Application of In Vitro Digestion Models in the Evaluation of Dietary Supplements
Abstract
:1. Introduction
2. Materials and Methods
- The type of method used to study simulated digestion;
- The research material used (food, dietary supplement).
3. Digestive Mechanisms
4. In Vitro Methods
4.1. From Simple to Advanced Methods of Simulated Digestion
4.2. Development of In Vitro Methods
5. Application of In Vitro-Simulated Digestion Models to Assess the Bioavailability of Ingredients from Foods, Including Dietary Supplements
5.1. The Effect of a Meal on the Bioaccessibility of a Dietary Supplement Ingredient
5.2. The Effect of Chemical/Pharmaceutical Form on the Bioaccessibility of Dietary Supplement Ingredients
5.3. The Effect of the Carrier Used on the Bioaccessibility of a Dietary Supplement Ingredient
5.4. Other Purposes of Studying the Impact of the Bioaccessibility of Dietary Supplement Ingredients
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | Product | In Vitro Model | Reference |
---|---|---|---|
Dairy products | |||
Lipids and proteins | Bovine milk fat globule membrane ingredient (MFGMi) and whey–casein infant formula with added MFGMi | Solubility (INFOGEST 2.0) | [75] |
Meat products | |||
Proteins | Chinese dry-cured hams | Solubility | [76] |
Plant products | |||
Proteins, amino acids | Peanuts, All-Bran® wheat bran cereal, pigeon peas, black beans, zein, whey protein isolate (WPI), and collagen | Solubility (INFOGEST 2.0) | [77] |
Polysaccharides | 3% solutions of starch, dextran, pectin, and modified citrus pectin | Solubility (INFOGEST 2.0) | [78] |
Zinc | Faba bean (Vicia Faba L.) flour and legume fractions, finger millet (Eleucine coracana) flour | Dializalibity | [79,80] |
Soluble dietary fiber | Whole grain noodles | Solubility | [81] |
Magnesium | Mexican tortilla | Solubility | [82] |
Cooper, iron, magnesium, manganese, and zinc | Purées, instant cereals, and infant formulas | Solubility (INFOGEST 2.0) | [83] |
Cooper, mercury, arsenic, cadmium, lead, chromium, nickel, and zinc | Edible and medicinal plants | Solubility | [84] |
Selenium and iodine | Radish Raphanus sativus | Solubility | [85] |
Iron | Corn-masa tortillas, semisynthetic (SS) meals | Solubility, dialyzability, uptake by Caco-2 cells and/or transport assays | [86,87] |
Folates | Orange juice, bread | TIM (dynamic model) | [88,89] |
Carotenoids | Spinach and condensed milk (4% fat), carrots, salad meal | Solubility, uptake by Caco-2 cells | [90,91,92] |
Carotenoids | Stinging nettle (Urtica dioica L.) in egg pasta | Solubility (INFOGEST 2.0) | [93] |
Chlorophylls | Guacamole, virgin olive oil, tortellini, basil hummus, creamed spinach, vegetable pasta, green tea chocolate, avocado and kiwi juices, and pesto sauce | Solubility (INFOGEST 2.0) | [94] |
Polyphenols | Cocoa, boiled and roasted peanuts; frozen sweet cherries (Prunus avium L.) | Solubility, uptake by Caco-2 cells | [95,96,97] |
Lutein and zeaxanthin | Microalgae Scenedesmus almeriensis | Solubility | [98] |
Lycopene and α-Tocopherol | Whole food | TIM (dynamic model) with Caco-2 cell | [51] |
Oil products | |||
Carotenoids and chlorophylls | Oil matrix | Solubility | [99] |
Other | |||
Calcium | Diets rich in Maillard reaction products | Solubility, dialyzability, Caco-2 cell uptake, and transport | [100] |
Dietary Supplements (Compounds) | Type of In Vitro Model | Model Construction | Reference |
---|---|---|---|
Macrocompounds | |||
Mixed-polysaccharide | Dynamic model (SHIME) (stomach–small intestine–ascending–transverse and descending colon) | Stomach–small intestine–ascending–transverse and descending colon (pH regulator 5.6–5.9, 6.2–6.5, and 6.6–6.9 in the ascending colon, transverse colon, and descending colon, respectively; 72 h; 37 °C). Growth medium for the microbial inoculum consisted of a carbohydrate-based medium containing arabinogalactan (1 g/L), pectin (2 g/L), xylan (1 g/L), starch (4.2 g/L), glucose (0.4 g/L), yeast extract (3 g/L), peptone (1 g/L), mucin (4 g/L), and cysteine (0.5 g/L). The pH of the medium was 5.5. | [47] |
Proteins (amino acids) | Static (INFOGEST 2.0) (stomach–small intestine) | Stomach: 11.25 mL of simulated gastric fluid (6.9 mM of KCl, 0.9 mM of KH2PO4, 25 mM of NaHCO3, 47.2 mM of NaCl, 0.1 mM of MgCl2(H2O)6, and 0.5 mM of (NH4)2CO3) with 2.4 mL of porcine pepsin (25,000 UI/mL and 7.5 μL of 0.3 M CaCl2 (pH of 3.0, 2 h, 37 °C) Small intestine: 14.3 mL of simulated intestinal fluid (6.8 mM of KCl, 0.8 mM of KH2PO4, 85 mM of NaHCO3, 38.4 mM of NaCl, 0.33 mM of MgCl2(H2O)6) with 6.5 mL of pancreatin (800 UI/mL), 2.6 mL of bile acids (160 mmol/L and 52 μL of 0.3 M CaCl2) (pH of 7.0, 2 h, 37 °C) | [111] |
Microcompounds | |||
Magnesium | Static (INFOGEST 2.0) (mouth–stomach–small intestine) | Mouth: 15.1 mM of KCl, 3.7 mM of KH2PO4, 13.6 mM of NaHCO3, 0.15 mM of MgCl2(H2O)6, 0.5 mM of (NH4)2CO3, 1.1 mM of HCl, and 1.5 mM of CaCl2(H2O)2 Stomach: 6.9 mM of KCl, 0.9 mM of KH2PO4, 25 mM of NaHCO3, 47.2 mM of NaCl, 0.1 mM of MgCl2(H2O)6, and 0.5 mM of (NH4)2CO3 with pepsin and CaCl2 (2000 U/mL and 0.15 mM) (pH of 3.0, 2 h, 37 °C, 200 rpm). Small intestine: 6.8 mM of KCl, 0.8 mM of KH2PO4, 85 mM of NaHCO3, 38.4 mM of NaCl, and 0.33 mM of MgCl2(H2O)6 with pancreatin (100 U/mL and bile alts 10 mM) and CaCl2 (0.6 mM) (pH of 7.0, 2 h, 37 °C, 200 rpm) | [105] |
Iron | Static (stomach–small intestine) | Stomach: 0.5 mL of pepsin solution (2 mg of pepsin in 0.1 M of sodium hydrogen carbonate and 0.01 M of HCl) (pH of 2.0 ± 0.1, 2 h, 37 °C) Small intestine: 0.5 mL of digestive enzyme and bile salts (0.5 mg of pancretin and 3 mg of bile salts per 1 mL) (pH of 6.8–7.0, 2 h, 37 °C) | [108] |
Zinc | Static—dialyzability (stomach–small intestine) | Stomach: 0.5 mL of pepsin (pH of 2.0, 2 h, 37 °C, 140 rpm) Small intestine: 2.5 mL of intestinal solution (pH of 7.0, 2 h, 37 °C, 140 rpm) + dialysis membrane with 10 mL of PIPES | [102] |
Selenium | Static—dialyzability (stomach–small intestine) | Stomach: 2 mL of 10% pepsin (pH of 2.0, 2 h, 37 °C) Small intestine: 5 mL of 0.4% pancreatin (pH of 6.5, 2 h, 37 °C) + cellulose dialysis tube | [104] |
Selenium | Static (stomach–small intestine) | Stomach: 0.166 g of pepsin (pH of 2.0, 2 h, 37 °C) Small intestine: 0.034 g of pancreatin and 0.213 bile salts (pH of 5, 2 h, 37 °C) + dialysis membrane | [110] |
Vitamin C | Static (mouth–stomach–small intestine) | Mouth: 5 mL of oral medium (1,7 mL of NaCl, 8 mL of urea, 15 mg of uric acid, 580 mg of α-amylase, and 50 mg of mucin in 500 mL) (pH of 7.0 ± 0.1, 5 min, 37 °C) Stomach: gastric juice (6.5 HCl, 18 mL of CaCl2•2H2O, 1 g of bovine serum albumin, 5 g of pepsin, and 3 g of mucin in 500 mL (pH of 1.5 ± 0.1, 2 h, 37 °C) Small intestine: 10 mL of duodenal juice (6.4 mL of KCl, 9 mL of CaCl2•2H2O, 1 g of bovine serum albumin, 18 g of pancreatin, and 3 g of lipase in 500 mL) (pH of 7.0 ± 0.1, 2 h) and 5 mL of bile juice (68 mL of NaHCO3, 10 mL of CaCl2•2H2O, 18 g of bovine serum albumin, and 60 g of bile) (pH of 7.0 ± 0.1, 2 h) | [103] |
Vitamin K | Static (INFOGEST 2.0) (mouth–stomach–small intestine) | Mouth: 1 mL of saliva (2 min, 37 °C) Stomach: 2 mL of simulated gastric fluid with pepsin (2000 U/mL) and gastric lipase (60 U/mL) (pH of 3.0, 2 h, 37 °C) Small intestine: 4 mL of simulated intestinal fluid with bile (10 mM of bile salt) and pancreatin (trypsin activity of 100 U/mL) (pH of 7.0, 2 h, 37 °C) | [107] |
Vitamin C, A, folic acid | Static (mouth–stomach–small intestine) | Mouth: 6 mL of saliva (pH of 6.5 ± 0.2, 5 min, 55 rpm, 37 ± 2 °C Stomach: 12 mL of gastric juice (pH of 1.5 ± 0.5, 2 h) Small intestine: 12 mL of duodenal juice and 6 mL of bile (pH of 6.0 ± 0.5, 2 h) | [106] |
Other compounds | |||
Coenzyme Q10 | Static (stomach–small intestine) | Stomach: 10 mg of pepsin (of pH 2.0, 1 h) Small intestine: 20 mg of pancreatic enzyme and 250 mg of bile salt (pH of 7.0, 2 h) | [112] |
Curcumin and Epigallocatechin Gallate (EGCG) | Static (stomach–small intestine) | Stomach: 10 mg of pepsin (pH of 1.5, 37 °C, 0–1 h) Small intestine: 20 mg of trypsin enzyme and 250 mg of bile salt extract (pH of 7.0, 37 °C, 1–2 h) | [109] |
Procyanidin | Static (INFOGEST 2.0) (stomach–small intestine) | Stomach: 1.6 mL ca.2500 U of porcine pepsin stock solution and 5.0 µL of 0.3 M CaCl2 mixed with 7.5 mL of 1.25-fold concentrated buffer solution: 6.9 mM of KCl, 0.9 mM of KH2PO4, 25 mM of NaHCO3, 47.2 mM of NaCl, 0.1 mM of MgCl2(H2O)6, 0.5 mM of (NH4)2CO3, and 15.6 mM of HCl; 1.6 mL of ca. 2500 U/mL porcine pepsin (pH of 3.0, 2 h at 37 °C, 100 rpm) Small intestine: 3.75 mL 800 U/mL of pancreatin solution, 1.87 mL of fresh bile, and 30 µL of 0.3 M of CaCl2 mixed mixed with 8.25 mL of 6.8 mM of KCl, 0.8 mM of KH2PO4, 85 mM of NaHCO3, 38.4 mM of NaCl, and 0.33 mM of MgCl2(H2O)6 and 8.4 mM of HCl (pH of 7.0, 6 h at 37 °C, 100 rpm) | [113] |
Quercetin | Static (stomach–small intestine) | Stomach: 20 mL of simulated gastric fluids (2 g of NaCl and 7 mL of HCl/1 L distilled water and adjusted to pH of 1.2; then NaOH added to pH 2.5; after that, 0.064 g of pepsine added (2 h, min, 37 °C, 50 rpm) Small intestine: 187.5 mg of bile salt and 0.144 g of pancreatin (pH of 7.0, 4 h at 37 °C, 50 rpm) | [114,115] |
Resveratrol | Static (stomach–small intestine) | Stomach: 15 mL of simulated gastric fluid (double-distilled water adjusted to pH of 1.2 with HCl, containing 50 mM of NaCl, and 3.2 mg/mL of pepsin) (pH of 2.5, 37 °C, 80 rpm) Small intestine: 4 mL of 12.5 mg/mL bile salt in phosphate-buffered solution (pH of 7.0, 5 mM) and 2.5 mL of 8 mg/mL pancreatin solution (pH of 7.0, 5 mM of phosphate buffer) (pH of 7.0, 4 h, 37 °C, 100 rpm) | [116] |
Prebiotics | Static (INFOGEST 2.0) (mouth–stomach–small intestine) | Mouth: 5 mL of phosphate-buffered saline (PBS) mixed with 3.5 mL of simulated salivary fluid, 0.5 mL of 1500 U/mL of α-amylase, 25 μL of 0.3 M CaCl2, and 975 μL of distilled water (2 min, 37 °C, 150 rpm) Stomach: 7.5 mL of simulated gastric fluid, 1.6 mL of 25,000 U/mL porcine pepsin, and 5 μL of 0.3 M of CaCl2 and 695 μL of distilled water (pH of 2.5–3, 2 h, 100 rpm) Small intestine: 11 mL of simulated intestinal fluid, 5 mL of 800 U/mL pancreatin, 2.5 mL of 160 mM of bile salt, and 40 μL of 0.3 M of CaCl2 and 1.10 mL of distilled water (pH of 7, 2 h, 100 rpm) | [117] |
Probiotics | Static (stomach–small intestine) | Stomach: pepsin (3 mg/mL) in sterile saline (0.5% w/v) (pH of 2.0, 3 h) Small intestine: pancreatin USP (1 mg/mL) in sterile saline (0.5% w/v) (pH of 8.0, 4 h) | [118] |
Probiotics | Static (mouth–stomach–small intestine) | Mouth: 9.0 mL of peptone water (pH of 6.9, 2 min, 37 °C, 200 rpm) Stomach: 0.05 mL of pepsin (pH of 2.0, 1.5 h, 37 °C, 130 rpm) Duodenum: 0.125 mL of pancreatin, 0.125 mL of bovine bile (pH of 5.0, 20 min, 37 °C, 45 rpm) Ileum: 0.125 mL of pancreatin, 0.125 mL of bovine bile (pH of 6.5, 90 min, 37 °C, 45 rpm) | [119] |
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Ośko, J.; Nasierowska, K.; Grembecka, M. Application of In Vitro Digestion Models in the Evaluation of Dietary Supplements. Foods 2024, 13, 2135. https://doi.org/10.3390/foods13132135
Ośko J, Nasierowska K, Grembecka M. Application of In Vitro Digestion Models in the Evaluation of Dietary Supplements. Foods. 2024; 13(13):2135. https://doi.org/10.3390/foods13132135
Chicago/Turabian StyleOśko, Justyna, Katarzyna Nasierowska, and Małgorzata Grembecka. 2024. "Application of In Vitro Digestion Models in the Evaluation of Dietary Supplements" Foods 13, no. 13: 2135. https://doi.org/10.3390/foods13132135
APA StyleOśko, J., Nasierowska, K., & Grembecka, M. (2024). Application of In Vitro Digestion Models in the Evaluation of Dietary Supplements. Foods, 13(13), 2135. https://doi.org/10.3390/foods13132135