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1.  Effect of a High-Fiber Diet Compared With a Moderate-Fiber Diet on Calcium and Other Mineral Balances in Subjects With Type 2 Diabetes 
Diabetes Care  2009;32(6):990-995.
High levels of dietary fiber, especially soluble fiber, are recommended to lower serum cholesterol levels and improve glycemic control in patients with type 2 diabetes. It is not clear, however, how high levels of fiber affect mineral balance.
In a randomized crossover study, 13 patients with type 2 diabetes were fed a high-fiber (50 g total and 25 g soluble fiber) and a moderate-fiber (24 g total and 8 g soluble fiber) diet of the same energy, macronutrient, calcium, magnesium, and phosphorus content for 6 weeks each. Intestinal calcium absorption was determined by fecal recovery of 47Ca. Stool weight and mineral content were assessed during 3 days, and 24-h urinary mineral content and serum chemistry were assessed over 5 days at the end of each phase. The results were compared by repeated-measures ANOVA.
Compared with the moderate-fiber diet, the high-fiber diet increased stool weight (165 ± 53 vs. 216 ± 63 g/day, P = 0.02) and reduced 24-h urinary calcium (3.3 ± 1.7 vs. 2.4 ± 1.2 mmol/day, P = 0.003) and phosphorus (29.2 ± 5.5 vs. 26.0 ± 3.2 mmol/day, P = 0.003) excretion and serum calcium concentration (2.33 ± 0.06 vs. 2.29 ± 0.07 mmol/l, P = 0.04). Calcium absorption, stool calcium, magnesium, and phosphorus content and serum phosphorus concentration were not significantly different with the two diets.
A high-fiber diet rich in soluble fiber has a small impact on calcium and phosphorus balance in subjects with type 2 diabetes. It may be prudent to ensure adequate intake of calcium and other minerals in individuals consuming a high-fiber diet.
PMCID: PMC2681046  PMID: 19279300
2.  Changes in dominant groups of the gut microbiota do not explain cereal-fiber induced improvement of whole-body insulin sensitivity 
Diets high in cereal-fiber (HCF) have been shown to improve whole-body insulin sensitivity. In search for potential mechanisms we hypothesized that a supplemented HCF-diet influences the composition of the human gut microbiota and/or biomarkers of colonic carbohydrate fermentation.
We performed a randomized controlled 18-week intervention in group-matched overweight participants. Fecal samples of 69 participants receiving isoenergetic HCF (cereal-fiber 43 g/day), or control (cereal-fiber 14 g/day), or high-protein (HP, 28% of energy-intake, cereal-fiber 14 g/day), or moderately high cereal fiber/protein diets (MIX; protein 23% of energy-intake, cereal-fiber 26 g/day) with comparable fat contents were investigated for diet-induced changes of dominant groups of the gut microbiota, and of fecal short-chain fatty-acids (SCFA) including several of their proposed targets, after 0, 6, and 18-weeks of dietary intervention. In vitro fermentation of the cereal fiber extracts as used in the HCF and MIX diets was analyzed using gas chromatography. Diet-induced effects on whole-body insulin-sensitivity were measured using euglycaemic-hyperinsulinemic clamps and re-calculated in the here investigated subset of n = 69 participants that provided sufficient fecal samples on all study days.
Gut microbiota groups and biomarkers of colonic fermentation were comparable between groups at baseline (week 0). No diet-induced differences were detected between groups during this isoenergetic intervention, neither in the full model nor in uncorrected subgroup-analyses. The cereal-fiber extract as used for preparation of the supplements in the HCF and MIX groups did not support in vitro fermentation. Fecal acetate, propionate, and butyrate concentrations remained unchanged, as well as potential targets of increased SCFA, whereas valerate increased after 6-weeks in the HP-group only (p = 0.037). Insulin-sensitivity significantly increased in the HCF-group from week-6 (baseline M-value 3.8 ± 0.4 vs 4.3 ± 0.4 mg·kg-1·min-1, p = 0.015; full model 0-18-weeks, treatment-x-time interaction, p = 0.046).
Changes in the composition of the gut microbiota and/or markers of colonic carbohydrate fermentation did not contribute explaining the observed early onset and significant improvement of whole-body insulin sensitivity with the here investigated HCF-diet.
Trial registration
This trial was registered at as NCT00579657
PMCID: PMC3264513  PMID: 22177085
cereal fiber; whole-body insulin sensitivity; gut microbiota; short chain fatty acids (SCFA); colonic fermentation
3.  The Interaction of Dietary Fibers and Cholesterol upon the Plasma Lipids and Lipoproteins, Sterol Balance, and Bowel Function in Human Subjects 
Journal of Clinical Investigation  1977;60(6):1429-1437.
To identify any metabolic effects of dietary fiber upon cholesterol metabolism in man, six adult volunteer subjects were fed eucaloric cholesterol-free formula diets, with and without added dietary fiber for two 4-wk periods. A large quantity of dietary fiber was fed, some 60 g of plant cell wall material (or 16 g of crude fiber) derived from corn, beans, bran, pectin, and purified cellulose. This provided about five times the fiber intake of the typical American diet. The addition of fiber to the cholesterol-free diet did not change either the plasma cholesterol level (171±21 mg/dl, SEM, to 167±18) or the triglyceride (103±39 to 93±27 mg/dl). The excretion of both endogenous neutral steroids and bile acids were unchanged with fiber (505±41 to 636±75 mg/day and 194±23 to 266±47 mg/day, respectively.) However, total fecal steroid excretion was increased 699±29 to 902±64 mg/day, P < 0.025). With fiber, intestinal transit time was decreased (59±9 to 35±8 h, P < 0.005), and both the wet and dry stool weights were greatly increased.
A second group of six subjects was fed similar diets containing 1,000 mg cholesterol derived from egg yolk. The addition of fiber to the 1,000-mg cholesterol diet did not alter either plasma cholesterol level (233±26 to 223±36 mg/dl) or triglyceride (102±19 to 83±11 mg/dl). The excretion of endogenous neutral steroids (618±84 to 571±59 mg/day), of bile acids (423±122 to 401±89 mg/day), and of total fecal steroids (1,041±175 to 972±111 mg/day) were unchanged by fiber. The absorption of dietary cholesterol was not altered when fiber was added to the 1,000-mg cholesterol diet (44.0±3.3 to 42.9±2.5%). A two-way analysis of variance utilizing both groups of subjects indicated a significant (P < 0.001) effect of dietary cholesterol upon the plasma cholesterol concentration.
We concluded that a large quantity of dietary fiber from diverse sources had little or no effect upon the plasma lipids and sterol balance in man in spite of the fact that intestinal transit time and stool bulk changed greatly.
PMCID: PMC372501  PMID: 915007
4.  Effect of fiber supplementation on the microbiota in critically ill patients 
AIM: To determine tolerance to fiber supplementation of semi-elemental tube feeds in critically ill patients and measure its effect on colonic microbiota and fermentation.
METHODS: Thirteen intensive care unit patients receiving jejunal feeding with a semi-elemental diet for predominantly necrotizing pancreatitis were studied. The study was divided into 2 parts: first, short-term (3-9 d) clinical tolerance and colonic fermentation as assessed by fecal short chain fatty acid (SCFA) concentrations and breath hydrogen and methane was measured in response to progressive fiber supplementation increasing from 4 g tid up to normal requirement levels of 8 g tid; second, 4 patients with diarrhea were studied for 2-5 wk with maximal supplementation to additionally assess its influence on fecal microbiota quantitated by quantitative polymerase chain reaction (qPCR) of microbial 16S rRNA genes and Human Intestinal Tract Chip (HITChip) microarray analysis. Nearly all patients were receiving antibiotics (10/13) and acid suppressants (11/13) at some stage during the studies.
RESULTS: In group 1, tolerance to progressive fiber supplementation was good with breath hydrogen and methane evidence (P = 0.008 and P < 0.0001, respectively) of increased fermentation with no exacerbation of abdominal symptoms and resolution of diarrhea in 2 of 4 patients. In group 2 before supplementation, fecal microbiota mass and their metabolites, SCFA, were dramatically lower in patients compared to healthy volunteers. From qPCR and HITChip analyses we calculated that there was a 97% reduction in the predominant potential butyrate producers and starch degraders. Following 2-5 wk of fiber supplementation there was a significant increase in fecal SCFA (acetate 28.4 ± 4.1 μmol/g to 42.5 ± 3.1 μmol/g dry weight, P = 0.01; propionate 1.6 ± 0.5 vs 6.22 ± 1.1, P = 0.006 and butyrate 2.5 ± 0.6 vs 5.9 ± 1.1, P = 0.04) and microbial counts of specific butyrate producers, with resolution of diarrhea in 3 of 4 patients.
CONCLUSION: Conventional management of critically ill patients, which includes the use of elemental diets and broad-spectrum antibiotics, was associated with gross suppression of the colonic microbiota and their production of essential colonic fuels, i.e., SCFA. Our investigations show that fiber supplementation of the feeds has the potential to improve microbiota mass and function, thereby reducing the risks of diarrhea due to dysbiosis.
PMCID: PMC3240905  PMID: 22180847
Critical illness; Acute pancreatitis; Microbiota; Enteral nutrition; Fiber
5.  Increasing butyrate concentration in the distal colon by accelerating intestinal transit 
Gut  1997;41(2):245-251.
Background—Populations at low risk of colonic cancer consume large amounts of fibre and starch and pass acid, bulky stools. One short chain fatty acid (SCFA), butyrate, is the colon's main energy source and inhibits malignant transformation in vitro. 
Aim—To test the hypothesis that altering colonic transit rate alters colonic pH and the SCFA content of the stools. 
Patients—Thirteen healthy adults recruited by advertisement. 
Methods—Volunteers consumed, in turn, wheat bran, senna and loperamide, each for nine days with a two week washout period between study periods, dietary intake being unchanged. Before, and in the last four days of each intervention, whole gut transit time (WGTT), defaecation frequency, stool form, stool β-glucuronidase activity, stool pH, stool SCFA concentrations and intracolonic pH (using a radiotelemetry capsule for continuous monitoring) were assessed. 
Results—WGTT decreased, stool output and frequency increased with wheat bran and senna, vice versa with loperamide. The pH was similar in the distal colon and stool. Distal colonic pH fell with wheat bran and senna and tended to increase with loperamide. Faecal SCFA concentrations, including butyrate, increased with senna and fell with loperamide. With wheat bran the changes were non-significant, possibly because of the short duration of the study. Baseline WGTT correlated with faecal SCFA concentration (r=−0.511, p=0.001), with faecal butyrate (r=−0.577, p<0.001) and with distal colonic pH (r=0.359, p=0.029). 
Conclusion—Bowel transit rate is a determinant of stool SCFA concentration including butyrate and distal colonic pH. This may explain the inter-relations between colonic cancer, dietary fibre intake, stool output, and stool pH. 

Keywords: bowel cancer; colonic pH; fibre; intestinal transit; pH; short chain fatty acids
PMCID: PMC1891451  PMID: 9301506
6.  Gastrointestinal flora and gastrointestinal status in children with autism -- comparisons to typical children and correlation with autism severity 
BMC Gastroenterology  2011;11:22.
Children with autism have often been reported to have gastrointestinal problems that are more frequent and more severe than in children from the general population.
Gastrointestinal flora and gastrointestinal status were assessed from stool samples of 58 children with Autism Spectrum Disorders (ASD) and 39 healthy typical children of similar ages. Stool testing included bacterial and yeast culture tests, lysozyme, lactoferrin, secretory IgA, elastase, digestion markers, short chain fatty acids (SCFA's), pH, and blood presence. Gastrointestinal symptoms were assessed with a modified six-item GI Severity Index (6-GSI) questionnaire, and autistic symptoms were assessed with the Autism Treatment Evaluation Checklist (ATEC).
Gastrointestinal symptoms (assessed by the 6-GSI) were strongly correlated with the severity of autism (assessed by the ATEC), (r = 0.59, p < 0.001). Children with 6-GSI scores above 3 had much higher ATEC Total scores than those with 6-GSI-scores of 3 or lower (81.5 +/- 28 vs. 49.0 +/- 21, p = 0.00002).
Children with autism had much lower levels of total short chain fatty acids (-27%, p = 0.00002), including lower levels of acetate, proprionate, and valerate; this difference was greater in the children with autism taking probiotics, but also significant in those not taking probiotics. Children with autism had lower levels of species of Bifidobacter (-43%, p = 0.002) and higher levels of species of Lactobacillus (+100%, p = 0.00002), but similar levels of other bacteria and yeast using standard culture growth-based techniques. Lysozyme was somewhat lower in children with autism (-27%, p = 0.04), possibly associated with probiotic usage. Other markers of digestive function were similar in both groups.
The strong correlation of gastrointestinal symptoms with autism severity indicates that children with more severe autism are likely to have more severe gastrointestinal symptoms and vice versa. It is possible that autism symptoms are exacerbated or even partially due to the underlying gastrointestinal problems. The low level of SCFA's was partly associated with increased probiotic use, and probably partly due to either lower production (less sacchrolytic fermentation by beneficial bacteria and/or lower intake of soluble fiber) and/or greater absorption into the body (due to longer transit time and/or increased gut permeability).
PMCID: PMC3072352  PMID: 21410934
7.  Stopping or reducing dietary fiber intake reduces constipation and its associated symptoms 
AIM: To investigate the effect of reducing dietary fiber on patients with idiopathic constipation.
METHODS: Sixty-three cases of idiopathic constipation presenting between May 2008 and May 2010 were enrolled into the study after colonoscopy excluded an organic cause of the constipation. Patients with previous colon surgery or a medical cause of their constipation were excluded. All patients were given an explanation on the role of fiber in the gastrointestinal tract. They were then asked to go on a no fiber diet for 2 wk. Thereafter, they were asked to reduce the amount of dietary fiber intake to a level that they found acceptable. Dietary fiber intake, symptoms of constipation, difficulty in evacuation of stools, anal bleeding, abdominal bloating or abdominal pain were recorded at 1 and 6 mo.
RESULTS: The median age of the patients (16 male, 47 female) was 47 years (range, 20-80 years). At 6 mo, 41 patients remained on a no fiber diet, 16 on a reduced fiber diet, and 6 resumed their high fiber diet for religious or personal reasons. Patients who stopped or reduced dietary fiber had significant improvement in their symptoms while those who continued on a high fiber diet had no change. Of those who stopped fiber completely, the bowel frequency increased from one motion in 3.75 d (± 1.59 d) to one motion in 1.0 d (± 0.0 d) (P < 0.001); those with reduced fiber intake had increased bowel frequency from a mean of one motion per 4.19 d (± 2.09 d) to one motion per 1.9 d (± 1.21 d) on a reduced fiber diet (P < 0.001); those who remained on a high fiber diet continued to have a mean of one motion per 6.83 d (± 1.03 d) before and after consultation. For no fiber, reduced fiber and high fiber groups, respectively, symptoms of bloating were present in 0%, 31.3% and 100% (P < 0.001) and straining to pass stools occurred in 0%, 43.8% and 100% (P < 0.001).
CONCLUSION: Idiopathic constipation and its associated symptoms can be effectively reduced by stopping or even lowering the intake of dietary fiber.
PMCID: PMC3435786  PMID: 22969234
Dietary fiber; Constipation; Chronic idiopathic constipation; Abdominal bloating
8.  Supplementation of the diet with the functional fiber PolyGlycoplex® is well tolerated by healthy subjects in a clinical trial 
Nutrition Journal  2009;8:9.
The relationship of dietary fiber to overall health is of great importance, as beneficial effects have been demonstrated with the use of fiber from diverse sources, some traditional, other novel. PolyGlycopleX® (PGX®) is a unique proprietary product composed of three water-soluble polysaccharides, that when processed using novel technology give rise to a final product – a soluble, highly viscous functional fiber.
Because of its potential use in food and dietary supplements, a randomized, double-blind, placebo controlled clinical study was conducted to evaluate the tolerance to PGX ingestion for 21 days, to a maximum dose level of 10 g per day, in healthy male and female volunteers. The main objective of the study was to evaluate the overall gastrointestinal (GI) tolerance, while secondary objectives were to evaluate possible changes in hematological, biochemical, urinary and fecal parameters.
Results show that PGX is well tolerated as part of a regular diet with only mild to moderate adverse effects, similar to those seen with a moderate intake of dietary fiber in general, and fruits and vegetables. Because PGX is a highly viscous, functional fiber, it also demonstrates several physiological responses including, but not limited to maintaining healthy total and LDL cholesterol and uric acid levels.
PMCID: PMC2657159  PMID: 19196472
9.  Fiber and Prebiotics: Mechanisms and Health Benefits 
Nutrients  2013;5(4):1417-1435.
The health benefits of dietary fiber have long been appreciated. Higher intakes of dietary fiber are linked to less cardiovascular disease and fiber plays a role in gut health, with many effective laxatives actually isolated fiber sources. Higher intakes of fiber are linked to lower body weights. Only polysaccharides were included in dietary fiber originally, but more recent definitions have included oligosaccharides as dietary fiber, not based on their chemical measurement as dietary fiber by the accepted total dietary fiber (TDF) method, but on their physiological effects. Inulin, fructo-oligosaccharides, and other oligosaccharides are included as fiber in food labels in the US. Additionally, oligosaccharides are the best known “prebiotics”, “a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-bring and health.” To date, all known and suspected prebiotics are carbohydrate compounds, primarily oligosaccharides, known to resist digestion in the human small intestine and reach the colon where they are fermented by the gut microflora. Studies have provided evidence that inulin and oligofructose (OF), lactulose, and resistant starch (RS) meet all aspects of the definition, including the stimulation of Bifidobacterium, a beneficial bacterial genus. Other isolated carbohydrates and carbohydrate-containing foods, including galactooligosaccharides (GOS), transgalactooligosaccharides (TOS), polydextrose, wheat dextrin, acacia gum, psyllium, banana, whole grain wheat, and whole grain corn also have prebiotic effects.
PMCID: PMC3705355  PMID: 23609775
dietary fiber; prebiotics; fermentation; microbiota; short chain fatty acids; immune function
10.  Symptoms Associated with Dietary Fiber Supplementation over Time in Individuals with Fecal Incontinence 
Nursing Research  2011;60(3 Suppl):S58-S67.
Knowledge about adverse symptoms over time from fiber supplementation is lacking.
To compare the severity of adverse gastrointestinal (GI) symptoms during supplementation with dietary fiber or placebo over time in adults with fecal incontinence. Secondary aims were to determine the relationship between symptom severity and emotional upset and their association with study attrition and reducing fiber dose.
Subjects (N=189, 77% female, 92% white, (age = 58 years, SD = 14) with fecal incontinence were randomly assigned to placebo or a supplement of 16g total dietary fiber/day from one of three sources: gum arabic, psyllium, or carboxymethylcellulose. They reported GI symptoms daily during baseline (14 days), incremental fiber dosing (6 days), and two segments of steady full fiber dose (32 days total).
Severity of symptoms in all groups was minimal. Adjusting for study segment and day, a greater feeling of fullness in the psyllium group was the only symptom that differed from symptoms in the placebo group. Odds of having greater severity of flatus, belching, fullness, and bloating were 1.2–2.0 times greater in the steady dose segment compared to baseline. There was a positive association between symptom severity and emotional upset. Subjects with a greater feeling of fullness or bloating or higher scores for total symptom severity or emotional upset were more likely to withdraw from the study sooner or reduce fiber dose.
Persons with fecal incontinence experience a variety of GI symptoms over time. Symptom severity and emotional upset appear to influence fiber tolerance and study attrition. Supplements seemed well tolerated.
PMCID: PMC3400503  PMID: 21543963
fiber; diet; fecal incontinence; gastrointestinal symptoms; time
11.  Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake. 
Environmental Health Perspectives  1994;102(12):1058-1066.
Measurements of intake and uptake of cadmium in relation to diet composition were carried out in 57 nonsmoking women, 20-50 years of age. A vegetarian/high-fiber diet and a mixed-diet group were constructed based on results from a food frequency questionnaire. Duplicate diets and the corresponding feces were collected during 4 consecutive days in parallel with dietary recording of type and amount of food ingested for determination of the dietary intake of cadmium and various nutrients. Blood and 24-hr urine samples were collected for determination of cadmium, hemoglobin, ferritin, and zinc. There were no differences in the intake of nutrients between the mixed-diet and the high-fiber diet groups, except for a significantly higher intake of fiber (p < 0.001) and cadmium (p < 0.002) in the high-fiber group. Fecal cadmium corresponded to 98% in the mixed-diet group and 100% in the high-fiber diet group. No differences in blood cadmium (BCd) or urinary cadmium (UCd) between groups could be detected. There was a tendency toward higher BCd and UCd concentrations with increasing fiber intake; however, the concentrations were not statistically significant at the 5% level, indicating an inhibitory effect of fiber on the gastrointestinal absorption of cadmium. Sixty-seven percent of the women had serum ferritin < 30 micrograms/l, indicating reduced body iron stores, which were highly associated with higher BCd (irrespective of fiber intake). BCd was mainly correlated with UCd, serum ferritin, age, anf fibre intake. UCd and serum ferritin explained almost 60% of the variation in BCd.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1567470  PMID: 7713018
12.  Soluble Fiber Dextrin and Soluble Corn Fiber Supplementation Modify Indices of Health in Cecum and Colon of Sprague-Dawley Rats 
Nutrients  2013;5(2):396-410.
The objective of this study was to evaluate health outcomes resulting from dietary supplementation of novel, low-digestible carbohydrates in the cecum and colon of Sprague-Dawley rats randomly assigned to one of four treatment groups for 21 days: 5% cellulose (Control), Pectin, soluble fiber dextrin (SFD), or soluble corn fiber (SCF). Rats fed Pectin had a higher average daily food intake, but no differences in final body weights or rates of weight gain among treatments were observed. No differences were observed in total short-chain fatty acid (SCFA) or branched-chain fatty acid (BCFA) concentrations in the cecum and colon of rats fed either SFD or SCF. The SFD and SCF treatments increased cecal propionate and decreased butyrate concentrations compared to Control or Pectin. Pectin resulted in increased BCFA in the cecum and colon. Supplementation of SFD and SCF had no effect on cecal microbial populations compared to Control. Consumption of SFD and SCF increased total and empty cecal weight but not colon weight. Gut histomorphology was positively affected by SFD and SCF. Increased crypt depth, goblet cell numbers, and acidic mucin were observed in both the cecum and colon of rats supplemented with SFD, SCF, and Pectin. These novel, low-digestible carbohydrates appear to be beneficial in modulating indices of hindgut morphology when supplemented in the diet of the rat.
PMCID: PMC3635201  PMID: 23381099
cecal fermentation; histomorphology; soluble fiber dextrin; soluble corn fiber
13.  Foods with added fiber improve stool frequency in individuals with chronic kidney disease with no impact on appetite or overall quality of life 
BMC Research Notes  2013;6:510.
Fiber intake may be low in individuals with chronic kidney disease (CKD) due to diet restriction and/or poor appetite associated with uremic symptoms, contributing to constipation and reduced quality of life. This report describes the effects of foods with added fiber on gastrointestinal function and symptoms, clinical markers, and quality of life in CKD patients.
Adults with CKD (n = 15; 9 F, 6 M; 66 ± 15 y) were provided with cereal, cookies and snack bars without added fiber for 2 weeks, followed by similar foods providing 23 g/d of added fiber for 4 weeks, to incorporate into their usual diets. Participants completed the Kidney Disease Quality of Life (KDQOL-36) questionnaire, the Simplified Nutritional Appetite Questionnaire (SNAQ) and the Epworth Sleepiness Scale (ESS) bi-weekly, the Gastrointestinal Symptom Rating Scale (GSRS) weekly, and daily stool frequency and compliance. Control and intervention serum cholesterol and glucose were assessed. Providing 23 g/d of added fiber increased stool frequency (1.3 ± 0.2 to 1.6 ± 0.2 stools/d; P = 0.02), decreased total cholesterol (175 ± 12 to 167 ± 11 mg/dL; P = 0.02) and improved TC:HDL ratio (4.0 ± 0.3 to 3.7 ± 0.2; P = 0.02). GSRS and SNAQ scores did not change, but SNAQ scores suggested poor appetite in 7 participants with or without added fiber. KDQOL Mental Health Composite decreased from 53 ± 2 to 48 ± 2 (P = 0.01) while Physical Health Composite increased from 31 ± 2 to 35 ± 3 (P = 0.02), with no change in overall QOL. The ESS score decreased from 10 ± 1 to 8 ± 1 (P = 0.04).
Consuming foods with added fiber may be an effective means of increasing fiber intakes, improving stool frequency, and lipid profile in individuals with CKD.
Trial registration, # NCT01842087
PMCID: PMC4235217  PMID: 24304924
Chronic kidney disease; Fiber; Quality of life; Gastrointestinal function; Appetite; GSRS; SNAQ; ESS
14.  The Short-Chain Fatty Acid Uptake Fluxes by Mice on a Guar Gum Supplemented Diet Associate with Amelioration of Major Biomarkers of the Metabolic Syndrome 
PLoS ONE  2014;9(9):e107392.
Studies with dietary supplementation of various types of fibers have shown beneficial effects on symptoms of the metabolic syndrome. Short-chain fatty acids (SCFAs), the main products of intestinal bacterial fermentation of dietary fiber, have been suggested to play a key role. Whether the concentration of SCFAs or their metabolism drives these beneficial effects is not yet clear. In this study we investigated the SCFA concentrations and in vivo host uptake fluxes in the absence or presence of the dietary fiber guar gum. C57Bl/6J mice were fed a high-fat diet supplemented with 0%, 5%, 7.5% or 10% of the fiber guar gum. To determine the effect on SCFA metabolism, 13C-labeled acetate, propionate or butyrate were infused into the cecum of mice for 6 h and the isotopic enrichment of cecal SCFAs was measured. The in vivo production, uptake and bacterial interconversion of acetate, propionate and butyrate were calculated by combining the data from the three infusion experiments in a single steady-state isotope model. Guar gum treatment decreased markers of the metabolic syndrome (body weight, adipose weight, triglycerides, glucose and insulin levels and HOMA-IR) in a dose-dependent manner. In addition, hepatic mRNA expression of genes involved in gluconeogenesis and fatty acid synthesis decreased dose-dependently by guar gum treatment. Cecal SCFA concentrations were increased compared to the control group, but no differences were observed between the different guar gum doses. Thus, no significant correlation was found between cecal SCFA concentrations and metabolic markers. In contrast, in vivo SCFA uptake fluxes by the host correlated linearly with metabolic markers. We argue that in vivo SCFA fluxes, and not concentrations, govern the protection from the metabolic syndrome by dietary fibers.
PMCID: PMC4159349  PMID: 25203112
15.  Association between dietary fiber and markers of systemic inflammation in the Women’s Heath Initiative Observational Study 
Systemic inflammation may play an important role in the development of atherosclerosis, type 2 diabetes, and some cancers. Few studies have comprehensively assessed the direct relationships between dietary fiber and inflammatory cytokines, especially in minority populations. Using baseline data from 1,958 postmenopausal women enrolled in the Women’s Heath Initiative Observational Study, we examined cross-sectional associations between dietary fiber intake and markers of systemic inflammation (including serum C-reactive protein (hs-CRP), interleukin 6 (IL-6), and tumor necrosis factor α receptor 2 (TNF-α-R2)), as well as differences in these associations by ethnicity.
Multiple linear regression models were used to assess the relationship between fiber intake and makers of systemic inflammation.
After adjustment for covariates, intake of dietary fiber were inversely associated with both IL-6 (P values for trend were 0.01 for total fiber, 0.004 for soluble fiber, and 0.001 for insoluble fiber) and TNF-α-R2 (P values for trend were 0.002 for total, 0.02 for soluble, and <0.001 for insoluble fiber). Although the sample sizes were small in minority Americans, results were generally consistent with that found among European-Americans. We did not observe any significant association between intake of dietary fiber and hs-CRP.
These findings lend support to the hypothesis that a high-fiber diet is associated with lower plasma levels of IL-6 and TNF-α-R2. Contrary to previous reports, however, there was no association between fiber and hs-CRP among postmenopausal women. Future studies on the influence of diet on inflammation should include IL-6 and TNF-α-R2 and enroll participants from ethnic minorities.
PMCID: PMC2603616  PMID: 18562168
dietary fiber; C-reactive protein; interleukin-6; tumor necrosis factor-alpha receptor 2; inflammation; cytokines; epidemiology; cardiovascular disease; nutrition
16.  Dietary fiber is associated with circulating concentrations of C-reactive protein in breast cancer survivors: the HEAL study 
Inflammation is a suspected risk factor for breast cancer and its subsequent prognosis. The extent to which dietary and lifestyle factors might influence inflammation is important to examine. Specifically, dietary fiber may reduce systemic inflammation, but this relationship has not been examined among breast cancer survivors. We examined associations between dietary fiber and serum concentrations of C-reactive protein (CRP) and serum amyloid-A (SAA), among 698 female breast cancer survivors from the Health, Eating, Activity, and Lifestyle (HEAL) Study. Data are from interviews and clinical visits conducted 24 months post-study enrollment. Multivariate-adjusted linear regression estimated associations of total, soluble and insoluble fiber with serum concentrations of CRP and SAA. Logistic regression estimated the odds of elevated CRP (defined as >3.0 mg/L) across tertiles of dietary fiber intake. Mean total dietary fiber intake was 13.9 ± 6.4 g/day. Mean CRP and SAA were 3.32 ± 3.66 mg/L and 7.73 ± 10.23 mg/L, respectively. We observed a multivariate-adjusted inverse association between total dietary fiber intake and CRP concentrations (β, −0.029; 95% CI, −0.049, −0.008). Results for insoluble fiber were similar (β, −0.039; 95% CI, −0.064, −0.013). Among survivors who consumed >15.5 g/day of insoluble dietary fiber, a 49% reduction in the likelihood of having elevated CRP concentrations (OR, 0.51; 95% CI, 0.27, 0.95) was observed compared to those who consumed <5.4 g/day (p = 0.053). Our results suggest that diets high in fiber may benefit breast cancer survivors via reductions in systemic inflammation; elevated inflammation may be prognostic for reduced survival.
PMCID: PMC3743439  PMID: 21455669
dietary fiber; breast cancer; C-reactive protein; serum amyloid A; inflammation
17.  Association between dietary fiber and serum C-reactive protein1-3 
High sensitivity C-reactive protein (CRP) is a marker of acute inflammation recently recognized as an independent predictor of future cardiovascular disease and diabetes. The identification of modifiable factors, such as diet, that influence serum CRP concentrations may provide the means for reducing the risk of these diseases. Data on longitudinal associations between dietary fiber intake and CRP are currently lacking.
The purpose of this study was to examine longitudinal associations between dietary fiber intake and CRP.
Data collection took place at baseline and quarterly (every 13 wk) thereafter for a total of 5 visits, each including measurements of body composition, CRP, diet, and physical activity. Relations between serum CRP and dietary fiber were assessed by using linear mixed models and logistic regression, adjusted for covariates.
A total of 524 subjects had multiple measurements of CRP and dietary factors. The average total dietary fiber intake was 16.11 g/d. Average serum CRP was 1.78 mg/L. We observed an inverse association between intake of total dietary fiber (separately for soluble and insoluble fiber) and CRP concentrations in both cross-sectional and longitudinal analyses. The likelihood of elevated CRP concentrations was 63% lower (OR: 0.37; 95% CI: 0.16, 0.87) in participants in the highest quartile of total fiber intake than in participants in the lowest quartile.
Our results suggest that dietary fiber is protective against high CRP, which supports current recommendations for a diet high in fiber.
PMCID: PMC1456807  PMID: 16600925
Dietary fiber; C-reactive protein; epidemiology; cardiovascular disease; nutrition
18.  Alternative Dietary Fiber Sources in Companion Animal Nutrition 
Nutrients  2013;5(8):3099-3117.
The US has a pet population of approximately 70 million dogs and 74 million cats. Humans have developed a strong emotional bond with companion animals. As a consequence, pet owners seek ways to improve health, quality of life and longevity of their pets. Advances in canine and feline nutrition have contributed to improved longevity and well-being. Dietary fibers have gained renewed interest in the pet food industry, due to their important role in affecting laxation and stool quality. More recently, because of increased awareness of the beneficial effects of dietary fibers in health, as well as the popularity of functional foods and holistic and natural diets, alternative and novel carbohydrates have become widespread in human and pet nutrition. Fiber sources from cereal grains, whole grains and fruits have received increasing attention by the pet food industry and pet owners. While limited scientific information is available on the nutritional and nutraceutical properties of alternative fiber sources, studies indicate that corn fiber is an efficacious fiber source for pets, showing no detrimental effects on palatability or nutrient digestibility, while lowering the glycemic response in adult dogs. Fruit fiber and pomaces have good water-binding properties, which may be advantageous in wet pet food production, where a greater water content is required, along with low water activity and a firm texture of the final product. Rice bran is a palatable fiber source for dogs and may be an economical alternative to prebiotic supplementation of pet foods. However, it increases the dietary requirement of taurine in cats. Barley up to 40% in a dry extruded diet is well tolerated by adult dogs. In addition, consumption of complex carbohydrates has shown a protective effect on cardiovascular disease and oxidative stress. Alternative fiber sources are suitable ingredients for pet foods. They have been shown to be nutritionally adequate and to have potential nutraceutical properties.
PMCID: PMC3775244  PMID: 23925042
companion animal; beet pulp; cellulose; corn fiber; fruit fiber; rice bran; whole grains
19.  Effect of dietary fiber on constipation: A meta analysis 
AIM: To investigate the effect of dietary fiber intake on constipation by a meta-analysis of randomized controlled trials (RCTs).
METHODS: We searched Ovid MEDLINE (from 1946 to October 2011), Cochrane Library (2011), PubMed for articles on dietary fiber intake and constipation using the terms: constipation, fiber, cellulose, plant extracts, cereals, bran, psyllium, or plantago. References of important articles were searched manually for relevant studies. Articles were eligible for the meta-analysis if they were high-quality RCTs and reported data on stool frequency, stool consistency, treatment success, laxative use and gastrointestinal symptoms. The data were extracted independently by two researchers (Yang J and Wang HP) according to the described selection criteria. Review manager version 5 software was used for analysis and test. Weighted mean difference with 95%CI was used for quantitative data, odds ratio (OR) with 95%CI was used for dichotomous data. Both I2 statistic with a cut-off of ≥ 50% and the χ2 test with a P value < 0.10 were used to define a significant degree of heterogeneity.
RESULTS: We searched 1322 potential relevant articles, 19 of which were retrieved for further assessment, 14 studies were excluded for various reasons, five studies were included in the analysis. Dietary fiber showed significant advantage over placebo in stool frequency (OR = 1.19; 95%CI: 0.58-1.80, P < 0.05). There was no significant difference in stool consistency, treatment success, laxative use and painful defecation between the two groups. Stool frequency were reported by five RCTs, all results showed either a trend or a significant difference in favor of the treatment group, number of stools per week increased in treatment group than in placebo group (OR = 1.19; 95%CI: 0.58-1.80, P < 0.05), with no significant heterogeneity among studies (I2= 0, P = 0.77). Four studies evaluated stool consistency, one of them presented outcome in terms of percentage of hard stool, which was different from others, so we included the other three studies for analysis. Two studies reported treatment success. There was significant heterogeneity between the studies (P < 0.1, I2 > 50%). Three studies reported laxative use, quantitative data was shown in one study, and the pooled analysis of the other two studies showed no significant difference between treatment and placebo groups in laxative use (OR = 1.07; 95%CI 0.51-2.25), and no heterogeneity was found (P = 0.84, I2= 0). Three studies evaluated painful defecation: one study presented both quantitative and dichotomous data, the other two studies reported quantitative and dichotomous data separately. We used dichotomous data for analysis.
CONCLUSION: Dietary fiber intake can obviously increase stool frequency in patients with constipation. It does not obviously improve stool consistency, treatment success, laxative use and painful defecation.
PMCID: PMC3544045  PMID: 23326148
Dietary fiber; Constipation; Meta-analysis; Stool frequency; Stool consistency
20.  Gum Guar fiber associated with fructose reduces serum triacylglycerol but did not improve the glucose tolerance in rats 
The increased intake of dietary fructose can be associated with alterations on energy homeostasis and lipid/carbohydrate metabolism, such as insulin resistance and dislipidemia. On the other hand, the ingestion of soluble fiber gum guar could improve benefic mechanism on glucose tolerance and lipids profile.
The aim of the present study were to investigate the effects of the supplemental feeding partially hydrolyzed gum guar on glucose and lipid homeostasis, in rats fed with fructose solution.
The study was performed on thirty day-old male Wistar rats randomly assigned into four groups: control(C) or treated with fructose (F-20%), fiber (FB-5%), or fructose plus fiber (F-20% + FB-5% = FF) solution for 30 days on glucose tolerance (OGTT), triacylglycerol concentration in the liver by chloroform/methanol method, glucose, triacylglycerol and total cholesterol serum concentration by assayed by enzymatic colorimetric method, insulin receptor (IR) concentration in the liver by Western Blotting.
The total body weight gain was not different between groups; in regards of total caloric intake, in the F group was significantly higher and in the FB group was lower than other groups. The triacylglycerol concentration in the liver of FF group was significantly higher than F group, the triacylglycerol concentration in the serum was higher the F group compared with other groups. The OGTT reveal impaired on glucose tolerance in the F, FB, FF compared with C. The IR concentration in the liver was lower in the F, FB, FF compared with C, no significant difference was observed between groups for IR concentration in the gastrocnemius muscle. No significant difference was observed between groups for carcass fat content and serum total cholesterol.
Fructose induced important alterations on glucose tolerance and lipid metabolism, despite of fiber showed reversion of part this alterations. The association fructose plus fiber to seem decrease insulin receptor concentration in the liver, with consequent impair on glucose tolerance.
PMCID: PMC2984456  PMID: 20979642
21.  Postprandial effects of polydextrose on satiety hormone responses and subjective feelings of appetite in obese participants 
Nutrition Journal  2015;14:2.
Dietary fibers are associated with enhanced satiety. However, the mechanism of different dietary fibers contributing to satiety-related gastrointestinal (GI) peptide release, especially in an obese population, is still poorly understood. Polydextrose (PDX), a water-soluble glucose polymer, has demonstrated its ability to reduce energy intake at a subsequent meal, but its mechanism of action requires further research. Also, there is limited evidence on its capacity to regulate subjective feelings of appetite. This study examines the effects of PDX on postprandial secretion of satiety-related GI peptides, short chain fatty acids (SCFAs), lactic acid, and subjective appetite ratings in obese participants.
18 non-diabetic, obese participants (42.0 y, 33.6 kg/m2) consumed a high-fat meal (4293 kJ, 36% from fat) with or without PDX (15 g) in an acute, multicenter, randomized, double-blind, placebo-controlled and crossover trial. Postprandial plasma concentrations of satiety-related peptides, namely ghrelin, cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), as well as SCFAs and lactic acid were assessed. GI peptide, SCFA and lactate concentrations were then modeled using a linear mixed-effects model.
The subjective feelings of hunger, satisfaction, and desire to eat were evaluated using visual analogue scales (VAS), which were analyzed as incremental areas under the curve (iAUC) during the satiation and satiety periods.
We found that PDX supplementation increased plasma GLP-1 levels more than the placebo treatment (P = 0.02). In the whole group, GLP-1 concentrations found in participants older than 40 years old were significantly lower (P = 0.01) as compared to those aged 40 years or less. There were no statistically significant differences in postprandial ghrelin, CCK, or PYY responses. The lactic acid concentrations were significantly (P = 0.01) decreased in the PDX group, while no significant changes in SCFAs were found. PDX reduced iAUC for hunger by 40% (P = 0.03) and marginally increased satisfaction by 22.5% (P = 0.08) during the post-meal satiety period.
Polydextrose increased the postprandial secretion of the satiety hormone GLP-1 and reduced hunger after a high-fat meal. PDX also reduced the elevated postprandial lactic acid levels in plasma. Therefore, PDX may offer an additional means to regulate inter-meal satiety and improve postprandial metabolism in obese participants.
PMCID: PMC4320494  PMID: 25555562
Dietary fiber; GLP-1; Hunger; Lactate; Lactic acid; Obesity; Polydextrose; Satiety; VAS
22.  Fiber intake and inflammation in type 1 diabetes 
Higher intake of dietary fiber is associated with lower risk of coronary heart disease, the leading cause of mortality among people with type 1 diabetes. The protective effect includes the anti-inflammatory properties of some foods. Population-based studies have shown an inverse association between some nutritional habits and high sensitive -C-reactive protein (hs-CRP). This study aimed to ascertain the association between fiber intake and hs-CPR levels in patients with type 1 diabetes.
This cross-sectional study was conducted with 106 outpatients with type 1 diabetes; age 40 ± 11 years; diabetes duration of 18 ± 8.8 years. Dietary intake was evaluated by 3-day weighed-diet records. Patients were categorized in 2 groups, according to fiber intake (>20 g/day and <20 g/day).
The group with fiber intake > 20 g/day had lower hs-CRP levels [median (25th-75th) 0.7 mg/dl (0.4-2.4) vs. 1.9 mg/dl (1.0-4.4); P = 0.002], than the other group. Controlled for HbA1c and energy intake, an inverse relation was observed between hs-CRP levels and total fiber [ß = − 0.030 (SE: 0.0120), P = 0.02], soluble fiber [ß = − 0.078 (SE: 0.0421), P = 0.06] and insoluble fiber [ß = − 0.039 (SE: 0.01761), P = 0.026]. Even, after additional adjustment fibers remained associated with lower hs-CRP levels. Total fibers were stratified in 4 groups: < 10 g/day, from 10 to < 20 g/day, from 20 to 30 g/day and > 30 g/day. Compared to the group who ingested < 10 g/day of total fiber (referent group), the group who consumed > 30 g/d had significantly lower hs-CRP levels [−2.45 mg/L, P = 0.012] independent of the HbA1c values.
The present study suggests that an increased consumption of dietary fiber > 30 g/day may play a role in reducing inflammation in individuals with type 1 diabetes.
PMCID: PMC4083349  PMID: 25002911
Type 1 diabetes; Fiber intake; Inflammation
23.  Free fatty acid receptor 3 is a key target of short chain fatty acid 
Channels  2014;8(3):169-171.
Nervous system (NS) activity participates in metabolic homeostasis by detecting peripheral signal molecules derived from food intake and energy balance. High quality diets are thought to include fiber-rich foods like whole grain rice, breads, cereals, and grains. Several studies have associated high consumption of fiber-enriched diets with a reduced risk of diabetes, obesity, and gastrointestinal disorders. In the lower intestine, anaerobic fermentation of soluble fibers by microbiota produces short chain fatty acids (SCFAs), key energy molecules that have a recent identified leading role in the intestinal gluconeogenesis, promoting beneficial effects on glucose tolerance and insulin resistance1. SCFAs are also signaling molecules that bind to specific G-protein coupled receptors (GPCRs) named Free Fatty Acid Receptor 3 (FFA3, GPR41) and 2 (FFA2, GPR43). However, how SCFAs impact NS activity through their GPCRs is poorly understood.
Recently, studies have demonstrated the presence of FFA2 and FFA3 in the sympathetic NS of rat, mouse and human2, 3. Two studies have showed that FFA3 activation by SCFAs increases firing and norepinephrine (NE) release from sympathetic neurons3, 4. However, the recent study from the Ikeda Laboratory2 revealed that activation of FFA3 by SCFAs impairs N-type calcium channel (NTCC) activity, which contradicts the idea of FFA3 activation leading to increased action potential evoked NE release. Here we will discuss the scope of the latter study and the putative physiological role of SCFAs and FFAs in the sympathetic NS.
PMCID: PMC4203745  PMID: 24762451
Short chain fatty acids; N-type calcium channels; CaV2.2; FFA3; GPR41; FFA2; GPR43
24.  The effect of high fiber snacks on digestive function and diet quality in a sample of school-age children 
Nutrition Journal  2013;12:153.
Dietary fiber (DF) intake in American children is suboptimal, increasing the risk of GI distress and contributing to poor diet quality. The objective of this study was to determine the effect of introducing two high-fiber snacks per day on gastrointestinal function as well as nutrient and food group intake in healthy children ages 7–11 years old.
This study was a randomized controlled prospective intervention study of children 7–11 years of age (n = 81) attending a rural Midwestern elementary school. Children were randomized by classroom to consume two high-fiber snacks per day (total of 10-12 g DF) or their usual snacks for 8 weeks. Participants completed two 24-hour dietary recalls and a questionnaire about their GI health at baseline, mid-intervention (week 4), and post-intervention. Dietary data was entered into NDSR 2011 and t-tests utilized to assess changes. Analyses were completed in SAS 9.2.
Children consumed at least half their snack 94% of the time when a snack was chosen (89% of time). Participants in both the intervention and control group had healthy scores on the GI health questionnaire at all time points. The intervention group increased DF (P = 0.0138) and whole grain (WG) intake (P = 0.0010) at mid-intervention but after the intervention returned to their baseline DF intake (P = 0.2205) and decreased their WG intake (P = 0.0420) compared to baseline. Eating high-fiber snacks increased DF intake by 2.5 g per day (21% increase), suggesting displacement of other fiber-rich foods.
Study results indicate that children accept high-fiber foods, thus making these high-fiber foods and snacks consistently available will increase DF intake.
PMCID: PMC4222504  PMID: 24274323
Fiber; Whole grains; Diet quality; Constipation; Children
25.  Evidence-Based Approach to Fiber Supplements and Clinically Meaningful Health Benefits, Part 1 
Nutrition Today  2015;50(2):82-89.
Dietary fiber that is intrinsic and intact in fiber-rich foods (eg, fruits, vegetables, legumes, whole grains) is widely recognized to have beneficial effects on health when consumed at recommended levels (25 g/d for adult women, 38 g/d for adult men). Most (90%) of the US population does not consume this level of dietary fiber, averaging only 15 g/d. In an attempt to bridge this “fiber gap,” many consumers are turning to fiber supplements, which are typically isolated from a single source. Fiber supplements cannot be presumed to provide the health benefits that are associated with dietary fiber from whole foods. Of the fiber supplements on the market today, only a minority possess the physical characteristics that underlie the mechanisms driving clinically meaningful health benefits. The first part (current issue) of this 2-part series will focus on the 4 main characteristics of fiber supplements that drive clinical efficacy (solubility, degree/rate of fermentation, viscosity, and gel formation), the 4 clinically meaningful designations that identify which health benefits are associated with specific fibers, and the gel-dependent mechanisms in the small bowel that drive specific health benefits (eg, cholesterol lowering, improved glycemic control). The second part (next issue) of this 2-part series will focus on the effects of fiber supplements in the large bowel, including the 2 mechanisms by which fiber prevents/relieves constipation (insoluble mechanical irritant and soluble gel-dependent water-holding capacity), the gel-dependent mechanism for attenuating diarrhea and normalizing stool form in irritable bowel syndrome, and the combined large bowel/small bowel fiber effects for weight loss/maintenance. The second part will also discuss how processing for marketed products can attenuate efficacy, why fiber supplements can cause gastrointestinal symptoms, and how to avoid symptoms for better long-term compliance.
PMCID: PMC4415962  PMID: 25972618

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