adherence to the Mediterranean diet was found to be associated with a reduced risk of cholecystectomy, according to the result of the same scale we performed in our study [19].

In observational studies, dietary fibers have found to have a preventive effect on gallstone formation by decreasing deoxycholic acid formation and cholesterol saturation by accelerating intestinal passage. In the Nurses’ Health Study (NHS), high fiber intake, particularly a diet containing insoluble fiber, was found to be associated with a lower risk of cholecystectomy [20]. Also, dietary high cholesterol intake has found to increase gallstone cholesterol saturation and increase gallstone risk [21]. Again, in studies, more intake of polyunsaturated or monounsaturated fatty acids has been associated with reduced risk of gallstones [22]. Based on these findings, the fact that the Mediterranean diet consists of fiber-rich foods (fruits, vegetables, legumes, and whole wheat bread) and olive oil as a source of dietary fat can help explain its protective role against gallstone disease.

In this study, when the breastfeeding period of women evaluated as months, it was observed that the control group had more breastfeeding time than the group with gallstones. In our risk analysis, a one-month increase in breastfeeding time reduced the possibility of gallstones. Also, in the correlation analysis, DBP showed a significant negative correlation with the duration of breastfeeding. There are no other studies in the literature evaluating the relationship between breastfeeding time and gallstones. Research has shown that breastfeeding reduces obesity and type 2 diabetes in women. For example, mothers who breastfeed their babies were, on average, 8 kg lighter than mothers who did not breastfeed after 6 years [23]. A meta-analysis involving 6 cohort studies found a strong association between breastfeeding and low diabetes rates [24]. Based on the results of these studies, it can be thought that breastfeeding reduces obesity and type 2 diabetes, which are among the gallstone risk factors, thus protecting against stone formation. However, more detailed studies are needed to determine the effect of breastfeeding and gallstones in this group of patients.

Another risk factor that thought to be effective in the formation of gallstones is the increase in body weight above normal. Nurses’ Health Survey showed that there is a direct relationship between symptomatic gallbladder stones and body mass index (BMI). In obese women (BMI≥30 kg/m²), gallstone risk is twice as high as normal body weight (BMI < 24 kg/m²) [25]. In a study in which 239 men and 208 women participated, those with gallstones found to have a higher BMI value than the control group [26]. In another study with adult women, the average BMI in women with gallstones found to be higher than the average BMI of women in the control group [27]. Our study showed that BMI was higher in patients with gallstones consistent with the results of previous studies.

The waist circumference is an anthropometric value that reflects the visceral and subcutaneous fat accumulated in the abdominal region and widely used today to assess the presence of obesity. It considered a high-risk cause for many diseases for women >88 cm [28]. Because waist circumference is an indicator of obesity, it can be an important assessment tool in gallstones. Studies have shown that patients with gallstones usually have a higher waist circumference than their peers. For example, in a study comparing 447 gallstone patients and 7741 healthy individuals, waist circumference is wider in those with gallstones [26]. In our study, it found that women with waist circumference in gallstones were higher than the control group.

High fasting glucose level is a marker of many diseases, especially diabetes, but also an important factor in the pathophysiology. In patients with gallstones, fasting glucose value considered to be an important factor due to the presence of diseases such as diabetes and metabolic syndrome among the risk factors of the disease. When the biochemical parameters of the groups evaluated, the fasting glucose value was found higher in the group with gallstones compared to the control group. Chen et al. (2012) found that fasting blood glucose was higher in patients with gallstones than in the control group [29].

Another biochemical parameter we evaluated in our study is serum uric acid value. Uric acid thought to play a role in the pathogenesis of some diseases, such as non-alcoholic fatty liver disease, by influencing inflammation. Several studies have indicated that there is a relationship between gallstone disease and especially non-alcoholic fatty liver disease [30]. However, in our study, there was no difference in uric acid levels between the two groups.

CRP is the acute phase protein produced in the liver and is a marker of systemic inflammation. Studies show that systemic inflammation may be associated with gallstone disease as well as cardiovascular diseases and metabolic syndrome [31, 32]. In our study, it examined whether there is a relationship between CRP and gallstones. Comparing serum levels, CRP levels were found higher in those with gallstones. In our study, it observed that there was an inverse relationship with the correlation analysis between breastfeeding duration and CRP regardless of disease. Ruhl et al. (2011), in their study, similarly found that those with gallstones had higher serum CRP levels compared to healthy individuals [33].

Our study is the first study to evaluate the gallstone disease risk factors extensively and to inform the literature that the duration of breastfeeding in women has a protective effect against the disease. The most interesting findings of our study are that breastfeeding and the Mediterranean Diet reduce the risk of gallstone disease. More studies are needed to determine the role of breastfeeding and the Mediterranean diet in the pathophysiology of gallstones.

Footnotes

Acknowledgments

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