Therapist telephone-delivered CBT and web-based CBT compared with treatment as usual in refractory irritable bowel syndrome: the ACTIB three-arm RCT.

BACKGROUND: Irritable bowel syndrome (IBS) affects 10-22% of people in the UK. Abdominal pain, bloating and altered bowel habits affect quality of life and can lead to time off work. Current treatment relies on a positive diagnosis, reassurance, lifestyle advice and drug therapies, but many people suffer ongoing symptoms. Cognitive-behavioural therapy (CBT) is recommended in guidelines for patients with ongoing symptoms but its availability is limited. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of therapist telephone-delivered CBT (TCBT) and web-based CBT (WCBT) with minimal therapist support compared with treatment as usual (TAU) in refractory IBS. DESIGN: This was a three-arm randomised controlled trial. SETTING: This trial took place in UK primary and secondary care. PARTICIPANTS: Adults with refractory IBS (clinically significant symptoms for 12 months despite first-line therapies) were recruited from 74 general practices and three gastroenterology centres from May 2014 to March 2016. INTERVENTIONS: TCBT - patient CBT self-management manual, six 60-minute telephone sessions over 9 weeks and two 60-minute booster sessions at 4 and 8 months (8 hours' therapist time). WCBT - interactive, tailored web-based CBT, three 30-minute telephone sessions over 9 weeks and two 30-minute boosters at 4 and 8 months (2.5 hours' therapist time). MAIN OUTCOME MEASURES: Primary outcomes - IBS symptom severity score (IBS SSS) and Work and Social Adjustment Scale (WSAS) at 12 months. Cost-effectiveness [quality-adjusted life-years (QALYs) and health-care costs]. RESULTS: In total, 558 out of 1452 patients (38.4%) screened for eligibility were recruited - 186 were randomised to TCBT, 185 were randomised to WCBT and 187 were randomised to TAU. The mean baseline Irritable Bowel Syndrome Symptom Severity Score (IBS SSS) was 265.0. An intention-to-treat analysis with multiple imputation was carried out at 12 months; IBS SSS were 61.6 points lower in the TCBT arm [95% confidence interval (CI) 89.5 to 33.8; p < 0.001] and 35.2 points lower in the WCBT arm (95% CI 57.8 to 12.6; p = 0.002) than in the TAU arm (IBS SSS of 205.6). The mean WSAS score at 12 months was 10.8 in the TAU arm, 3.5 points lower in the TCBT arm (95% CI 5.1 to 1.9; p < 0.001) and 3.0 points lower in the WCBT arm (95% CI 4.6 to 1.3; p = 0.001). For the secondary outcomes, the Subject's Global Assessment showed an improvement in symptoms at 12 months (responders) in 84.8% of the TCBT arm compared with 41.7% of the TAU arm [odds ratio (OR) 6.1, 95% CI 2.5 to 15.0; p < 0.001] and 75.0% of the WCBT arm (OR 3.6, 95% CI 2.0 to 6.3; p < 0.001). Patient enablement was 78.3% (responders) for TCBT, 23.5% for TAU (OR 9.3, 95% CI 4.5 to 19.3; p < 0.001) and 54.8% for WCBT (OR 3.5, 95% CI 2.0 to 5.9; p < 0.001). Adverse events were similar between the trial arms. The incremental cost-effectiveness ratio (ICER) (QALY) for TCBT versus TAU was £22,284 and for WCBT versus TAU was £7724. Cost-effectiveness reduced after imputation for missing values. Qualitative findings highlighted that, in the CBT arms, there was increased capacity to cope with symptoms, negative emotions and challenges of daily life. Therapist input was important in supporting WCBT. CONCLUSIONS: In this large, rigorously conducted RCT, both CBT arms showed significant improvements in IBS outcomes compared with TAU. WCBT had lower costs per QALY than TCBT. Sustained improvements in IBS symptoms are possible at an acceptable cost. Suggested future research work is longer-term follow-up and research to translate these findings into usual clinical practice. FUTURE WORK: Longer-term follow-up and research to translate these findings into usual clinical practice is needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN44427879. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme and will be published in full in Health Technology Assessment; Vol. 23, No. 17. See the NIHR Journals Library website for further project information. The University of Southampton sponsored this study. Funding was received from the NIHR HTA Board and the NIHR Clinical Research Network and support was received from the NIHR Clinical Research Network.

Irritable bowel syndrome (IBS) is a common bowel disorder causing pain, bloating and diarrhoea or constipation, which can affect quality of life. Treatment relies on a positive diagnosis, reassurance, lifestyle advice and drug therapies. However, many patients suffer ongoing distressing symptoms. Guidelines recommend cognitive­behavioural therapy (CBT) for patients with ongoing IBS symptoms. However, access to therapy is limited because of cost and therapist availability. We previously developed web-based CBT (WCBT), which is more accessible, less expensive and requires less therapist time than traditional therapist telephone-delivered CBT (TCBT). The aim of the current trial was to assess the clinical effectiveness and cost-effectiveness of these two approaches. Participants were randomly assigned to TCBT, WCBT or treatment as usual (TAU). The TCBT group received a CBT manual and six 1-hour telephone CBT sessions with trained therapists over 9 weeks and two booster sessions at 4 and 8 months. The WCBT group received access to the interactive CBT website with eight online sessions at home over 9 weeks, with similar content to the therapist CBT, and received three 30-minute therapist telephone-delivered CBT sessions and two boosters at 4 and 8 months. There were 558 adults with ongoing IBS symptoms who took part from 74 general practice surgeries and three hospital clinics in London and the south of England. The main study outcomes were the IBS Symptom Severity Score and the Work and Social Adjustment Scale, which measures people's ability to function and live their lives. The results of these were collected at the start of the study and at 3, 6 and 12 months. Significant improvement in symptoms was found in the two therapy groups compared with TAU at 3, 6 and 12 months. Cost-effectiveness and wider benefits (e.g. ability to cope and mood) also showed positive results, indicating that sustained improvements in IBS symptoms are possible at an acceptable cost.

Sugar Restriction Leads to Increased Ad Libitum Sugar Intake by Overweight Adolescents in an Experimental Test Meal Setting.

BACKGROUND: The impact of sugar restriction on subsequent sugar intake by overweight adolescents is unknown. OBJECTIVE: Our aim was to examine the effect of sugar restriction on subsequent ad libitum sugar intake by overweight adolescents and whether habitual sugar intake and impulsivity influence the effect of sugar restriction on subsequent sugar intake. DESIGN: This was an in-laboratory crossover feeding trial with sugar-exposure and sugar-restriction conditions. PARTICIPANTS/SETTING: Eighty-seven overweight Latino and African-American adolescents underwent both meal conditions in two separate 8-hour in-laboratory visits. INTERVENTION: Participants had access to ad libitum snack trays for 3 hours after the condition-specific meals. MAIN OUTCOME MEASURES: Ad libitum sugar intake during the snack period was measured at each visit. Habitual sugar intake and impulsivity were assessed at baseline. STATISTICAL ANALYSES PERFORMED: Repeated measures analysis of covariance was used to examine the within-person effect of meal condition on ad libitum sugar intake. Mixed models were used to examine the moderating effects of habitual sugar intake and impulsivity on the meal condition-ad libitum sugar intake relationship. RESULTS: Participants consumed more ad libitum sugar during the snack period in the sugar-restriction condition than in the sugar-exposure condition (sugar restriction=78.63±38.84 g, sugar exposure=70.86±37.73 g; F=9.64, P=0.002). There was no relationship between habitual sugar intake and how much ad libitum sugar participants consumed during either condition. Higher impulsivity was associated with greater ad libitum sugar intake during both conditions (sugar restriction: b=.029, standard error=.01, P<0.05; sugar exposure: b=.034, standard error=.01, P<0.05). CONCLUSIONS: Findings suggest that overweight adolescents restricted from sugar intake consume greater amounts of sugar when they are later given access to high-sugar foods. Overweight adolescents with higher impulsivity appear to consume greater amounts of sugar regardless of previous levels of sugar consumption. Compensatory sugar intake and trait impulsivity may have implications for dietary interventions in this population.

The impact of sugar sweetened beverage intake on hunger and satiety in minority adolescents.

Limited research has examined the effects of habitual SSB consumption on hunger/fullness ratings and gut hormones. This study hypothesized that high versus low intakes of habitual SSBs would result in greater hunger, decreased fullness, and a blunted gut hormone response, however the high versus low fiber group would exhibit decreased hunger and increased fullness. This was a randomized crossover feeding trial with 47 African American and Hispanic adolescents. The experiment included three 24-hour recalls to assess habitual dietary intake. During the test meal phase, subjects were served breakfast and lunch. During the ad libitum meal phase, subjects were fed an ad libitum dinner. During the test meal phase, blood was drawn every 30 minutes for 3 hours. During the ad libitum meal phase, hunger and fullness visual analogue scales were completed. For this analysis, subjects were grouped into the following habitual SSB categories: low SSB (≤1 SSB serv/day), medium SSB (>1 - <2 serv/day), and high SSB (≥2 serv/day). Fiber categories were created based on quartiles of intake. Mixed modeling was used to explore how SSB and fiber categories predicted ghrelin/PYY values and hunger/fullness ratings across time within and between test meals. The following a priori covariates included: sex, ethnicity, age, and obesity status. The low SSB group had higher fullness ratings over the ad libitum meal compared to the high SSB group (ß =-0.49, CI=(-0.89, -0.08), p=0.02) and higher ghrelin concentrations than the medium and high SSB group over the test meal phase (ß =-1.86, CI=(-2.81, -0.92), p<0.01). Habitual SSB intake appears to play a key role in moderating fullness responses possibly via ghrelin.

Effects of high-sugar and high-fiber meals on physical activity behaviors in Latino and African American adolescents.

OBJECTIVE: This crossover experimental study examined the acute effects of high-sugar/low-fiber (HSLF) vs. low-sugar/high-fiber (LSHF) meals on sedentary behavior (SB) and light-plus activity (L+) in minority adolescents with overweight and obesity. METHODS: 87 Latino and African American adolescents (mean age = 16.3 ± 1.2 years, mean BMI z-score = 2.02 ± 0.52, 56.8% Latino, 51.1% male) underwent two experimental meal conditions during which they consumed HSLF or LSHF meals. Physical activity and SB were measured using accelerometers, and blood glucose and insulin were collected every 30 minutes over 5 hours. Mixed models were used to examine the temporal trends of SB and L+, whether the temporal trends of SB and L+ differed by meal condition, and the influence of blood glucose and insulin on the activity behaviors. RESULTS: SB and L+ fluctuated over time during the HSLF condition but were stable during the LSHF condition. SB and L+ were influenced by the blood glucose response to the HSLF meals. Insulin did not influence SB or L+ in either meal condition. CONCLUSIONS: Sugar and fiber content of meals can have differing acute impacts on activity behaviors in minority adolescents with overweight and obesity, possibly due to differing metabolic responses.

Association of usual self-reported dietary intake with ecological momentary measures of affective and physical feeling states in children.

BACKGROUND: Little is known about the relationship between dietary intake and affective and physical feeling states in children. PURPOSE: The current study used Ecological Momentary Assessment (EMA) to examine how usual dietary intake is cross-sectionally associated with both average affective and physical feeling state ratings and rating variability in children. METHODS: Children (N = 110, mean age = 11.0 ± 1.2 years, 52.5% male, 30.1% Hispanic/Latino) completed EMA measures of affective and physical feeling states 3-7 times per day for a full or partial day (weekday evenings and weekend days and evenings) over a 4-day period. Usual intake of pre-selected dietary components was measured prior to the EMA measurement period using the Block Kids Food Screener. Statistical analyses included mixed models and mixed-effects location scale models. RESULTS: Greater usual fiber intake was cross-sectionally associated with higher average positive affect (PA) ratings, lower variability of NA ratings, and higher variability of physical fatigue ratings. Lower usual glycemic load of diet was cross-sectionally associated with lower variability of NA ratings. Lower usual added sugar intake was cross-sectionally associated with higher average physical energy ratings and lower variability of NA ratings. CONCLUSIONS: Although temporal precedence was not established by these findings, they indicate that characteristics of children's usual dietary intake are cross-sectionally associated with both the average and variability of affective and physical feeling states. EMA offers a promising avenue through which to explore the associations between affective states and diet and has the potential to provide insight into nuances of this relationship.

Mindfulness meditation and improvement in sleep quality and daytime impairment among older adults with sleep disturbances: a randomized clinical trial.

IMPORTANCE: Sleep disturbances are most prevalent among older adults and often go untreated. Treatment options for sleep disturbances remain limited, and there is a need for community-accessible programs that can improve sleep. OBJECTIVE: To determine the efficacy of a mind-body medicine intervention, called mindfulness meditation, to promote sleep quality in older adults with moderate sleep disturbances. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial with 2 parallel groups conducted from January 1 to December 31, 2012, at a medical research center among an older adult sample (mean [SD] age, 66.3 [7.4] years) with moderate sleep disturbances (Pittsburgh Sleep Quality Index [PSQI] >5). INTERVENTIONS: A standardized mindful awareness practices (MAPs) intervention (n = 24) or a sleep hygiene education (SHE) intervention (n = 25) was randomized to participants, who received a 6-week intervention (2 hours per week) with assigned homework. MAIN OUTCOMES AND MEASURES: The study was powered to detect between-group differences in moderate sleep disturbance measured via the PSQI at postintervention. Secondary outcomes pertained to sleep-related daytime impairment and included validated measures of insomnia symptoms, depression, anxiety, stress, and fatigue, as well as inflammatory signaling via nuclear factor (NF)-κB. RESULTS: Using an intent-to-treat analysis, participants in the MAPs group showed significant improvement relative to those in the SHE group on the PSQI. With the MAPs intervention, the mean (SD) PSQIs were 10.2 (1.7) at baseline and 7.4 (1.9) at postintervention. With the SHE intervention, the mean (SD) PSQIs were 10.2 (1.8) at baseline and 9.1 (2.0) at postintervention. The between-group mean difference was 1.8 (95% CI, 0.6-2.9), with an effect size of 0.89. The MAPs group showed significant improvement relative to the SHE group on secondary health outcomes of insomnia symptoms, depression symptoms, fatigue interference, and fatigue severity (P < .05 for all). Between-group differences were not observed for anxiety, stress, or NF-κB, although NF-κB concentrations significantly declined over time in both groups (P < .05). CONCLUSIONS AND RELEVANCE: The use of a community-accessible MAPs intervention resulted in improvements in sleep quality at immediate postintervention, which was superior to a highly structured SHE intervention. Formalized mindfulness-based interventions have clinical importance by possibly serving to remediate sleep problems among older adults in the short term, and this effect appears to carry over into reducing sleep-related daytime impairment that has implications for quality of life. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01534338.

Community-Based Mindfulness Program for Disease Prevention and Health Promotion: Targeting Stress Reduction.

PURPOSE: Poorly managed stress leads to detrimental physical and psychological consequences that have implications for individual and community health. Evidence indicates that U.S. adults predominantly use unhealthy strategies for stress management. This study examines the impact of a community-based mindfulness training program on stress reduction. DESIGN: This study used a one-group pretest-posttest design. SETTING: The study took place at the UCLA Mindful Awareness Research Center in urban Los Angeles. SUBJECTS: A sample of N = 127 community residents (84% Caucasian, 74% female) were included in the study. INTERVENTION: Participants received mindfulness training through the Mindful Awareness Practices (MAPs) for Daily Living I. MEASURES: Mindfulness, self-compassion, and perceived stress were measured at baseline and postintervention. ANALYSIS: Paired-sample t-tests were used to test for changes in outcome measures from baseline to postintervention. Hierarchical regression analysis was fit to examine whether change in self-reported mindfulness and self-compassion predicted postintervention perceived stress scores. RESULTS: There were statistically significant improvements in self-reported mindfulness (t = -10.67, p < .001, d = .90), self-compassion (t = -8.50, p < .001, d = .62), and perceived stress (t = 9.28, p < .001, d = -.78) at postintervention. Change in self-compassion predicted postintervention perceived stress (ß = -.44, t = -5.06, p < .001), but change in mindfulness did not predict postintervention perceived stress (ß = -.04, t = -.41, p = .68). CONCLUSION: These results indicate that a community-based mindfulness training program can lead to reduced levels of psychological stress. Mindfulness training programs such as MAPs may offer a promising approach for general public health promotion through improving stress management in the urban community.

Association between home availability and vegetable consumption in youth: a review.

OBJECTIVE: To systematically review literature examining the association between vegetable home availability and vegetable intake in youth. DESIGN: Articles were identified through December 2012 using a search of PubMed, PsychINFO and OVID/Medline databases, using the following keywords in varying combinations: home, environment, availability, vegetable, intake, consumption, children. Quantitative studies examining home vegetable availability and vegetable intake in children and adolescents were included. Fifteen studies were included that met inclusion criteria. SETTING: Studies were conducted in the USA (n 8), Australia (n 1), Greece (n 1), Iceland (n 1), Denmark (n 1), the UK (n 1), the Netherlands (n 1) and a combination of nine European countries (n 1). SUBJECTS: Various populations of children and adolescents were examined. RESULTS: Seven of the studies (47 %) found a positive association between vegetable availability and intake, with the others reporting null findings. There were no clear patterns of association by study design, age of subjects included, comprehensiveness of measures, or inclusion of covariates in analyses. Child report of home availability was associated with child vegetable intake (n 6, all found a positive association), while parent report of home availability was only minimally associated (n 9, one found a positive association; P=0.001 from post hoc Fisher's exact test comparing parent v. child report). CONCLUSIONS: Parent perception of availability may be closer to truth, given the parental role in food shopping and preparation. Therefore, to impact child vegetable intake, absolute availability may not be as important as child perception of vegetables in the home. Child perception of availability may be altered by level of familiarity with vegetables.

Mindfulness-based intervention for prodromal sleep disturbances in older adults: design and methodology of a randomized controlled trial.

Sleep problems are prevalent among older adults, often persist untreated, and are predictive of health detriments. Given the limitations of conventional treatments, non-pharmacological treatments such as mindfulness-based interventions (MBIs) are gaining popularity for sleep ailments. However, nothing is yet known about the impact of MBIs on sleep in older adults with prodromal sleep disturbances. This article details the design and methodology of a 6-week parallel-group RCT calibrated to test the treatment effect of the Mindful Awareness Practices (MAPs) program versus sleep hygiene education for improving sleep quality, as the main outcome, in older adults with prodromal sleep disturbances. Older adults with current sleep disturbances will be recruited from the urban Los Angeles community. Participants will be randomized into two standardized treatment conditions, MAPs and sleep hygiene education. Each condition will consist of weekly 2-hour group-based classes over the course of the 6-week intervention. The primary objective of this study is to determine if mindfulness meditation practice as engaged through the MAPs program leads to improved sleep quality relative to sleep hygiene education in older adults with prodromal sleep disturbances.

Vegetable consumption is linked to decreased visceral and liver fat and improved insulin resistance in overweight Latino youth.

There are limited data on the influence of vegetable consumption on adiposity and metabolic health, specifically nonstarchy vegetables and vegetables that are dark green and deep orange/yellow (also known as nutrient-rich vegetables). Our study examines the relationship between vegetable intake and adiposity, liver fat, and insulin dynamics in overweight Latino youth. This cross-sectional study of 175 overweight (body mass index ≥85th percentile) Latino youth (aged 8 to 18 years), with data collected during 2006-2011, included the following: dietary intake via multiple 24-hour recalls, total body fat via dual-energy x-ray absorptiometry, adipose tissue distribution and liver fat via magnetic resonance imaging, and insulin dynamics via frequently sampled intravenous glucose tolerance test. Linear regression and analysis of covariance were used for analysis, with the following a priori covariates: age, sex, energy intake, and total body fat. Participants who consumed the most nonstarchy vegetables (mean intake=1.7±1.0 servings/day) compared with the least (mean intake=0.1±0.1 servings/day) had 44% less liver fat (10.0%±8.5% vs 5.6%±8.7%; P=0.01). Nutrient-rich vegetable intake was positively correlated with insulin sensitivity (r=0.19; P=0.03). Consumers of nutrient-rich vegetables (mean intake=0.3±0.4 servings/day [n=107]), compared with nonconsumers (n=68), had 31% increased insulin sensitivity (1.6±1.6 vs 2.1±1.3×10(⁻4)/min/µU/mL; P=0.03) and 17% less visceral adipose tissue (2.3±0.9 vs 1.9±0.7 L; P=0.01). Consumption of specific vegetable types by overweight Latino youth is associated with positive metabolic outcomes, including reduced visceral and liver fat and risk factors for type 2 diabetes, even when consumed in small quantities. These may be relevant targets for interventions.

Behavioral contributions to the pathogenesis of type 2 diabetes.

Behavioral contributions to the pathogenesis of prediabetes and Type 2 diabetes (T2D) include lifestyle behaviors including dietary intake, exercise, sedentariness, sleep, and stress. The purpose of this paper is to review evidence for the metabolic pathways by which the behavior is linked to T2D. Evidence for interventions, which change each of the lifestyle behaviors, is discussed. The article will close with a brief discussion on how new technologies may provide opportunities to better understand relationships between moment-to-moment fluctuations in behaviors and diabetes pathogenesis, as well as provide opportunities to personalize and adapt interventions to achieve successful behavior change and maintenance of that change. Especially promising are new technologies, which assist in tracking lifestyle behaviors along with clinical and metabolic outcomes.

mHealth approaches to child obesity prevention: successes, unique challenges, and next directions.

Childhood obesity continues to be a significant public health issue. mHealth systems offer state-of-the-art approaches to intervention design, delivery, and diffusion of treatment and prevention efforts. Benefits include cost effectiveness, potential for real-time data collection, feedback capability, minimized participant burden, relevance to multiple types of populations, and increased dissemination capability. However, these advantages are coupled with unique challenges. This commentary discusses challenges with using mHealth strategies for child obesity prevention, such as lack of scientific evidence base describing effectiveness of commercially available applications; relatively slower speed of technology development in academic research settings as compared with industry; data security, and patient privacy; potentially adverse consequences of increased sedentary screen time, and decreased focused attention due to technology use. Implications for researchers include development of more nuanced measures of screen time and other technology-related activities, and partnering with industry for developing healthier technologies. Implications for health practitioners include monitoring, assessing, and providing feedback to child obesity program designers about users' data transfer issues, perceived security and privacy, sedentary behavior, focused attention, and maintenance of behavior change. Implications for policy makers include regulation of claims and quality of apps (especially those aimed at children), supporting standardized data encryption and secure open architecture, and resources for research-industry partnerships that improve the look and feel of technology. Partnerships between academia and industry may promote solutions, as discussed in this commentary.

Current mHealth technologies for physical activity assessment and promotion.

CONTEXT: Novel mobile assessment and intervention capabilities are changing the face of physical activity (PA) research. A comprehensive systematic review of how mobile technology has been used for measuring PA and promoting PA behavior change is needed. EVIDENCE ACQUISITION: Article collection was conducted using six databases from February to June 2012 with search terms related to mobile technology and PA. Articles that described the use of mobile technologies for PA assessment, sedentary behavior assessment, and/or interventions for PA behavior change were included. Articles were screened for inclusion and study information was extracted. EVIDENCE SYNTHESIS: Analyses were conducted from June to September 2012. Mobile phone-based journals and questionnaires, short message service (SMS) prompts, and on-body PA sensing systems were the mobile technologies most utilized. Results indicate that mobile journals and questionnaires are effective PA self-report measurement tools. Intervention studies that reported successful promotion of PA behavior change employed SMS communication, mobile journaling, or both SMS and mobile journaling. CONCLUSIONS: mHealth technologies are increasingly being employed to assess and intervene on PA in clinical, epidemiologic, and intervention research. The wide variations in technologies used and outcomes measured limit comparability across studies, and hamper identification of the most promising technologies. Further, the pace of technologic advancement currently outstrips that of scientific inquiry. New adaptive, sequential research designs that take advantage of ongoing technology development are needed. At the same time, scientific norms must shift to accept "smart," adaptive, iterative, evidence-based assessment and intervention technologies that will, by nature, improve during implementation.

Role of single nucleotide polymorphisms of pro-inflammatory cytokine genes in the relationship between serum lipids and inflammatory parameters, and the lipid-lowering effect of fish oil in healthy males.

BACKGROUND AND AIMS: Lipid metabolism, obesity and inflammation are intimately related. Plasma triglycerides increase during the inflammatory response to pathogens and obesity increases inflammatory stress. Pro-inflammatory cytokines are secreted by adipocytes in uninfected obese subjects. Polymorphisms (SNPs) in cytokine genes influence the intensity of cytokine production and inflammatory stress. Fish oil has lipid-lowering and anti-inflammatory properties. The influence of cytokine gene polymorphisms on the interaction between adiposity, inflammation and the properties of fish oil is unknown. METHODS: Fasting plasma triglycerides, acute phase proteins and BMI were studied in 159 healthy men and the effect of 6 g/d fish oil for 12 weeks on the former two parameters studied. Subjects were genotyped for SNPs at positions -511, -174, +252 and -308 in the IL-1beta, IL-6, LT-alpha (TNF-beta) and TNF-alpha genes, respectively. Data were divided into three sub-groups of BMI, 16.7-22.8, 22.9-24.9 and 25.1-33.7 kg/m2, respectively. RESULTS: Correlations were apparent between CRP and triglycerides in the highest tertile r = 0.324, P < 0.05 and between CRP and serum amyloid in all tertiles. Mean concentrations of all three molecules were higher in the middle and highest tertile than in the lowest. Irrespective of BMI, CRP and triglycerides were positively correlated in subjects with a TNF-alpha-308GG, LT-alpha AG, IL-1beta-511TT and IL-6-174GG genotype. The latter three genotypes are associated with enhanced inflammation. Genotype and BMI interacted. Concentrations of triglyceride rose significantly with increasing tertile only in subjects with a LT-alpha AA genotype. CRP concentrations rose in subjects with a LT-alpha AG genotype. Triglycerides were lowered by fish oil. Pre-supplementation concentrations were correlated with the decrease, r = -0.494 P < 0.0001. Genotype influenced the effects of fish oil. A fall occurred in triglycerides, across tertiles of BMI, only in individuals possessing a LT-alpha+252 AA genotype. Irrespective of BMI, possession of an A allele of this SNP was necessary for the correlation to occur. CONCLUSIONS: Possession of genotypes associated with raised inflammatory stress strengthen the association between fasting plasma triglycerides and CRP. The ability of fish oil to exert a lipid-lowering, anti-inflammatory influence in healthy men is influenced by BMI and possession of the LT-alpha+252 A allele.

The ability of fish oil to suppress tumor necrosis factor alpha production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor alpha production.

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) mediates inflammation. High TNF-alpha production has adverse effects during disease. Polymorphisms in the TNF-alpha and lymphotoxin alpha genes influence TNF-alpha production. Fish oil suppresses TNF-alpha production and has variable antiinflammatory effects on disease. OBJECTIVE: We examined the relation between TNF-alpha and lymphotoxin alpha genotypes and the ability of dietary fish oil to suppress TNF-alpha production by peripheral blood mononuclear cells (PBMCs) in healthy men. DESIGN: Polymorphisms in the TNF-alpha (TNF*1 and TNF*2) and lymphotoxin alpha (TNFB*1 and TNFB*2) genes were determined in 111 healthy young men. TNF-alpha production by endotoxin-stimulated PBMCs was measured before and 12 wk after dietary supplementation with fish oil (6 g/d). RESULTS: Homozygosity for TNFB*2 was 2.5 times more frequent in the highest than in the lowest tertile of inherent TNF-alpha production. The percentage of subjects in whom fish oil suppressed TNF-alpha production was lowest (22%) in the lowest tertile and doubled with each ascending tertile. In the highest and lowest tertiles, mean TNF-alpha production decreased by 43% (P < 0.05) and increased by 160% (P < 0.05), respectively. In the lowest tertile of TNF-alpha production, only TNFB*1/TNFB*2 heterozygous subjects were responsive to the suppressive effect of fish oil. In the middle tertile, this genotype was 6 times more frequent than the other lymphotoxin alpha genotypes among responsive individuals. In the highest tertile, responsiveness to fish oil appeared unrelated to lymphotoxin alpha genotype. CONCLUSION: The ability of fish oil to decrease TNF-alpha production is influenced by inherent TNF-alpha production and by polymorphisms in the TNF-alpha and lymphotoxin alpha genes.