Composition for use in patients with ileostomy

Abstract

The present invention relates to a composition for use in the treatment of a condition selected from malabsorption in patients with ileostomy, malnutrition in patients with ileostomy, sodium depletion in patients with ileostomy and / or dehydration in patients with ileostomy.

Description

[0001] Composition for use in patients with ileostomy

[0002] Technical field

[0003] The present invention relates to a composition for use in the treatment of a condition selected from malabsorption in patients with ileostomy, malnutrition in patients with ileostomy, sodium depletion in patients with ileostomy and / or dehydration in patients with ileostomy.

[0004] Background

[0005] Ileostomy patients often experience malabsorption and / or malnutrition (Ng et al, 2013, Fish et al., 2017), including dehydration, electrolyte deficiencies, and secondary hyperaldosteronism, (Rud et al., 2023) which may lead to acute and chronic kidney injury (Beck-Kaltenbach et al., 2011; Li et al., 2017; Smith et al., 2021), even long after their ileostomy surgery (Ladefoged et al., 1985, Gallagher et al., 1962, Clarke et al., 1967). Because of increased intestinal losses of bicarbonate, the patients are prone to acid-base disorders which may be life-threatening and can present as metabolic acidosis. Moreover ileostomy patients generally have a lower quality-of-life than the background population (Schiergens et al., 2017, Rud et al., 2022) due to complaints such as fatigue, dizziness, cramps and concentration disturbances.

[0006] Summary

[0007] There is an urgent need for novel treatments to improve the quality-of-life for ileostomy patients which often suffer from malabsorption, malnutrition, electrolyte deficiencies such as sodium depletion, secondary hyperaldosteronism and / or dehydration.

[0008] The present inventors have surprisingly found that administering a composition comprising whey protein to ileostomy patients has several positive effects in these patients, including positive effects on malabsorption and malnutrition.

[0009] In a first aspect, the present disclosure concerns a composition for use in the treatment of a condition selected from malabsorption in patients with ileostomy, malnutrition in patients with ileostomy, sodium depletion in patients with ileostomy and / or dehydration in patients with ileostomy, wherein the composition comprises a) whey protein, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) Optionally K+, and f) Optionally Ca++.

[0010] In a second aspect, the present disclosure concerns a composition, such as a liquid composition, wherein the composition comprises a) whey protein, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) Optionally K+, and f) Optionally Ca++.

[0011] In a third aspect, the present disclosure concerns a solid composition, wherein the solid composition comprises a) 40 to 70 g protein / 100 g dry matter, b) 20 to 50 g carbohydrate / 100 g dry matter, c) 0.5 to 2 g Na+ / 100 g dry matter, d) 0.0001 to 0.05 g Mg+7100 g dry matter, e) 0.01 to 3 g K+ / 100 g dry matter, and f) 1.5 g Ca++ / 100 g dry matter.

[0012] Description of Drawings

[0013] Figure 1. Faecal output before and after four-week interventions with either whey protein isolate, caseinate or whey protein hydrolysate. Each line represents one patient and box and whiskers show median, interquartile range and range.

[0014] A. Whey protein isolate: A=74, p=0.41. Caseinate: A=84, p=0.35. Whey protein hydrolysate: A=67, p=0.48. B. Whey protein isolate: A=365, p=0.012. Caseinate: A=14, p=0.92. Whey protein hydrolysate: A=172, p=0.23. C. Whey protein isolate: A=4.0, p=0.72. Caseinate: A=1.9, p=0.87. Whey protein hydrolysate: A=5.0, p=0.66. D. Whey protein isolate: A=7.8, p=0.001. Caseinate: A=1.1 , p=0.59. Whey protein hydrolysate: A=2.4, p=0.28. E. Whey protein isolate: A=4.0, p=0.020. Caseinate: A=0.8, p=0.65. Whey protein hydrolysate: A=2.7, p=0.13. F. Whey protein isolate: A=7.6, p=0.023. Caseinate: A=5.6, p=0.09. Whey protein hydrolysate: A=2.0, p=0.56.

[0015] A values are differences between pre- and post-intervention measurements adjusted for intra-patient variability, period and treatment sequence. Abbreviations: Ca, calcium;

[0016] F, faecal; Mg, magnesium; K, potassium; Na, sodium; B: baseline; T: treatment.

[0017] Figure 2. Urinary output before and after four-week interventions with either whey protein isolate, caseinate or whey protein hydrolysate. Each line represents one patient and box and whiskers show median, interquartile range and range.

[0018] A. Whey protein isolate: A=194, p=0.07. Caseinate: A=46, p=0.62. Whey protein hydrolysate: A=22, p=0.76. B. Whey protein isolate: RR=1.25, p=0.68. Caseinate: RR=1.20, p=0.68. Whey protein hydrolysate: RR=1.09, p=0.79 (RR: relative risk). C. Whey protein isolate: A=1.8, p=0.74. Caseinate: A=3.3, p=0.53. Whey protein hydrolysate: A=13.1 , p=0.02. D. Whey protein isolate: A=0.3, p=0.17. Caseinate: A=0.0, p=0.87. Whey protein hydrolysate: A=0.1 , p=0.61.

[0019] A values are differences between pre- and post-intervention measurements adjusted for intra-patient variability, period and treatment sequence. Abbreviations: K, potassium; Mg, magnesium; Na, sodium; U, urinary; B: baseline; T: treatment.

[0020] Figure 3. Biochemistry before and after four-week interventions with either whey protein isolate, caseinate or whey protein hydrolysate. Each line represents one patient and box and whiskers show median, interquartile range and range.

[0021] A. Whey protein isolate: A=4674, p=0.019. Caseinate: A=1983, p=0.30. Whey protein hydrolysate: A=1279, p=0.52. B. Whey protein isolate: A=1.0, p=0.054. Caseinate: A=0.8, p=0.14. Whey protein hydrolysate: A=0.3, p=0.51. C. Whey protein isolate: A=2.8, p=0.033. Caseinate: A=0.2, p=0.85. Whey protein hydrolysate: A=1.1 , p=0.41. D. Whey protein isolate: A=1.7, p=0.040. Caseinate: A=1.4, p=0.08. Whey protein hydrolysate: A=1.2, p=0.14.

[0022] A values are differences between pre- and post-intervention measurements adjusted for intra-patient variability, period, and treatment sequence. Abbreviations: CO2, (venous blood) carbon dioxide; eGFR, estimated glomerular filtration rate; Na, sodium; P, plasma; B: baseline; T: treatment. Figure 4. Glucagon-like peptide 1 secretion following ingestion of 500 mL of composition (ORS) comprising whey protein isolate (WPI), caseinate (Cas) or whey protein hydrolysate (WPH).

[0023] Figure 5. A. Urine pH; B. Urine ammonium excretion; C. Urine titratable acid excretion; D. Urine net acid excretion.

[0024] Figure 6. A. Urine pH; B. Urine ammonium excretion; C. Urine titratable acid excretion;

[0025] D. Urine net acid excretion.

[0026] Figure 7. A. Net endogenous acid production; B. Association between acid production and excretion; C. Difference in production and excretion.

[0027] NEAP: net endogenous acid production, NAE: net acid excretion.

[0028] Figure 8. Palatability of the updated WPI recipe (version 2.3), rated by four participants. High scores indicate good taste.

[0029] Figure 9. Estimated intestinal bicarbonate loss for the updated WPI recipe (version 2.3).

[0030] Figure 10. A. Urine volume; B. Urine sodium; C. Aldosterone; D. Total carbon dioxide;

[0031] E. Bicarbonate; F. Base excess.

[0032] Figure 11. A. Urine volume; B. Urine ammonium; C. Urine titratable acid excretion; D. Urine net acid excretion.

[0033] Detailed description

[0034] Complaints such as fatigue, dizziness, cramps and concentration disturbances typically experienced by ileostomy patients, have been associated with low sodium intake, low renal sodium excretion (u-Na) and high plasma aldosterone levels [Haalboom et al., 1987], Dietary treatment of patients with an ileostomy have been proposed as remedies for alleviation of the symptoms, including both elemental and polymeric diets along with certain liquid compositions (Jeppesen et al., 2013, Sundaram et al., 2002 Newton et al., 1982, Nightingale et al., 1992). Problematically, all of these diets and compositions are typically hyperosmolar, which potentially leads to decreased absorption (Rud et al., 2019) and increased ileostomy output.

[0035] The present inventors have evaluated how protein type comprised in compositions and hydrolysation of these protein affect ileostomy output and absorption proxies in patients with an ileostomy. Surprisingly it was found, that compositions comprising whey protein have advantageous effects compared to compositions comprising calcium caseinate, for instance in terms of improved nutrient absorption. Compositions comprising whey protein isolate seem particularly advantageous, such as seem particularly advantageous in decreasing intestinal losses of magnesium, potassium, and calcium.

[0036] Definitions

[0037] The term "malabsorption" as used herein refers to the impaired absorption of digested nutrients, including vitamins and trace elements, from the small intestine or large bowel. Intestinal malabsorption may occur for many nutrients or for specific macronutrients, namely carbohydrates, fats or proteins, as well as for micronutrients, such as calcium, magnesium, sodium, potassium, iron, and vitamins.

[0038] The term "malnutrition" as used herein refers to deficiencies in nutrient intake, imbalance of essential nutrients and / or impaired nutrient utilization caused by . Malnutrition is a medical condition caused by poor absorption, or excessive loss of nutrients.

[0039] The term “osmolality" as used herein refers to a measure of the osmotic pressure of dissolved solute particles in an aqueous solution. The solute particles include both ions and non-ionized molecules. Osmolality is expressed as the concentration of osmotically active particles (i.e., osmoles) dissolved in 1 kg of solution. Osmolality is measured routinely, e.g. by a Freezing point depression osmometer.

[0040] The term “iso-osmolar” as used herein refers to a solution having an osmolality between 230-290 mOsm / kg.

[0041] The term “whey” as used herein refers to the liquid obtained after cheese processing steps of milk, where casein in milk is precipitated and cheese curd and whey is obtained. The whey can have different protein content dependent on how the milk used to prepare the cheese curd and whey is treated before processing into curd and whey.

[0042] The term “whey protein” as used herein refers to protein that is found in whey or in milk serum.

[0043] The term “whey protein isolate” as well as the term “whey isolate” as used herein refer to intact whey protein, and whey protein which not actively has been subjected to hydrolysis procedures. The term “whey protein isolate” as well as the term “whey isolate” as used herein may refer to the dry portion of whey obtained by the removal of non-protein constituents from whey so that the dry whey product contains more than 86 percent whey protein.

[0044] The term “caseinate” as used herein refers to a salt of casein protein with a base. Salts with alkali metals (such as, for example, sodium or potassium) or alkaline-earth metals (such as calcium) are suitable to the invention. "Casein protein" means all members of the milk fraction designated caseins, comprising alpha-, beta-, gamma- kappa- and lambda-caseins, and their mixtures, either synthetic or natural, in particular originating from milk cow.

[0045] The term “whey protein hydrolysate” as well as the term “whey hydrolysate” as used herein refers to a hydrolysed whey protein material. The term "hydrolysed whey protein" refers to intact protein which has been hydrolysed into peptide fragments whereby a majority of peptides fragments have a molecular weight of less than 1000 Daltons. Hydrolysed whey proteins include hydrolysed protein hydrolysates prepared from acid or enzyme treated whey protein.

[0046] The term "comprising” as used herein is to be interpreted as specifying the presence of the stated features, steps, or components as referred to, but does not preclude the presence or addition of one or more additional features, steps or components, or groups thereof. When a composition comprises a specified range or a maximum level of a given compound, the term comprising is to be interpreted such that said composition may comprise other compounds or components in addition to said given compound, but not more than the upper limit of said range or more than said maximum level of said given compound. Composition

[0047] One embodiment of the present disclosure relates to a composition, such as a liquid composition, for use in the treatment of a condition selected from malabsorption in patients with ileostomy, malnutrition in patients with ileostomy, sodium depletion in patients with ileostomy and / or dehydration in patients with ileostomy, wherein said composition comprises a) whey protein, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) Optionally K+, and f) Optionally Ca++.

[0048] Another embodiment of the present disclosure relates to a composition, such as a liquid composition, wherein the composition comprises a) whey protein, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) Optionally K+, and f) Optionally Ca++.

[0049] Another embodiment of the present disclosure relates a solid composition, wherein the solid composition comprises a) 40 to 70 g protein / 100 g dry matter, b) 20 to 50 g carbohydrate / 100 g dry matter, c) 0.5 to 2 g Na+ / 100 g dry matter, d) 0.0001 to 0.05 g Mg+7100 g dry matter, e) 0.01 to 3 g K+ / 100 g dry matter, and f) 1.5 g Ca++ / 100 g dry matter.

[0050] In one embodiment, the composition of the present disclosure comprises a) 0.5 to 20 g whey protein per 100 g, b) 0.5 to 20 g carbohydrate per 100 g, such as glucose, c) 0.5 to 100 mmol / L Na+, d) 0.001 to 10 mmol / L Mg++, e) 0.001 to 100 mmol / L K+, and f) 0.001 to 20 mmol / L Ca++.

[0051] In one embodiment, the composition of the present disclosure comprises a) 0.5 to 20 g whey protein per 100 g, b) 0.5 to 20 g carbohydrate per 100 g, such as glucose, c) 0.5 to 100 mmol / L Na+, d) 0.001 to 100 mmol Mg++.

[0052] In one embodiment, the composition of the present disclosure comprises a) 2 to 5 g whey protein per 100 g, b) 1 to 4 g carbohydrate per 100 g, such as glucose, c) 20 to 90 mmol / L Na+d) 0.001 to 25 mmol / L Mg++, e) 0.01 to 50 mmol / L K+, and f) 0.01 to 3 mmol / L Ca++.

[0053] In one embodiment, the composition of the present disclosure comprises a) 3 to 7 g whey protein per 100 g, such as 3 to 7 g whey protein isolate per 100 g, b) 90 to 130 mmol / L carbohydrate, such as glucose, c) 55 to 95 mmol / L Na+: d) 2 to 30 mmol / L Mg++, and e) optionally 5-40 mmol / L HCO3'.

[0054] In one embodiment, the composition of the present disclosure comprises a) 4 to 6 g whey protein per 100 g, such as 4 to 6 g whey protein isolate per 100 g, b) 100 to 120 mmol / L carbohydrate, such as glucose, c) 65 to 85 mmol / L Na+: d) 5 to 20 mmol / L Mg++, and e) optionally 10-30 mmol / L HCO3'.

[0055] In one embodiment, the composition of the present disclosure comprises a) 4.5 to 5.5 g whey protein per 100 g, such as 4.5 to 5.5 g whey protein isolate per 100 g, b) 105 to 115 mmol / L carbohydrate, such as glucose, c) 70 to 80 mmol / L Na+: d) 5 to 15 mmol / L Mg++, and e) optionally 15-25 mmol / L HCO3'.

[0056] In one embodiment, the composition of the present disclosure comprises a) 4.9 to 5.1 g whey protein per 100 g, such as 4.9 to 5.1 g whey protein isolate per 100 g, b) 110 to 112 mmol / L carbohydrate, such as glucose, c) 74 to 76 mmol / L Na+: d) 9 to 11 mmol / L Mg++, and e) optionally 19-21 mmol / L HCO3'.

[0057] In one embodiment, the liquid composition of the present disclosure comprises a) water, b) 3 to 7 g whey protein per 100 g, such as 3 to 7 g whey protein isolate per 100 g, c) 90 to 130 mmol / L carbohydrate, such as glucose, d) 55 to 95 mmol / L Na+: e) 2 to 30 mmol / L Mg++, and f) optionally 5-40 mmol / L HCO3'.

[0058] In one embodiment, the liquid composition of the present disclosure comprises a) water, b) 4 to 6 g whey protein per 100 g, such as 4 to 6 g whey protein isolate per 100 g, c) 100 to 120 mmol / L carbohydrate, such as glucose, d) 65 to 85 mmol / L Na+: e) 5 to 20 mmol / L Mg++, and f) optionally 10-30 mmol / L HCO3'.

[0059] In one embodiment, the liquid composition of the present disclosure comprises a) water, b) 4.5 to 5.5 g whey protein per 100 g, such as 4.5 to 5.5 g whey protein isolate per 100 g, c) 105 to 115 mmol / L carbohydrate, such as glucose, d) 70 to 80 mmol / L Na+: e) 5 to 15 mmol / L Mg++, and f) optionally 15-25 mmol / L HCO3'.

[0060] In one embodiment, the liquid composition of the present disclosure comprises a) water, b) 4.9 to 5.1 g whey protein per 100 g, such as 4.9 to 5.1 g whey protein isolate per 100 g, c) 110 to 112 mmol / L carbohydrate, such as glucose, d) 74 to 76 mmol / L Na+: e) 9 to 11 mmol / L Mg++, and f) optionally 19-21 mmol / L HCO3'.

[0061] Whey protein

[0062] The inventors of the present invention have demonstrated that compositions comprising whey proteins have beneficial effects on nutritional absorption in ileostomy patients. Example 1 investigates the effects of intake of liquid compositions comprising i) whey protein isolate, ii) whey protein hydrolysate and iii) caseinate, respectively, on ileostomy patients. Example 1 shows that administration of compositions comprising whey protein is associated with positive effects in these patients, and in particular administration of compositions comprising whey isolate is associated with positive effects in ileostomy patients.

[0063] In one embodiment, the composition of the present disclosure comprises whey protein.

[0064] In one embodiment, the composition of the present disclosure comprises 0.05 to 20 g whey protein per 100 g, such as 1 to 15 g whey protein per 100 g, such as 1 to 14 g whey protein per 100 g, such as 1 to 13 g / 100 g whey, such as 1 to 12 g whey protein per 100 g, such as 1 to 11 g whey protein per 100 g, such as 1 to 10 g whey protein per 100 g, such as 2 to 9 g whey protein per 100 g, such as 3 to 8 g whey protein per 100 g, such as 3 to 7 g whey protein per 100 g, such as 3 to 5 g whey protein per 100 g-

[0065] In one embodiment, the composition of the present disclosure comprises 1 to 8 g whey protein per 100 g, such as 2 to 7 g whey protein per 100 g, such as 3 to 6 g whey protein per 100 g, such as 3.5 to 6 g whey protein per 100 g, such as 3 to 5 g whey protein per 100 g, such as 4 to 6 g whey protein per 100 g, such as 4 to 5 g whey protein per 100 g.

[0066] In one embodiment, the composition of the present disclosure comprises 1 to 8 g whey protein isolate per 100 g, such as 2 to 7 g whey protein isolate per 100 g, such as 3 to 6 g whey protein isolate per 100 g, such as 3.5 to 6 g whey protein isolate per 100 g, such as 3 to 5 g whey protein isolate per 100 g, such as 4 to 6 g whey protein isolate per 100 g, such as 4 to 5 g whey protein isolate per 100 g.

[0067] In one embodiment, the composition of the present disclosure comprises 2 to 6 g whey protein per 100 g, such as 2 to 5.5 g whey protein per 100 g, such as 2 to 5 g whey protein per 100 g, such as 3 to 4.5 g whey protein per 100 g, such as 3.5 to 4.5 g whey protein per 100 g.

[0068] In one embodiment, the composition of the present disclosure comprises 1 to 6 % (v / w) whey protein, such as 2 to 5.5 % (v / w) whey protein, such as 3 to 5.5 % (v / w) whey protein, such as 3 to 5 % (v / w) whey protein, such as 3.5 to 4.5 % (v / w), such as 2.5 to 4.0 % (v / w) whey protein, whey protein such as 2.7 to 3.5 % (v / w) whey protein.

[0069] In one embodiment, the composition of the present disclosure comprises 1 to 6 % (v / w) whey protein isolate, such as 2 to 5.5 % (v / w) whey protein isolate, such as 3 to 5.5 % (v / w) whey protein isolate, such as 3 to 5 % (v / w) whey protein isolate, such as 3.5 to 4.5 % (v / w) whey protein isolate, such as 2.5 to 4.0 % (v / w) whey protein isolate, such as 2.7 to 3.5 % (v / w) whey protein isolate.

[0070] In one embodiment, the composition of the present disclosure comprises at least 0.05 g whey protein per 100 g, such as at least 0.1 g whey protein per 100 g, such at least 0.5 g whey protein per 100 g, such as at least 1 g whey protein per 100 g, such as at least 2 g whey protein per 100 g, such as at least 3 g whey protein per 100 g, such as at least 4 g whey protein per 100 g, such as at least 5 g whey protein per 100 g, such as at least 6 g whey protein per 100 g, such as at least 7 g whey protein per 100 g, such as at least 8 g whey protein per 100 g.

[0071] In one embodiment, the composition of the present disclosure comprises whey protein in the range of 0.05% to 15% (w / v) whey protein, such as 2% to 10 % (w / v) whey protein, such as 3% to 8% (w / v) whey protein, such as 4% to 5% (w / v) whey protein.

[0072] In one embodiment, the whey protein is whey protein isolate and / or whey protein hydrolysate.

[0073] In one embodiment, the whey protein is whey protein isolate.

[0074] In one embodiment, the whey protein is whey protein hydrolysate.

[0075] In one embodiment, the whey protein is bovine.

[0076] Carbohydrates

[0077] In one embodiment, the composition of the present disclosure comprises carbohydrate.

[0078] In one embodiment, the composition of the present disclosure comprises 0.05 to 15 g carbohydrate per 100 g, such as 0.5 to 13 g carbohydrate per 100 g, such as 1 to 10 g carbohydrate per 100 g, such as 1 to 8 g carbohydrate per 100 g, such as 1.5 to 7.5 g carbohydrate per 100 g, such as 1 .5 to 7 g carbohydrate per 100 g, such as 2 to 6 g carbohydrate per 100 g, such as 2 to 5 g carbohydrate per 100 g, such as 2 to 4 g carbohydrate per 100 g, such as 2.2 to 3.3 g carbohydrate per 100 g.

[0079] In one embodiment, the composition of the present disclosure comprises 0.5 to 6 g carbohydrate per 100 g, such as 0.5 to 5.5 g carbohydrate per 100 g, such as 0.5 to 5 g carbohydrate per 100 g, such as 0.5 to 4.5 g carbohydrate per 100 g, such as 0.5 to 4 g carbohydrate per 100 g, such as 0.5 to 3.5 g carbohydrate per 100 g, such as 0.5 to 3 g carbohydrate per 100 g, such as 0.5 to 2.5 g carbohydrate per 100 g.

[0080] In one embodiment, the composition of the present disclosure comprises 1 to 6 g carbohydrate per 100 g, such as 1 to 4 g carbohydrate per 100 g, such as 1 .5 to 6 g carbohydrate per 100 g, such as 2 to 6 g carbohydrate per 100 g, such as 2.1 to 6 g carbohydrate per 100 g, such as 2.5 to 6 g carbohydrate per 100 g, such as 3 to 6 g carbohydrate per 100 g, such as 2 to 5 g carbohydrate per 100 g, such as 1.5 to 4 g carbohydrate per 100 g, such as 1.5 to 3 g carbohydrate per 100 g.

[0081] In one embodiment, the composition of the present disclosure comprises at least 0.05 g carbohydrate per 100 g, such as at least 0.5 g carbohydrate per 100 g, such at least 1 g carbohydrate per 100 g, such as at least 1.5 g carbohydrate per 100 g, such as at least 1.6 g carbohydrate per 100 g, such as at least 1.7 g carbohydrate per 100 g, such as at least 1.8 g carbohydrate per 100 g, such as at least 1.9 g carbohydrate per 100 g, such as at least 2 g carbohydrate per 100 g, such as at least 2.1 g carbohydrate per 100 g, such as at least 2.2 g carbohydrate per 100 g, such as at least 2.3 g carbohydrate per 100 g, such as at least 2.4 g carbohydrate per 100 g, such as at least 2.5 g carbohydrate per 100 g, such as at least 2.6 g carbohydrate per 100 g, such as at least 2.7 g carbohydrate per 100 g, such as at least 2.8 g carbohydrate per 100 g, such as at least 2.9 g carbohydrate per 100 g, such as at least 3 g carbohydrate per 100 g, such as at least 4 g carbohydrate per 100 g, such as at least 5 g carbohydrate per 100 g, such as at least 6 g carbohydrate per 100 g.

[0082] In one embodiment, the composition of the present disclosure comprises carbohydrate in the range of 0.05% to 15% (w / v) carbohydrate, such as 1% to 13 % (w / v) carbohydrate, such as 1.5 % to 6% (w / v) carbohydrate, such as 2% to 4% (w / v) carbohydrate, such as 2.2% to 3.3% (w / v) carbohydrate.

[0083] In one embodiment, the composition of the present disclosure comprises carbohydrate in the range of 0.05 to 500 mmol / L, such as 0.05 to 400 mmol / L, such as 0.05 to 300 mmol / L, such as 0.05 to 200 mmol / L, such as 5 mmol to 200 mmol / L, such as 25 to 200 mmol / L, such as 50 to 200 mmol / L, such as 60 to 180 mmol / L.

[0084] In one embodiment, the composition of the present disclosure comprises carbohydrate in the range of 0.05 to 500 mmol / L, such as 60 to 180 mmol / L, such as 60 to 70 mmol / L, such as 70 to 80 mmol / L, such as 80 to 90 mmol / L, such as 90 to 100 mmol / L, such as 100 to 110 mmol / L, such as 110 to 120 mmol / L, such as 120 to 130 mmol / L, such as 130 to 140 mmol / L, such as 140 to 150 mmol / L, such as 150 to 160 mmol / L, such as 160 to 170 mmol / L, such as 170 to 180 mmol / L. In one embodiment, the carbohydrate is a monosaccharide, a disaccharide and / or a polysaccharide.

[0085] In one embodiment, the carbohydrate is selected from the group consisting of glucose, saccharose, and maltodextrin.

[0086] In one embodiment, the carbohydrate is glucose.

[0087] In one embodiment, the composition of the present disclosure comprises 0.05 to 500 mmol / L glucose, such as 0.05 to 400 mmol / L glucose, such as 0.05 to 300 mmol / L glucose, such as 0.05 to 200 mmol / L glucose, such as 5 mmol to 200 mmol / L glucose, such as 25 to 200 mmol / L glucose, such as 50 to 200 mmol / L glucose, such as 75 to 175 mmol / L glucose, such as 60 to 180 mmol / L glucose, such as 100 to 150 mmol / L glucose, such as 100 to 140 mmol / L glucose, such as 100 to 120 mmol / L glucose, such as 110 to 150 mmol / L glucose.

[0088] In one embodiment, the composition of the present disclosure comprises 1 to 7 g glucose per 100 g, such as 1 to 6 g glucose per 100 g, such as 1 to 5 g glucose per 100 g, such as 1 to 4 g glucose per 100 g, such as 1.5 to 4 g glucose per 100 g, such as 2 to 4 g glucose per 100 g, such as 1.5 to 3.5 g glucose per 100 g, such as 2 to 3.5 g glucose per 100 g.

[0089] Na+(sodium)

[0090] In ileostomy patients there is a high prevalence of sodium depletion. Accordingly, compositions which can help treat sodium depletion in patients with ileostomy are needed.

[0091] In one embodiment, the composition of the present disclosure comprises Na+. The Na+can be introduced in small amounts through the water and / or whey protein, and in larger amounts by addition of a Na+salt, such as sodium chloride.

[0092] In one embodiment, the composition of the present disclosure comprises 1 to 150 mmol / L Na+, such as 1 to 120 mmol / L Na+, such as 1 to 100 mmol / L Na+, such as 5 to 100 mmol / L Na+, such as 10 to 100 mmol / L Na+, such as 200 to 100 mmol / L Na+, such as 300 to 100 mmol / L Na+, such as 30 to 90 mmol / L Na+, such as 40 to 90 mmol / L Na+, such as 50 to 90 mmol / L Na+, such as 60 to 80 mmol / L Na+.

[0093] In one embodiment, the composition of the present disclosure comprises 1 to 150 mmol / L Na+, such as 1 to 100 mmol / L Na+, such as 10 to 100 mmol / L Na+, such as 10 to 90 mmol / L Na+such as 15 to 90 mmol / L Na+, such as 20 to 90 mmol / L Na+, such as 30 to 90 mmol / L Na+, such as 40 to 95 mmol / L Na+, such as 50 to 90 mmol / L Na+, such as 360 to 90 mmol / L Na+, such as 70 to 90 mmol / L Na+, such as 80 to 90 mmol / L Na+.

[0094] In one embodiment, the composition of the present disclosure comprises 10 to 50 mmol / L Na+, such as 15 to 50 mmol / L Na+, such as 20 to 50 mmol / L Na+, such as 30 to 50 mmol / L Na+, such as 30 to 45 mmol / L Na+, such as 33 to 45 mmol / L Na+.

[0095] Water

[0096] In one embodiment the composition of the present invention is a liquid composition. In one embodiment the composition of the present invention is an aqueous composition.

[0097] In one embodiment, the composition of the present disclosure comprises water. In one embodiment the composition comprises tap water. As tap water comprises low amounts, such as less than 1 mmol / l, of minerals such as magnesium, potassium, calcium, sodium and others, the tap water will introduce small amounts of such ions.

[0098] K+(potassium)

[0099] In one embodiment, the composition of the present disclosure comprises K+.

[0100] The K+can be introduced in small amounts through the water and / or whey protein, and in larger amounts by addition of a K+salt. In one embodiment the K+salt is potassium chloride.

[0101] In one embodiment, the composition of the present disclosure comprises 0.001 to 100 mmol / L K+, such as 0.001 to 100 mmol / L K+, such as 0.001 to 90 mmol / L K+, such as 10 to 90 mmol / L K+, such as 10 to 80 mmol / L K+, such as 10 to 70 mmol / L K+, such as 10 to 60 mmol / L K+, such as 10 to 50 mmol / L K+.

[0102] In one embodiment, the composition of the present disclosure comprises 0.001 to 50 mmol / L K+, such as 0.01 to 50 mmol / L K+, such as 0.1 to 50 mmol / L K+, such as 1 to 50 mmol / L K+, such as 5 to 50 mmol / L K+, such as 10 to 50 mmol / L K+, such as 10 to 45 mmol / L K+, such as 15 to 45 mmol / L K+.

[0103] In one embodiment, the composition of the present disclosure comprises 10 to 30 mmol / L K+, such as 10 to 35 mmol / L K+, such as 10 to 30 mmol / L K+, such as 15 to 25 mmol / L K+, such as 16 to 24 mmol / L K+, such as 17 to 21 mmol / L K+.

[0104] In one embodiment, the composition of the present disclosure comprises 30 to 60 mmol / L K+, such as 35 to 55 mmol / L K+, such as 35 to 50 mmol / L K+, such as 35 to 45 mmol / L K+, such as 37 to 44 mmol / L K+, such as 39 to 42 mmol / L K+.

[0105] Mg++(magnesium)

[0106] In one embodiment, the composition of the present disclosure comprises Mg++.

[0107] The Mg++can be introduced in small amounts through the water and / or whey protein, and in larger amounts by addition of a Mg++salt. In one embodiment the Mg++salt is an inorganic salt. In one embodiment the Mg++salt is an organic salt. In one embodiment the Mg++salt is magnesium sulphate. In one embodiment the Mg++salt is magnesium citrate hydrate.

[0108] In one embodiment, the composition of the present disclosure comprises 0.001 to 40 mmol / L Mg++, such as 0.001 to 30 mmol / L Mg++, such as 0.001 to 25 mmol / L Mg++, such as 0.001 to 5 mmol / L Mg++, such as 0.001 to 3 mmol / L Mg++, such as 0.001 to 2 mmol / L Mg++, such as 0.001 to 1 mmol / L Mg++, such as 0.005 to 1 mmol / L Mg++, such as 0.005 to 0.9 mmol / L Mg++, such as 0.005 to 0.8 mmol / L Mg++, such as 0.005 to 0.7 mmol / L Mg++, such as 0.005 to 0.6 mmol / L Mg++, such as 0.005 to 0.5 mmol / L Mg++, such as 0.005 to 0.4 mmol / L Mg++such as 0.01 to 0.4 mmol / L Mg++, such as 0.2 to 0.3 mmol / L Mg++.

[0109] In one embodiment, the composition of the present disclosure comprises 0.001 to 200 mmol / L Mg++, such as 0.001 to 100 mmol / L Mg++, such as 0.001 to 50 mmol / L Mg++, such as 0.001 to 25 mmol / L Mg++, such as 0.01 to 25 mmol / L Mg++, such as 0.1 to 25 mmol / L Mg++, such as 0.5 to 25 mmol / L Mg++, such as 1 to 25 mmol / L Mg++, such as 1 to 10 mmol / L Mg++, such as 5 to 25 mmol / L Mg++, such as 5 to 20 mmol / L Mg++, such as 10 to 25 mmol / L Mg++, such as 15 to 25 mmol / L Mg++, such as 20 to 25 mmol / L Mg HCO3 (bicarbonate, hydrogen carbonate)

[0110] In one embodiment, the composition of the present disclosure comprises HCO3'.

[0111] The HCCh' can be introduced in small amounts through the water and / or whey protein, and in larger amounts by addition of a HCO3' salt. In one embodiment the HCO3' salt is sodium bicarbonate.

[0112] In one embodiment, the composition of the present disclosure comprises 0.001 to 40 mmol / L HCO3', such as 0.001 to 30 mmol / L HCO3', such as 0.001 to 25 mmol / L HCO3', such as 0.001 to 5 mmol / L HCO3', such as 0.001 to 3 mmol / L HCO3', such as 0.001 to 2 mmol / L HCO3', such as 0.001 to 1 mmol / L HCO3', such as 0.005 to 1 mmol / L HCO3', such as 0.005 to 0.9 mmol / L HCO3', such as 0.005 to 0.8 mmol / L HCO3', such as 0.005 to 0.7 mmol / L HCO3', such as 0.005 to 0.6 mmol / L HCO3', such as 0.005 to 0.5 mmol / L HCO3', such as 0.005 to 0.4 mmol / L HCOs’ such as 0.01 to 0.4 mmol / L HCO3', such as 0.2 to 0.3 mmol / L HCO3'.

[0113] In one embodiment, the composition of the present disclosure comprises 0.001 to 200 mmol / L HCO3', such as 0.001 to 100 mmol / L HCO3', such as 0.001 to 50 mmol / L HCO3', such as 0.001 to 25 mmol / L HCO3', such as 0.01 to 25 mmol / L HCO3', such as 0.1 to 25 mmol / L HCO3', such as 0.5 to 25 mmol / L HCO3', such as 1 to 25 mmol / L HCO3', such as 5 to 25 mmol / L HCO3', such as 10 to 25 mmol / L HCO3', such as 15 to 25 mmol / L HCO3', such as 20 to 25 mmol / L HCO3'.

[0114] In one embodiment, the HCO3' is present as CO2 (carbon dioxide), H2CO3 (carbonic acid), HCO3' (bicarbonate, hydrogen carbonate), CO3” (carbonate) or mixtures thereof.

[0115] Ca++(calcium)

[0116] In one embodiment, the composition of the present disclosure comprises Ca++.

[0117] The Ca++can be introduced in small amounts through the water and / or whey protein, and in larger amounts by addition of a Ca++salt. In one embodiment the Ca++salt is calcium chloride.

[0118] In one embodiment, the composition of the present disclosure comprises 0.001 to 50 mmol / L Ca++, such as 0.001 to 40 mmol / L Ca++, such as 0.001 to 30 mmol / L Ca++, such as 0.001 to 20 mmol / L Ca++, such as 0.001 to 10 mmol / L Ca++, such as 0.01 to 10 mmol / L Ca++, such as 0.01 to 9 mmol / L Ca++, such as 0.01 to 8 mmol / L Ca++, such as 0.01 to 7 mmol / L Ca++, such as 0.01 to 6 mmol / L Ca++, such as 0.01 to 5 mmol / L Ca++, such as 0.01 to 4 mmol / L Ca++, such as 0.01 to 3 mmol / L Ca++, such as 0.01 to 2 mmol / L Ca++, such as 0.01 to 1 mmol / L Ca++.

[0119] In one embodiment, the composition of the present disclosure comprises 0.001 to 2 mmol / L Ca++, such as 0.01 to 2 mmol / L Ca++, such as 0.05 to 2 mmol / L Ca++, such as 0.08 to 2 mmol / L Ca++, such as 0.1 to 2 mmol / L Ca++.

[0120] In one embodiment, the composition of the present disclosure comprises 0.001 to 2 mmol / L Ca++, such as 0.01 to 1.9 mmol / L Ca++, such as 0.01 to 1.8 mmol / L Ca++, such as 0.01 to 1 .7 mmol / L Ca++, such as 0.01 to 1.6 mmol / L Ca++, such as 0.01 to 1 .5 mmol / L Ca++, such as 0.05 to 1.5 mmol / L Ca++.

[0121] Additional ingredients

[0122] In one embodiment, the composition of the present disclosure comprises additional ingredients, such as additional protein, fat or flavour.

[0123] In one embodiment, the composition of the present disclosure comprises additional protein. In one embodiment the additional protein is animal protein, such as caseinate. In one embodiment the additional protein is plant based protein.

[0124] In one embodiment, the composition of the present disclosure comprises fat. The fat can be introduced in small amounts through the whey protein, or in larger amounts by addition of a fat. In one embodiment the fat is animal fat. In one embodiment the fat is a vegetable oil.

[0125] It may be important for long-term administration of the composition of the present invention, that the composition is palatable to the patient. Thus, In one embodiment, the composition of the present disclosure comprises one or more flavours. In one embodiment the flavour is vanilla. In one embodiment the flavour is chocolate. In one embodiment the flavour is white chocolate. In one embodiment the flavour is citrus flavour. In one embodiment the flavour is orange. In one embodiment the flavour is combinations of vanilla, chocolate, orange and citrus flavour. Solid composition

[0126] In one embodiment, the composition of the present disclosure is a solid composition, such as a dry matter, such as a powder, such as a dry powder. In one embodiment, the composition is a dry powder. In one embodiment the composition is distributed to the patient as a powder, which the patient can dissolve in water prior to administration, to prepare a liquid composition of the present disclosure. In one embodiment, the powder is contained in a sachet and / or distributed to the patient in a sachet. In one embodiment the content of one sachet can be dissolved in a given amount of water, to prepare the liquid composition of the present invention. In one embodiment, the content of one sachet is for one administration.

[0127] In one embodiment, the solid composition of the present disclosure comprises a) 40 to 70 g protein / 100 g dry matter, such as 45 to 65 g protein / 100 g dry matter, such as 50 to 60 g protein / 100 g dry matter, b) 20 to 50 g carbohydrate / 100 g dry matter, such as 25 to 45 g carbohydrate / 100 g dry matter, 30 to 40 g carbohydrate / 100 g dry matter, c) 0.5 to 2 g Na+ / 100 g dry matter, such as 0.7 to 1.8 g Na7100 g dry matter, 0.9 to 1.5 g Na+ / 100 g dry matter, d) 0.0001 to 0.05 g Mg+7100 g dry matter, such as 0.001 to 0.04 g Mg++ / 100 g dry matter, 0.01 to 0.03 g Mg++ / 100 g dry matter, e) 0.01 to 3 g K+ / 100 g dry matter, such as 0.05 to 2 g K+ / 100 g dry matter, such as 0.1 to 1 g K+ / 100 g dry matter, and f) 0.01 to 1.5 g Ca++ / 100 g dry matter, such as 0.05 to 1 g Ca++ / 100 g dry matter, such as 0.1 to 0.5 g Ca++ / 100 g dry matter.

[0128] In one embodiment, the solid composition is comprised in a sachet, wherein the sachet comprises a) 9.5 to 12.5 g protein, such as 9 to 12 g protein, such as 10 to 11 g protein, b) 5.4 to 8 g carbohydrate, such as 5.8 to 7.5 g carbohydrate, such as 6 to 7 g carbohydrate, c) 0.180 to 0.270 g Na+, such as 0.200 to 0.250 g Na+, such as 0.210 to 0.240 g Na+, d) 0.001 to 0.003 g Mg++, such as 0.001 to 0.0025 g Mg++, such as 0.001 to 0.002 g Mg++, e) 0.045 to 0.425 g K+, such as 0.05 to 0.4 g K+, such as 0.1 to 0.3 g K+, f) 0.005 to 0.2 g Ca++, such as 0.05 to 0.15 g Ca++, such as 0.8 to 0.1 g Ca++.

[0129] In one embodiment, the sachet comprises 20-24 g of solid composition. In one embodiment, the liquid composition of the present disclosure is prepared by dissolving the solid composition contained in one sachet in 250 ml of water.

[0130] Osmolality

[0131] In one embodiment, the composition of the present disclosure is iso-osmolar.

[0132] In one embodiment, the composition of the present disclosure has an osmolality of 100 to 400 mOsm / kg, such as 230 to 290 mOsm / kg.

[0133] In one embodiment, the composition of the present disclosure has an osmolality between 100 to 400 mOsm / kg, such as 200 to 400 mOsm / kg, such as 210 to 350 mOsm / kg, such as 230 to 300 mOsm / kg, such as 230 to 290 mOsm / kg, such as 220 to 290 mOsm / kg.

[0134] In one embodiment, the composition of the present disclosure has an osmolality between 200 to 300 mOsm / kg, such as 210 to 290 mOsm / kg, such as 220 to 280 mOsm / kg, such as 230 to 270 mOsm / kg, such as 240 to 260 mOsm / kg.

[0135] In one embodiment, the composition of the present disclosure has an osmolality between 260 to 270 mOsm / kg, such as 262 to 265 mOsm / kg.

[0136] In one embodiment, the composition of the present disclosure has an osmolality between 245 to 255 mOsm / kg, such as 246 to 250 mOsm / kg.

[0137] In one embodiment, the composition of the present disclosure has an osmolality of approximately 280 mOsm / kg. Administration

[0138] In one embodiment, the composition of the present disclosure is for oral intake.

[0139] In one embodiment, the composition of the present disclosure is palatable.

[0140] In one embodiment, the composition of the present disclosure is administered, such as ingested, twice daily.

[0141] In one embodiment, the composition of the present disclosure is ingested twice daily.

[0142] In one embodiment, the composition of the present disclosure is administered, such as ingested, for 1-8 weeks, such as 2-6 weeks, such as 3-5 weeks.

[0143] In one embodiment, the composition of the present disclosure is administered, such as ingested, twice daily for 1-8 weeks, such as 2-6 weeks, such as 3-5 weeks.

[0144] In one embodiment, the composition of the present disclosure is administered, such as ingested, twice daily for 4 weeks.

[0145] In one embodiment, the composition of the present disclosure is administered, such as ingested, for multiple weeks, such as 10, 20, 30, 40, 50 or 60 weeks.

[0146] In one embodiment, the composition of the present disclosure is administered, such as ingested, for multiple months, such as 2, 3, 4, 5, 6, 7, 8, 9 and 10 months.

[0147] In one embodiment, the composition of the present disclosure is administered, such as ingested, for multiple years, such as 2, 3, 4, 5, 6, 7, 8, 9 and 10 years, or more.

[0148] In one embodiment, the composition of the present disclosure no food or fluid is administered and / or ingested 30 min before the composition of the present invention is ingested.

[0149] In one embodiment, the composition of the present disclosure no food or fluid is administered and / or ingested 30 min after the composition of the present invention is ingested. Doses

[0150] In one embodiment, daily administration of the composition results in a daily protein supplement on 10-100 g whey protein, such as 10-80 g whey protein, such as 10-60 g whey protein, such as 10-50 g whey protein, such as 15-50 g whey protein, such as 20- 50 g whey protein, such as 20-24 g whey protein.

[0151] In one embodiment, daily administration of the composition results in a daily protein supplement on 10-40 g whey protein, such as 15-20 g whey protein, such as 20-25 g whey protein, such as 25-30 g whey protein, such as 30-35 g whey protein.

[0152] In one embodiment, daily administration of the composition results in a daily fluid intake in the range 250-2000 ml, such as 250-1750 ml, such as 250-1500 ml, such as 250- 1500 ml, such as 300-1500 ml, such as 300-800 ml, such as 400-700 ml, such as 450- 600 ml, such as at least 500-550 ml.

[0153] In one embodiment, daily administration of the composition results in a daily fluid intake on at least 400-500 ml, such as at least 500-600 ml, such as at least 60-700 ml, such as at least 700-800 ml, such as at least 800-900 ml, such as at least 900-1000 ml, such as at least 100-1100 ml, such as at least 1100-1200 ml, such as at least 1200-1300 ml, such as at least 1300-1400 ml, such as at least 1400-1500 ml, such as at least 1500- 1600 ml.

[0154] Uses and effects in ileostomy patients

[0155] Patients with an ileostomy are at risk of dehydration, electrolyte deficiencies, and secondary hyperaldosteronism, which may lead to acute and chronic kidney injury. The risks apply to both patients with a temporary stoma and those with a permanent stoma. Moreover, ileostomy patients are prone to acid-base disorders, such as metabolic acidosis which may be life-threatening, because of increased intestinal losses of bicarbonate.

[0156] Intake of the whey-based composition of the present invention has been demonstrated to result in decreased intestinal losses of minerals such as magnesium, potassium, calcium and bicarbonate, increased Glucagon-like peptide 1 (GLP-1) secretion, and moreover to have positive effects on fluid and sodium balance, secondary hyperaldosteronism, kidney function and bone health in ileostomy patients. In one embodiment, the composition of the present conditions is for use in treatment of conditions related to malabsorption and / or malnutrition in ileostomy patients.

[0157] In one embodiment, the composition of the present disclosure is for use in the treatment or prevention of malabsorption in patients with ileostomy.

[0158] In one embodiment, the composition of the present disclosure is for use in the treatment or prevention of malnutrition in patients with ileostomy.

[0159] In one embodiment, the composition of the present disclosure is for use in the treatment or prevention of sodium depletion in patients with ileostomy.

[0160] In one embodiment, the composition of the present disclosure is for use in the treatment or prevention of dehydration in patients with ileostomy.

[0161] In one embodiment the composition of the present invention administration of the composition results in improved nutrient absorption.

[0162] In one embodiment, administration of the composition results in improved absorption of energy.

[0163] In one embodiment, administration of the composition results in decreased dry matter ileostomy output.

[0164] In one embodiment, administration of the composition results in decreased dry matter ileostomy output, such as a decrease on more than 5 g, such 10 g, such as 17 g, such as 20 g, such as 30 g, or more.

[0165] In one embodiment, administration of the composition results in decreased energy loss in ileostomy output.

[0166] In one embodiment, administration of the composition results in decreased energy loss in ileostomy output, such as an increase on more than 200 kJ, such as 300 kJ, such as 365 kJ, such as 400 kJ, such as 500 kJ or more. In one embodiment, administration of the composition results in decreased sodium (Na+) loss in ileostomy output.

[0167] In one embodiment, administration of the composition results in decreased faecal potassium (K+).

[0168] In one embodiment, administration of the composition results in decreased faecal magnesium (Mg++) on at least 2 mmol / L, such as more than 3 mmol / L, such as more than 4 mmol / L, such as more than 5 mmol / L, such as more than 6 mmol / L, such as more than 7 mmol / L, such as 7.8 mmol / L, such as more than 8 mmol / L, such as more than 10 mmol / L.

[0169] In one embodiment, administration of the composition results in increased calcium (Ca++) uptake.

[0170] In one embodiment, administration of the composition results in decreased faecal calcium (Ca++).

[0171] In one embodiment, administration of the composition results in decreased faecal calcium (Ca++) on at least 2 mmol / L, such as more than 3 mmol / L, such as more than 4 mmol / L, such as more than 5 mmol / L, such as more than 6 mmol / L, such as more than 7 mmol / L, such as 7.6 mmol / L, such as more than 8 mmol / L, such as more than 10 mmol / L.

[0172] In one embodiment, administration of the composition results in increased uptake of sodium (Na+).

[0173] In one embodiment, administration of the composition results in increased urinary sodium (Na+).

[0174] In one embodiment, administration of the composition results in increased uptake of magnesium (Mg++). In one embodiment, administration of the composition results in increased urinary magnesium (Mg++).

[0175] In one embodiment, administration of the composition results in increased uptake of potassium (K+).

[0176] In one embodiment, administration of the composition results in increased urinary potassium (K+).

[0177] In one embodiment, administration of the composition results in increased urinary potassium (K+) of at least 5 mmol / d, such as more than 6 mmol / d, , such as more than 8 mmol / d, such as more than 10 mmol / d, such as more than 12 mmol / d, such as 13.1 mmol / d, such as more than 14 mmol / d.

[0178] In one embodiment, administration of the composition results in increased plasma bicarbonate.

[0179] In one embodiment, administration of the composition results in decreased intestinal loss of carbonate, such as decreased intestinal loss of bicarbonate.

[0180] In one embodiment, administration of the composition results in increased Glucagon- like peptide 1 (GLP-1) secretion.

[0181] In one embodiment, administration of the composition results in improved fluid and sodium balance.

[0182] In one embodiment, administration of the composition results in decrease in P- aldosterone.

[0183] In one embodiment, administration of the composition results in decreased P- aldosterone levels on at least 1 pmol / L, such as at least 2 pmol / L, such as at least 3 pmol / L, such as at least 4 pmol / L, such as 4.6 pmol / L, such as at least 5 pmol / L, such as at least 6 pmol / L.

[0184] In one embodiment, administration of the composition results in decreased levels of secondary hyperaldosteronism. In one embodiment, administration of the composition results in improved kidney function.

[0185] In one embodiment, administration of the composition results in lower risk of metabolic acidosis.

[0186] In one embodiment, administration of the composition results in improvement of bone markers.

[0187] In one embodiment, administration of the composition results in improved insulin sensitivity.

[0188] In one embodiment, administration of the composition results in increased bone formation.

[0189] In one embodiment, administration of the composition results in increased muscle function.

[0190] In one embodiment administration of the composition results in increased hand grip strength.

[0191] In one embodiment, administration of the composition results in decreased fatigue.

[0192] In one embodiment, administration of the composition results in decreased fatigue levels, such as a decrease in fatigue score of at least 0.5 point, such as at least 1 point, such as 1.3 points, such as at least 2 points.

[0193] In one embodiment, administration of the composition results in improved psychometry.

[0194] In one embodiment, administration of the composition results in improved reaction time stability.

[0195] In one embodiment, administration of the composition results in improved cognitive function. In one embodiment, the composition of the present disclosure is used in a method for treating malabsorption, malnutrition, sodium depletion and / or dehydration in a subject having an ileostomy.

[0196] In one embodiment, the composition of the present disclosure is used in a method for treating malabsorption, malnutrition, sodium depletion and / or dehydration in a subject having an ileostomy, wherein the method comprises administering to the subject the composition of the present disclosure.

[0197] In another embodiment, the present disclosure relates to a method for treating malabsorption, malnutrition, sodium depletion and / or dehydration in a subject having an ileostomy, wherein said method comprises administering to said subject a composition comprising a) whey protein, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) Optionally K+, and f) Optionally Ca++.

[0198] In another embodiment, the present disclosure relates to a method for treating malabsorption, malnutrition, sodium depletion and / or dehydration in a subject having an ileostomy, wherein said method comprises administering to said subject a composition comprising a) whey protein, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) K+, and f) Ca++.

[0199] In one embodiment, the composition of the present disclosure is used in a method for treating malabsorption, malnutrition, sodium depletion and / or dehydration in a subject having an ileostomy, wherein said method comprises administering to said subject a composition comprising a) whey protein, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) Optionally K+, and f) Optionally Ca++.

[0200] Other patient groups

[0201] As presented elsewhere in the present application, intake of the whey-based composition of the present invention results in increased uptake of electrolytes such as potassium, increased GLP-1 secretion, as well as positive effects on fluid and sodium balance, secondary hyperaldosteronism, kidney function and improved bone health.

[0202] These effects are not only relevant for ileostomy patients, but also for subjects suffering from other types of malnutrition and / or malabsorption related diseases and disorders. Examples of subjects that will benefit from the whey-based composition of the present invention include athletes, elderly, people in postmenopause, patients with osteoporosis or osteopenia, patients with magnesium deficiency, patients suffering from gastrointestinal diseases, kidney diseases and / or acid / base disorders.

[0203] In one embodiment, the composition of the present disclosure is for use in the treatment or prevention of conditions related to malabsorption and / or malnutrition.

[0204] In one embodiment, the conditions related to malabsorption and / or malnutrition includes dehydration, sodium depletion, magnesium deficiency, secondary hyperaldosteronism, acid / base disorders such as metabolic acidosis, osteoporosis, osteopenia, postmenopausal osteoporosis, gastrointestinal diseases and disorders, such as inflammatory bowel disease and kidney diseases.

[0205] In one embodiment, the composition of the present invention is for treatment or prevention of sodium depletion. In one embodiment, the composition of the present invention is for treatment or prevention of dehydration. Items

[0206] 1 . A composition for use in the treatment or prevention of a condition associated with malabsorption, malnutrition, sodium depletion and / or dehydration, wherein said composition comprises a) whey protein, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) Optionally K+, and f) Optionally Ca++.

[0207] 2 . A composition for use in the treatment of a condition selected from malabsorption in patients with ileostomy, malnutrition in patients with ileostomy, sodium depletion in patients with ileostomy and / or dehydration in patients with ileostomy, wherein said composition comprises a) whey protein, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) Optionally K+, and f) Optionally Ca++.

[0208] 3. The composition for use according to any one of the preceding items, wherein the composition is a liquid composition.

[0209] 4 . The composition for use according to any one of the preceding items, wherein the composition comprises water, such as tap water.

[0210] 5. The composition for use according to any one of the preceding items, wherein the composition has an osmolality of 100 to 400 mOsm / kg, such as 230 to 290 mOsm / kg.

[0211] 6 . The composition for use according to any one of the preceding items, wherein the composition comprises 0.05 to 20 g whey protein per 100 g, such as 1 to 15 g whey protein per 100 g, such as 1 to 14 g whey protein per 100 g, such as 1 to 13 g / 100 g whey, such as 1 to 12 g whey protein per 100 g, such as 1 to 11 g whey protein per 100 g, such as 1 to 10 g whey protein per 100 g, such as 2 to 9 g whey protein per 100 g, such as 3 to 8 g whey protein per 100 g, such as 3 to 7 g whey protein per 100 g, such as 3 to 5 g whey protein per 100 g. The composition for use according to any one of the preceding items, wherein the composition comprises 1 to 8 g whey protein per 100 g, such as 2 to 7 g whey protein per 100 g, such as 3 to 6 g whey protein per 100 g, such as 3 to 5 g whey protein per 100 g such as 3.5 to 6 g whey protein per 100 g, such as 4 to 6 g whey protein per 100 g, such as 4 to 5 g whey protein per 100 g. The composition for use according to any one of the preceding items, wherein the composition comprises 2 to 6 g whey protein per 100 g, such as 2 to 5.5 g whey protein per 100 g, such as 2 to 5 g whey protein per 100 g, such as 3 to 4.5 g whey protein per 100 g, such as 3.5 to 4.5 g whey protein per 100 g. The composition for use according to any one of the preceding items, wherein the composition comprises 1 to 6 % (v / w) whey protein, such as 2 to 5.5 % (v / w) whey protein, such as 3 to 5.5 % (v / w) whey protein, such as 3 to 5 % (v / w) whey protein, such as 3.5 to 4.5 % (v / w), such as 2.5 to 4.0 % (v / w) whey protein, whey protein such as 2.7 to 3.5 % (v / w) whey protein. The composition for use according to any one of the preceding items, wherein the composition comprises 1 to 6 % (v / w) whey protein isolate, such as 2 to 5.5 % (v / w) whey protein isolate, such as 3 to 5.5 % (v / w) whey protein isolate, such as 3 to 5 % (v / w) whey protein isolate, such as 3.5 to 4.5 % (v / w) whey protein isolate, such as 2.5 to 4.0 % (v / w) whey protein isolate, such as 2.7 to 3.5 % (v / w) whey protein isolate. The composition for use according to any one of the preceding items, wherein the composition comprises at least 0.05 g whey protein per 100 g, such as at least 0.1 g whey protein per 100 g, such at least 0.5 g whey protein per 100 g, such as at least 1 g whey protein per 100 g, such as at least 2 g whey protein per 100 g, such as at least 3 g whey protein per 100 g, such as at least 4 g whey protein per 100 g, such as at least 5 g whey protein per 100 g, such as at least 6 g whey protein per 100 g, such as at least 7 g whey protein per 100 g, such as at least 8 g whey protein per 100 g. The composition for use according to any one of the preceding items, wherein the composition comprises whey protein in the range of 0.05% to 15% (w / v) whey protein, such as 2% to 10 % (w / v) whey protein, such as 3% to 8% (w / v) whey protein, such as 4% to 5% (w / v) whey protein. The composition for use according to any one of the preceding items, wherein the whey protein is whey protein isolate and / or whey protein hydrolysate. The composition for use according to any one of the preceding items, wherein the whey protein is whey protein isolate. The composition for use according to any one of the preceding items, wherein the whey protein is whey protein hydrolysate. The composition for use according to any one of the preceding items, wherein the whey protein is bovine. The composition for use according to any one of the preceding items, wherein the composition comprises 0.05 to 15 g carbohydrate per 100 g, such as 0.5 to 13 g carbohydrate per 100 g, such as 1 to 10 g carbohydrate per 100 g, such as 1 to 8 g carbohydrate per 100 g, such as 1.5 to 7.5 g carbohydrate per 100 g, such as 1.5 to 7 g carbohydrate per 100 g, such as 2 to 6 g carbohydrate per 100 g, such as 2 to 5 g carbohydrate per 100 g, such as 2 to 4 g carbohydrate per 100 g, such as 2.2 to 3.3 g carbohydrate per 100 g. The composition for use according to any one of the preceding items, wherein the composition comprises 0.5 to 6 g carbohydrate per 100 g, such as 0.5 to 5.5 g carbohydrate per 100 g, such as 0.5 to 5 g carbohydrate per 100 g, such as 0.5 to 4.5 g carbohydrate per 100 g, such as 0.5 to 4 g carbohydrate per 100 g, such as 0.5 to 3.5 g carbohydrate per 100 g, such as 0.5 to 3 g carbohydrate per 100 g, such as 0.5 to 2.5 g carbohydrate per 100 g. The composition for use according to any one of the preceding items, wherein the composition comprises 1 to 6 g carbohydrate per 100 g, such as 1 to 4 g carbohydrate per 100 g, such as 1.5 to 6 g carbohydrate per 100 g, such as 2 to 6 g carbohydrate per 100 g, such as 2.1 to 6 g carbohydrate per 100 g, such as 2.5 to 6 g carbohydrate per 100 g, such as 3 to 6 g carbohydrate per 100 g, such as 2 to 5 g carbohydrate per 100 g, such as 1.5 to 4 g carbohydrate per 100 g, such as 1.5 to 3 g carbohydrate per 100 g. The composition for use according to any one of the preceding items, wherein the composition comprises at least 0.05 g carbohydrate per 100 g, such as at least 0.5 g carbohydrate per 100 g, such at least 1 g carbohydrate per 100 g, such as at least 1.5 g carbohydrate per 100 g, such as at least 1.6 g carbohydrate per 100 g, such as at least 1.7 g carbohydrate per 100 g, such as at least 1.8 g carbohydrate per 100 g, such as at least 1.9 g carbohydrate per 100 g, such as at least 2 g carbohydrate per 100 g, such as at least 2.1 g carbohydrate per 100 g, such as at least 2.2 g carbohydrate per 100 g, such as at least 2.3 g carbohydrate per 100 g, such as at least 2.4 g carbohydrate per 100 g, such as at least 2.5 g carbohydrate per 100 g, such as at least 2.6 g carbohydrate per 100 g, such as at least 2.7 g carbohydrate per 100 g, such as at least 2.8 g carbohydrate per 100 g, such as at least 2.9 g carbohydrate per 100 g, such as at least 3 g carbohydrate per 100 g, such as at least 4 g carbohydrate per 100 g, such as at least 5 g carbohydrate per 100 g, such as at least 6 g carbohydrate per 100 g. The composition for use according to any one of the preceding items, wherein the composition comprises carbohydrate in the range of 0.05% to 15% (w / v) carbohydrate, such as 1% to 13 % (w / v) carbohydrate, such as 1.5 % to 6% (w / v) carbohydrate, such as 2% to 4% (w / v) carbohydrate, such as 2.2% to 3.3% (w / v) carbohydrate. The composition for use according to any one of the preceding items, wherein the composition comprises carbohydrate in the range of 0.05 to 500 mmol / L, such as 0.05 to 400 mmol / L, such as 0.05 to 300 mmol / L, such as 0.05 to 200 mmol / L, such as 5 mmol to 200 mmol / L, such as 25 to 200 mmol / L, such as 50 to 200 mmol / L, such as 60 to 180 mmol / L.

[0212] 23. The composition for use according to any one of the preceding items, wherein the composition comprises carbohydrate in the range of 0.05 to 500 mmol / L, such as 60 to 180 mmol / L, such as 60 to 70 mmol / L, such as 70 to 80 mmol / L, such as 80 to 90 mmol / L, such as 90 to 100 mmol / L, such as 100 to 110 mmol / L, such as 110 to 120 mmol / L, such as 120 to 130 mmol / L, such as 130 to 140 mmol / L, such as 140 to 150 mmol / L, such as 150 to 160 mmol / L, such as 160 to 170 mmol / L, such as 170 to 180 mmol / L.

[0213] 24. The composition for use according to any one of the preceding items, wherein the carbohydrate is a monosaccharide, a disaccharide and / or a polysaccharide.

[0214] 25. The composition for use according to any one of the preceding items, wherein the carbohydrate is selected from the group consisting of glucose, saccharose, and maltodextrin.

[0215] 26. The composition for use according to any one of the preceding items, wherein the carbohydrate is glucose.

[0216] 27. The composition for use according to any one of the preceding items, wherein the composition comprises 0.05 to 500 mmol / L glucose, such as 0.05 to 400 mmol / L glucose, such as 0.05 to 300 mmol / L glucose, such as 0.05 to 200 mmol / L glucose, such as 5 mmol to 200 mmol / L glucose, such as 25 to 200 mmol / L glucose, such as 50 to 200 mmol / L glucose, such as 75 to 175 mmol / L glucose, such as 100 to 150 mmol / L glucose such as 60 to 180 mmol / L glucose.

[0217] 28. The composition for use according to any one of the preceding items, wherein the composition comprises 1 to 150 mmol / L Na+, such as 1 to 120 mmol / L Na+, such as 1 to 100 mmol / L Na+, such as 5 to 100 mmol / L Na+, such as 10 to 100 mmol / L Na+, such as 200 to 100 mmol / L Na+, such as 300 to 100 mmol / L Na+, such as 30 to 90 mmol / L Na+such as 40 to 90 mmol / L Na+, such as 50 to 90 mmol / L Na+’ such as 60 to 80 mmol / L Na+.

[0218] 29. The composition for use according to any one of the preceding items, wherein the composition comprises 1 to 150 mmol / L Na+, such as 1 to 100 mmol / L Na+, such as 10 to 100 mmol / L Na+, such as 10 to 90 mmol / L Na+such as 15 to 90 mmol / L Na+, such as 20 to 90 mmol / L Na+, such as 30 to 90 mmol / L Na+, such as 40 to 95 mmol / L Na+, such as 50 to 90 mmol / L Na+, such as 360 to 90 mmol / L Na+, such as 70 to 90 mmol / L Na+, such as 80 to 90 mmol / L Na+.

[0219] 30. The composition for use according to any one of the preceding items, wherein the composition comprises 10 to 50 mmol / L Na+, such as 15 to 50 mmol / L Na+, such as 20 to 50 mmol / L Na+, such as 30 to 50 mmol / L Na+, such as 30 to 45 mmol / L Na+, such as 33 to 45 mmol / L Na+.

[0220] 31 . The composition for use according to any one of the preceding items, wherein the composition comprises equimolar concentrations of whey protein and Na+.

[0221] 32. The composition for use according to any one of the preceding items, wherein the composition comprises 0.001 to 100 mmol / L K+, such as 0.001 to 100 mmol / L K+, such as 0.001 to 90 mmol / L K+, such as 10 to 90 mmol / L K+, such as 10 to 80 mmol / L K+, such as 10 to 70 mmol / L K+, such as 10 to 60 mmol / L K+, such as 10 to 50 mmol / L K+.

[0222] 33. The composition for use according to any one of the preceding items, wherein the composition comprises 5 to 50 mmol / L K+, such as 10 to 50 mmol / L K+, such as 10 to 45 mmol / L K+, such as 15 to 45 mmol / L K+.

[0223] 34. The composition for use according to any one of the preceding items, wherein the composition comprises 10 to 30 mmol / L K+, such as 10 to 35 mmol / L K+, such as 10 to 30 mmol / L K+, such as 15 to 25 mmol / L K+, such as 16 to 24 mmol / L K+, such as 17 to 21 mmol / L K+. 35. The composition for use according to any one of the preceding items, wherein the composition comprises 30 to 60 mmol / L K+, such as 35 to 55 mmol / L K+, such as 35 to 50 mmol / L K+, such as 35 to 45 mmol / L K+, such as 37 to 44 mmol / L K+, such as 39 to 42 mmol / L K+.

[0224] 36. The composition for use according to any one of the preceding items, wherein the composition comprises 0.001 to 40 mmol / L Mg++, such as 0.001 to 30 mmol / L Mg++, such as 0.001 to 25 mmol / L Mg++, such as 0.001 to 5 mmol / L Mg++, such as 0.001 to 3 mmol / L Mg++, such as 0.001 to 2 mmol / L Mg++, such as 0.001 to 1 mmol / L Mg++, such as 0.005 to 1 mmol / L Mg++, such as 0.005 to 0.9 mmol / L Mg++, such as 0.005 to 0.8 mmol / L Mg++, such as 0.005 to 0.7 mmol / L Mg++, such as 0.005 to 0.6 mmol / L Mg++, such as 0.005 to 0.5 mmol / L Mg++, such as 0.005 to 0.4 mmol / L Mg++such as 0.01 to 0.4 mmol / L Mg++, such as 0.2 to 0.3 mmol / L Mg++.

[0225] 37 . The composition for use according to any one of the preceding items, wherein the composition comprises 0.001 to 200 mmol / L Mg++, such as 0.001 to 100 mmol / L Mg++, such as 0.001 to 50 mmol / L Mg++, such as 0.001 to 25 mmol / L Mg++, such as 0.01 to 25 mmol / L Mg++, such as 0.1 to 25 mmol / L Mg++, such as 0.5 to 25 mmol / L Mg++, such as 1 to 25 mmol / L Mg++, such as 1 to 10 mmol / L Mg++, such as 5 to 25 mmol / L Mg++, such as 5 to 20 mmol / L Mg++, such as 10 to 25 mmol / L Mg++, such as 15 to 25 mmol / L Mg++, such as 20 to 25 mmol / L Mg++.

[0226] 38 . The composition for use according to any one of the preceding items, wherein the composition comprises 0.001 to 40 mmol / L HCO3', such as 0.001 to 30 mmol / L HCO3', such as 0.001 to 25 mmol / L HCO3', such as 0.001 to 5 mmol / L HCO3', such as 0.001 to 3 mmol / L HCO3', such as 0.001 to 2 mmol / L HCO3', such as 0.001 to 1 mmol / L HCO3', such as 0.005 to 1 mmol / L HCO3', such as 0.005 to 0.9 mmol / L HCO3', such as 0.005 to 0.8 mmol / L HCO3', such as 0.005 to 0.7 mmol / L HCO3', such as 0.005 to 0.6 mmol / L HCO3', such as 0.005 to 0.5 mmol / L HCO3', such as 0.005 to 0.4 mmol / L HCCh' such as 0.01 to 0.4 mmol / L HCO3', such as 0.2 to 0.3 mmol / L HCO3'.

[0227] 39 . The composition for use according to any one of the preceding items, wherein the composition comprises 0.001 to 200 mmol / L HCO3', such as 0.001 to 100 mmol / L HCO3', such as 0.001 to 50 mmol / L HCO3', such as 0.001 to 25 mmol / L HCO3', such as 0.01 to 25 mmol / L HCO3', such as 0.1 to 25 mmol / L HCO3', such as 0.5 to 25 mmol / L HCO3', such as 1 to 25 mmol / L HCO3', such as 5 to 25 mmol / L HCO3', such as 10 to 25 mmol / L HCO3', such as 15 to 25 mmol / L HCO3', such as 20 to 25 mmol / L HCO3'.

[0228] 40 . The composition for use according to any one of the preceding items, wherein the HCO3' is present as CO2, H2CO3, HCO3', CO3” or mixtures thereof.

[0229] 41 . The composition for use according to any one of the preceding items, wherein the composition comprises 0.001 to 50 mmol / L Ca++, such as 0.001 to 40 mmol / L Ca++, such as 0.001 to 30 mmol / L Ca++, such as 0.001 to 20 mmol / L Ca++, such as 0.001 to 10 mmol / L Ca++, such as 0.01 to 10 mmol / L Ca++, such as 0.01 to 9 mmol / L Ca++, such as 0.01 to 8 mmol / L Ca++, such as 0.01 to 7 mmol / L Ca++, such as 0.01 to 6 mmol / L Ca++, such as 0.01 to 5 mmol / L Ca++, such as 0.01 to 4 mmol / L Ca++, such as 0.01 to 3 mmol / L Ca++, such as 0.01 to 2 mmol / L Ca++, such as 0.01 to 1 mmol / L Ca++.

[0230] 42 . The composition for use according to any one of the preceding items, wherein the composition comprises 0.001 to 2 mmol / L Ca++, such as 0.01 to 2 mmol / L Ca++, such as 0.05 to 2 mmol / L Ca++, such as 0.08 to 2 mmol / L Ca++, such as 0.1 to 2 mmol / L Ca++.

[0231] 43 . The composition for use according to any one of the preceding items, wherein the composition comprises 0.001 to 2 mmol / L Ca++, such as 0.01 to 1.9 mmol / L Ca++, such as 0.01 to 1.8 mmol / L Ca++, such as 0.01 to 1.7 mmol / L Ca++, such as 0.01 to 1.6 mmol / L Ca++, such as 0.01 to 1.5 mmol / L Ca++, such as 0.05 to 1 .5 mmol / L Ca++.

[0232] 44 . The composition for use according to any one of the preceding items, wherein the composition is iso-osmolar.

[0233] 45 . The composition for use according to any one of the preceding items, wherein the composition has an osmolality between 100 to 400 mOsm / kg, such as 200 to 400 mOsm / kg, such as 210 to 350 mOsm / kg, such as 230 to 300 mOsm / kg, such as 230 to 290 mOsm / kg such as 220 to 290 mOsm / kg.

[0234] 46. The composition for use according to any one of the preceding items, wherein the composition has an osmolality between 200 to 300 mOsm / kg, such as 210 to 290 mOsm / kg, such as 220 to 280 mOsm / kg, such as 230 to 270 mOsm / kg, such as 240 to 260 mOsm / kg.

[0235] 47. The composition for use according to any one of the preceding items, wherein the composition has an osmolality between 260 to 270 mOsm / kg, such as 262 to 265 mOsm / kg.

[0236] 48. The composition for use according to any one of the preceding items, wherein the composition has an osmolality between 245 to 255 mOsm / kg, such as 246 to 250 mOsm / kg.

[0237] 49. The composition for use according to any one of the preceding items, wherein the composition has an osmolality of approximately 280 mOsm / kg.

[0238] 50. The composition for use according to any one of the preceding items, wherein the composition comprises a) whey protein, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) K+, and f) Ca++.

[0239] 51 . The composition for use according to any one of the preceding items, wherein the composition comprises a) 0.5 to 20 g whey protein per 100 g, b) 0.5 to 20 g carbohydrate per 100 g, such as glucose, c) 0.5 to 100 mmol / L Na+, d) 0.001 to 10 mmol / L Mg++, e) 0.001 to 100 mmol / L K+, f) 0.001 to 20 mmol / L Ca++.

[0240] 52 . The composition for use according to any one of the preceding items, wherein the composition comprises a) 40 to 70 g protein / 100 g dry matter, b) 20 to 50 g carbohydrate / 100 g dry matter, c) 0.5 to 2 g Na+ / 100 g dry matter, d) 0.0001 to 0.05 g Mg+7100 g dry matter, e) 0.01 to 3 g K+ / 100 g dry matter, and f) 0.01 to 1.5 g Ca++ / 100 g dry matter.

[0241] 53. A composition for use according to any one of the preceding items, wherein the composition comprises a) 0.5 to 20 g whey protein per 100 g, b) 0.5 to 20 g carbohydrate per 100 g, such as glucose, c) 0.5 to 100 mmol / L Na+.

[0242] 54. A composition for use according to any one of the preceding items, wherein the composition comprises a) 0.5 to 20 g whey protein per 100 g, b) 0.5 to 20 g carbohydrate per 100 g, such as glucose, c) 0.5 to 100 mmol / L Na+d) 0.001 to 100 mmol Mg++.

[0243] 55. The composition for use according to any one of the preceding items, wherein the composition comprises a) 2 to 5 g whey protein per 100 g, b) 1 to 4 g carbohydrate per 100 g, such as glucose, c) 20 to 90 mmol / L Na+, d) 0.001 to 25 mmol / L Mg++, e) 0.01 to 50 mmol / L K+, and f) 0.01 to 3 mmol / L Ca++.

[0244] 56. The composition for use according to any one of the preceding items, wherein the composition comprises a) 3 to 7 g whey protein per 100 g, such as 3 to 7 g whey protein isolate per 100 g, b) 90 to 130 mmol / L carbohydrate, such as glucose, c) 55 to 95 mmol / L Na+: d) 2 to 30 mmol / L Mg++, and e) optionally 5-40 mmol / L HCO3'. The composition for use according to any one of the preceding items, wherein the composition comprises a) 4 to 6 g whey protein per 100 g, such as 4 to 6 g whey protein isolate per 100 g, b) 100 to 120 mmol / L carbohydrate, such as glucose, c) 65 to 85 mmol / L Na+: d) 5 to 20 mmol / L Mg++, and e) optionally 10-30 mmol / L HCO3'. The composition for use according to any one of the preceding items, wherein the composition comprises a) 4.5 to 5.5 g whey protein per 100 g, such as 4.5 to 5.5 g whey protein isolate per 100 g, b) 105 to 115 mmol / L carbohydrate, such as glucose, c) 70 to 80 mmol / L Na+: d) 5 to 15 mmol / L Mg++, and e) optionally 15-25 mmol / L HCO3'. The composition for use according to any one of the preceding items, wherein the composition comprises a) 4.9 to 5.1 g whey protein per 100 g, such as 4.9 to 5.1 g whey protein isolate per 100 g, b) 110 to 112 mmol / L carbohydrate, such as glucose, c) 74 to 76 mmol / L Na+: d) 9 to 11 mmol / L Mg++, and optionally 19-21 mmol / L HCO3'. The composition for use according to any one of the preceding items, wherein the composition is a liquid composition and comprises a) water, b) 3 to 7 g whey protein per 100 g, such as 3 to 7 g whey protein isolate per 100 g, c) 90 to 130 mmol / L carbohydrate, such as glucose, d) 55 to 95 mmol / L Na+: e) 2 to 30 mmol / L Mg++, and f) optionally 5-40 mmol / L HCO3'. The composition for use according to any one of the preceding items, wherein the composition is a liquid composition and comprises a) water, b) 4 to 6 g whey protein per 100 g, such as 4 to 6 g whey protein isolate per 100 g, c) 100 to 120 mmol / L carbohydrate, such as glucose, d) 65 to 85 mmol / L Na+: e) 5 to 20 mmol / L Mg++, and f) optionally 10-30 mmol / L HCO3'. The composition for use according to any one of the preceding items, wherein the composition is a liquid composition and comprises a) water, b) 4.5 to 5.5 g whey protein per 100 g, such as 4.5 to 5.5 g whey protein isolate per 100 g, c) 105 to 115 mmol / L carbohydrate, such as glucose, d) 70 to 80 mmol / L Na+: e) 5 to 15 mmol / L Mg++, and f) optionally 15-25 mmol / L HCO3'. The composition for use according to any one of the preceding items, wherein the composition is a liquid composition and comprises a) water, b) 4.9 to 5.1 g whey protein per 100 g, such as 4.9 to 5.1 g whey protein isolate per 100 g, c) 110 to 112 mmol / L carbohydrate, such as glucose, d) 74 to 76 mmol / L Na+: e) 9 to 11 mmol / L Mg++, and f) optionally 19-21 mmol / L HCO3'.

[0245] 64. The composition for use according to any one of the preceding items, wherein the composition comprises additional protein, such as caseinate.

[0246] 65. The composition for use according to any one of the preceding items, wherein the composition further comprises fat.

[0247] 66. The composition for use according to any one of the preceding items, wherein the composition further comprises one or more flavours, such as vanilla, such as chocolate, such as white chocolate, such as orange and / or combinations.

[0248] 67. The composition for use according to any one of the preceding items, wherein the composition is for oral intake.

[0249] 68. The composition for use according to any one of the preceding items, wherein the composition is palatable.

[0250] 69. The composition for use according to any one of the preceding items, wherein the composition is administered, such as ingested, twice daily.

[0251] 70. The composition for use according to any one of the preceding items, wherein the composition is ingested twice daily.

[0252] 71 . The composition for use according to any one of the preceding items, wherein the composition is administered, such as ingested, for 1-8 weeks, such as 2-6 weeks, such as 3-5 weeks. 72 . The composition for use according to any one of the preceding items, wherein the composition is administered, such as ingested, twice daily for 1-8 weeks, such as 2-6 weeks, such as 3-5 weeks.

[0253] 73. The composition for use according to any one of the preceding items, wherein the composition is administered, such as ingested, twice daily for 4 weeks.

[0254] 74. The composition for use according to any one of the preceding items, wherein the composition is administered, such as ingested, for multiple weeks, such as 10, 20, 30, 40, 50 or 60 weeks.

[0255] 75. The composition for use according to any one of the preceding items, wherein the composition is administered, such as ingested, for multiple months, such as 2, 3, 4, 5, 6, 7, 8, 9 and 10 months.

[0256] 76. The composition for use according to any one of the preceding items, wherein the composition is administered, such as ingested, for multiple years, such as 2, 3, 4, 5, 6, 7, 8, 9 and 10 years, or more.

[0257] 77. The composition for use according to any one of the preceding items, wherein no food or fluid is administered and / or ingested 30 min before the composition is ingested.

[0258] 78. The composition for use according to any one of the preceding items, wherein no food or fluid is administered and / or ingested 30 min after the composition is ingested.

[0259] 79. The composition for use according to any one of the preceding items, wherein daily administration of the composition results in a daily protein supplement on 10-100 g whey protein, such as 10-80 g whey protein, such as 10-60 g whey protein, such as 10-50 g whey protein, such as 15-50 g whey protein, such as 20-50 g whey protein, such as 20-24 g whey protein. The composition for use according to any one of the preceding items, wherein daily administration of the composition results in a daily protein supplement on 10-40 g whey protein, such as 15-20 g whey protein, such as 20-25 g whey protein, such as 25-30 g whey protein, such as 30-35 g whey protein. The composition for use according to any one of the preceding items, wherein daily administration of the composition results in a daily fluid intake in the range 250-2000 ml, such as 250-1750 ml, such as 250-1500 ml, such as 250-1500 ml, such as 300-1500 ml, such as 300-800 ml, such as 400-700 ml, such as 450-600 ml, such as at least 500-550 ml. The composition for use according to any one of the preceding items, wherein daily administration of the composition results in a daily fluid intake on at least 400-500 ml, such as at least 500-600 ml, such as at least 60-700 ml, such as at least 700-800 ml, such as at least 800-900 ml, such as at least 900- 1000 ml, such as at least 100-1100 ml, such as at least 1100-1200 ml, such as at least 1200-1300 ml, such as at least 1300-1400 ml, such as at least 1400- 1500 ml, such as at least 1500-1600 ml. The composition for use according to any one of the preceding items, wherein the condition is malabsorption in patients with ileostomy. The composition for use according to any one of the preceding items, wherein the condition is malnutrition in patients with ileostomy. The composition for use according to any one of the preceding items, wherein the condition is sodium depletion in patients with ileostomy. The composition for use according to any one of the preceding items, wherein the condition is dehydration in patients with ileostomy. The composition for use according to any one of the preceding items, wherein administration of the composition results in improved nutrient absorption. 88 . The composition for use according to any one of the preceding items, wherein administration of the composition results in improved absorption of energy.

[0260] 89 . The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased dry matter ileostomy output.

[0261] 90 . The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased dry matter ileostomy output, such as a decrease on more than 5 g, such 10 g, such as 17 g, such as 20 g, such as 30 g, or more.

[0262] 91 . The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased energy loss in ileostomy output.

[0263] 92 . The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased energy loss in ileostomy output, such as an increase on more than 200 kJ, such as 300 kJ, such as 365 kJ, such as 400 kJ, such as 500 kJ or more.

[0264] 93 . The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased sodium (Na+) loss in ileostomy output.

[0265] 94 . The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased faecal potassium (K+).

[0266] 95 . The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased faecal magnesium (Mg++) on at least 2 mmol / L, such as more than 3 mmol / L, such as more than 4 mmol / L, such as more than 5 mmol / L, such as more than 6 mmol / L, such as more than 7 mmol / L, such as 7.8 mmol / L, such as more than 8 mmol / L, such as more than 10 mmol / L. The composition for use according to any one of the preceding items, wherein administration of the composition results in increased calcium (Ca++) uptake. The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased faecal calcium (Ca++). The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased faecal calcium (Ca++) on at least 2 mmol / L, such as more than 3 mmol / L, such as more than 4 mmol / L, such as more than 5 mmol / L, such as more than 6 mmol / L, such as more than 7 mmol / L, such as 7.6 mmol / L, such as more than 8 mmol / L, such as more than 10 mmol / L. The composition for use according to any one of the preceding items, wherein administration of the composition results in increased uptake of sodium (Na+). . The composition for use according to any one of the preceding items, wherein administration of the composition results in increased urinary sodium (Na+). . The composition for use according to any one of the preceding items, wherein administration of the composition results in increased uptake of magnesium (Mg++). . The composition for use according to any one of the preceding items, wherein administration of the composition results in increased urinary magnesium (Mg++). 1 03. The composition for use according to any one of the preceding items, wherein administration of the composition results in increased uptake of potassium (K+).

[0267] 1 04. The composition for use according to any one of the preceding items, wherein administration of the composition results in increased urinary potassium (K+).

[0268] 1 05. The composition for use according to any one of the preceding items, wherein administration of the composition results in increased urinary potassium (K+) of at least 5 mmol / d, such as more than 6 mmol / d, such as more than 8 mmol / d, such as more than 10 mmol / d, such as more than 12 mmol / d, such as 13.1 mmol / d, such as more than 14 mmol / d.

[0269] 1 06. The composition for use according to any one of the preceding items, wherein administration of the composition results in increased plasma bicarbonate.

[0270] 1 07. The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased intestinal losses of carbonate, such as bicarbonate.

[0271] 1 08. The composition for use according to any one of the preceding items, wherein administration of the composition results in increased Glucagon-like peptide 1 (GLP-1) secretion.

[0272] 1 09. The composition for use according to any one of the preceding items, wherein administration of the composition results in improved fluid and sodium balance.

[0273] 1 1 0. The composition for use according to any one of the preceding items, wherein administration of the composition results in decrease in P-aldosterone.

[0274] 1 1 1 . The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased P-aldosterone levels on at least 1 pmol / L, such as at least 2 pmol / L, such as at least 3 pmol / L, such as at least 4 pmol / L, such as 4.6 pmol / L, such as at least 5 pmol / L, such as at least 6 pmol / L.

[0275] 1 1 2. The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased levels of secondary hyperaldosteronism.

[0276] 1 1 3. The composition for use according to any one of the preceding items, wherein administration of the composition results in improved kidney function.

[0277] 1 1 4. The composition for use according to any one of the preceding items, wherein administration of the composition results in lower risk of metabolic acidosis.

[0278] 1 1 5. The composition for use according to any one of the preceding items, wherein administration of the composition results in improvement of bone markers.

[0279] 1 1 6. The composition for use according to any one of the preceding items, wherein administration of the composition results in improved insulin sensitivity.

[0280] 1 1 7. The composition for use according to any one of the preceding items, wherein administration of the composition results in increased bone formation.

[0281] 1 1 8. The composition for use according to any one of the preceding items, wherein administration of the composition results in improved bone health.

[0282] 1 1 9. The composition for use according to any one of the preceding items, wherein administration of the composition results in increased muscle function.

[0283] 1 20. The composition for use according to any one of the preceding items, wherein administration of the composition results in increased hand grip strength. . The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased fatigue. . The composition for use according to any one of the preceding items, wherein administration of the composition results in decreased fatigue levels, such as a decrease in fatigue score of at least 0.5 point, such as at least 1 point, such as 1 .3 points, such as at least 2 points. . The composition for use according to any one of the preceding items, wherein administration of the composition results in improved psychometry. . The composition for use according to any one of the preceding items, wherein administration of the composition results in improved reaction time stability. . The composition for use according to any one of the preceding items, wherein administration of the composition results in improved cognitive function. . A method for treating malabsorption, malnutrition, sodium depletion and / or dehydration in a subject having an ileostomy, wherein said method comprises administering to said subject a composition comprising a) whey protein, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) Optionally K+, and f) Optionally Ca++. . A method for treating malabsorption, malnutrition, sodium depletion and / or dehydration in a subject, wherein said method comprises administering to said subject a composition comprising a) whey protein, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) Optionally K+, and f) Optionally Ca++. . The method according to any one of the preceding items, wherein said composition is a liquid composition, such as an aqueous composition. . The method according to any one of the preceding items, wherein said composition is administered orally. . The composition as defined in any one of the preceding items for use in the treatment or prevention of diseases and disorders related to malabsorption and / or malnutrition. . The composition as defined in any one of the preceding items for use in the treatment or prevention of sodium depletion. . The composition as defined in any one of the preceding items for use in the treatment or prevention of dehydration. . The composition as defined in any one of the preceding items for use in the treatment or prevention of diseases and disorders related to bone health, such as osteopenia, osteoporosis and postmenopausal osteoporosis. . The composition as defined in any one of the preceding items for use in the treatment or prevention of magnesium deficiency. . The composition as defined in any one of the preceding items for use in the treatment or prevention of acid / base disorders, such as metabolic acidosis. . The composition as defined in any one of the preceding items for use in the treatment or prevention of kidney diseases caused by malnutrition and / or malabsorption. . The composition as defined in any one of the preceding items for use in the treatment or prevention of kidney diseases, such as acute and / or chronic kidney injuries, wherein the kidney disease is caused by malnutrition and / or malabsorption. Examples

[0284] Example 1 - Protein-based oral rehydration solutions for patients with an ileostomy

[0285] Abbreviations

[0286] ANOVA, one-way analysis of variance; BIA, bioelectrical impedance analysis; BMD, bone mineral density; Ca, calcium; Cl, confidence interval; CO2, carbon dioxide; COPA, Danish Ostomy Association; CRT, continuous reaction time; CTx, carboxy-terminal collagen crosslinks; d, day; DXA, dual-energy -ray absorptiometry; eGFR, estimated glomerular filtration rate; F, faecal; FFMI, fat-free Mass Index; GCP, Good Clinical Practice; GLP, glucagon-like peptide; IBD-F, Inflammatory Bowel Disease Fatigue Scale; HGS, hand grip strength; IQR, interquartile range; ITT, intention-to-treat; Mg, magnesium; Na, sodium; ORS, oral rehydration solutions; P, plasma; P1 PN, procollagen 1 intact N-terminal propeptide; PN, parenteral nutrition or fluid support; PSE, portosystemic encephalopathy; QoL, quality-of-life; REDCap, Research Electronic Data Capture; SD, standard deviation; S2S, 30-second sit-to-stand test; T2DM, type 2 diabetes mellitus; II, urine; VAS, visual analogue scale.

[0287] Methods

[0288] Study design

[0289] The data presented in this Example originates from a randomised, double-blinded, active comparator-controlled 3 x 3 crossover intervention study. The study had three interventions, and I participants were randomised in blocks of three and allocated to sequence i) ABC, ii) BCA or iii) CAB.

[0290] A medical laboratory technician generated the random allocation sequence at www.sealedenvelope.com and stored the list in a sealed envelope in the study trial master file. Sachets with the intervention product were packed offsite and labelled with numbers, and the manufacturer placed the identification list in another sealed envelope, which was also stored in the trial master file. A laboratory technician packed the sachets consecutively according to the allocation sequence without knowing the content behind each number. The participants and the investigators were blinded to the interventions, and the study was not unblinded until the statistical analyses and outcome assessments had been completed. A sample size of eight patients was needed to demonstrate a minimal relevant difference of 300 g ileostomy output / d following the interventions, assuming a standard deviation between within-patient measurements of 240 g / d, an a of 0.05 and a p of 0.8. Enrolment continued until eight participants had completed all three intervention periods. A total of 13 patients was included, of whom 10 completed all three interventions.

[0291] Participants

[0292] Eligible patients were adults (>18 years old) who had had an ileostomy for at least six months. Patients were required to have episodical or chronic sodium depletion defined by two urine samples with sodium levels <20 mmol / L, sampled at least 28 days apart, and no clinical signs of activity if they had inflammatory bowel disease. Any treatment was allowed except for systemic steroids >10 mg / day. Patients were ineligible if they received parenteral nutrition or intravenous fluid support >4,000 mL / month, had an ongoing infection (C-reactive protein above 8 mg / L or a core temperature >38.0°C) or had self-reported intolerance to dairy products, including lactose intolerance. Patients were also ineligible if unable to comprehend the trial procedures, if they were (or planned to be) pregnant, had known severe renal insufficiency (eGFR <20 mL / min) or diabetes mellitus (HbA1c >48 mmol / mol [6.5%]). Pacemakers, cochlear implants or other electrical implants excluded the participants from bioelectrical impedance analysis (BIA) measurements.

[0293] Interventions

[0294] The proteins used to develop the ORS were whey protein isolate (Lacprodan® Dl- 9224), caseinate (Miprodan® 40) and whey protein hydrolysate (Lacprodan® DI-3091). All three interventions consisted of a four-week (3-5-week) intervention period during which the participants ingested 500 mL of the intervention solution daily. The washout between interventions was >2 weeks.

[0295] The participants were instructed to dissolve sachets of intervention powder in 250 mL of tap water twice daily and not ingest anything else for at least 30 minutes before and after ingesting the mix. The ORS contained 40-48 g protein / L, 34-45 mmol sodium / L and had an osmolality of 248-270 mOsm / kg. Glucose was used to attain the same osmolality in the three intervention solutions; whey protein isolate (Lacprodan® Dl- 9224) ORS contained 32 g / L, caseinate (Miprodan® 40) ORS contained 26 g / L and whey protein hydrolysate (Lacprodan® DI-3091) ORS contained 22 g / L. The exact contents are presented in Table 1. The exact contents in the sachets varied due to production processes. The mixed solutions differed slightly with respect to look and taste, but the patients had no knowledge of which solutions contained which protein The patients were instructed to return any unused sachets so that their compliance could be assessed.

[0296] Table 1. Content in the tested protein-based ORS’s.

[0297] Content Whey Whey Casein- Caseinate Whey Whey protein protein ate vo protein protein isolate isolate vw hydrolysate hydrolysate vw vo vw vo

[0298] Energy (kJ / 100g) 123 124 124 123 121 120

[0299] Protein (g / 100g) 4.0 4.0 4.7 4.3 4.8 4.8

[0300] Glucose (g / 100g) 3.2 3.3 2.5 2.8 2.3 2.2

[0301] Fat (g / 100g) 0.02 0.01 0.05 0.05 0.02 0.02

[0302] Na+(mmol / L) 42 34 34 45 42 39

[0303] K+(mmol / L) 21 17 5 5 41 41

[0304] Mg++(mmol / L) 0.2 0.2 0.2 0.2 0.3 0.3

[0305] Ca++(mmol / L) 1 1 18 18 1 1

[0306] Osmolality 264 263 270 253 248 249

[0307] (mOsm / kg)

[0308] Content varied in sachets due to manufacturing processes. The values are calculated from duplicate analyses of two sachets of each type of ORS. Abbreviations: Ca++, calcium; K+, potassium; Mg++, magnesium; Na+, sodium; vw; vanilla and white chocolate; vo, vanilla and orange.

[0309] Outcomes

[0310] The primary outcome was ileostomy output (wet weight). Secondary outcomes were faecal (F-) electrolytes (sodium [Na], potassium [K], magnesium [Mg], calcium [Ca]), F- energy content, F-dry weight, urine (U-)volume, U-electrolytes (Na, K, Mg), II- osmolality, U-creatinine, U-carbamide, plasma (P-) electrolytes (Na, K, Mg), P- osmolality, P-aldosterone, eGFR, total venous carbon dioxide (CO2), P-creatinine, P- carbamide, P-carboxy-terminal collagen crosslinks (CTx), P-procollagen 1 intact N- terminal propeptide (P1PN), dietary intake (Na, K, Mg, Ca, kJ), palatability, body weight and composition, hand grip strength (HGS), 30-second sit-to-stand (S2S) count, QoL, fatigue and cognitive function.

[0311] Data collection and processing

[0312] The participants collected ileostomy output and urine in 3,000 mL containers (Sarstedt, Numbrecht, Germany) 24 hours before and after each of the four-week interventions and delivered it to the investigators. Ileostomy output was weighed and homogenised by mixing with demineralised H2O. The homogenate was freeze dried with a Heto Lyolab 3000 Freeze Dryer (Fisher Scientific, Loughborough, UK) and energy content was measured with an I KA C6000 oxygen bomb calorimeter (Global Standards, Staufen, Germany). F-electrolyte concentrations (Na, K, Mg, Ca) were measured with a flame atomic absorption spectrometer, PinAAcle 500 (PerkinElmer, Waltham, Massachusetts, USA).

[0313] Twelve hours before ileostomy and urine collection, the participants started to follow an individual food and fluid menu and continued on this menu during the 24-hour collection period. The 36-hour menu was tailored to each patient according to their preferences and habitual intake prior to study initiation, and the patients were instructed to follow the plan closely, to weigh their food and fluid intake on a kitchen scale and to register any deviations. The 36-hour menus were repeated before and after each intervention to minimise any variance in output caused by differences in intake. The patients received sodium sachets to use if they wanted to add sodium to their diet and returned any unused sachets to the investigators to allow for intake assessment. Dietary intake was calculated with Vitakost software (Vitakost Aps, Kolding, Denmark). The participants were asked to weigh themselves daily on a bathroom scale at home during the four-week intervention periods.

[0314] Before and after each intervention, the participants arrived at the hospital after an overnight fast (>6 hours) for blood sampling, BIA, questionnaires, psychometric tests and muscle function tests. Body composition and bone mineral density (BMD) of the lumbar spine and the femoral neck were measured once as a baseline measure by dual-energy x-ray absorptiometry (DXA). Muscle function was assessed by HGS using a digital hand dynamometer (JAMAR Plus, Patterson Medical Supply, Cedarburg, Wisconsin, USA) and a 30-second S2S. Danish sex- and age-specific reference values were used as cut-offs for HGS and S2S [Kristensen et al., 2022], BIA was measured at 50 kHz with a stand-on multi-frequency BIA (Seca mBCA 515, Seca GmbH, Hamburg, Germany).

[0315] The Inflammatory Bowel Disease Fatigue Scale (IBD-F), part I, was used to assess fatigue. The IBD-F contains five questions about fatigue rated on a Likert scale from 0- 4 [Czuber-Dochan et al., 2014], A high score indicates fatigue, and the Danish average is 7 (±3.9) points [Bager et al., 2018], The patients answered a stoma-specific QoL questionnaire (Stoma-QoL) [Prieto et al., 2005] consisting of 20 questions on a four- point Likert scale. The raw score was converted to a Stoma-QoL score from 0-100, where 100 was the best possible QoL. The mean Stoma-QoL score for Danish patients with an ileostomy is 58.8 (±12) [Rud et al., 2022], As a simple patient-reported outcome measure, the patients estimated their current QoL on a scale from 1-100, with 100 indicating the highest possible score.

[0316] Continuous reaction times (CRT) were measured by recording reaction times to 150 sound stimuli delivered at a 2-6-second interval during a 10-minutek period with EKHO software (Bitmatic, Odder, Denmark). CRT index values below 1.9 indicate a loss of reaction time stability [Lauridsen et al., 2013], The portosystemic encephalopathy (PSE) test is a five-part paper-and-pencil test battery used to assess cognitive function. Patients score between -18 to +6, and a score below -4 is pathological Weissenborn et al., 2001],

[0317] Palatability was assessed by a visual analogue scale (VAS) [Flint et al., 2000], The patients were asked to rate the taste and aftertaste of the solutions from 0-100. Higher scores indicated higher palatability. The patients were aware that we used active comparators and, at the end of the trial, they were asked to assess which treatment they perceived as more active.

[0318] Ethical statement and data handling

[0319] The study was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained before enrolment. The Good Clinical Practice (GCP) unit at the University Hospitals in Aalborg and Aarhus monitored the study (R. no. 2019-794) according to GCP principles. The Central Denmark Regional Committee on Health Research Ethics approved the study protocol (R. no.1-10-72-111-19), and the study was registered with the Danish Data Protection Agency (R. no.1-16-02-311-19) and the Danish Medicines Agency (R. no.2019054045). Additionally, the study was registered with ClinicalTrials.gov (study identifier NCT04141826) before study initiation. All data were collected and stored using Research Electronic Data Capture (REDCap) software hosted at Aarhus University (www.redcap.au.dk) [Harris et al., 2009, Harris et al., 2019],

[0320] Statistical analyses

[0321] Data analyses were conducted in ST ATA software version 17 (StataCorp. College Station, Texas, USA) and figures were made in GraphPad Prism version 9.5.1 (GraphPad Software, San Diego, California, USA).

[0322] Results are presented as mean ± standard deviation (SD) or 95% confidence intervals (95%CI) unless otherwise specified. A mixed effects model with patients and periods as random effects was used to assess the independent effects of the interventions. This model allowed us to assess each intervention and compare the three interventions, while adjusting for within-patient variability and possible sequence and period effects, and to estimate effects despite missing values. All comparisons are results from this mixed effect model unless otherwise specified. Model validation was performed by examining QQ-plots and the spread of standardised residuals versus fitted values. Data were dichotomised if the model validation still failed following log transformation. Dichotomous data were analysed using Fisher’s exact tests, Chi2tests or binary regression analyses. Continuous grouped data with only one measurement were assessed with one-way analyses of variance (ANOVA) tests. The blinding was assessed by a binominal test. The outcomes and analyses were prespecified in the protocol, but we replaced repeated measures ANOVA with a mixed effects model to be able to include patients with missing data, and we added binary tests to assess dichotomised data and two exploratory analyses (a Spearman’s correlation and a sensitivity analysis). All outcomes were analysed according to intention-to-treat (ITT).

[0323] Results

[0324] Study population

[0325] Fourteen patients with an ileostomy were included in this study of whom 13 completed at least one intervention period and were included in the analyses. The participants had a median age of 52 years (interquartile range [IQR] 47-66), and the median years with their ileostomy was 16 years (IQR 6-25) (Table 2, below). The median remaining small bowel length was 310 (IQR 258-313) cm. The remaining bowel length could not be estimated in one patient (no. 4) due to a history of multiple and extensive resections. All patients but one received no regular intravenous support. One participant (no. 5) had intestinal failure and received 1,000 mL of NaCI with magnesium sulphate once every third week. These infusions were scheduled at least two weeks before a project day to minimise any carry-over effect on the study outcome measures.

[0326] Table 2. Characteristics of patients with an ileostomy included in this study (n=13). The length of the remaining small intestines was estimated to be 350 cm if the length was not measured following surgery. #40 cm was subtracted if the patient had previously had an ileo-anal reservoir (pouch). Abbreviations: ALMI, Appendicular Lean Mass Index; BMI, Body Mass Index; Ca, calcium; F, faecal, FFMI, fat-free mass; IQR, interquartile range; K, potassium; Mg, magnesium, Na, sodium; PhA, phase angle; SD, standard deviation; ll-Na, urinary sodium excretion.

[0327] Characteristics n Summary

[0328] Age, year, median (IQR) 13 52 (47-66) Women, n (%) 13 11 (85%)

[0329] Years with ileostomy, median (IQR) 13 16 (6-25)

[0330] Indication for ileostomy, n (%) 13

[0331] Ulcerative colitis 4 (31%)

[0332] Crohn’s disease 4 (31%)

[0333] Cancer 1 (8%)

[0334] Constipation 1 (8%)

[0335] Miscellaneous 3 (23%)

[0336] Hirschsprung’s disease 1 (8%)

[0337] Diverticulitis 1 (8%)

[0338] Sigmoid volvulus 1 (8%)

[0339] Estimated bowel length, cm, median (IQR) 12 310 (258-313)

[0340] End-ileostomy with complete small bowel* 1 350

[0341] End-ileostomy after previous pouch* 4 310

[0342] End-ileostomy after ileal resection 7 285 (220-315)

[0343] Ileostomy output, g / d, mean (SD) 13 1410 (±247)

[0344] F-Na mmol / d, mean (SD) 13 147 (±32)

[0345] F-K, mmol / d, mean (SD) 13 24 (±9)

[0346] F-Mg, mmol / d, mean (SD) 13 23 (±11)

[0347] F-Ca, mmol / d, mean (SD) 13 40 (±18)

[0348] U-volume, mL / d, median (IQR) 13 979 (841-1 ,288)

[0349] U-Na, mmol / d, median (IQR) 13 12 (<10-12)

[0350] U-K, mmol / d, mean (SD) 13 73 (±33)

[0351] U-Mg, mmol / d 13 1.7 (±1.3)

[0352] Comorbidities, n (%) 13

[0353] Hypertension 1 (8%)

[0354] Renal insufficiency 1 (8%)

[0355] Osteoporosis 4 (31%)

[0356] Osteopenia 4 (31%)

[0357] Regular medications, n (%) 13 7 (54%)

[0358] Antimotility 4 (31%)

[0359] Antisecretory 5 (39%)

[0360] Prednisolone 1 (8%)

[0361] Biological 1 (8%)

[0362] Anthropometric measures

[0363] Weight, kg, mean (SD) 13 76 (±14)

[0364] BMI, kg / m2, mean (SD) 13 26.6 (±4)

[0365] PhA, degree, mean (SD) 12 4.98 (±0.7)

[0366] Resistance, 50 kHz, mean (SD) 12 665 (±88)

[0367] FFMI (BIA), kg / m2, mean (SD) 12 16.1 (±1.7)

[0368] ALMI, kg / m2, mean (SD) 10 6.5 (±1)

[0369] Ileostomy output

[0370] The mean wet-weight ileostomy output at baseline was 1,410 (± 247) g / d. In all three groups, ileostomy output, measured during 24 hours before and after each four-week intervention period, were similar following intake of 500 mL / d of solutions containing whey protein isolate, caseinate or whey protein hydrolysate (p=0.36) (Figure 1a). Dry matter ileostomy output decreased by 17 g / d (95%CI , -30 to -3, p=0.018) following intake of the ORS with whey protein isolate, but no overall differences were observed between the three interventions (p=0.16). Energy loss in the ileostomy output decreased by -365 kJ / d (95%CI, -643 to -87, p=0.012) following whey protein isolate ORS, but the difference between the interventions was not statistically significant (p=0.20) (Figure 1 b). Sodium loss in the ileostomy output (F-Na) did not differ between the interventions (p=0.85) (Figure 1c). Faecal potassium (F-K) loss dropped by 7.8 mmol / L (95%CI , -12.0 to -3.6, p=0.001) following whey protein isolate ORS, and the overall difference in intestinal potassium loss between treatments was statistically significant (p=0.016) (Figure 1d). F-Mg loss was -4.0 mmol / L lower after whey protein isolate ORS (95%CI , -7.4 to -0.7, p=0.020), but no overall differences were observed between the interventions (p=0.11 ) (Figure 1e). F-Ca was 7.6 mmol / L lower after whey protein isolate ORS (95%CI, -14.0 to -1.2, p=0.023), and the differences between the interventions were statistically significant (p=0.020) (Figure 1f).

[0371] Urinary output

[0372] At baseline, U-Na was below the detection limit (<10 mmol / d) in six patients, and U-Mg was low (<3.3 mmol / d) in nine patients. When comparing all three interventions, we observed no statistically significant differences in Urine volume (U-volume) (p=0.20) (Figure 2a) or in urinary sodium (U-Na) (Fishers’ exact test, p=1.00) (Figure 2b). A sensitivity analysis applying cut-offs at 10, 20 and 50 mmol Na / d also did not reveal any changes (Table 3, below). Urinary potassium (U-K) increased by 13.1 mmol / d (95%CI, 2.2 to 24.1) after whey protein hydrolysate ORS (p=0.020) (Figure 2c), but no overall differences were observed between the interventions (p=0.15). No individual treatment effects or overall differences were observed between the interventions in urinary magnesium (U-Mg) excretion (p=0.67) (Figure 2d). Additional urinary outputs are listed in Table 4, (p. 60).

[0373] Table 3. Urinary sodium excretion before and after four-week interventions with either whey protein isolate, caseinate or whey protein hydrolysate, dichotomised with cut-offs at 10, 20 and 50 mmol / d. Abbreviations: U-Na, urinary sodium excretion.

[0374] Whey protein Caseinate Whey protein isolate hydrolysate U-Na Baseline Week 4 p Baseline Week p Baseline Week 4 p

[0375] 4

[0376] <10 mmol / d 8 7 7 6 5 4

[0377] >10 mmol / d 4 5 5 6 7 7

[0378] 1.00 1.00 1.00

[0379] <20 mmol / d 11 9 11 9 10 6

[0380] >20 mmol / d 1 3 1 3 2 5

[0381] 0.59 0.59 0.19

[0382] <50 mmol / d 11 12 11 10 11 11

[0383] >50 mmol / d 1 0 1 2 1 0

[0384] 1.00 1.00 1.00

[0385] Biochemistry

[0386] At baseline, median P-aldosterone was 9,151 (IQR 1,401-11,656) pmol / L, and ten patients were above the reference threshold of 1,197 pmol / L. P-aldosterone decreased by 4,674 pmol / L following whey protein isolate ORS (95%CI , -8,536 to -812, p=0.019) (Figure 3a). P-aldosterone did not differ significantly between interventions (p=0.11 ). A positive correlation was found between F-K and P-aldosterone (Spearman’s Rho=0.59, p=0.035, n=13). The mean baseline P-Na was 138 (±3) mmol / L, and P-Na tended to increase following the ORS with whey protein isolate (1 mmol / L, 95%CI , 0 to 2, p=0.054), but no overall differences were seen between the interventions (p=0.65) (Figure 3b). Median baseline eGFR was 86 (IQR 48-90), which increased 2.8 mL / min / 1.73m2following whey protein isolate ORS (95%CI, 0.3 to 5.4, p=0.03), but with no overall difference between the interventions (p=0.35) (Figure 3c). The mean baseline total venous P-CO2 was 24.9 (±3.8), which increased by 1.7 mmol / L following whey protein isolate ORS (95%CI , 0.1 to 3.3, p=0.04), but no overall differences were found between the interventions (p=0.93) (Figure 3d).

[0387] Mean P-P1PN was 60.5 pg / L at baseline, and one patient had levels below the sex- and age-specific reference ranges. The median baseline P-CTx was 0.61 pg / L. One patient was below the sex- and age-specific reference range, and three patients were above.

[0388] Both bone markers improved statistically significantly following whey protein isolate ORS (Table 4, p. 60), suggesting that both ileostomy patients, and other patients suffering for malnutrition-related diseases and disorders, patients with osteoporosis or osteopenia, would benefit from the whey-based ORS. Bioimpedance analyses

[0389] At baseline, the mean body weight was 75 (±14) kg. Body weight did not change following either of the interventions, and no differences were found between the interventions (p=0.75) (Table 4, p. 60). Whole-body resistance at 50 kHz tended to decrease by 21 Q (95%CI , -43 to 1) following caseinate ORS (p=0.06), but no overall differences were found between the three interventions (p=0.50).

[0390] Muscle function

[0391] At baseline, the median 30-second S2S count was 17 (IQR 14-21), and all patients were above the minimal sex- and age-specific reference range. S2S increased statistically significantly following all three interventions, by 1.6-1.8 S2S (Table 4, p. 60); and no overall difference was seen between the interventions (p=0.98).

[0392] The mean HGS (hand-grip strength) was 33.7 (±8.5) kg at baseline and two patients had values below the minimal sex- and age-specific cut-off. HGS improved by 2.3 kg (95%CI, 0.4 to 4.1) following intake of whey protein hydrolysate ORS (p=0.016), but the difference between the three interventions was not statistically significant (p=0.08) (Table 4, p. 60).

[0393] Quality of life, fatigue and psychometry

[0394] Stoma-QoL was 61.7 (±7) at baseline and did not change following the interventions (Table 4, p. 60). The patients’ baseline fatigue score was 8.5 (±4), and seven (54%) were above the Danish average of 7 points, indicating increased fatigue levels. Fatigue scores decreased by 1.3 points (95%CI, -2.5 to -0.004) after ORS with whey protein hydrolysate (p=0.049), but no overall differences were seen between the interventions (p=0.37).

[0395] The mean CRT (continuous reaction time) index was 1.842 at baseline, and four participants were below the minimal threshold of 1.9 points, indicating impaired reaction time stability. At baseline, the patients had median PSE (portosystemic encephalopathy) scores of 1 (IQR 0-1), and all participants had baseline scores above the minimal cut-off of -4 points. PSE improved by one point following whey protein isolate ORS (p=0.020) and by 1.8 points following whey protein hydrolysate ORS (p<0.001). The overall difference in PSE between interventions was statistically significant (p=0.025), favouring ORS with whey protein hydrolysate. Table 4. Indicators of changes in absorption or fluid / electrolyte balance between before and after four-week interventions with either whey protein isolate, caseinate or whey protein hydrolysate. A values are differences between pre- and post-intervention measurements adjusted for intra-patient variability, period and sequence of treatments. Abbreviations: 30 second S2S, 30 second sit-to-stand, FFMI, fat-free mass index; CRT, continuous reaction times; CTX, P-carboxy-terminal collagen crosslinks, P1 PN, P- procollagen 1 intact N-terminal propeptide, PSE, portosystemic encephalopathy; QoL, quality-of-life. _

[0396] Whey protein _ Whey protein Between

[0397] Caseinate isolate hydrolysate treatments

[0398] A 95% Cl p- A 95% Cl p- A 95% Cl p- p-value value value value

[0399] Urine

[0400] Creatinine 0.4 (-0.5 to 0.35 0.3 (-0.5 to 0.57 0.2 (-0.7 to 0.65 0.93

[0401] (mmol / d) 1.3) 1.1) 1.1)

[0402] Carbamide 106 (67 to <0.001 93 (54 to <0.001 116 (76 to <0.001 0.69

[0403] (mmol / d) 146) 132) 156)

[0404] Osmolality 108 (47 to 0.001 27 (-36 to 0.38 58 (-5 to 0.06 0.18

[0405] (mOsm / kg) 169) 91) 122)

[0406] Plasma

[0407] Osmolality 1.7 (-0.9 to 0.20 0.9 (-1.7 to 0.50 2.4 (-0.3 to 0.08 0.74

[0408] (mOsm / kg) 4.3) 3.5) 5.0)

[0409] Creatinine -8.3 (-15.6 to 0.029 -0.8 (-8.1 to 0.84 0.7 (-6.9 to 0.85 0.19

[0410] (pmol / L) -0.9) 6.6) 8.3)

[0411] Carbamide -0.3 (-2.1 to 0.71 0.7 (-1.1 to 0.45 1.2 (-0.7 to 0.20 0.48

[0412] (mmol / L) 1.5) 2.5) 3.0)

[0413] Renin -38 (-65 to - 0.006 -10 (-37 to 0.47 -13 (-41 to 0.34 0.26

[0414] (int.enh. / L) 12) 17) 14)

[0415] Potassium 0.1 (-0.1 to 0.19 0.0 (-0.2 to 0.61 0.0 (-0.2 to 0.60 0.32

[0416] (mmol / L) 0.3) 0.1) 0.1)

[0417] Albumin (g / L) 1.3 (-0.4 to 0.32 1.8 (0.2 to 0.032 1.4 (-0.3 to 0.12 0.87

[0418] 2.9) 3.5) 3.1)

[0419] Insulin (pmol / L) - (-30.5 to 0.028 - (-35.0 to 0.08 - (-34.5 to 0.11 0.90

[0420] 20.9 -2.4) 16.4 2.1) 15.5 3.6)

[0421] C-peptide -3.4 (-6.1 to - 0.001 -1.3 (-3.2 to 0.19 -0.4 (-2.4 to 0.67 0.047

[0422] (pmol / L) 1.9) 0.7) 1.6)

[0423] P1 NP (pg / L) 13.8 (4.3 to 0.006 5.0 (-4.6 to 0.30 4.1 (-5.7 to 0.40 0.29

[0424] 23.4) 14.6) 14.0)

[0425] CTx (pg / L) - (-0.21 to 0.017 - (-0.14 to 0.29 0.03 (-0.06 to 0.50 0.10

[0426] 0.12 -0.02) 0.05 0.04) 0.13)

[0427] BIA

[0428] Body weight 0.2 (-0.3 to 0.42 0.4 (-0.1 to 0.14 0.5 (-0.1 to 0.08 0.75

[0429] (kg) 0.8) 1.1) 1.1)

[0430] Phase angle - (-0.26 to 0.30 - (0.29 to 0.15 0.01 (-0.16 to 0.89 0.51

[0431] (degrees) 0.09 0.08) 0.12 0.05) 0.19)

[0432] Resistance 50 -13 (-34 to 9) 0.24 -21 (-43 to 0.06 -3 (-25 to 0.78 0.50 kHz (Q) 1) 19)

[0433] Reactance 50 -2 (-6 to 2) 0.26 -3 (-7 to 0) 0.07 0 (-4 to 3) 0.87 0.50 kHz (Q) FFMI (kg / m2) 0.1 (-0.2 to 0.40 0.2 (-0.1 to 0.16 0.0 (0.3 to 0.79 0.72

[0434] 0.4) 0.5) 0.4)

[0435] Muscle function

[0436] 30 second S2S 1.8 (0.3 to 0.018 1.6 (0.2 to 0.031 1.8 (0.3 to 0.021 0.98

[0437] (count) 3.2) 3.0) 3.2)

[0438] HGS (kg) -0.5 (-2.2 to 0.56 1.5 (-0.3 to 0.10 2.3 (0.4 to 0.016 0.08

[0439] 1.2) 3.3) 4.1)

[0440] QoL, fatigue and psychometry

[0441] Stoma-QoL 0.4 (-1.6 to 0.69 1.0 (-1.0 to 0.30 0.0 (-2.1 to 0.99 0.77

[0442] 2.4) 3.0) 2.1)

[0443] Self-evaluated 1.7 (-5.4 to 0.64 3.1 (-7.2 to 0.38 0.1 (-7.2 to 0.99 0.83

[0444] QoL 8.7) 7.4) 7.4)

[0445] Fatigue -0.1 (-1.3 to 0.89 -0.3 (-1.6 to 0.58 -1.3 (-2.5 to 0.049 0.37

[0446] 1.1) 0.9) 0.0)

[0447] PSE score 1.00 (0.17 to 0.020 0.12 (-0.70 to 0.77 1 .79 (0.93 to <0.001 0.025

[0448] 1.83) 0.94) 2.64)

[0449] CRT index - (-0.30 to 0.47 0.08 (-0.14 to 0.43 0.08 (-0.14 to 0.50 0.45

[0450] 0.08 0.14) 0.30) 0.30)

[0451] Safety, palatability and assessment of blinding

[0452] During the project period, 13 adverse events and four serious adverse events were reported. None were considered to have any relation to the interventions, which were well-tolerated.

[0453] The ORS with whey protein isolate was the most palatable of the three intervention solutions, with a mean VAS score of 84 (±14). Caseinate ORS scored 76 (±18) and ORS with whey protein hydrolysate scored 43 (±25). Whey protein hydrolysate ORS was statistically significantly less palatable than whey protein isolate and caseinate ORS (ANOVA, p<0.001). The participants rated the aftertaste similarly as the taste; 81 (±19) for whey protein isolate, 73 (±19) for caseinate and whey protein hydrolysate had a statistically significantly less palatable aftertaste (42 [±24], p<0.001).

[0454] Five participants believed that ORS with whey protein isolate was the most active treatment, five participants thought that caseinate ORS was the most active treatment and three participants believed that whey protein hydrolysate ORS was the most active treatment.

[0455] Glucagon-like peptide 1 secretion

[0456] The secretion of the hormone Glucagon-like peptide 1 (GLP-1) was measured at specific time intervals for six hours following ingestion of respectively 500 mL of whey protein isolate ORS (WPI), caseinate ORS (Cas) and whey protein hydrolysate ORS (WPH) in 13 patients with an ileostomy. All participants were fasting for at least 6 hours prior to the interventions, and both participants and investigators were blinded.

[0457] The urine acid-base balance was measured before and after a 4-week intervention with the WPI-based ORS and compared the baseline results with healthy controls.

[0458] As presented in Figure 4, secretion of GLP-1 increases significantly more following ingestion of the WPI-based ORS, than respectively the two interventions, Cas and WPH. Increased GLP-1 secretion causes beneficial effects in ileostomy patients, both in terms of suppression of gastric emptying and gastric acid secretion, which potentially decreases ileostomy output.

[0459] Urine pH, urine ammonium excretion and acid excretion

[0460] As presented in Figure 5, patients with an ileostomy generally have lower urine pH (5A), higher excretion of ammonium (5B), higher titratable acid excretion (5C), and higher urinary net excretion of acids (5D) compared with healthy controls. The effects are a result of high losses of bicarbonate in the ileostomy output, and results in an increased risk of metabolic acidosis.

[0461] As presented in Figure 6, treated of patients with an ileostomy with WPI-based ORS for four weeks, resulted in diverging changes in urine pH (6A), numerically higher urine ammonium excretion (6B), and higher excretion of titratable acids (6C) and net acid excretion (6D). The effects are a result of a combination of an increased acid load from the protein-based ORS and a decreased loss of bicarbonate in the ileostomy output.

[0462] Acid production

[0463] As presented in Figure 7, net endogenous acid production increases following WPI treatment (7A). The association between net endogenous acid production and net acid excretion follows similar slopes at baseline and following treatment, however with different y-interceptions, implying a reduced need for acid excretion (7B), which likely is related to a reduced loss of intestinal hydrogen carbonate (bicarbonate) following WPI treatment, of approximately -11 mmol / day (70). This supports the interpretation that intake of WPI-ORS results in reduced losses of bicarbonate in the ileostomy output, and protection of the body’s acid-base balance, with decreased strain on the kidneys. solutions for

[0464] Study with WPI recipe version 2.3

[0465] Based on experience from the first study (Example 1), an updated WPI ORS recipe (version 2.3) was prepared and tested in a study.

[0466] The version 2.3 recipe is a ready- to-d rink solution) with the following contents: o Whey protein isolate: 5 g / 100g (resulting in a protein content of 4.5% (w / v)) o Glucose: 111 mmol / L o Sodium: 75 mmol / L o Magnesium: 10 mmol / L o Bicarbonate: 21 mmol / L o Water

[0467] Four patients with an ileostomy participated in the study with the WPI recipe version 2.3. The participants ingested 1000 ml / day, during 5-7 days. Blood and urine were collected before (baseline) and after treatment, along with a short survey to assess palatability and tolerability.

[0468] Results:

[0469] Palatability

[0470] On a visual analog scale, where high scores indicate good taste, the four participants rated the palatability a median of 77 mm of 100 (range 34-100) (Figure 8).

[0471] None of the four participants reported any challenges or adverse advents after drinking 1000 mL / d of the WPI ORS version 2.3. Two participants noted that it was easy to make (compared with regular homemade rehydration solutions). One participant reported that the new solution gave a faster relief of dehydration symptoms than regular homemade rehydration solutions.

[0472] Urine volume, Urine sodium, Plasma Aldosterone, Total plasma CO2, Plasma hydrogen carbonate and Base excess.

[0473] Urine volume increased in three of four participants (Figure 10A), and the urine sodium excretion increased in all participants (Figure 10B). The median increase in urine volume and urine sodium excretion was 605 ml / day (Figure 10A) and 36.5 mmol / day (Figure 10B), indicate improved fluid and sodium balance.

[0474] Plasma Aldosterone decreased in four participants (Figure 10C). The median plasma aldosterone reduction was 444 pmol / L (Figure 10C), also indicating that the participant's fluid and sodium balances improved.

[0475] Total plasma CO2 increased in all participants (Figure 10D), the plasma hydrogen carbonate (bicarbonate) increased in all participants (Figure 10E), and the base excess increased in all participants (10F). The median increase in plasma total carbon dioxide was 5 mmol / L (Figure 10D), for hydrogen carbonate the median increase was 2.9 mmol / L (Figure 10E), and the median increase for base excess was 2.9 mmol / L (Figure 10F), indicating reduced metabolic acidosis.

[0476] The updated WPI recipe (version 2.3) comprises carbonate, unlike the WPI ORS of Example 1. When including the ingested hydrogen carbonate in the calculation of estimated intestinal hydrogen carbonate losses, an approximate decrease of =13 mmol / d is observed (Figure 9).

[0477] Overall, the results indicate that also the updated WPI-based ORS (recipe version 2.3) reduces intestinal losses of hydrogen carbonate in patients with an ileostomy.

[0478] Urine pH, Urine ammonium excretion, Excretion of titratable acids and Urine net acid excretion

[0479] Urine pH (Figure 11 A) and urine ammonium excretion (Figure 11 B) had diverging directions following WPI-version 2.3, as also observed in Example 1. Excretion of titratable acids (Figure 11C) and urine net acid excretion (Figure 11 D) both decrease following intake of WPI recipe 2.3.

[0480] Additional data

[0481] The bone-health marker P-Procollagen 1 (P1 NP) increased by a median of 4.5 pg / L following intake of the updated WPI recipe 2.3, indicating increased bone formation, similar the results presented in Example 1. Table 5. P1NP Data. WPI OPS recipe version 2.3.

[0482] Minimum P25 Median P75 Maximum

[0483] P1 NP -2.000 -0.750 4.500 9.000 10.000

[0484] Conclusion

[0485] The results of Example 1 indicate that among three chosen protein types (whey protein isolate, caseinate, and hydrolyzed whey protein), whey protein isolate not only results in the net best improvement of fluid and electrolyte status but also seems to have beneficial endocrine (GLP-1) and bone-related properties.

[0486] The results obtained for the updated WPI ORS recipe (version 2.3), with specific additions of sodium, hydrogen carbonate (bicarbonate), and magnesium, further demonstrate improvements of electrolyte absorption, indicating specific and beneficial properties including decreased intestinal losses of hydrogen carbonate. Finally, the test persons found the test product palatable, and easy to manage.

[0487] References

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Claims

Claims1. A liquid composition for use in the treatment of a condition selected from malabsorption in patients with ileostomy, malnutrition in patients with ileostomy, sodium depletion in patients with ileostomy and / or dehydration in patients with ileostomy, wherein said composition comprises a) whey protein, such as whey protein isolate, b) carbohydrate, such as glucose, c) Na+, d) Mg++, e) water, f) optionally K+, and g) optionally Ca++.

2. The liquid composition for use according to any one of the preceding claims, wherein the water is tap water.

3. The liquid composition for use according to any one of the preceding claims, wherein the composition has an osmolality between 200 to 350 mOsm / kg, such as between 220 to 320 mOsm / kg, such as 230 to 300 mOsm / kg, such as 230 to 290 mOsm / kg,4. The liquid composition for use according to any one of the preceding claims, wherein the composition comprises 1 to 8 g whey protein per 100 g, such as 2 to 7 g whey protein per 100 g, such as 3 to 6 g whey protein per 100 g, such as 3.5 to 6 g whey protein per 100 g, such as 4 to 6 g whey protein per 100 g, such as 4 to 5 g whey protein per 100 g.

5. The liquid composition for use according to any one of the preceding claims, wherein the whey protein is whey protein isolate.

6. The liquid composition for use according to any one of the preceding claims, wherein the composition comprises 1 to 7 g carbohydrate per 100 g, such as 1 to 6 g carbohydrate per 100 g, such as 1 to 5 g carbohydrate per 100 g, such as1 to 4 g carbohydrate per 100 g, such as 2 to 4 g carbohydrate per 100 g, such as 2 to 3.5 g carbohydrate per 100 g.

7. The liquid composition for use according to any one of the preceding claims, wherein the carbohydrate is glucose.

8. The liquid composition for use according to any one of the preceding claims, wherein the composition comprises 10 to 70 mmol / L Na+, such as 10 to 60 mmol / L Na+, such as 10 to 50 mmol / L Na+, such as 15 to 50 mmol / L Na+, such as 20 to 50 mmol / L Na+, such as 30 to 50 mmol / L Na+, such as 30 to 45 mmol / L Na+, such as 33 to 45 mmol / L Na+.

9. The liquid composition for use according to any one of the preceding claims, wherein the composition comprises 0.01 to 2 mmol / L Mg++, such as 0.01 to 1 mmol / L Mg++, such as 0.05 to 1 mmol / L Mg++, such as 0.05 to 0.9 mmol / L Mg++, such as 0.05 to 0.8 mmol / L Mg++, such as 0.05 to 0.7 mmol / L Mg++, such as 0.05 to 0.6 mmol / L Mg++, such as 0.05 to 0.5 mmol / L Mg++, such as 0.05 to 0.4 mmol / L Mg++such as 0.1 to 0.4 mmol / L Mg++, such as 0.2 to 0.3 mmol / L Mg++.

10. The liquid composition for use according to any one of the preceding claims, wherein the composition comprises 0.001 to 50 mmol / L K+, such as 0.01 to 50 mmol / L K+, such as 0.1 to 50 mmol / L K+, such as 1 to 50 mmol / L K+, such as 5 to 50 mmol / L K+, such as 10 to 50 mmol / L K+, such as 10 to 45 mmol / L K+, such as 15 to 45 mmol / L K+.11 . The liquid composition for use according to any one of the preceding claims, wherein the composition comprises 0.001 to 2 mmol / L Ca++, such as 0.01 to 2 mmol / L Ca++, such as 0.1 to 1.9 mmol / L Ca++, such as 0.1 to 1.8 mmol / L Ca++, such as 0.1 to 1.7 mmol / L Ca++, such as 0.1 to 1.6 mmol / L Ca++, such as 0.1 to 1 .5 mmol / L Ca++, such as 0.5 to 1 .5 mmol / L Ca++.

12. The liquid composition for use according to any one of the preceding claims, wherein the composition comprises a) 3 to 6 g whey protein isolate per 100 g, b) 2 to 5 g carbohydrate per 100 g, such as glucose,c) 20 to 50 mmol / L Na+, d) 0.05 to 1 mmol / L Mg++, e) 10 to 50 mmol / L K+, f) 0.5 to 3 mmol / L Ca++; and g) water.

13. The liquid composition for use according to any one of the preceding claims, wherein daily administration of the composition results in a daily protein supplement on 25-35 g whey protein.

14. The liquid composition for use according to any one of the preceding claims, wherein the composition is for oral intake.

15. The liquid composition for use according to any one of the preceding claims, wherein administration of the composition results in improved nutrient absorption, improved absorption of energy and / or decreased dry matter ileostomy output.

16. The liquid composition for use according to any one of the preceding claims, wherein the composition comprises a) water, b) 4 to 6 g whey protein per 100 g, such as 4 to 6 g whey protein isolate per 100 g, c) 100 to 120 mmol / L carbohydrate, such as glucose, d) 65 to 85 mmol / L Na+: e) 5 to 20 mmol / L Mg++, and f) optionally 10-30 mmol / L HCCh'.

17. A liquid composition comprising a) water, b) 4 to 5 g whey protein per 100 g, c) 2 to 3.5 g glucose per 100 g, d) 30 to 45 mmol / L Na+, e) 0.2 to 0.3 mmol / L Mg++, f) 15 to 45 mmol / L K+,g) 0.9 to 1.1 mmol / L Ca++.

18. A liquid composition comprising a) water, b) 4 to 6 g whey protein per 100 g, such as 4 to 6 g whey protein isolate per 100 g, c) 100 to 120 mmol / L carbohydrate, such as glucose, d) 65 to 85 mmol / L Na+: e) 5 to 20 mmol / L Mg++, and f) optionally 10-30 mmol / L HCOa'.

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