Last update and review: October 17, 2020.
A short summary.
Marciani et al., 2013 (1), investigated the impact of different foods on gall bladder emptying. Gall bladder emptying was measured with the help of magnetic resonance imaging.
Fat was the food that stimulated gall bladder emptying the most. 10 grams of fat in 20ml of fat emulsion resulted at a maximum contraction of 42%. And even 2 grams of fat in 4 grams of fat emulsion strongly stimulated gall bladder contraction. Indeed, 2 grams of fat was enough to cause a gall bladder contraction by 27% (see Supplementary table 1 below).
Contraction of gall bladder in response to different foods as measured by Marciani et al., 2013 (1).
The composition of the ten test foods:
A=25 ml dairy emulsion; B=25 ml dairy emulsion+300 mg potato protease inhibitor; C=67.5 g yogurt drink; D=67.5 g yogurt drink; 3 g protein; E=67.5 g yogurt drink+80 mg curcumin; F=250 ml coffee; G=250 ml tea; H=250 ml semi-skimmed milk; I=20 ml high-fat emulsion; and J=4 ml high-fat emulsion.
Gall bladder emptying was measured with the help of magnetic resonance imaging (MRI).
Marciani, 2013 (1):
We designed two randomized, investigator-blind, cross-over studies in healthy subjects using magnetic resonance imaging (MRI) to measure gall bladder volumes serially and non-invasively.
Impact of four milk-based beverages with different fat content: 1.5, 3.5, 6.5 and 10 grams.
In the second experiment, “study 2”, the researchers gave milk-based beverages with different fat content to their subjects. They investigated if contractions of gall bladder and blood levels of cholecystokinin (CCK) correlated.
We can see on the graph and in the table below, that there was no differnce between 1.5 and 3.5 grams of fat in terms of their impact on gall bladder contractions. 6.5 and 10 grams of fat in a milk-based dirnk were more stimulating. But all drinks had an effect.
Protein is also a potent stimulant of CCK, whereas carbohydrate is not.
Marciani, 2013 (1):
Protein is also a potent stimulant of CCK, whereas carbohydrate is not.
Fasting gall bladder volumes can differ widely.
There was a s
Marciani et al., 2013 (1):
We have also observed that the fasted gall bladder volume varied remarkably between individuals and that individual day-to-day variability can have wide coefficients of variation of up to 42%.
Discussion of the results by the authors.
Marciani et al., 2013 (1):
The largest gall bladder volume change was observed with the positive fat-containing control (20 ml of high-fat emulsion). However, gall bladder emptying induced by amounts of fat as low as 7 g (perfused in the jejunum) 35 had been observed previously. Our data show that a very low amount of fat (2 g fat in 4 ml of high-fat emulsion) nevertheless achieved a marked gall bladder volume change of 27%. The potato protease inhibitor achieved a modest gall bladder volume change. The same potato protease inhibitor did not significantly affect healthy volunteers’ plasma CCK at twice the dose we used. 36 The 80 mg curcumin stimulus was the fourth best performer achieving a mean 23% maximum gall bladder volume change. This was, however, much lower than the 40% volume change reported at 1 h in a previous ultrasonography study. 37 Whether the reason for this difference might rest on the different imaging technologies used or in the delivery vehicle (a yogurt drink in our study versus plain curcumin ingested with a glass of water in that report) is unclear. When looking at the correlation with meal components, the maximum % gall bladder volume change correlated positively and significantly with the fat content of the samples (with or without the stanol included in the calculation, Pearson’s Po0.0052 andPo0.0012, respectively) but neither with the protein nor with the volume of the meals. The main conclusion from this initial scouting study was that long-chain fat with a high degree of emulsification was the best performer in stimulating gall bladder emptying, likely to be explained with current knowledge 2 via the cholecystokinin (CCK) duodenal response and to be tested in our second study. Semiskimmed milk performed well and this was one of the reasons driving the choice of a milk-based beverage as vehicle for increasing amounts of emulsified fat, while keeping protein and volume the same, in Study 2. Protein is also a potent stimulant of CCK, whereas carbohydrate is not. 10 Gastric emptying of stable fat emulsions is slow 8 that may be a factor contributing to the longest time to maximum gall bladder volume change shown by the 20 ml high-fat emulsion.
The main hypothesis of Study 2 that the best performer of Study 1 (emulsified fat in this case) will have a dose response effect on maximum % gall bladder volume change was correct. This correlated well with increased plasma CCK levels in keeping with the well-established role of fat in releasing CCK, which depends on fatty acid chain length, 38,39 and the role of CCK in regulating gall bladder emptying. 40 Interestingly the milk-based beverage with the lowest amount of fat (1.5 g) achieved already a marked mean maximum percentage gall bladder volume change of 33% over the length of time investigated. Our meals were all low calorie (for example, 90 kcal for the 20 ml high-fat emulsion). Much larger volume changes have been observed with higher calorie meals. A 70% gall bladder volume change was reported 45 min after a 465 kcal mixed solid-liquid meal 41 and 70% gall bladder volume change 70 min after a 675 kcal fat emulsion test meal 8 in healthy subjects. From the test-retest studies, we have also observed that the fasted gall bladder volume varied remarkably between individuals and that individual day-to-day variability can have wide coefficients of variation of up to 42%. An influence of gender, age and body size on gall bladder volume has been reported from large surveys. 42–44 Our mean fasted value of 26 ml is higher than previously reported values in the 18-ml range, 37 and this could be because of imaging technology and/or subjects’ cohort differences. One possible explanation for the large intra individual variation in fasting gall bladder volumes is the cephalic phase response to food. The subjects may have been exposed to food-related sensory stimulation at home or on their way to the study site. Cephalic, pre-ingestive neural signals at the thought, sight or smell of food can trigger a number of physiological and secretory responses, 45 while sham feeding clearly induces gall bladder emptying. 46 Although in this study it was not possible to control the subjects’ environment overnight before the morning measurements, future studies could consider this option in the study design. Gall bladder volume may also fluctuate with the cyclic variations of the migrating motor complex and motilin levels. 47 We observed a correlation between gall bladder fasting volume size and individuals’ body frame but this was not surprising. 43 Because of the different volume, taste/aroma, color and texture of the samples, we could not exclude the presence of a possible ingestive cephalic component of gall bladder emptying inthesedata. One thought for future studies would be to manufacture the new test samples as equal in volume/texture/ flavor/color as possible. Cephalic effects could also help to explain the wide variation in time to maximum gall bladder volume change, which varied not just inter-subjects but also between study days. It is worth noting that in some of the experiments carried out the time to maximum gall bladder volume change was 65 min, indicating that the volume change could possibly have been greater at later times than the period investigated. The time period investigated is a limitation of this study, and it would be desirable in future studies to extend the monitoring time window to at least 120 min to fully capture the time course of the emptying of the gall bladder. Intravenous infusion of CCK 48 could be used as a gall bladder emptying standard for comparison. In conclusion, various food ingredients are capable of inducing varying degrees of gall bladder emptying. Among the various food ingredients and actives tested here, fat and semi-skimmed milk induced the most profound volume changes. Fat showed the strongest effect, which correlated with plasma CCK levels. Improved knowledge of how to stimulate bile release using food ingredients will be useful to improve in vitro/in vivo correlation of bioavailability testing of hydrophobic drugs. It could improve performance of cholesterol-lowering plant stanol and sterol products and possibly aid understanding of some cholesterol gallstone disease.
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A Test of Physiological Literacy.
1. Can vitamin D and vitamin C intakes influence bile acide production by liver?
2. If you take probiotics, would you take them before, after or with a drink containing 10 grams of fat?
Selected references:
1. Marciani L, Cox EF, Hoad CL, et al. Eur J Clin Nutr. 2013;67(11):1182-1187.