No Effect of High Eating Frequency Compared with Low Eating Frequency on Appetite and Inflammation Biomarkers: Results from a Randomized Crossover Clinical Trial.

BACKGROUND: Eating frequency (EF) focuses on the total number of eating occasions per day and may influence metabolic health. OBJECTIVES: We sought to examine the effect of high compared with low EF on appetite regulation and inflammatory biomarkers among healthy adults. METHODS: Data are from a randomized, crossover trial (the Frequency of Eating and Satiety Hormones study). Participants (n = 50) completed 2 isocaloric 21-d study periods of low EF (3 eating occasions/d) and high EF (6 eating occasions/d) in random order with a 14-d washout period in between. Participants were free-living and consumed their own food, using study-directed, structured meal plans with identical foods and total energy in both study periods. On days 1 and 21 of each EF period, fasting blood was collected during in-person clinic visits to assess plasma concentrations of ghrelin, leptin, adiponectin, and high-sensitivity C-reactive protein (hs-CRP). Linear mixed models with EF, diet sequence, and period as fixed effects and participant as random effect were used to estimate the intervention effect. Interaction effects between EF and body fat percentage were examined. RESULTS: Among the 50 participants who completed the trial, 39 (78%) were women, 30 (60%) were Non-Hispanic White, and 40 (80%) had a body mass index of <25 kg/m2, and the mean age was 32.1 y. The differences between high and low EF in fasting ghrelin (geometric mean difference: 17.76 ng/mL; P = 0.60), leptin (geometric mean difference: 2.09 ng/mL; P = 0.14), adiponectin (geometric mean difference: 381.7 ng/mL; P = 0.32), and hs-CRP (geometric mean difference: -0.018 mg/dL; P = 0.08) were not statistically significant. No significant interaction was observed between EF and body fat percentage on appetite regulation and inflammatory biomarkers. CONCLUSIONS: No differences was observed in fasting ghrelin, leptin, adiponectin, and hs-CRP comparing high and low EF. Future studies are needed to understand the physiology of EF and appetite as they relate to metabolic health. This trial was registered at clinicaltrials.gov as NCT02392897.

Randomized Trial Testing the Effects of Eating Frequency on Two Hormonal Biomarkers of Metabolism and Energy Balance.

BACKGROUND: Eating frequency (EF) may influence obesity-related disease risk by attenuating postprandial fluctuations in hormones involved in metabolism, appetite regulation, and inflammation. MATERIALS/METHODS: This randomized crossover intervention trial tested the effects of EF on fasting plasma insulin-like growth factor-I (IGF-1) and leptin. Fifteen subjects (4 males, 11 females) completed two eucaloric intervention phases lasting 21 days each: low EF ("low-EF"; 3 eating occasions/day) and high EF ("high-EF"; 8 eating occasions/day). Subjects were free-living and consumed their own meals using individualized structured meal plans with instruction from study staff. Subjects completed fasting blood draws and anthropometry on the first and last day of each study phase. The generalized estimated equations modification of linear regression tested the intervention effect on fasting serum IGF-1 and leptin. RESULTS: Mean (± SD) age was 28.5 ± 8.70 years, and mean (± SD) Body Mass Index was 23.3 (3.4) kg/m2. We found lower mean serum IGF-1 following the high-EF condition compared to the low-EF condition (P < 0.001). There was no association between EF and plasma leptin (P = 0.83). CONCLUSION: These results suggest that increased EF may lower serum IGF-1, which is a hormonal biomarker linked to increased risk of breast, prostate, and colorectal cancer.

Higher Eating Frequency Does Not Decrease Appetite in Healthy Adults.

BACKGROUND: Consumption of small, frequent meals is suggested as an effective approach to control appetite and food intake and might be a strategy for weight loss or healthy weight maintenance. Despite much speculation on the topic, scientific evidence is limited to support such a relation in the absence of changes to diet composition. OBJECTIVE: We examined the effects of high compared with low eating frequency (EF) on self-reported appetite as a secondary outcome in a controlled trial. METHODS: We conducted a randomized, crossover intervention trial in 12 participants (4 men, 8 women) who completed 2 isocaloric 3-wk intervention phases of low EF (3 eating occasions/d) compared with high EF (8 eating occasions/d). On the last morning of each study phase, participants completed a 4-h appetite testing session. During the appetite testing session, participants completing the low EF phase consumed a meal at 0800. Participants completing the high EF intervention consumed the same meal spread evenly over 2 eating occasions at 0800 and 1030. Standardized ratings of hunger, desire to eat, fullness, thirst, and nausea were completed every 30 min with the use of paper-and-pencil semianchored 100-mm visual analog scales. A composite appetite score was calculated as the mean of hunger, desire to eat, and the inverse of fullness (calculated as 100-fullness rating). Linear regression analysis compared ratings between low EF and high EF conditions. RESULTS: The mean composite appetite score was higher in the high EF condition for the total testing period (baseline through 1200) (P < 0.05) and for the time period from baseline through 1030 (P < 0.001). CONCLUSION: The results from this study in 12 healthy adults do not support the popularized notion that small, frequent meals help to decrease overall appetite. This trial was registered at clinicaltrials.gov as NCT02548026.

Eating frequency and risk of colorectal cancer.

PURPOSE: Eating frequency is a modifiable aspect of dietary behavior that may affect risk of colorectal cancer (CRC). Although most previous case-control studies indicate a positive association, two prospective studies suggest an inverse association between eating frequency and CRC risk, with evidence of effect modification by diet composition. We examined the association between eating frequency and CRC in a large, prospective cohort study, and explored whether this relationship was modified by sex, coffee consumption, or dietary glycemic load. METHODS: Between 2000 and 2002, 67,912 western Washington residents aged 50-76 reported average daily meal and snack frequency using a mailed questionnaire as part of the vitamins and lifestyle study. Participants were followed for CRC through linkage with SEER through 2008, over which time 409 CRC cases developed. Hazard Ratios and 95 % Confidence Intervals were obtained using Cox regression. RESULTS: In age- and sex-adjusted models higher (5+ times/d) vs. lower (1-2 times/d) eating frequency was associated with a HR of 0.62 (95 % CI 0.43-0.88, Ptrend = 0.001). However, following further adjustment for BMI, race/ethnicity, alcohol, and other known CRC risk factors, the relationship was no longer statistically significant (HR: 0.76; 95 % CI 0.51, 1.14). No effect modification was observed by sex (Pinteraction = 0.45), coffee consumption (Pinteraction = 0.44), or dietary glycemic load (Pinteraction = 0.90). In subgroup analyses by tumor site, higher vs. lower eating frequency was associated with lower risk for colon (HR 0.65 95 % CI 0.39-1.07, Ptrend = 0.04), but not rectal cancers (HR = 1.08 95 % CI 0.54-2.18, Ptrend = 0.94). CONCLUSION: The weak inverse association observed between eating frequency and CRC is consistent with findings from other prospective studies. Modification of this relationship by diet quality and participant characteristics should be considered in the future studies.

Developing a definition of biofortification through the synthesis of food biofortification publications: a scoping review protocol.

OBJECTIVE: The objective of this review is to develop a definition of biofortification through the synthesis of food biofortification publications and to document the breadth of the research on this topic. INTRODUCTION: Biofortification of a food source is a human health intervention. Due to the varying definitions of this concept, biofortification can be difficult to describe. Originally, biofortification was defined as the use of plant breeding methods to produce staple foods dense in minerals and vitamins. Research using the term focused on mineral, vitamin, and protein improvement of staple foods. However, the field has expanded to include non-staple foods as well as different methodological approaches to biofortification (eg, transgenic, molecular breeding). Researchers require a broad overview of the evidence and consensus on a definition to ensure effective communication within this scientific community. INCLUSION CRITERIA: Inclusion criteria will be broad to ensure that existing definitions of biofortification are captured across the different areas of study in this field. The review will consider research published in English. Inclusion will not be limited by participant type, date of publication, or context. The concept will be strictly biofortification. METHODS: A broad search strategy will be utilized for AGRICOLA, AGRIS, Web of Science, PubAg, CINAHL, PubMed, Cochrane Library, Epistemonikos, JBI Evidence Synthesis, Google Scholar, and Washington State University Libraries' integrated catalog. A limited search for gray literature will be conducted. The data extracted will include study and author characteristics. Tables and figures will demonstrate the breadth of the evidence.

Supplementing chicken broth with monosodium glutamate reduces hunger and desire to snack but does not affect energy intake in women.

The effect of monosodium glutamate (MSG) supplementation in soup or broth on satiety is not well understood. In the present study, the relative effects of four chicken broths with or without added MSG on motivational ratings and energy intakes at the next meal were compared using a double-blinded, within-subject design. A total of thirty-five normal-weight women, aged 20-40 years, took part in four study sessions. The four broths were base chicken broth (63 kJ), broth with added MSG (1.19 g) and nucleotides (0.03 g), broth with added MSG (1.22 g), and broth with added fat (BAF; 681 kJ). The preloads were presented twice at 09.00 and 11.15 hours for a maximum cumulative dose of 2.44 g MSG. Motivational ratings were collected before and at 15 min intervals post-ingestion for a total of 210 min. A test lunch meal was served at 12.00 hours, and plate waste was measured. The addition of MSG to chicken broth did not increase energy intakes at lunch or affect motivational ratings over the entire testing session. Both hunger and desire to snack between the second preload exposure and the test meal were significantly reduced in the MSG condition relative to the base broth condition (both, P = 0.03). However, only the BAF significantly suppressed energy intakes at lunch compared with the base broth control condition. Supplementing chicken broth with MSG can increase subjective ratings for satiety but does not alter energy intake at the next meal relative to an equal energy broth without added MSG.

Soluble fiber dextrin enhances the satiating power of beverages.

This study compared the effects of four types of fiber on satiety and energy intakes at the next meal using a standard double-blinded preload study design. Study participants (14 men and 22 women) each took part in 6 study sessions. Study preloads were a combination of a solid snack and a liquid beverage (energy range 0.78-0.83 MJ) containing four different types of fiber: soluble fiber dextrin (12 g), soluble corn fiber (11.8 g), polydextrose (11.8 g), and resistant starch (11.2g). All four fibers were compared to two control conditions of equal volume: an isoenergetic, low-fiber preload and a lower-energy, low-fiber preload. All preloads were presented twice for a total of 0.35-1.65 MJ and 1-24 g fiber. Satiety ratings were collected for 20 min intervals for 220 min during the morning testing session. A test meal was served at 1200 h and plate waste measured. The five higher-energy preloads led to higher fullness and lower hunger ratings compared to the low-energy control but were not significantly different from each other. Relative to the isoenergetic control, only soluble fiber dextrin significantly suppressed energy intakes (p=0.023). Supplementing beverages with soluble fiber dextrin affects short term energy intake and may have implications for weight control.

Associations of Number of Daily Eating Occasions with Type 2 Diabetes Risk in the Women's Health Initiative Dietary Modification Trial.

BACKGROUND: Over 23 million Americans have type 2 diabetes (T2D). Eating habits such as breakfast consumption, time-restricted eating, and limiting daily eating occasions have been explored as behaviors for reducing T2D risk, but prior evidence is inconclusive. OBJECTIVES: Our objectives were to examine associations between number of daily eating occasions and T2D risk in the Women's Health Initiative Dietary Modification Trial (WHI-DM) and whether associations vary by BMI, age, or race/ethnicity. METHODS: Participants were postmenopausal women in the WHI-DM who comprised a 4.6% subsample completing 24-h dietary recalls (24HRs) at years 3 and 6 as part of trial adherence activities (n = 2159). Numbers of eating occasions per day were obtained from the year 3 24HRs, and participants were grouped into approximate tertiles as 1-3 (n = 795), 4 (n = 713), and ≥5 (n = 651) daily eating occasions as the exposure. Incident diabetes was self-reported on semiannual questionnaires as the outcome. RESULTS: Approximately 15% (15.4%, n = 332) of the WHI-DM 24HR cohort reported incident diabetes at follow-up. Cox proportional hazards regression tested associations of eating occasions with T2D adjusted for neighborhood socioeconomic status, BMI, waist circumference, race/ethnicity, family history of T2D, recreational physical activity, Healthy Eating Index-2005, 24HR energy intake, and WHI-DM arm. Compared with women reporting 1-3 meals/d, those consuming 4 meals/d had a T2D HR = 1.38 (95% CI: 1.03, 1.84) without further increases in risk for ≥5 meals/d. In stratified analyses, associations for 4 meals/d compared with 1-3 meals/d were stronger in women with BMI <30.0 kg/m2 (HR = 1.55; 95% CI: 1.00, 2.39) and women aged ≥60 (HR = 1.61; 95% CI: 1.11, 2.33). CONCLUSIONS: Four meals per day compared with 1-3 meals/d was associated with increased risk of T2D in postmenopausal women, but no dose-response effect was observed for additional eating occasions. Further studies are needed to understand eating occasions in relation to T2D risk.

Rationale and design of the frequency of eating and Satiety Hormones (FRESH) study: A randomized cross-over clinical trial.

BACKGROUND: The goal of the Frequency of Eating and Satiety Hormones (FRESH) Study is to understand the relationship between eating frequency (EF) and biomarkers of appetite and disease risk. This report gives the study rationale and design. METHODS: The FRESH study was conducted in n = 50 overweight and obese, but otherwise healthy, male and female adults aged 18-50 years. The protocol included four in-person clinic visits for protocol instruction, blood draws, anthropometry, and meal testing; all other activities were done at home. Participants completed two 21-day phases in random order with a two-week washout between phases. One phase was high EF (6 eating occasions/day) and the other was low EF (3 eating occasions/day). Each phase specified time of day for each eating occasion. Participants prepared their own meals throughout the study using study-provided individualized, structured meal plans ensuring that calories, macronutrients and micronutrients were identical during both study phases. Fasting blood was collected before and after each phase to test intervention effects on the biomarkers. At the end of each phase participants also completed extended appetite testing with meals prepared by the study clinic. RESULTS: Participants were recruited using print, radio, and digital ads. 60 participants consented to enroll; 10 dropped out due to work or school scheduling conflicts and 50 (target sample size) completed the study. Compliance was assessed by completion of daily on-line meal plan checklists. CONCLUSIONS: The FRESH study will provide data on whether higher vs. lower daily EF in the context of constant energy and nutrient intake may be harmful or beneficial based on intervention effects on biomarkers of health and disease risk.

Sugars and satiety: does the type of sweetener make a difference?

BACKGROUND: Widespread use of high-fructose corn syrup (HFCS) in beverages has been linked to rising obesity rates. One hypothesis is that HFCS in beverages has little satiating power. OBJECTIVE: The objective of the study was to compare the relative effect of commercial beverages containing sucrose or HFCS on hunger, satiety, and energy intakes at the next meal with the use of a within-subject design. DESIGN: Thirty-seven volunteers (19 men, 18 women) aged 20-29 y consumed isocaloric cola beverages (215 kcal) sweetened with sucrose, HFCS 42, or HFCS 55. HFCS 42 contains 42% fructose, and HFCS 55 contains 55% fructose. Diet cola (2 kcal), 1%-fat milk (215 kcal), and no beverage were the control conditions. The 5 beverages were consumed at 1010 (2 h after a standard breakfast). Participants rated hunger, thirst, and satiety at baseline and at 20-min intervals after ingestion. A tray lunch (1708 kcal) was served at 1230, and energy intakes were measured. The free sugars content of sucrose-sweetened cola was assayed at the time of the study. RESULTS: We found no differences between sucrose- and HFCS-sweetened colas in perceived sweetness, hunger and satiety profiles, or energy intakes at lunch. The 4 caloric beverages tended to partially suppress energy intakes at lunch, whereas the no-beverage and diet beverage conditions did not; the effect was significant (P<0.05) only for 1%-fat milk. Energy intakes in the diet cola and the no-beverage conditions did not differ significantly. CONCLUSION: There was no evidence that commercial cola beverages sweetened with either sucrose or HFCS have significantly different effects on hunger, satiety, or short-term energy intakes.

A low-calorie beverage supplemented with low-viscosity pectin reduces energy intake at a subsequent meal.

The addition of fiber to foods and beverages has been linked with greater satiety and reduced energy intakes at the next meal. However, measures of satiety can be influenced by the time interval between beverage consumption and the next meal. The objective of this study was to determine how the time interval between consumption and a subsequent test meal impacts the satiating power of a low-calorie beverage supplemented with low-viscosity pectin fiber. Forty-two participants (20 men, 22 women) each participated in 4 study sessions. Study preloads were 2 low-calorie beverages (355 mL, 8 kcal) containing either 0 g fiber (no fiber) or 8 g low-viscosity fiber (added fiber). These preloads were consumed either 90 min before lunch or 15 min before lunch. Every 15 min, participants rated hunger, desire to eat, fullness, and thirst using 100-mm visual analogue scales. A test lunch was served and plate waste was measured. Beverages with added fiber reduced energy intakes at lunch relative to those without fiber. A short delay (15 min) between beverage consumption and a subsequent meal was associated with higher satiety ratings and reduced energy intakes, regardless of fiber content. The addition of low-viscosity pectin to low-calorie beverages reduced energy intakes at the next meal, presenting a possible tool for intake regulation. A short time interval between consumption of a low-calorie beverage and a meal also increased satiety and decreased food intake, reflecting the short-lived effect of volume.

Added soluble fiber enhances the satiating power of low-energy-density liquid yogurts.

BACKGROUND: Low-energy-density foods with high satiating power may be useful tools for weight management. Energy density of yogurts can range from 0.4 to 1.8 kcal/g. OBJECTIVE: To test the effects of added inulin, a soluble fiber, on the satiating properties of low-energy-density and high-energy-density yogurt beverages (16 oz or 472 mL). DESIGN: The study followed a within-subject preload design with repeated measures. Each participant completed six conditions, presented in a counterbalanced order. SUBJECTS: Participants were 18 men and 20 women, aged 18 to 35 years. INTERVENTION: The experimental conditions were two high-energy-density yogurt beverages (440 kcal; 0.9 kcal/g) and two low-energy-density yogurt beverages (180 kcal; 0.4 kcal/g) with or without inulin (6 g) and an equal volume of orange juice (180 kcal). A no beverage control condition was used as well. MAIN OUTCOME MEASURES: Repeated ratings of hunger, fullness, and desire to eat and energy consumption at the lunch meal served 120 minutes post-ingestion were the main measures. STATISTICAL ANALYSES PERFORMED: Repeated measures analyses of variance were used to analyze motivational ratings and energy and nutrient intakes at the test meal. RESULTS: Yogurt beverages and liquid orange juice significantly suppressed appetite and promoted satiety relatively to the no beverage condition. Yogurt beverages had greater satiating power than did orange juice, as evidenced by higher satiety ratings and reduced energy intakes at lunch. The satiating power of low-energy-density yogurt with inulin was comparable to that of high-energy-density yogurt. CONCLUSIONS: Energy presented in liquid form can have satiating power. Added fiber can potentiate the satiating properties of low-energy-density liquid yogurts. Adding fiber to low-energy-density foods may be an effective way to suppress appetite and control food intake.