Nutritional and health benefits of semi-elemental diets: A comprehensive summary of the literature

Table 1 Selected studies of semi-elemental whey hydrolyzed protein diets and Crohn’s disease and other gastrointestinal complications

Ref.	Study population	Design	Feeding mode (comparison)	No. patients (comparison)	Feeding duration	Relevant results1
Polk et al[11]	Children, tanner stage I-II, mean age 13.6	Prospective cross-over	Isotonic hydrolyzed whey formula administered via nocturnal nasogastric infusion (patients served as their controls based on observations at least a year before the study)	6 (6, served as own controls)	Intermittent diet program for 1 yr	Height increased 2.6 ± 0.8 to 9.3 ± 0.9 cm/yr (P < 0.0001) Weight increased 3.0 ± 1.2 to 6.63 ± 1.2 kg/yr (P < 0.02) Somatomedin C increase 0.7 ± 0.1 to 1.8 ± 0.3 UL (P < 0.0001) Albumin increase 3.4 ± 0.2 to 4.0 ± 0.1 g/dL (P < 0.0003) CDAI increase 64 ± 3.4 to 80.1 ± 2.2 (P < 0.01) (disease activity inversely correlates with numerical score)
Hussey et al[13]	Children with active CD, mean age 11.4	Prospective, NR, open-label pilot	Peptamen with Prebio via nasogastric tubes	10 - single group	6 wk	Height increased 143.8 ± 13 to 144.5 ± 13.1 cm (P < 0.01) Weight increases 31.9 ± 7.2 to 36.5 ± 8.1 kg (P < 0.0001) PCDAI decrease 40 ± 13 to 5 ± 6 (P < 0.0001) (lower score corresponds to lower disease activity) Albumin increase 3.1 ± 0.4 to 3.8 ± 0.4 g/dL (P < 0.01) PEDIBDQ increase 198 ± 31 to 243 ± 34 (P < 0.01) (higher score indicating better quality of life)
Royall et al[14]	Adults with moderate to severely active CD	RCT	Peptamen administered via a nasoduodenal feeding tube (Vivonex-TEN, amino acid based formula)	21 (19)	3 wk	Remission rates after 3 wk: 75% in the peptide group, 84% in the amino acid group Remission rates after 1 yr: 40% in the peptide group, 31% in the amino acid group Weight increased 2.0 ± 0.5 kg in the peptide group and 1.7 ± 0.3 kg in the amino acid group (P < 0.0005 within group differences after 3 wk) Total phospholipids (mg/mL) concentration increase in the peptide group (1.37 ± 0.1 to 1.71 ± 0.15) (P < 0.025) (no difference in amino acid group)
Mansfield et al[15]	Adults with active CD	RCT	Pepti-2000 LF Liquid received through nasogastric tube (Elemental 028)	22 (22)	4 wk	Remission rates after 4 wk: 36% in the Pepti-2000 group and 36% in the E028 group Mean percent ideal body weight: Pepti-2000 group increased from 92 ± 4 to 95 ± 4 and E028 group remained the same at 83 ± 5
Middleton et al[16]	Adults with active CD	RCT	Pepdite 2+ given orally or through nasogastric tube if necessary (Elemental 028/Elemental 028 + LCT/Elemental 028 + MCT)	18 (17/22/19)	3 wk	Remission rates after 3 wk: 87% in Pepdite 2+ group, 92% in the E028 group, 55% in the E028 LCT group, and 92% in the E028 MCT group Mean CRP: Decreased significantly in E028 group and E028 MCT group, but non-significantly decreased in Pepdite 2+ group and E028 LCT group (values not provided)
Zoli et al[17]	Adults with moderately active CD	RCT	Peptamen received orally (0.5 mg/kg per day prednisolone)	10 (10)	2 wk	Peptide group: CD activity score (CDAS): 5.6 ± 0.8 to 2 ± 1.4 (P < 0.01) ESR: 21.4 ± 6 to 16.7 ± 6.7 (P < 0.05) Permeability index: 4.9 ± 5.3 to 2.1 ± 2 (P < 0.01) BMI: 18.5 ± 3 to 19.2 ± 3.1 (P < 0.02) Prealbumin: 22.2 ± 8 to 23.5 ± 7.8 (P < 0.01) Retinol binding protein: 3.7 ± 0.7 to 4 ± 0.8 (P < 0.02) In vivo cell-mediated immunity (Multitest IMC): 4.2 ± 2.1 to 5.9 ± 2.3 (P < 0.01) (in the corticosteroid group, there were significant findings for improvement of simple CD activity index and fat free mass)
Pereira et al[18]	Adults with mildly active CD and healthy laboratory staff	Follow-up study (secondary study)	Peptamen received orally (0.5 mg/kg per day prednisolone)	13 CD patients (17 healthy controls)	2 wk	No significant differences between groups in clinical response to treatment, markers of disease activity, or plasma phospholipid classes (data not reported)
Malchow et al[19]	Adults with active CD	RCT	Survimed given orally (12-48 mg/d 6-methyl prednisolone and 3 g/d sulfasalazine)	51 (44)	6 wk	Percent underweight after 3 wk: 15.1% in Survimed group and 13.4% in steroid group Crohn’s disease activity index after 3 wk: 87.2 in Survimed group and 88.8 in steroid group Number of soft stools per week after 3 wk: 43.2 in Survimed group and 60.0 in steroid group
Lochs et al[20]	Adults with acute active CD	RCT	Peptisorb received through nasogastric tube (12-48 mg/d 6-methyl prednisolone and 3 g/d sulfasalazine)	55 (52)	6 wk	Remission rates after 6 wk: 52.7% in the Peptisorb group and 78.8% in the steroid group (P < 0.01) Body weight: increased in Peptisorb group from 55.6 ± 1.8 kg to 58.9 ± 1.6 kg, and increased in steroid group from 53.5 ± 1.3 kg to 56.8 ± 1.2 kg after treatment Number of soft stools per week: Decreased in Peptisorb group from 31.9 ± 4.3 to 9.7 ± 1.8 and decreased in steroid group from 37.1 ± 2.9 to 9.4 ± 1.5 after treatment
Lindor et al[21]	Adults with active CD	RCT	Vital HN received orally or through nasogastric tube if necessary (0.75 mg/kg per day prednisone)	9 (10)	1 mo	Decrease in Crohn’s disease activity index of 50 points or more after 1 mo: 33% in vital HN group and 70% in steroid group
Sakurai et al[22]	Adults with active CD	RCT	Twinline received through nasogastric tube (Elental)	18 (18)	6 wk	Remission rates after 6 wk: 72% (47%-90%) in Twinline group and 67% (41%-87%) in the Elental group Crohn’s disease activity index after 6 wk: 82 in Twinline group and 102 in Elental group
Khoshoo et al[5]	Children with gastrointestinal dysmotility (n = 9), CD (n = 3), mild short bowel syndrome (n = 2)	Randomized, double-blind, cross-over clinical study	Peptamen Junior and Peptamen Junior with fiber and prebiotics	14	1 formula for 2 wk, 5 d washout, 2nd formula for 2 wk	Flatulence/gas among 9 children with a neurological disorder: Significantly less for the fiber formula (P < 0.05) Frequency of bowel movements: No difference between groups (P > 0.05) Stool frequency in the CD group: Higher with the fiber formula but no change in consistency (data not reported)
Parekh et al[23]	Patients undergoing intestinal rehab with varying diseases [radiation enteritis (n = 5), ulcerative colitis (n = 1), bowel volvulus (n = 1), mesenteric ischemia (n = 1)]	Cross-over study	Semi-elemental/polymeric diet with a switch to an isocaloric, isotonic, semi-elemental formula with prebiotics	2 (6)	4.9 mo after an initiation of 60 d post-abdominal resection; second diet for a mean of 2.9 mo	Weight change: Mean loss of 5.1% in the semi-elemental/polymeric group, mean gain of 5.7% in the isocaloric, isotonic, semi-elemental formula with prebiotics group
Hamaoui et al[10]	Patients undergoing major abdominal surgery	Randomized prospective study	Reabilan HN, small peptide based formula via jejunostomy (equicaloric isonitrogenous total PN)	11 (8)	Primary analyses within 1 wk of enrollment	Mean daily stool output: 93.1 ± 68.5 g/d in the Reabilan group, 22.2 ± 35.3 g/d in the PN group (P < 0.05) No significant differences between groups for serum albumin, prealbumin, or plasma transferrin Average daily cost of supplies: $44.36 ± 8.50 for the Reabilan group, $102.10 ± 11.77 for the PN group (P < 0.001); non-nutrient supplies accounted for 13% of the cost in the Reabilan group vs 43% in the PN group
Kowalski et al[25]	Patients who received a post ITx	Retrospective case review	Peptide product (amino acid product)	34 (15)	Primary analyses within 6 mo	Time to full feedings post ITx from baseline to 1 to 2 yr: Peptide group z-scores: -2.71, -2.36, -2.32 (monotonic trend) Amino acid group z-scores: -2.46, -2.29, -2.35 Time to reaching full feeds (among those receiving rATG therapy): 3 mo in the peptide group, 5 mo in the amino acid group (P > 0.05)
Murray et al[24]	Children with short bowel syndrome	Randomized cross-over study	Peptamen (Vivonex TEN, high carbohydrate)	6	Two, 7 d periods	Mean ostomy output: 39 cc/kg per day in the Peptamen group, 49 cc/kg per day in the Vivonex TEN group Fat excretion: Identical in both groups (P = 0.9) Trace element analysis: Greater excretion of copper (P = 0.0002) and sulfur (P = 0.02) in the Vivonex TEN group

¹Numerous results are reported within individual studies, please refer to the studies for a full summary of results. RCT: Randomized controlled clinical trial; NR: Non-randomized; CD: Crohn’s disease; CDAI: CD activity index; PCDAI: Pediatric CD activity index; PEDIBDQ: Pediatric inflammatory bowel disease questionnaire; LCT: Long-chain triglycerides; MCT: Medium-chain triglycerides; ESR: Erythrocyte sedimentation rate; BMI: Body mass index; PN: Parenteral nutrition; ITx: Intestinal transplant.