On the importance of intraindividual variation in nutritional research.

Nutritional intervention studies, like those with pre- and probiotics, are often hampered by low effect sizes, reducing the power to demonstrate potential efficacy. Here, we perform computer simulations of a hypothetical clinical trial using such an intervention in order to elucidate determining factors that can be influenced in order to optimise the statistical power. Our simulations demonstrate that steering the study population towards a low intraindividual variation dramatically improves statistical power. A more than 10-fold decrease of number-to-treat could be reached. Also, a careful balancing between the number of subjects and measurements per subject, in combination with possible stratification of the subjects into responders and non-responders, based on inherent intraindividual variation, improves the likelihood to reach statistically significant results. Our results also show that traditional dogmas, with respect to clinical trials, i.e. aiming at low interindividual variation and a high number (n) of study participants, should be re-evaluated in favour of reducing intraindividual variation. This reduction in intraindividual variation could be achieved by maintaining a steady lifestyle, including dietary habits among others, within the timeframe of the intervention study.

Plasma very long-chain n-3 polyunsaturated fatty acids and age-related hearing loss in older adults.

OBJECTIVES: Age-related hearing loss is a common social and health problem in the older adult population. Up until now, very little scientific attention has been given to the potential role of fatty acids in age-related hearing loss. In this study we investigated whether plasma very long-chain n-3 polyunsaturated fatty acids (PUFAs) are associated with age-related hearing loss over three years. DESIGN: Cross-sectional and 3-year longitudinal analyses. SETTING: Wageningen, the Netherlands. PARTICIPANTS: 720 men and postmenopausal women (50-70 years of age) without middle ear dysfunction or unilateral hearing loss. MEASUREMENTS: Fatty acid proportions were measured in plasma cholesteryl esters. Hearing thresholds (in decibels, dB) at baseline and after three years were measured with pure-tone audiometry. Hearing loss was calculated as the increase in mean hearing thresholds in the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz) frequencies over three years. RESULTS: Subjects in the highest quartile of plasma very long-chain n-3 PUFA had less hearing loss in the low frequencies over three years than subjects in the lowest quartile (p < 0.01, ANCOVA, difference in mean adjusted hearing thresholds= -1.2 dB). There were no significant differences between the quartiles of plasma very long-chain n-3 PUFA in hearing loss in the high frequencies (p=0.49, ANCOVA). These associations are adjusted for baseline mean hearing thresholds, age, sex, level of education and alcohol consumption. CONCLUSION: This study is the first to show an inverse association between plasma very long-chain n-3 PUFAs and age-related hearing loss. These results are encouraging, but require confirmation from future studies.

The effects of butyrate enemas on visceral perception in healthy volunteers.

Fermentation of dietary fibres by colonic microbes leads to the production of short chain fatty acids (mainly propionate, butyrate and acetate), which are utilized by the colonic mucosa. Previous studies showed positive effects of butyrate on parameters of oxidative stress, inflammation and apoptosis. Recent studies in rats, however, showed that butyrate increased visceral sensitivity. The aim of this study was to determine the effects of physiologically relevant concentrations of butyrate on visceral perception in healthy human subjects. Eleven healthy volunteers participated in this randomized double-blind, placebo controlled cross-over study. The study consisted of three periods of 1 week each, in which the volunteers daily self-administered rectal enemas containing 100, 50 mmol L(-1) butyrate, or placebo (saline) prior to sleeping. A rectal barostat measurement was performed at the start and the end of each test period for the measurement of pain, urge and discomfort. Butyrate treatment resulted in a dose-dependent reduction of pain, urge and discomfort throughout the entire pressure range of the protocol. At a pressure of 4 mmHg, 50 and 100 mmol L(-1) butyrate concentrations resulted in a 23.9% and 42.1% reduction of pain scores, respectively, and the discomfort scores decreased by 44.2% and 69.0% respectively. At a pressure of 67 mmHg, 50 and 100 mmol L(-1) of butyrate decreased the pain scores by 23.8% and 42%, respectively, and discomfort scores 1.9% and 5.2% respectively. Colonic administration of butyrate, at physiologically relevant concentrations, dose-dependently decreases visceral sensitivity in healthy volunteers.

Review article: the role of butyrate on colonic function.

BACKGROUND: Butyrate, a short-chain fatty acid, is a main end-product of intestinal microbial fermentation of mainly dietary fibre. Butyrate is an important energy source for intestinal epithelial cells and plays a role in the maintenance of colonic homeostasis. AIM: To provide an overview on the present knowledge of the bioactivity of butyrate, emphasizing effects and possible mechanisms of action in relation to human colonic function. METHODS: A PubMed search was performed to select relevant publications using the search terms: 'butyrate, short-chain fatty acid, fibre, colon, inflammation, carcinogenesis, barrier, oxidative stress, permeability and satiety'. RESULTS: Butyrate exerts potent effects on a variety of colonic mucosal functions such as inhibition of inflammation and carcinogenesis, reinforcing various components of the colonic defence barrier and decreasing oxidative stress. In addition, butyrate may promote satiety. Two important mechanisms include the inhibition of nuclear factor kappa B activation and histone deacetylation. However, the observed effects of butyrate largely depend on concentrations and models used and human data are still limited. CONCLUSION: Although most studies point towards beneficial effects of butyrate, more human in vivo studies are needed to contribute to our current understanding of butyrate-mediated effects on colonic function in health and disease.

Nutritional aspects in patients with functional gastrointestinal disorders and motor dysfunction in the gut. Working team report of the Swedish Motility Group (SMoG).

In reviews regarding the management of patients with functional gastrointestinal disorders and motility disturbances within the gut nutritional aspects and dietary advice is often put forward as being of great importance. However, there are relatively few high-quality, interventional studies in the literature supporting an important role for general dietary advice to improve symptoms in these patients. Nutritional supplementation to patients with malnutrition due to severe dysfunction of the gastrointestinal tract is of course less controversial, even though different views on how this should be performed exist. The content of this article is based on presentations given by the authors during the second meeting of the Swedish Motility Group held in Gothenburg in March 2005, and aims to give an overview on the role of dietary advice and nutritional supplementation to patients with gastrointestinal dysfunction of different severity.

Altered omega-3 polyunsaturated fatty acid status in depressed post-myocardial infarction patients.

OBJECTIVE: Lower levels of long-chain omega-3 polyunsaturated fatty acids (n-3 LCPUFAs) and increased inflammation have been associated with both depressive disorder and myocardial infarction (MI). The present study investigated whether patients who develop depression post-MI, have higher arachidonic acid/eicosapentanoic acid (AA/EPA) ratios than non-depressed post-MI patients and whether depressed post-MI patients have signs of increased inflammation as measured by C-reactive protein (CRP). METHOD: Serum AA/EPA ratio and plasma CRP levels were quantified in 50 post-MI patients, of which 29 were depressed and 21 non-depressed. RESULTS: Compared with the non-depressed group, depressed post-MI patients had significantly higher AA/EPA ratios. No significant difference was observed in CRP levels. CONCLUSION: Depressed post-MI patients had lower levels of n-3 LCPUFAs as measured by mean AA/EPA ratio and no signs of increased inflammation as determined by CRP levels.

Gastric digestion of bovine lactoferrin in vivo in adults.

Lactoferrin (LF), an iron-binding glycoprotein present in milk and other endocrine and exocrine secretions, may exert a number of physiologic effects in the intestines. To study the effects of oral LF supplementation in vivo in the gastrointestinal tract, information about the gastric survival of LF in vivo is important. We tested 12 healthy volunteers (age 21 +/- 0.3 y) on 3 separate d according to a randomized, cross-over design. A test drink containing 4.5 g of bovine LF (20% iron-saturated LF; apoLF) in the presence of a gastric pH buffer (0.1 mol/L sodium citrate/citric acid; apoLFbuf), apoLF without the buffer (apoLF) or iron-saturated LF (holoLF) was administered into the stomach using nasogastric intubation. Gastric emptying rate, determined by a marker dilution technique, did not differ among any of these drinks. Gastric survival of LF, analyzed by gel permeation chromatography under denaturing conditions, was 64%, 62% and 79% after consumption of the apoLFbuf, apoLF and holoLF test drinks, respectively. Addition of the gastric pH buffer initially lowered intragastric pH because of its hydroxide buffering effect. However, it did not elevate intragastric pH over a prolonged period and thereby inhibit intragastric LF breakdown. We conclude that after oral administration, substantial amounts of apoLF and holoLF survive gastric transit.

Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.

OBJECTIVE: Malnutrition is observed frequently in patients with inflammatory bowel disease (IBD). Knowledge of the nutritional status in patients with recently diagnosed IBD is limited. The aim of this study was to establish a comprehensive picture of the nutritional status in recently diagnosed IBD patients. SUBJECTS: Sixty-nine IBD patients (23 Crohn's disease (CD) and 46 with ulcerative colitis (UC)) within 6 months of diagnosis and 69 age- and sex-matched population controls were included in the study. METHODS: The nutritional status was assessed by: (1) body composition (anthropometry and dual-energy X-ray absorptiometry); (2) dietary intake (dietary history); (3) biochemical indexes of nutrition; and (4) muscle strength (isokinetic dynamometer). RESULTS: Body weight and body mass index were significantly lower in UC patients compared with controls. The mean daily intake of carbohydrates was significantly higher in CD patients and the intakes of protein, calcium, phosphorus, and riboflavin were significantly lower in UC patients compared with controls, respectively. Serum concentrations of several nutrients (beta-carotene, magnesium, selenium and zinc) were significantly lower in UC patients compared with controls. Serum vitamin B12 concentration was significantly lower in CD patients. Muscle strength did not significantly differ between IBD patients and controls. CONCLUSIONS: This study showed that the nutritional status of IBD patients was already affected negatively at time of diagnosis. It needs to be elucidated whether nutritional supplementation in recently diagnosed IBD patients may improve the clinical course of the disease.

Nutritional supplementation with N-3 fatty acids and antioxidants in patients with Crohn's disease in remission: effects on antioxidant status and fatty acid profile.

In patients with Crohn's disease (CD), malnutrition is frequently observed and is generally accepted to be an important issue. The aim of this study was to investigate the effects of 3 months of supplementation with a liquid formula containing either antioxidants (AO) or n-3 fatty acids plus AO on the antioxidant status and fatty acid profile of plasma phospholipids and adipose tissue, respectively, in patients with long-standing CD currently in remission. In a randomized, double-blind placebo-controlled study, CD patients received either placebo, AO, or n-3 fatty acids plus AO for 3 months in addition to their regular diet. In all, 25/37 CD patients completed the study. AO status was assessed by blood biochemical parameters. A statistical per-protocol analysis was performed. Serum concentrations of selenium, vitamin C, and vitamin E, the activity of superoxide dismutase and total antioxidant status were significantly (p < 0.05) increased after AO supplementation. Furthermore, compared with controls, serum concentrations of beta-carotene, selenium, and vitamin C and the activity of glutathione peroxidase (GPx) were significantly (p < 0.05) lower before supplementation; however, after AO supplementation these levels were not significantly different from controls (except for GPx). N-3 fatty acids plus AO supplementation significantly (p < 0.05) decreased the proportion of arachidonic acid, and increased the proportion of eicosapentanoic acid and docosahexanoic acid in both plasma phospholipids and adipose tissue. Supplementation with antioxidants improved antioxidant status in patients with CD in remission. In addition, supplementation with n-3 fatty acids plus antioxidants significantly changed the eicosanoid precursor profile, which may lead to the production of eicosanoids with attenuated proinflammatory activity. This study indicates that an immunomodulating formula containing n-3 fatty acids and/or AO may have the potential to play a role in the treatment of CD.

[Gastrointestinal surgery and gastroenterology. X. Obstipation: treatment]. / Gastro-intestinale chirurgie en gastro-enterologie. X. Obstipatie: behandeling.

Treatment of the symptom of constipation is usually symptomatic. Correction of abnormal lifestyle and dietary habits may constitute a sufficient treatment of constipation. In addition, bulk-forming agents and osmotically active laxatives may be used. Only when these measurements are insufficiently effective, may more drastic treatment options such as contact laxatives and enemas may be used. In cases of spastic pelvic floor syndrome physiotherapy of the pelvic floor is indicated.

Nutrition and inflammatory bowel disease: an update.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory process, the aetiology of which remains unknown. Nutrition may play an important role in the pathogenesis and treatment of IBD. The evidence regarding the role of specific dietary components in the pathogenesis of IBD is still inconclusive. Many studies have been subject to methodological limitations; studies of better design are necessary to confirm the hypothesis that nutritional factors may indeed play a role in the development of IBD. Several studies have reported nutritional and functional deficiencies in IBD patients, especially in Crohn's disease. It is, however, hard to discriminate between disease-induced and malnutrition-induced changes in nutritional parameters. Maintaining adequate nutritional status has been suggested to be beneficial to the course of the disease in IBD. Studies have provided further insight into the possible beneficial effects of nutritional supplementation as primary and adjunctive therapy in IBD. The effects of specific nutritional therapy may be caused by alterations in intestinal flora and hence in the production of intraluminal proinflammatory substances. Immunonutrients such as n-3 fatty acids and antioxidants may also play a role in the treatment of IBD. In this paper, the relation between nutritional aetiological factors, nutritional status and nutritional therapy is discussed in detail.

Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls.

OBJECTIVES: Fatty acid metabolism is involved in the immune response and inflammation processes in patients with Crohn's disease (CD). Fatty acid changes may be relevant to the clinical course of the disease. The aim of this study was to compare the qualitative and quantitative fat intake and fatty acid composition of plasma phospholipids and adipose tissue in a defined population of CD patients with those in matched controls. METHODS: Dietary fat intake and fatty acid profile of plasma phospholipids and adipose tissue were assessed in two patient populations: 20 patients with recently diagnosed CD and 32 patients with longstanding (> 10 yr) CD clinically in remission, matched for age and gender with healthy controls. RESULTS: We observed no significant differences in quantitative or qualitative fat intake between CD patients and controls. Percentages of linoleic acid and alpha-linolenic acid in plasma phospholipids or adipose tissue were not significantly different between patients and controls. However, we observed a significantly (p < 0.05) lower percentage of the sum of the n-3 fatty acids, with significantly (p < 0.01) higher levels of clupanodonic acid (22:5n-3) and significantly (p < 0.05) lower levels of docosahexaenoic (22:6n-3) and arachidonic acid (20:4n-6). The aberrant fatty acid profile was more evident in patients with longstanding CD than in patients with recently diagnosed CD. CONCLUSION: The aberrant fatty acid profile found in these CD patients is a result of altered metabolism rather than of essential fatty acid malabsorption. The reported findings may be important in the pathophysiology of CD and hence in the choice of fatty acids to be used when therapeutic supplementation is considered in CD patients.

Effect of different starchy foods in composite meals on gastric emptying rate and glucose metabolism. I. Comparisons between potatoes, rice and white beans.

Thirteen healthy subjects participated in the study. Three meals of equal energy content consisting of hamburgers and mashed potatoes, polished rice or white beans were studied. The various meals were labelled with 2.6 MBq 51Cr and gastric emptying was studied by a movable NaI (T1) detector. Blood glucose and plasma insulin were measured after an overnight fast and after ingestion of the testmeal. Gastric emptying of mashed potatoes was faster than that of polished rice (P less than 0.02) and of white beans (P less than 0.05). Blood glucose and plasma insulin responses to the meal with mashed potatoes were greater than to that with polished rice (P less than 0.01), which also produced a greater glucose response than that with white beans (P less than 0.01). The correlation coefficient (rs) between difference in gastric emptying and difference in blood glucose or plasma insulin response was 0.95 (P less than 0.01) when comparing meals of mashed potatoes and polished rice. No correlation was found between gastric emptying and blood glucose or plasma insulin after the white bean meal. We conclude that glucose and insulin responses to potatoes and rice are strongly related to gastric emptying rate, but other factors dominate the control of these responses to white beans.