Soluble Fiber Improves Management of Diarrhea in Elderly Patients Receiving Enteral Nutrition ()
1. Introduction
Enteral nutrition support is required when oral food intake is insufficient or is likely to be absent for a period of more than 5 - 7 days. Furthermore, support may be required in patients with insufficient oral food intake over longer periods [1]. Patients are suitable for longer term enteral nutrition if they have a functioning and accessible gastrointestinal tract. Thus, enteral nutrition is used for in-patients and out-patients in a wide range of disease states [2].
Diarrhea during enteral nutrition is a common complication. Whelan et al. reported that the incidence of diarrhea was 2% - 95% in enteral feeding cases [3]. Gastrointestinal symptoms during enteral nutrition can be influenced by various factors, such as administration method of the nutrient (composition, temperature, and rate of application), antibiotic prescription, abnormal secretion of water, enteropathogenic colonization, and the disease state [4-7]. The administration of low-residue formulas in enteral nutrition has been reported to induce small intestinal mucosal atrophy or enhance intestinal tract permeability [8,9].
Dietary fiber is a non-digestible carbohydrate that selectively stimulates the activity and/or growth of intestinal flora. Dietary fiber can be fermented into methane, hydrogen, carbon dioxide, and short-chain fatty acids (SCFA) by intestinal flora [10]. Fermentability of soluble fiber by intestinal flora is generally much greater than that of insoluble fiber [11]. SCFA, the most important energy substance for the colonic mucosal epithelium, promotes the absorption of water and sodium, regulates bowel function, and reverses colonic fluid secretion induced by enteral nutrition [12]. Therefore, dietary fiber supplementation has been recommended to normalize bowel function, improve feeding tolerance, and reduce diarrhea in patients receiving enteral nutrition [13]. (Elia, 2008, Systematic review and meta-analysis: the clinical and physiological effects of fibre-containing enteral formulae)However, the efficacy of dietary fiber supplementation has not been examined in detail.
In this study, we determined whether supplementation with soluble dietary fiber in an enteral formula improves diarrhea or loose stools in tube-fed patients. The clinical availability of soluble dietary fiber was evaluated by measuring the frequency of bowel movements, fecal features, plasma diamine oxidase (DAO) activity, which reflects the integrity and maturity of the small intestinal mucosa [14], and concentration of plasma SCFA.
2. Materials and Methods
2.1. Subjects
This study was conducted in 15 elderly in-patients of the Kameyama Kaisei hospital. Patients in medical wards necessitating enteral nutrition through a gastrostomy tube with loose stools or diarrhea were eligible. Patients with gastrointestinal diseases, or those using antibiotics, antidiarrheal agents, or probiotics were excluded from the study. All patients, or their legal representative, received an explanation of the study and gave their informed consent. The study was approved by the Human Research Ethics Committee of Kinjo Gakuin University.
2.2. Enteral Formula
Patients received fiber-free formula for 1 week (before fiber administration), then fiber-enriched formula for 3 weeks (fiber administration period), and then fiber-free formula for 1 week (discontinue fiber). During the fiberfree formula, patients received an enteral formula (K-2S, Kewpie Co.) that contained, per 100 mL feed; 100 kcal, 3.5 g protein, 93 mg sodium, 74 mg potassium, 60 mg calcium, 41 mg phosphorus, and was fiber free (Table 1). During the fiber-enriched formula, patients received fiber-free formula supplemented with soluble dietary fiber 5.2 g per day. A soluble dietary fiber, EDF (Fibro Co., Ltd.), was used. EDF is a powder containing 2.6 g of psyllium per package. This product contains 1.0 - 5.0 mg of sodium, has 2.9 kcal, and can be easily dissolved in water. Both fiber-free and fiber-enriched formula were administered twice a day through a gastrostomy tube with a continuous injector.
2.3. Blood Sample
To determine plasma DAO activity and SCFA concentration, a 5 mL blood sample was collected in the morning after an overnight fast the day before administration of fiber and then at weekly intervals after fiber administration, including 1 week after discontinuation. Blood samples were centrifuged (1000 × g, for 10 min) and plasma aliquots were stored at −20˚C until determination.
2.4. Fecal Analysis
Patients were asked to fill out a daily questionnaire reporting the frequency of their bowel movements and stool consistency. Stool consistency was assessed using the Bristol Stool Form Scale [15]. The Bristol Stool Form Scale was devised on the basis of 7 categories in
Table 1. Enteral nutrition constituents administered.
which stools were scored according to cohesion and crack, as follows: 1) separate hard lumps, like nuts; 2) sausage-shaped, but lumpy; 3) like a sausage but with cracks on its surface; 4) like a sausage or snake, and smooth and soft; 5) soft blobs with clear-cut edges; 6) fluffy pieces with ragged edges, a mushy stool; and 7) watery, no solid pieces, entirely liquid.
2.5. Plasma DAO Activity
Plasma DAO activity was measured using a high sensitivity colorimetric method according to Takagi et al. [16]. Briefly, a 0.04 mL sample was incubated with 0.6 mL of 25 mmol/L piperazine-N,N 9-bis(2-ethanesulphonic acid) buffer (pH 7.2) at 37˚C for 30 min. Then, 0.6 mL of 25 mmol/L 2-(4-morpholino) ethanesulphonic acid with 0.1 mol/L DA-67, 2.4 units/L peroxidase and 5000 units/L ascorbate oxidase was added to the mixture and incubation was allowed to proceed for 60 min. The enzyme reaction was stopped by the addition of 0.04 mL of 30 mmol/L sodium diethyldithiocarbamate and absorbance was measured at 668 nm.
2.6. SCFA Analysis
The concentration of plasma SCFA was measured using high performance liquid chromatography (HPLC) [17]. The HPLC apparatus used was a Shimadzu LC-20A system (Shimadzu, Kyoto, Japan). The UV-VIS detector was set to 400 nm and a YMC-Pack FA column (6.0 × 250 mm; YMC, Kyoto, Japan) was used with a column oven (CTO-20AC; Shimadzu) heated to 50˚C. The mobile phase consisted of acetonitrile-methanol-water (30: 16:54 v/v, pH 4 - 5 adjusted by 0.01 N HCl) and the flow rate was 1.2 mL/min. Ethanol (400 μL) was added to 100 μL of each plasma sample and vortexed. After centrifugation at 14,000 rpm for 20 min, the supernatant was added to 200 μL of an internal standard (50 μM) and fatty acid was pre-labeled using a Shortand Long-Chain Fatty Acid Analysis Kit (YMC, Kyoto, Japan). SCFA derivatives were extracted with n-hexane and diethyl ether, and were then evaporated to dryness. The residue was reconstituted with methanol and injected into the HPLC system.
2.7. Data Analysis
All data are expressed as means ± standard error, and statistical analysis was performed using Statview version 5.0, or the statistical software R version 2.10.1. To compare continuous variables, a one-way analysis of variance followed by Dunnett’s test for post-hoc analysis was performed. Steel’s test was used to compare ordered variables. Differences between means were considered to be significant at a P-value of <0.05.
3. Results
3.1. Patients
Fifteen patients (7 men and 8 women) necessitating enteral nutrition through a gastrostomy tube due to cerebrovascular diseases (e.g. cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage) were recruited for this study; however, one patient was subsequently excluded due to the discontinuation of enteral feeding. The remaining 14 patients (7 men and 7 women) were aged 79.0 ± 7.8 years.
3.2. Frequency of Bowel Movements
Changes in bowel frequency are shown in Figure 1. There were no significant differences in bowel frequency between baseline and after soluble fiber supplementation.
3.3. Stool Consistency
Figure 2 shows the differences in stool consistency. The Bristol Stool Form Scale was sequentially lower during the 3-week fiber administration period than that before soluble fiber supplementation, and these changes were significant after 3 weeks of fiber supplementation (4.86 ± 0.66 on the 3rd week vs. 5.67 ± 0.52 at baseline; P < 0.05 versus the baseline). The score increased one week after the discontinuation of fiber administration.