BACKGROUND The inclusion of almonds in an energy-restricted diet has been reported both to enhance or to have no effect on weight loss. Their effects specifically on visceral body fat stores during energy restriction have not been widely examined. In addition, almond consumption has been associated with reduced blood pressure (BP), but whether this is linked to or independent of changes in body composition has to our knowledge not been examined. OBJECTIVE We evaluated the effects of consuming almonds as part of an energy-restricted diet on body composition, specifically visceral adipose tissue (VAT) and BP, compared to a nut-free energy-restricted diet. METHODS A randomized controlled 12-wk clinical trial of 86 healthy adults [body mass index (in kg/m2): 25-40] was conducted. Participants were randomly assigned to 1 of 2 energy-restricted (500-kcal deficit/d) diets: an almond-enriched diet (AED) (15% energy from almonds) or a nut-free diet (NFD). A linear mixed-model analysis on primary outcomes such as body weight, body fat, VAT, and BP was performed on all participants [intention-to-treat (ITT) analysis] and compliant participants (complier analysis). RESULTS Body weight, truncal and total fat percentage, VAT, and systolic BP decreased after 12 wk of energy restriction in both the ITT and complier analyses (P < 0.05). The complier analysis (but not the ITT analysis) indicated a greater mean ± SEM reduction in truncal fat (AED: -1.21% ± 0.26%; NFD: -0.48% ± 0.24%; P = 0.025), total fat (AED: -1.79% ± 0.36%; NFD: -0.74% ± 0.33%; P = 0.035), and diastolic BP (AED: -2.71 ± 1.2 mm Hg; NFD: 0.815 ± 1.1 mm Hg; P = 0.029), and a greater tendency for VAT loss (AED: -8.19 ± 1.8 cm2; NFD: -3.99 ± 1.7 cm2; P = 0.09) over time in the AED group than the NFD group. CONCLUSIONS Moderate almond consumption by compliant overweight and obese individuals during energy restriction results in greater proportional reductions of truncal and total body fat as well as diastolic BP and hence may help to reduce metabolic disease risk in obesity. This trial was registered at clinicaltrials.gov as NCT02360787.
{"title":"Almond Consumption during Energy Restriction Lowers Truncal Fat and Blood Pressure in Compliant Overweight or Obese Adults.","authors":"Jaapna Dhillon, Sze-Yen Tan, R. Mattes","doi":"10.3945/JN.116.238444","DOIUrl":"https://doi.org/10.3945/JN.116.238444","url":null,"abstract":"BACKGROUND\u0000The inclusion of almonds in an energy-restricted diet has been reported both to enhance or to have no effect on weight loss. Their effects specifically on visceral body fat stores during energy restriction have not been widely examined. In addition, almond consumption has been associated with reduced blood pressure (BP), but whether this is linked to or independent of changes in body composition has to our knowledge not been examined.\u0000\u0000\u0000OBJECTIVE\u0000We evaluated the effects of consuming almonds as part of an energy-restricted diet on body composition, specifically visceral adipose tissue (VAT) and BP, compared to a nut-free energy-restricted diet.\u0000\u0000\u0000METHODS\u0000A randomized controlled 12-wk clinical trial of 86 healthy adults [body mass index (in kg/m2): 25-40] was conducted. Participants were randomly assigned to 1 of 2 energy-restricted (500-kcal deficit/d) diets: an almond-enriched diet (AED) (15% energy from almonds) or a nut-free diet (NFD). A linear mixed-model analysis on primary outcomes such as body weight, body fat, VAT, and BP was performed on all participants [intention-to-treat (ITT) analysis] and compliant participants (complier analysis).\u0000\u0000\u0000RESULTS\u0000Body weight, truncal and total fat percentage, VAT, and systolic BP decreased after 12 wk of energy restriction in both the ITT and complier analyses (P < 0.05). The complier analysis (but not the ITT analysis) indicated a greater mean ± SEM reduction in truncal fat (AED: -1.21% ± 0.26%; NFD: -0.48% ± 0.24%; P = 0.025), total fat (AED: -1.79% ± 0.36%; NFD: -0.74% ± 0.33%; P = 0.035), and diastolic BP (AED: -2.71 ± 1.2 mm Hg; NFD: 0.815 ± 1.1 mm Hg; P = 0.029), and a greater tendency for VAT loss (AED: -8.19 ± 1.8 cm2; NFD: -3.99 ± 1.7 cm2; P = 0.09) over time in the AED group than the NFD group.\u0000\u0000\u0000CONCLUSIONS\u0000Moderate almond consumption by compliant overweight and obese individuals during energy restriction results in greater proportional reductions of truncal and total body fat as well as diastolic BP and hence may help to reduce metabolic disease risk in obesity. This trial was registered at clinicaltrials.gov as NCT02360787.","PeriodicalId":22788,"journal":{"name":"The Journal of Nutrition Health and Aging","volume":"84 1","pages":"2513-2519"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76797084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Palmer, Katherine Healy, Maxwell A. Barffour, W. Siamusantu, J. Chileshe, K. Schulze, K. West, A. Labrique
BACKGROUND Impaired dark adaptation is an early functional indicator of vitamin A deficiency that may be prevented by regular dietary intake of foods containing provitamin A carotenoids. OBJECTIVE We tested the impact of provitamin A carotenoid-biofortified maize consumption (∼15 μg β-carotene/g) on dark adaptation in Zambian children. METHODS We used a cluster-randomized trial of children aged 4-8 y (n = 1024) in Mkushi District, Zambia, and compared the regular consumption (2 meals/d, 6 d/wk for 6 mo) of biofortified orange maize (OM) to white maize (WM). The primary outcome was the serum retinol response. In a random sample (n = 542), we used a digital pupillometer to test pre- and postintervention responses to graded light stimuli (-2.9 to 0.1 log cd/m2) in a dark-adapted state. RESULTS At baseline, 11.7% of the children had serum retinol <0.7 μmol/L, 14.4% had impaired dark adaptation (pupillary threshold ≥ -1.11 log cd/m2), and 2.3% had night blindness. The mean ± SD pupillary responsiveness to light stimuli was poorer at baseline in the OM group (16.1% ± 6.6%) than the WM group (18.1% ± 6.4%) (P = 0.02) but did not differ at follow-up (OM: 17.6% ± 6.5%; WM: 18.3% ± 6.5%). Among children with serum retinol <1.05 μmol/L at baseline, there was greater improvement in pupillary responsiveness in the OM group (2.2%; 95% CI: 0.1%, 4.3%) than the WM group (0.2%; 95% CI: -1.1%, 1.5%; P = 0.01), but there were no differences in children with adequate baseline status. We found no effect of treatment on pupillary threshold or night blindness. CONCLUSIONS The regular consumption of provitamin A carotenoid-biofortified maize increased pupillary responsiveness among children with marginal or deficient vitamin A status, providing evidence of a functional benefit to consuming this biofortified crop. This trial was registered at clinicaltrials.gov as NCT01695148.
{"title":"Provitamin A Carotenoid-Biofortified Maize Consumption Increases Pupillary Responsiveness among Zambian Children in a Randomized Controlled Trial.","authors":"A. Palmer, Katherine Healy, Maxwell A. Barffour, W. Siamusantu, J. Chileshe, K. Schulze, K. West, A. Labrique","doi":"10.3945/JN.116.239202","DOIUrl":"https://doi.org/10.3945/JN.116.239202","url":null,"abstract":"BACKGROUND\u0000Impaired dark adaptation is an early functional indicator of vitamin A deficiency that may be prevented by regular dietary intake of foods containing provitamin A carotenoids.\u0000\u0000\u0000OBJECTIVE\u0000We tested the impact of provitamin A carotenoid-biofortified maize consumption (∼15 μg β-carotene/g) on dark adaptation in Zambian children.\u0000\u0000\u0000METHODS\u0000We used a cluster-randomized trial of children aged 4-8 y (n = 1024) in Mkushi District, Zambia, and compared the regular consumption (2 meals/d, 6 d/wk for 6 mo) of biofortified orange maize (OM) to white maize (WM). The primary outcome was the serum retinol response. In a random sample (n = 542), we used a digital pupillometer to test pre- and postintervention responses to graded light stimuli (-2.9 to 0.1 log cd/m2) in a dark-adapted state.\u0000\u0000\u0000RESULTS\u0000At baseline, 11.7% of the children had serum retinol <0.7 μmol/L, 14.4% had impaired dark adaptation (pupillary threshold ≥ -1.11 log cd/m2), and 2.3% had night blindness. The mean ± SD pupillary responsiveness to light stimuli was poorer at baseline in the OM group (16.1% ± 6.6%) than the WM group (18.1% ± 6.4%) (P = 0.02) but did not differ at follow-up (OM: 17.6% ± 6.5%; WM: 18.3% ± 6.5%). Among children with serum retinol <1.05 μmol/L at baseline, there was greater improvement in pupillary responsiveness in the OM group (2.2%; 95% CI: 0.1%, 4.3%) than the WM group (0.2%; 95% CI: -1.1%, 1.5%; P = 0.01), but there were no differences in children with adequate baseline status. We found no effect of treatment on pupillary threshold or night blindness.\u0000\u0000\u0000CONCLUSIONS\u0000The regular consumption of provitamin A carotenoid-biofortified maize increased pupillary responsiveness among children with marginal or deficient vitamin A status, providing evidence of a functional benefit to consuming this biofortified crop. This trial was registered at clinicaltrials.gov as NCT01695148.","PeriodicalId":22788,"journal":{"name":"The Journal of Nutrition Health and Aging","volume":"99 1","pages":"2551-2558"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78251043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Kirkpatrick, N. Potischman, K. Dodd, D. Douglass, T. Zimmerman, L. Kahle, F. Thompson, Stephanie M George, A. Subar
BACKGROUND The Automated Self-Administered 24-hour (ASA24) dietary recall system enhances the feasibility of collecting high-quality intake data in population-based studies. OBJECTIVE The aim of this study was to assess the accuracy of portion size reporting in the ASA24 compared with interviewer-administered recalls. METHODS True intake for 3 meals was ascertained in 81 adults aged 20-70 y from the Washington, DC area. Participants were randomly assigned to complete an unannounced ASA24 or an interviewer-administered Automated Multiple-Pass Method (AMPM) recall the following day. An adapted Bland-Altman approach was used to assess agreement between true and reported portion sizes. Linear regression was used to assess log-scale differences between true and reported portion sizes by recall mode. The proportions of reported portion sizes within 10% and 25% of truth were estimated. Analyses were conducted for all foods and drinks and predetermined categories. RESULTS Mean differences between true and reported portion sizes were 3.7 g for the ASA24 and 11.8 g for the AMPM. According to the Bland-Altman-type plots, between 92% and 100% (depending on food or drink category and recall mode) of observations fell within the limits of agreement. After adjustment for multiple testing, the mean ratio of reported to true portion sizes was significantly >1 for the categories of all foods and drinks, all foods excluding liquids, amorphous or soft foods, and small pieces among AMPM respondents. Misestimation in the AMPM was significantly different from that in the ASA24 for all foods and drinks and for all foods excluding liquids. Small proportions of reported portions fell within 10% (16.2% for the ASA24 and 14.9% for the AMPM) and 25% (37.5% for the ASA24 and 33.2% for the AMPM) of truth. CONCLUSIONS The results raise the possibility that digital images tailored to different types and formats of foods may facilitate improved estimation of amounts eaten but highlight the need for continued work in this aspect of dietary assessment. This trial was registered at clinicaltrials.gov as NCT00978406.
{"title":"The Use of Digital Images in 24-Hour Recalls May Lead to Less Misestimation of Portion Size Compared with Traditional Interviewer-Administered Recalls.","authors":"S. Kirkpatrick, N. Potischman, K. Dodd, D. Douglass, T. Zimmerman, L. Kahle, F. Thompson, Stephanie M George, A. Subar","doi":"10.3945/JN.116.237271","DOIUrl":"https://doi.org/10.3945/JN.116.237271","url":null,"abstract":"BACKGROUND\u0000The Automated Self-Administered 24-hour (ASA24) dietary recall system enhances the feasibility of collecting high-quality intake data in population-based studies.\u0000\u0000\u0000OBJECTIVE\u0000The aim of this study was to assess the accuracy of portion size reporting in the ASA24 compared with interviewer-administered recalls.\u0000\u0000\u0000METHODS\u0000True intake for 3 meals was ascertained in 81 adults aged 20-70 y from the Washington, DC area. Participants were randomly assigned to complete an unannounced ASA24 or an interviewer-administered Automated Multiple-Pass Method (AMPM) recall the following day. An adapted Bland-Altman approach was used to assess agreement between true and reported portion sizes. Linear regression was used to assess log-scale differences between true and reported portion sizes by recall mode. The proportions of reported portion sizes within 10% and 25% of truth were estimated. Analyses were conducted for all foods and drinks and predetermined categories.\u0000\u0000\u0000RESULTS\u0000Mean differences between true and reported portion sizes were 3.7 g for the ASA24 and 11.8 g for the AMPM. According to the Bland-Altman-type plots, between 92% and 100% (depending on food or drink category and recall mode) of observations fell within the limits of agreement. After adjustment for multiple testing, the mean ratio of reported to true portion sizes was significantly >1 for the categories of all foods and drinks, all foods excluding liquids, amorphous or soft foods, and small pieces among AMPM respondents. Misestimation in the AMPM was significantly different from that in the ASA24 for all foods and drinks and for all foods excluding liquids. Small proportions of reported portions fell within 10% (16.2% for the ASA24 and 14.9% for the AMPM) and 25% (37.5% for the ASA24 and 33.2% for the AMPM) of truth.\u0000\u0000\u0000CONCLUSIONS\u0000The results raise the possibility that digital images tailored to different types and formats of foods may facilitate improved estimation of amounts eaten but highlight the need for continued work in this aspect of dietary assessment. This trial was registered at clinicaltrials.gov as NCT00978406.","PeriodicalId":22788,"journal":{"name":"The Journal of Nutrition Health and Aging","volume":"24 1","pages":"2567-2573"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79003787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Kieffer, B. Piccolo, M. Marco, E. Kim, M. Goodson, M. Keenan, T. Dunn, K. Knudsen, S. Adams, Roy J Martin
BACKGROUND Enzyme-treated wheat bran (ETWB) contains a fermentable dietary fiber previously shown to decrease liver triglycerides (TGs) and modify the gut microbiome in mice. It is not clear which mechanisms explain how ETWB feeding affects hepatic metabolism, but factors (i.e., xenometabolites) associated with specific microbes may be involved. OBJECTIVE The objective of this study was to characterize ETWB-driven shifts in the cecal microbiome and to identify correlates between microbial changes and diet-related differences in liver metabolism in diet-induced obese mice that typically display steatosis. METHODS Five-week-old male C57BL/6J mice fed a 45%-lard-based fat diet supplemented with ETWB (20% wt:wt) or rapidly digestible starch (control) (n = 15/group) for 10 wk were characterized by using a multi-omics approach. Multivariate statistical analysis was used to identify variables that were strong discriminators between the ETWB and control groups. RESULTS Body weight and liver TGs were decreased by ETWB feeding (by 10% and 25%, respectively; P < 0.001), and an index of liver reactive oxygen species was increased (by 29%; P < 0.01). The cecal microbiome showed an increase in Bacteroidetes (by 42%; P < 0.05) and a decrease in Firmicutes (by 16%; P < 0.05). Metabolites that were strong discriminators between the ETWB and control groups included decreased liver antioxidants (glutathione and α-tocopherol); decreased liver carbohydrate metabolites, including glucose; lower hepatic arachidonic acid; and increased liver and plasma β-hydroxybutyrate. Liver transcriptomics revealed key metabolic pathways affected by ETWB, especially those related to lipid metabolism and some fed- or fasting-regulated genes. CONCLUSIONS Together, these changes indicate that dietary fibers such as ETWB regulate hepatic metabolism concurrently with specific gut bacteria community shifts in C57BL/6J mice. It is proposed that these changes may elicit gut-derived signals that reach the liver via enterohepatic circulation, ultimately affecting host liver metabolism in a manner that mimics, in part, the fasting state.
{"title":"Obese Mice Fed a Diet Supplemented with Enzyme-Treated Wheat Bran Display Marked Shifts in the Liver Metabolome Concurrent with Altered Gut Bacteria.","authors":"D. Kieffer, B. Piccolo, M. Marco, E. Kim, M. Goodson, M. Keenan, T. Dunn, K. Knudsen, S. Adams, Roy J Martin","doi":"10.3945/JN.116.238923","DOIUrl":"https://doi.org/10.3945/JN.116.238923","url":null,"abstract":"BACKGROUND\u0000Enzyme-treated wheat bran (ETWB) contains a fermentable dietary fiber previously shown to decrease liver triglycerides (TGs) and modify the gut microbiome in mice. It is not clear which mechanisms explain how ETWB feeding affects hepatic metabolism, but factors (i.e., xenometabolites) associated with specific microbes may be involved.\u0000\u0000\u0000OBJECTIVE\u0000The objective of this study was to characterize ETWB-driven shifts in the cecal microbiome and to identify correlates between microbial changes and diet-related differences in liver metabolism in diet-induced obese mice that typically display steatosis.\u0000\u0000\u0000METHODS\u0000Five-week-old male C57BL/6J mice fed a 45%-lard-based fat diet supplemented with ETWB (20% wt:wt) or rapidly digestible starch (control) (n = 15/group) for 10 wk were characterized by using a multi-omics approach. Multivariate statistical analysis was used to identify variables that were strong discriminators between the ETWB and control groups.\u0000\u0000\u0000RESULTS\u0000Body weight and liver TGs were decreased by ETWB feeding (by 10% and 25%, respectively; P < 0.001), and an index of liver reactive oxygen species was increased (by 29%; P < 0.01). The cecal microbiome showed an increase in Bacteroidetes (by 42%; P < 0.05) and a decrease in Firmicutes (by 16%; P < 0.05). Metabolites that were strong discriminators between the ETWB and control groups included decreased liver antioxidants (glutathione and α-tocopherol); decreased liver carbohydrate metabolites, including glucose; lower hepatic arachidonic acid; and increased liver and plasma β-hydroxybutyrate. Liver transcriptomics revealed key metabolic pathways affected by ETWB, especially those related to lipid metabolism and some fed- or fasting-regulated genes.\u0000\u0000\u0000CONCLUSIONS\u0000Together, these changes indicate that dietary fibers such as ETWB regulate hepatic metabolism concurrently with specific gut bacteria community shifts in C57BL/6J mice. It is proposed that these changes may elicit gut-derived signals that reach the liver via enterohepatic circulation, ultimately affecting host liver metabolism in a manner that mimics, in part, the fasting state.","PeriodicalId":22788,"journal":{"name":"The Journal of Nutrition Health and Aging","volume":"1 1","pages":"2445-2460"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89170630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiantao Ma, P. Jacques, J. Meigs, C. Fox, G. Rogers, Caren E. Smith, A. Hruby, E. Saltzman, N. McKeown
BACKGROUND Previous studies have shown an inconsistent relation between habitual beverage consumption and insulin resistance and prediabetes. OBJECTIVE The objective of the present study was to test the hypothesis that the consumption of sugar-sweetened beverages (SSBs), rather than diet soda, is associated with long-term progression of insulin resistance and the development of prediabetes. METHODS We analyzed the prospective association between cumulative mean consumption of SSBs or diet soda and incident prediabetes (n = 1685) identified across a median of 14 y of follow-up in participants [mean ± SD age: 51.9 ± 9.2 y; 59.6% women; mean ± SD body mass index (BMI; kg/m2): 26.3 ± 4.4] of the Framingham Offspring cohort. The prospective association between beverage consumption and change in homeostasis model assessment of insulin resistance (HOMA-IR; n = 2076) over ∼7 y was also analyzed. The cumulative mean consumption of SSBs and diet soda was estimated by using food-frequency questionnaires. Multivariable Cox proportional hazards models and linear regression models were implemented to estimate the HRs of incident prediabetes and change in HOMA-IR, respectively. RESULTS After adjustment for multiple potential confounders, including baseline BMI, we observed that SSB intake was positively associated with incident prediabetes (P-trend < 0.001); the highest SSB consumers (>3 servings/wk; median: 6 servings/wk) had a 46% higher risk of developing prediabetes than did the SSB nonconsumers (HR: 1.46; 95% CI: 1.16, 1.83). Higher SSB intake was also associated with a greater increase in HOMA-IR (P-trend = 0.006). No prospective associations were observed between diet soda intake and risk of prediabetes (P-trend = 0.24) or changes in HOMA-IR (P-trend = 0.25). These associations were similar after additional adjustment for change in BMI. CONCLUSION Regular SSB intake, but not diet soda intake, is associated with a greater increase in insulin resistance and a higher risk of developing prediabetes in a group of middle-aged adults.
{"title":"Sugar-Sweetened Beverage but Not Diet Soda Consumption Is Positively Associated with Progression of Insulin Resistance and Prediabetes.","authors":"Jiantao Ma, P. Jacques, J. Meigs, C. Fox, G. Rogers, Caren E. Smith, A. Hruby, E. Saltzman, N. McKeown","doi":"10.3945/JN.116.234047","DOIUrl":"https://doi.org/10.3945/JN.116.234047","url":null,"abstract":"BACKGROUND\u0000Previous studies have shown an inconsistent relation between habitual beverage consumption and insulin resistance and prediabetes.\u0000\u0000\u0000OBJECTIVE\u0000The objective of the present study was to test the hypothesis that the consumption of sugar-sweetened beverages (SSBs), rather than diet soda, is associated with long-term progression of insulin resistance and the development of prediabetes.\u0000\u0000\u0000METHODS\u0000We analyzed the prospective association between cumulative mean consumption of SSBs or diet soda and incident prediabetes (n = 1685) identified across a median of 14 y of follow-up in participants [mean ± SD age: 51.9 ± 9.2 y; 59.6% women; mean ± SD body mass index (BMI; kg/m2): 26.3 ± 4.4] of the Framingham Offspring cohort. The prospective association between beverage consumption and change in homeostasis model assessment of insulin resistance (HOMA-IR; n = 2076) over ∼7 y was also analyzed. The cumulative mean consumption of SSBs and diet soda was estimated by using food-frequency questionnaires. Multivariable Cox proportional hazards models and linear regression models were implemented to estimate the HRs of incident prediabetes and change in HOMA-IR, respectively.\u0000\u0000\u0000RESULTS\u0000After adjustment for multiple potential confounders, including baseline BMI, we observed that SSB intake was positively associated with incident prediabetes (P-trend < 0.001); the highest SSB consumers (>3 servings/wk; median: 6 servings/wk) had a 46% higher risk of developing prediabetes than did the SSB nonconsumers (HR: 1.46; 95% CI: 1.16, 1.83). Higher SSB intake was also associated with a greater increase in HOMA-IR (P-trend = 0.006). No prospective associations were observed between diet soda intake and risk of prediabetes (P-trend = 0.24) or changes in HOMA-IR (P-trend = 0.25). These associations were similar after additional adjustment for change in BMI.\u0000\u0000\u0000CONCLUSION\u0000Regular SSB intake, but not diet soda intake, is associated with a greater increase in insulin resistance and a higher risk of developing prediabetes in a group of middle-aged adults.","PeriodicalId":22788,"journal":{"name":"The Journal of Nutrition Health and Aging","volume":"66 1","pages":"2544-2550"},"PeriodicalIF":0.0,"publicationDate":"2016-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82764318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valeria E. Di Giovanni, C. Bourdon, Dominic Wang, Swapna Seshadri, E. Senga, Christian J Versloot, W. Voskuijl, R. Semba, Indi Trehan, R. Moaddel, M. I. Ordiz, Ling Zhang, J. Parkinson, M. Manary, R. Bandsma
Background: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. Objectives: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. Methods: We studied children aged 9–59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. Results: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. Conclusions: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.
{"title":"Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition123","authors":"Valeria E. Di Giovanni, C. Bourdon, Dominic Wang, Swapna Seshadri, E. Senga, Christian J Versloot, W. Voskuijl, R. Semba, Indi Trehan, R. Moaddel, M. I. Ordiz, Ling Zhang, J. Parkinson, M. Manary, R. Bandsma","doi":"10.3945/jn.116.239145","DOIUrl":"https://doi.org/10.3945/jn.116.239145","url":null,"abstract":"Background: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. Objectives: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. Methods: We studied children aged 9–59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. Results: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. Conclusions: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.","PeriodicalId":22788,"journal":{"name":"The Journal of Nutrition Health and Aging","volume":"27 10 1","pages":"2436 - 2444"},"PeriodicalIF":0.0,"publicationDate":"2016-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82709502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael S. Borack, P. Reidy, Syed H Husaini, M. Markofski, R. Deer, Abigail B Richison, B. Lambert, M. Cope, R. Mukherjea, K. Jennings, E. Volpi, B. Rasmussen
Background: Previous work demonstrated that a soy-dairy protein blend (PB) prolongs hyperaminoacidemia and muscle protein synthesis in young adults after resistance exercise. Objective: We investigated the effect of PB in older adults. We hypothesized that PB would prolong hyperaminoacidemia, enhancing mechanistic target of rapamycin complex 1 (mTORC1) signaling and muscle protein anabolism compared with a whey protein isolate (WPI). Methods: This double-blind, randomized controlled trial studied men 55–75 y of age. Subjects consumed 30 g protein from WPI or PB (25% soy, 25% whey, and 50% casein) 1 h after leg extension exercise (8 sets of 10 repetitions at 70% one-repetition maximum). Blood and muscle amino acid concentrations and basal and postexercise muscle protein turnover were measured by using stable isotopic methods. Muscle mTORC1 signaling was assessed by immunoblotting. Results: Both groups increased amino acid concentrations (P < 0.05) and mTORC1 signaling after protein ingestion (P < 0.05). Postexercise fractional synthesis rate (FSR; P ≥ 0.05), fractional breakdown rate (FBR; P ≥ 0.05), and net balance (P = 0.08) did not differ between groups. WPI increased FSR by 67% (mean ± SEM: rest: 0.05% ± 0.01%; postexercise: 0.09% ± 0.01%; P < 0.05), decreased FBR by 46% (rest: 0.17% ± 0.01%; postexercise: 0.09% ± 0.03%; P < 0.05), and made net balance less negative (P < 0.05). PB ingestion did not increase FSR (rest: 0.07% ± 0.03%; postexercise: 0.09% ± 0.01%; P ≥ 0.05), tended to decrease FBR by 42% (rest: 0.25% ± 0.08%; postexercise: 0.15% ± 0.08%; P = 0.08), and made net balance less negative (P < 0.05). Within-group percentage of change differences were not different between groups for FSR, FBR, or net balance (P ≥ 0.05). Conclusions: WPI and PB ingestion after exercise in older men induced similar responses in hyperaminoacidemia, mTORC1 signaling, muscle protein synthesis, and breakdown. These data add new evidence for the use of whey or soy-dairy PBs as targeted nutritional interventions to counteract sarcopenia. This trial was registered at clinicaltrials.gov as NCT01847261.
{"title":"Soy-Dairy Protein Blend or Whey Protein Isolate Ingestion Induces Similar Postexercise Muscle Mechanistic Target of Rapamycin Complex 1 Signaling and Protein Synthesis Responses in Older Men1234","authors":"Michael S. Borack, P. Reidy, Syed H Husaini, M. Markofski, R. Deer, Abigail B Richison, B. Lambert, M. Cope, R. Mukherjea, K. Jennings, E. Volpi, B. Rasmussen","doi":"10.3945/jn.116.231159","DOIUrl":"https://doi.org/10.3945/jn.116.231159","url":null,"abstract":"Background: Previous work demonstrated that a soy-dairy protein blend (PB) prolongs hyperaminoacidemia and muscle protein synthesis in young adults after resistance exercise. Objective: We investigated the effect of PB in older adults. We hypothesized that PB would prolong hyperaminoacidemia, enhancing mechanistic target of rapamycin complex 1 (mTORC1) signaling and muscle protein anabolism compared with a whey protein isolate (WPI). Methods: This double-blind, randomized controlled trial studied men 55–75 y of age. Subjects consumed 30 g protein from WPI or PB (25% soy, 25% whey, and 50% casein) 1 h after leg extension exercise (8 sets of 10 repetitions at 70% one-repetition maximum). Blood and muscle amino acid concentrations and basal and postexercise muscle protein turnover were measured by using stable isotopic methods. Muscle mTORC1 signaling was assessed by immunoblotting. Results: Both groups increased amino acid concentrations (P < 0.05) and mTORC1 signaling after protein ingestion (P < 0.05). Postexercise fractional synthesis rate (FSR; P ≥ 0.05), fractional breakdown rate (FBR; P ≥ 0.05), and net balance (P = 0.08) did not differ between groups. WPI increased FSR by 67% (mean ± SEM: rest: 0.05% ± 0.01%; postexercise: 0.09% ± 0.01%; P < 0.05), decreased FBR by 46% (rest: 0.17% ± 0.01%; postexercise: 0.09% ± 0.03%; P < 0.05), and made net balance less negative (P < 0.05). PB ingestion did not increase FSR (rest: 0.07% ± 0.03%; postexercise: 0.09% ± 0.01%; P ≥ 0.05), tended to decrease FBR by 42% (rest: 0.25% ± 0.08%; postexercise: 0.15% ± 0.08%; P = 0.08), and made net balance less negative (P < 0.05). Within-group percentage of change differences were not different between groups for FSR, FBR, or net balance (P ≥ 0.05). Conclusions: WPI and PB ingestion after exercise in older men induced similar responses in hyperaminoacidemia, mTORC1 signaling, muscle protein synthesis, and breakdown. These data add new evidence for the use of whey or soy-dairy PBs as targeted nutritional interventions to counteract sarcopenia. This trial was registered at clinicaltrials.gov as NCT01847261.","PeriodicalId":22788,"journal":{"name":"The Journal of Nutrition Health and Aging","volume":"19 1","pages":"2468 - 2475"},"PeriodicalIF":0.0,"publicationDate":"2016-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74016215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND The regulation of protein turnover in skeletal muscle is essential for the maintenance of integrity, growth, and function of this tissue. We recently reported that glycine enhances skeletal muscle growth in young pigs. However, the underlying mechanisms remain unknown. OBJECTIVE This study was conducted with a mouse myoblast cell line, C2C12, to test the hypothesis that glycine activates protein kinase B/mammalian target of rapamycin (Akt/mTOR), as well as inhibits 5'-adenosine monophosphate-activated protein kinase (AMPK) and the expression of genes for proteolysis. METHODS C2C12 myoblasts were cultured with 0, 0.25 (physiologic concentration in mouse plasma), 0.5, or 1.0 mmol glycine/L. Cell proliferation, activation of mammalian target of rapamycin complex 1 (mTORC1), AMPK signaling, mRNA levels of atrogin-1 and muscle-specific ring finger protein 1 (MuRF1), and protein synthesis and degradation were measured in the absence or presence of an Akt inhibitor, LY294002, or an AMPK activator, 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR). RESULTS Compared with control cells, 0.25-1.0 mmol glycine/L enhanced cell growth (by 12-15%) after 24 h (P < 0.05). Glycine treatment led to increased DNA replication (by 70-80%) while enhancing mTORC1 activation by upregulating Akt and inhibiting AMPK signaling (P < 0.05). Accordingly, glycine exposure increased (P < 0.05) the rate of protein synthesis (by 20-80%) and inhibited (P < 0.05) the rate of protein degradation (by 15-30%) in a concentration-dependent manner in C2C12 cells. These observations were validated by the use of an Akt inhibitor, LY294002, or an AMPK activator, AICAR. Moreover, glycine addition resulted in decreased mRNA levels for atrogin-1 and MuRF1 (by 20-40% and 30-50%, respectively; P < 0.05). The repressing effect of glycine on the expression of MuRF1, instead of atrogin-1, was abolished by LY294002 (P < 0.05). CONCLUSIONS These findings indicate that glycine plays a previously unrecognized role in enhancing protein synthesis and inhibiting protein degradation in C2C12 cells. Glycine regulates protein turnover by activating mTORC1 and by inhibiting the expression of genes for proteolysis. Our results indicate that glycine is a functional amino acid that improves muscle cell growth.
{"title":"Glycine Regulates Protein Turnover by Activating Protein Kinase B/Mammalian Target of Rapamycin and by Inhibiting MuRF1 and Atrogin-1 Gene Expression in C2C12 Myoblasts.","authors":"Kaiji Sun, Zhenlong Wu, Yun Ji, Guoyao Wu","doi":"10.3945/JN.116.231266","DOIUrl":"https://doi.org/10.3945/JN.116.231266","url":null,"abstract":"BACKGROUND\u0000The regulation of protein turnover in skeletal muscle is essential for the maintenance of integrity, growth, and function of this tissue. We recently reported that glycine enhances skeletal muscle growth in young pigs. However, the underlying mechanisms remain unknown.\u0000\u0000\u0000OBJECTIVE\u0000This study was conducted with a mouse myoblast cell line, C2C12, to test the hypothesis that glycine activates protein kinase B/mammalian target of rapamycin (Akt/mTOR), as well as inhibits 5'-adenosine monophosphate-activated protein kinase (AMPK) and the expression of genes for proteolysis.\u0000\u0000\u0000METHODS\u0000C2C12 myoblasts were cultured with 0, 0.25 (physiologic concentration in mouse plasma), 0.5, or 1.0 mmol glycine/L. Cell proliferation, activation of mammalian target of rapamycin complex 1 (mTORC1), AMPK signaling, mRNA levels of atrogin-1 and muscle-specific ring finger protein 1 (MuRF1), and protein synthesis and degradation were measured in the absence or presence of an Akt inhibitor, LY294002, or an AMPK activator, 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR).\u0000\u0000\u0000RESULTS\u0000Compared with control cells, 0.25-1.0 mmol glycine/L enhanced cell growth (by 12-15%) after 24 h (P < 0.05). Glycine treatment led to increased DNA replication (by 70-80%) while enhancing mTORC1 activation by upregulating Akt and inhibiting AMPK signaling (P < 0.05). Accordingly, glycine exposure increased (P < 0.05) the rate of protein synthesis (by 20-80%) and inhibited (P < 0.05) the rate of protein degradation (by 15-30%) in a concentration-dependent manner in C2C12 cells. These observations were validated by the use of an Akt inhibitor, LY294002, or an AMPK activator, AICAR. Moreover, glycine addition resulted in decreased mRNA levels for atrogin-1 and MuRF1 (by 20-40% and 30-50%, respectively; P < 0.05). The repressing effect of glycine on the expression of MuRF1, instead of atrogin-1, was abolished by LY294002 (P < 0.05).\u0000\u0000\u0000CONCLUSIONS\u0000These findings indicate that glycine plays a previously unrecognized role in enhancing protein synthesis and inhibiting protein degradation in C2C12 cells. Glycine regulates protein turnover by activating mTORC1 and by inhibiting the expression of genes for proteolysis. Our results indicate that glycine is a functional amino acid that improves muscle cell growth.","PeriodicalId":22788,"journal":{"name":"The Journal of Nutrition Health and Aging","volume":"73 1","pages":"2461-2467"},"PeriodicalIF":0.0,"publicationDate":"2016-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75985916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nikkie van der Wielen, J. T. ten Klooster, Susanne Muckenschnabl, R. Pieters, H. Hendriks, R. Witkamp, J. Meijerink
BACKGROUND Glucagon-like peptide 1 (GLP-1) contributes to satiety and plays a pivotal role in insulin secretion and glucose homeostasis. Similar to GLP-1, peptide YY (PYY) and cholecystokinin also influence food intake. The secretion of these hormones by enteroendocrine cells along the intestine is modulated by nutrients. Preparations from the Stevia rebaudiana plant, including rebaudioside A, are increasingly being used as noncaloric sweeteners. OBJECTIVE We investigated the effects of rebaudioside A on enteroendocrine cells by assessing both cell numbers as well as their secretory capacity in an organoid model. METHODS A 2-dimensional organoid model derived from duodenal, jejunal, and ileal crypts of a C57BL/6J mouse was developed and characterized with the use of gene expression and immunofluorescence. We stimulated these organoids with 10 mmol/L rebaudioside A for 1 h and measured their GLP-1, PYY, and cholecystokinin release. We also analyzed the effects of rebaudioside A on gene expression in enteroendocrine cells after an 18-h incubation. RESULTS The 2-dimensional organoids contained crypt cells and differentiated villus cells, including enterocytes and goblet and enteroendocrine cells. These enteroendocrine cells stained positive for GLP-1, PYY, and serotonin. The cultured 2-dimensional organoids maintained their location-specific gene expression patterns. Compared with the control, rebaudioside A induced GLP-1 secretion 1.7-fold in the duodenum (P < 0.01), 2.2-fold in the jejunum (P < 0.01), and 4.3-fold in the ileum (P < 0.001). PYY release was increased by rebaudioside A 3-fold in the ileum compared with the control (P < 0.05). Long-term (18-h) stimulation with the sweetener induced the expression of the enteroendocrine-specific markers chromogranin A, glucagon, Pyy, and cholecystokinin 3.5- (P < 0.001), 3.5- (P < 0.001), 3.8- (P < 0.05), and 6.5-fold (P < 0.001), respectively. CONCLUSIONS These results show novel ex vivo effects of rebaudioside A on enteroendocrine cells of the mouse small intestine and highlight potentially new applications for rebaudioside A in metabolic diseases.
{"title":"The Noncaloric Sweetener Rebaudioside A Stimulates Glucagon-Like Peptide 1 Release and Increases Enteroendocrine Cell Numbers in 2-Dimensional Mouse Organoids Derived from Different Locations of the Intestine.","authors":"Nikkie van der Wielen, J. T. ten Klooster, Susanne Muckenschnabl, R. Pieters, H. Hendriks, R. Witkamp, J. Meijerink","doi":"10.3945/JN.116.232678","DOIUrl":"https://doi.org/10.3945/JN.116.232678","url":null,"abstract":"BACKGROUND\u0000Glucagon-like peptide 1 (GLP-1) contributes to satiety and plays a pivotal role in insulin secretion and glucose homeostasis. Similar to GLP-1, peptide YY (PYY) and cholecystokinin also influence food intake. The secretion of these hormones by enteroendocrine cells along the intestine is modulated by nutrients. Preparations from the Stevia rebaudiana plant, including rebaudioside A, are increasingly being used as noncaloric sweeteners.\u0000\u0000\u0000OBJECTIVE\u0000We investigated the effects of rebaudioside A on enteroendocrine cells by assessing both cell numbers as well as their secretory capacity in an organoid model.\u0000\u0000\u0000METHODS\u0000A 2-dimensional organoid model derived from duodenal, jejunal, and ileal crypts of a C57BL/6J mouse was developed and characterized with the use of gene expression and immunofluorescence. We stimulated these organoids with 10 mmol/L rebaudioside A for 1 h and measured their GLP-1, PYY, and cholecystokinin release. We also analyzed the effects of rebaudioside A on gene expression in enteroendocrine cells after an 18-h incubation.\u0000\u0000\u0000RESULTS\u0000The 2-dimensional organoids contained crypt cells and differentiated villus cells, including enterocytes and goblet and enteroendocrine cells. These enteroendocrine cells stained positive for GLP-1, PYY, and serotonin. The cultured 2-dimensional organoids maintained their location-specific gene expression patterns. Compared with the control, rebaudioside A induced GLP-1 secretion 1.7-fold in the duodenum (P < 0.01), 2.2-fold in the jejunum (P < 0.01), and 4.3-fold in the ileum (P < 0.001). PYY release was increased by rebaudioside A 3-fold in the ileum compared with the control (P < 0.05). Long-term (18-h) stimulation with the sweetener induced the expression of the enteroendocrine-specific markers chromogranin A, glucagon, Pyy, and cholecystokinin 3.5- (P < 0.001), 3.5- (P < 0.001), 3.8- (P < 0.05), and 6.5-fold (P < 0.001), respectively.\u0000\u0000\u0000CONCLUSIONS\u0000These results show novel ex vivo effects of rebaudioside A on enteroendocrine cells of the mouse small intestine and highlight potentially new applications for rebaudioside A in metabolic diseases.","PeriodicalId":22788,"journal":{"name":"The Journal of Nutrition Health and Aging","volume":"26 1","pages":"2429-2435"},"PeriodicalIF":0.0,"publicationDate":"2016-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90698104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karen C. Goehring, B. Marriage, J. Oliver, J. Wilder, E. Barrett, R. Buck
BACKGROUND Evidence suggests that human milk oligosaccharides (HMOs) provide multiple benefits to infants, including prebiotic effects, gut maturation, antimicrobial activities, and immune modulation. Clinical intervention studies with HMOs are required to confirm these benefits in infants. OBJECTIVE Our objective was to investigate the effects of feeding formulas supplemented with the HMO 2'-fucosyllactose (2'-FL) on biomarkers of immune function in healthy term infants. METHODS We performed a substudy nested within a randomized, double-blind, controlled growth and tolerance study in healthy singleton infants (birth weight ≥2490 g) who were enrolled by 5 d of life and exclusively formula-fed (n = 317) or breastfed (n = 107) from enrollment to 4 mo of age. Formula-fed infants were randomly assigned to receive 1 of 3 formulas, all containing 2.4 g total oligosaccharides/L [control: galacto-oligosaccharides (GOS) only; experimental formulas: GOS + 0.2 or 1.0 g 2'-FL/L], and compared with a breastfed reference group. For this substudy, blood samples were drawn from infants at 6 wk of age (n = 31-42/group). Peripheral blood mononuclear cells (PBMCs) were isolated for cellular phenotyping and stimulated ex vivo with phytohemagglutinin for proliferation and cell cycle progression or respiratory syncytial virus (RSV). Cytokine concentrations were measured in plasma and in ex vivo-stimulated culture supernatants. RESULTS Breastfed infants and infants fed either of the experimental formulas with 2'-FL were not different but had 29-83% lower concentrations of plasma inflammatory cytokines than did infants fed the control formula [interleukin (IL) receptor antagonist (IL-1ra), IL-1α, IL-1β, IL-6, and tumor necrosis factor α (TNF-α)] (P ≤ 0.05). In ex vivo RSV-stimulated PBMC cultures, breastfed infants were not different than either of the groups fed formula with 2'-FL, but they had lower concentrations of TNF-α (31%) and interferon γ (IFN-γ 54%) (P ≤ 0.05) and tended to have lower IL-1ra (25%) and IL-6 (38%) (unadjusted P ≤ 0.05) and IL-1β (30%) (unadjusted P = 0.06) than did infants fed the control formula. CONCLUSIONS Our data indicate that infants fed formula supplemented with 2'-FL exhibit lower plasma and ex vivo inflammatory cytokine profiles, similar to those of a breastfed reference group. This trial was registered at clinicaltrials.gov as NCT01808105.
{"title":"Similar to Those Who Are Breastfed, Infants Fed a Formula Containing 2'-Fucosyllactose Have Lower Inflammatory Cytokines in a Randomized Controlled Trial.","authors":"Karen C. Goehring, B. Marriage, J. Oliver, J. Wilder, E. Barrett, R. Buck","doi":"10.3945/JN.116.236919","DOIUrl":"https://doi.org/10.3945/JN.116.236919","url":null,"abstract":"BACKGROUND\u0000Evidence suggests that human milk oligosaccharides (HMOs) provide multiple benefits to infants, including prebiotic effects, gut maturation, antimicrobial activities, and immune modulation. Clinical intervention studies with HMOs are required to confirm these benefits in infants.\u0000\u0000\u0000OBJECTIVE\u0000Our objective was to investigate the effects of feeding formulas supplemented with the HMO 2'-fucosyllactose (2'-FL) on biomarkers of immune function in healthy term infants.\u0000\u0000\u0000METHODS\u0000We performed a substudy nested within a randomized, double-blind, controlled growth and tolerance study in healthy singleton infants (birth weight ≥2490 g) who were enrolled by 5 d of life and exclusively formula-fed (n = 317) or breastfed (n = 107) from enrollment to 4 mo of age. Formula-fed infants were randomly assigned to receive 1 of 3 formulas, all containing 2.4 g total oligosaccharides/L [control: galacto-oligosaccharides (GOS) only; experimental formulas: GOS + 0.2 or 1.0 g 2'-FL/L], and compared with a breastfed reference group. For this substudy, blood samples were drawn from infants at 6 wk of age (n = 31-42/group). Peripheral blood mononuclear cells (PBMCs) were isolated for cellular phenotyping and stimulated ex vivo with phytohemagglutinin for proliferation and cell cycle progression or respiratory syncytial virus (RSV). Cytokine concentrations were measured in plasma and in ex vivo-stimulated culture supernatants.\u0000\u0000\u0000RESULTS\u0000Breastfed infants and infants fed either of the experimental formulas with 2'-FL were not different but had 29-83% lower concentrations of plasma inflammatory cytokines than did infants fed the control formula [interleukin (IL) receptor antagonist (IL-1ra), IL-1α, IL-1β, IL-6, and tumor necrosis factor α (TNF-α)] (P ≤ 0.05). In ex vivo RSV-stimulated PBMC cultures, breastfed infants were not different than either of the groups fed formula with 2'-FL, but they had lower concentrations of TNF-α (31%) and interferon γ (IFN-γ 54%) (P ≤ 0.05) and tended to have lower IL-1ra (25%) and IL-6 (38%) (unadjusted P ≤ 0.05) and IL-1β (30%) (unadjusted P = 0.06) than did infants fed the control formula.\u0000\u0000\u0000CONCLUSIONS\u0000Our data indicate that infants fed formula supplemented with 2'-FL exhibit lower plasma and ex vivo inflammatory cytokine profiles, similar to those of a breastfed reference group. This trial was registered at clinicaltrials.gov as NCT01808105.","PeriodicalId":22788,"journal":{"name":"The Journal of Nutrition Health and Aging","volume":"13 1","pages":"2559-2566"},"PeriodicalIF":0.0,"publicationDate":"2016-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80718220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}