Pub Date : 2024-07-14DOI: 10.1016/j.clnu.2024.07.008
Background
Concentrations of vitamin D (VitD) and 25-hydroxyvitamin D (25OHD) in breastmilk are low despite the essential role of VitD for normal infant bone development, yet additional metabolic forms of vitamin D may be present. This study evaluates the contribution of sulfated vitamin D metabolites, vitamin D3-sulfate (VitD3-S) and 25-hydroxyvitamin D3-sulfate (25OHD3-S) for lactating women and assesses the response to high-dose VitD3 supplementation.
Methods
Serum and breastmilk were measured before and after 28 days with 5000 IU/day VitD3 intake in 20 lactating women. Concentrations of VitD3-S and 25OHD3-S in milk, and 25OHD2, 25OHD3, 25OHD3-S, VitD3 and VitD3-S in serum were determined by mass spectrometry.
Results
Baseline vitamin D status was categorized as sufficient (mean ± SD serum 25OHD3 69 ± 19 nmol/L), and both serum VitD3 and 25OHD3 increased following supplementation (p < 0.001). 25OHD3-S was 91 ± 19 nmol/L in serum and 0.47 ± 0.09 nmol/L in breastmilk. VitD3-S concentrations were 2.92 ± 0.70 nmol/L in serum and 6.4 ± 3.9 nmol/L in breastmilk. Neither sulfated metabolite significantly changed with supplementation in either serum or breastmilk.
Conclusions
Sulfated vitamin D metabolites have prominent roles for women during lactation with 25OHD3-S highly abundant in serum and VitD3-S distinctly abundant in breastmilk. These data support the notion that 25OHD3-S and VitD3-S may have physiological relevance during lactation and nutritional usage for nursing infants.
背景尽管维生素 D 对婴儿骨骼的正常发育起着至关重要的作用，但母乳中维生素 D (VitD) 和 25- 羟基维生素 D (25OHD) 的浓度却很低，而且还可能存在其他代谢形式的维生素 D。本研究评估了硫酸化维生素 D 代谢物、维生素 D3-硫酸盐（VitD3-S）和 25-羟基维生素 D3-硫酸盐（25OHD3-S）对哺乳期妇女的贡献，并评估了对高剂量 VitD3 补充剂的反应。结果基线维生素 D 状态被归类为充足（平均值 ± SD 血清 25OHD3 69 ± 19 nmol/L），补充维生素 D 后血清 VitD3 和 25OHD3 均有所增加（p < 0.001）。血清中的 25OHD3-S 为 91 ± 19 nmol/L，母乳中为 0.47 ± 0.09 nmol/L。血清中维生素 D3-S 的浓度为 2.92 ± 0.70 nmol/L，母乳中为 6.4 ± 3.9 nmol/L。结论硫酸化维生素 D 代谢物在哺乳期对妇女具有重要作用，25OHD3-S 在血清中含量很高，而 VitD3-S 在母乳中含量明显较高。这些数据支持这样一种观点，即 25OHD3-S 和 VitD3-S 在哺乳期可能具有生理意义，并可为哺乳期婴儿提供营养。
{"title":"Sulfated vitamin D metabolites represent prominent roles in serum and in breastmilk of lactating women","authors":"","doi":"10.1016/j.clnu.2024.07.008","DOIUrl":"10.1016/j.clnu.2024.07.008","url":null,"abstract":"<div><h3>Background</h3><p>Concentrations of vitamin D (VitD) and 25-hydroxyvitamin D (25OHD) in breastmilk are low despite the essential role of VitD for normal infant bone development, yet additional metabolic forms of vitamin D may be present. This study evaluates the contribution of sulfated vitamin D metabolites, vitamin D<sub>3</sub>-sulfate (VitD<sub>3</sub>-S) and 25-hydroxyvitamin D<sub>3</sub>-sulfate (25OHD<sub>3</sub>-S) for lactating women and assesses the response to high-dose VitD<sub>3</sub> supplementation.</p></div><div><h3>Methods</h3><p>Serum and breastmilk were measured before and after 28 days with 5000 IU/day VitD<sub>3</sub> intake in 20 lactating women. Concentrations of VitD<sub>3</sub>-S and 25OHD<sub>3</sub>-S in milk, and 25OHD<sub>2</sub>, 25OHD<sub>3</sub>, 25OHD<sub>3</sub>-S, VitD<sub>3</sub> and VitD<sub>3</sub>-S in serum were determined by mass spectrometry.</p></div><div><h3>Results</h3><p>Baseline vitamin D status was categorized as sufficient (mean ± SD serum 25OHD<sub>3</sub> 69 ± 19 nmol/L), and both serum VitD<sub>3</sub> and 25OHD<sub>3</sub> increased following supplementation (<em>p</em> < 0.001). 25OHD<sub>3</sub>-S was 91 ± 19 nmol/L in serum and 0.47 ± 0.09 nmol/L in breastmilk. VitD<sub>3</sub>-S concentrations were 2.92 ± 0.70 nmol/L in serum and 6.4 ± 3.9 nmol/L in breastmilk. Neither sulfated metabolite significantly changed with supplementation in either serum or breastmilk.</p></div><div><h3>Conclusions</h3><p>Sulfated vitamin D metabolites have prominent roles for women during lactation with 25OHD<sub>3</sub>-S highly abundant in serum and VitD<sub>3</sub>-S distinctly abundant in breastmilk. These data support the notion that 25OHD<sub>3</sub>-S and VitD<sub>3</sub>-S may have physiological relevance during lactation and nutritional usage for nursing infants.</p></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0261561424002371/pdfft?md5=799207126f1c26f6f09a235534a3763f&pid=1-s2.0-S0261561424002371-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-14DOI: 10.1016/j.clnu.2024.07.007
Background and aims
Studies have consistently demonstrated associations between ultra-processed food and drink (UPFD) consumption and non-communicable diseases. However, there is a lack of data investigating relationships between UPFD intake and intermediate cardiometabolic disease markers. In this study we explored UPFD associations with lipoprotein subclasses.
Methods
This was a cross-sectional study of 1986 middle-to older-aged men and women randomly selected from a large primary care centre. The percentage contribution of UPFDs to total energy intake was calculated for each participant using the NOVA classification. Lipoprotein particle subclass concentrations and size were determined using nuclear magnetic resonance spectroscopy. Correlation and multivariate-adjusted linear regression analyses were performed to examine UPFD intake relationships with lipoprotein subclasses.
Results
In fully adjusted regression models, higher UPFD consumption was associated with reduced high-density lipoprotein (HDL) cholesterol concentrations (β = −0.024, p = 0.001), large low-density lipoprotein (LDL) levels (β = −18.645, p = 0.002), total and medium HDL concentrations (β = −0.328, p = 0.012; β = −0.510, p < 0.001), smaller LDL and HDL size (β = −0.026, p = 0.023; β = −0.023, p = 0.024), and increased medium very low-density lipoprotein levels (β = 0.053, p = 0.022), small LDL and HDL concentrations (β = 20.358, p = 0.02; β = 0.336, p = 0.011), and higher lipoprotein insulin resistance scores (β = 0.048, p = 0.012), reflecting greater lipoprotein-related insulin resistance.
Conclusions
Findings from this research suggest that increased intake of UPFDs is associated with a more pro-atherogenic, insulin-resistant metabolic profile in middle-to older-aged adults which may be a potential mechanism underlying reported associations between UPFD consumption and chronic disease risk and mortality.
{"title":"Ultra-processed food and drink consumption and lipoprotein subclass profiles: A cross-sectional study of a middle-to older-aged population","authors":"","doi":"10.1016/j.clnu.2024.07.007","DOIUrl":"10.1016/j.clnu.2024.07.007","url":null,"abstract":"<div><h3>Background and aims</h3><p>Studies have consistently demonstrated associations between ultra-processed food and drink (UPFD) consumption and non-communicable diseases. However, there is a lack of data investigating relationships between UPFD intake and intermediate cardiometabolic disease markers. In this study we explored UPFD associations with lipoprotein subclasses.</p></div><div><h3>Methods</h3><p>This was a cross-sectional study of 1986 middle-to older-aged men and women randomly selected from a large primary care centre. The percentage contribution of UPFDs to total energy intake was calculated for each participant using the NOVA classification. Lipoprotein particle subclass concentrations and size were determined using nuclear magnetic resonance spectroscopy. Correlation and multivariate-adjusted linear regression analyses were performed to examine UPFD intake relationships with lipoprotein subclasses.</p></div><div><h3>Results</h3><p>In fully adjusted regression models, higher UPFD consumption was associated with reduced high-density lipoprotein (HDL) cholesterol concentrations (β = −0.024, <em>p</em> = 0.001), large low-density lipoprotein (LDL) levels (β = −18.645, <em>p</em> = 0.002), total and medium HDL concentrations (β = −0.328, <em>p</em> = 0.012; β = −0.510, <em>p</em> < 0.001), smaller LDL and HDL size (β = −0.026, <em>p</em> = 0.023; β = −0.023, <em>p</em> = 0.024), and increased medium very low-density lipoprotein levels (β = 0.053, <em>p</em> = 0.022), small LDL and HDL concentrations (β = 20.358, <em>p</em> = 0.02; β = 0.336, <em>p</em> = 0.011), and higher lipoprotein insulin resistance scores (β = 0.048, <em>p</em> = 0.012), reflecting greater lipoprotein-related insulin resistance.</p></div><div><h3>Conclusions</h3><p>Findings from this research suggest that increased intake of UPFDs is associated with a more pro-atherogenic, insulin-resistant metabolic profile in middle-to older-aged adults which may be a potential mechanism underlying reported associations between UPFD consumption and chronic disease risk and mortality.</p></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S026156142400236X/pdfft?md5=787cbf55b3d3c9ad1a574db2e13c6ff8&pid=1-s2.0-S026156142400236X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141690153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-14DOI: 10.1016/j.clnu.2024.07.004
Parenteral nutrition (PN) is a life-saving procedure conducted to maintain a proper nutritional state in patients with severe intestinal failure who cannot be fed orally. A serious complication of PN therapy is liver failure, known as intestinal failure-associated liver disease (IFALD). The pathogenesis of IFALD is multifactorial and includes inhibition of the farnesoid X receptor (FXR) by PN components, bacteria translocation from impaired intestines, and intravenous line-associated bloodstream infection. Currently, the most frequently researched therapeutic option for IFALD is using lipid emulsions based on soy or fish oil and, therefore, free from phytosterols known as FXR antagonists. Nevertheless, the potential side effects of the lack of soybean oil delivery seem to outweigh the benefits, especially in the pediatric population. PN admixture provides all the necessary nutrients; however, it is deprived of exogenous natural bioactive compounds (NBCs) of plant origin, such as polyphenols, characterized by health-promoting properties. Among them, many substances have already been known to demonstrate the hepatoprotective effect in various liver diseases. Therefore, searching for new therapeutic options for IFALD among NBCs seems reasonable and potentially successful. This review summarizes the recent research on polyphenols and their use in treating various liver diseases, especially metabolic dysfunction-associated steatotic liver diseases (MASLD). Furthermore, based on scientific reports, we have described the molecular mechanism of action of selected NBCs that exert hepatoprotective properties. We also summarized the current knowledge on IFALD pathogenesis, described therapeutic options undergoing clinical trials, and presented the future perspective of the potential use of NBCs in PN therapy.
{"title":"Natural bioactive compounds–The promising candidates for the treatment of intestinal failure-associated liver disease","authors":"","doi":"10.1016/j.clnu.2024.07.004","DOIUrl":"10.1016/j.clnu.2024.07.004","url":null,"abstract":"<div><p>Parenteral nutrition (PN) is a life-saving procedure conducted to maintain a proper nutritional state in patients with severe intestinal failure who cannot be fed orally. A serious complication of PN therapy is liver failure, known as intestinal failure-associated liver disease (IFALD). The pathogenesis of IFALD is multifactorial and includes inhibition of the farnesoid X receptor (FXR) by PN components, bacteria translocation from impaired intestines, and intravenous line-associated bloodstream infection. Currently, the most frequently researched therapeutic option for IFALD is using lipid emulsions based on soy or fish oil and, therefore, free from phytosterols known as FXR antagonists. Nevertheless, the potential side effects of the lack of soybean oil delivery seem to outweigh the benefits, especially in the pediatric population. PN admixture provides all the necessary nutrients; however, it is deprived of exogenous natural bioactive compounds (NBCs) of plant origin, such as polyphenols, characterized by health-promoting properties. Among them, many substances have already been known to demonstrate the hepatoprotective effect in various liver diseases. Therefore, searching for new therapeutic options for IFALD among NBCs seems reasonable and potentially successful. This review summarizes the recent research on polyphenols and their use in treating various liver diseases, especially metabolic dysfunction-associated steatotic liver diseases (MASLD). Furthermore, based on scientific reports, we have described the molecular mechanism of action of selected NBCs that exert hepatoprotective properties. We also summarized the current knowledge on IFALD pathogenesis, described therapeutic options undergoing clinical trials, and presented the future perspective of the potential use of NBCs in PN therapy.</p></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0261561424002334/pdfft?md5=8b3ee8994875dabccda152a92840fca0&pid=1-s2.0-S0261561424002334-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141712151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-14DOI: 10.1016/j.clnu.2024.07.005
Background & aims
Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort.
Methods
ARIC Study participants at visit 3 (1993–1995) with completed food frequency questionnaire (FFQ) data and proteomics data were divided into internal discovery (n = 7690) and replication (n = 2543) data sets. Multivariable linear regression was used to examine associations between plant-based diet indices (PDIs) and 4955 individual proteins in the discovery sample. Then, proteins that were internally replicated in the ARIC Study were tested for external replication in FHS (n = 1358). Pathway overrepresentation analysis was conducted for diet-related proteins. C-statistics were used to predict if the proteins improved prediction of plant-based diet indices beyond participant characteristics.
Results
In ARIC discovery, a total of 837 diet-protein associations (PDI = 233; provegetarian = 182; hPDI = 406; uPDI = 16) were observed at false discovery rate (FDR) < 0.05. Of these, 453 diet-protein associations (PDI = 132; provegetarian = 104; hPDI = 208; uPDI = 9) were internally replicated. In FHS, 167/453 diet-protein associations were available for external replication, of which 8 proteins (PDI = 1; provegetarian = 0; hPDI = 8; uPDI = 0) replicated. Complement and coagulation cascades, cell adhesion molecules, and retinol metabolism were over-represented. C-C motif chemokine 25 for PDI and 8 proteins for hPDI modestly but significantly improved the prediction of these indices individually and collectively (P value for difference in C-statistics<0.05 for all tests).
Conclusions
Using large-scale proteomics, we identified potential candidate biomarkers of plant-based diets, and pathways that may partially explain the associations between plant-based diets and chronic conditions.
{"title":"Plasma proteins associated with plant-based diets: Results from the Atherosclerosis Risk in Communities (ARIC) study and Framingham Heart Study (FHS)","authors":"","doi":"10.1016/j.clnu.2024.07.005","DOIUrl":"10.1016/j.clnu.2024.07.005","url":null,"abstract":"<div><h3>Background & aims</h3><p>Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort.</p></div><div><h3>Methods</h3><p>ARIC Study participants at visit 3 (1993–1995) with completed food frequency questionnaire (FFQ) data and proteomics data were divided into internal discovery (n = 7690) and replication (n = 2543) data sets. Multivariable linear regression was used to examine associations between plant-based diet indices (PDIs) and 4955 individual proteins in the discovery sample. Then, proteins that were internally replicated in the ARIC Study were tested for external replication in FHS (n = 1358). Pathway overrepresentation analysis was conducted for diet-related proteins. C-statistics were used to predict if the proteins improved prediction of plant-based diet indices beyond participant characteristics.</p></div><div><h3>Results</h3><p>In ARIC discovery, a total of 837 diet-protein associations (PDI = 233; provegetarian = 182; hPDI = 406; uPDI = 16) were observed at false discovery rate (FDR) < 0.05. Of these, 453 diet-protein associations (PDI = 132; provegetarian = 104; hPDI = 208; uPDI = 9) were internally replicated. In FHS, 167/453 diet-protein associations were available for external replication, of which 8 proteins (PDI = 1; provegetarian = 0; hPDI = 8; uPDI = 0) replicated. Complement and coagulation cascades, cell adhesion molecules, and retinol metabolism were over-represented. C-C motif chemokine 25 for PDI and 8 proteins for hPDI modestly but significantly improved the prediction of these indices individually and collectively (P value for difference in C-statistics<0.05 for all tests).</p></div><div><h3>Conclusions</h3><p>Using large-scale proteomics, we identified potential candidate biomarkers of plant-based diets, and pathways that may partially explain the associations between plant-based diets and chronic conditions.</p></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-11DOI: 10.1016/j.clnu.2024.07.002
Background
Both overweight/obesity and a Western lifestyle are associated with a poorer prognosis in women with breast cancer. The primary aim of this analysis was to examine the effect of a telephone-delivered lifestyle intervention program on reducing body weight and waist circumference, decreasing cardiovascular risk factors and improving lifestyle.
Design
Data is derived from an open-label, randomized, controlled phase III study that evaluated two chemotherapy regimens and the impact of a 2-year lifestyle intervention on disease-free survival and secondary outcomes in women with intermediate-risk to high-risk breast cancer. Initially, 2292 women with a body mass index (BMI) between 24 and 40 kg/m2 were randomized into one of two arms of the lifestyle intervention study. After accounting for dropout, 1785 participants remained: 776 in the intervention group (IG) who received a telephone-delivered lifestyle intervention supported by mailed materials, and 1009 in the low-level intervention group (LLIG) who received only mailed educational materials with general recommendations for a healthy lifestyle. Body weight, waist circumference, dietary intake, physical activity, and cardiovascular disease risk parameters were measured repeatedly throughout the intervention and a subsequent 2-year follow-up period. Linear mixed models for repeated measures were used to assess differences in study outcomes between the LLIG and IG at each measured time point.
Results
IG participants showed a mean weight loss of −2.7 kg (kg) (versus +0.4 kg, LLIG) at 6 months, −2.8 kg (vs. +0.8 kg, LLIG) at 12 months and −1.8 kg at 24 months (versus +0.9 kg, LLIG). Significant between-group differences for weight loss and reduced waist circumference were observed at all time points until the end of the lifestyle intervention (all p-values < 0.0001), including post-intervention. Reduced energy intake and a higher alternate healthy eating index (AHEI) score in the IG was detected during the lifestyle intervention (AHEI at 24 months: IG 49.1% versus LLIG 42.0%, p < 0.001). Modest significant improvements in several cardiovascular risk factors were observed during the intervention, including fasting plasma glucose, HbA1c, systolic and diastolic blood pressure, and lipids.
Conclusions
A mainly telephone-delivered lifestyle intervention program can reduce body weight and waist circumference, improve diet quality, and decrease cardiometabolic risk in women with overweight/obesity and newly diagnosed, human epidermal growth factor receptor 2 (HER2)/neu-negative, intermediate-risk to high-risk breast cancer. Weight loss, reduced waist circumference and improved dietary patterns were maintained for up to two years post-intervention.
Trial registration
The protocol was registered under the EU Clinical Trials Register, https://www.clinicaltrials
{"title":"Effect of a comprehensive lifestyle intervention program on body weight and health behavior in women with breast cancer: Results from a randomized controlled trial","authors":"","doi":"10.1016/j.clnu.2024.07.002","DOIUrl":"10.1016/j.clnu.2024.07.002","url":null,"abstract":"<div><h3>Background</h3><p>Both overweight/obesity and a Western lifestyle are associated with a poorer prognosis in women with breast cancer. The primary aim of this analysis was to examine the effect of a telephone-delivered lifestyle intervention program on reducing body weight and waist circumference, decreasing cardiovascular risk factors and improving lifestyle.</p></div><div><h3>Design</h3><p>Data is derived from an open-label, randomized, controlled phase III study that evaluated two chemotherapy regimens and the impact of a 2-year lifestyle intervention on disease-free survival and secondary outcomes in women with intermediate-risk to high-risk breast cancer. Initially, 2292 women with a body mass index (BMI) between 24 and 40 kg/m<sup>2</sup> were randomized into one of two arms of the lifestyle intervention study. After accounting for dropout, 1785 participants remained: 776 in the intervention group (IG) who received a telephone-delivered lifestyle intervention supported by mailed materials, and 1009 in the low-level intervention group (LLIG) who received only mailed educational materials with general recommendations for a healthy lifestyle. Body weight, waist circumference, dietary intake, physical activity, and cardiovascular disease risk parameters were measured repeatedly throughout the intervention and a subsequent 2-year follow-up period. Linear mixed models for repeated measures were used to assess differences in study outcomes between the LLIG and IG at each measured time point.</p></div><div><h3>Results</h3><p>IG participants showed a mean weight loss of −2.7 kg (kg) (versus +0.4 kg, LLIG) at 6 months, −2.8 kg (vs. +0.8 kg, LLIG) at 12 months and −1.8 kg at 24 months (versus +0.9 kg, LLIG). Significant between-group differences for weight loss and reduced waist circumference were observed at all time points until the end of the lifestyle intervention (all p-values < 0.0001), including post-intervention. Reduced energy intake and a higher alternate healthy eating index (AHEI) score in the IG was detected during the lifestyle intervention (AHEI at 24 months: IG 49.1% versus LLIG 42.0%, p < 0.001). Modest significant improvements in several cardiovascular risk factors were observed during the intervention, including fasting plasma glucose, HbA1c, systolic and diastolic blood pressure, and lipids.</p></div><div><h3>Conclusions</h3><p>A mainly telephone-delivered lifestyle intervention program can reduce body weight and waist circumference, improve diet quality, and decrease cardiometabolic risk in women with overweight/obesity and newly diagnosed, human epidermal growth factor receptor 2 (HER2)/neu-negative, intermediate-risk to high-risk breast cancer. Weight loss, reduced waist circumference and improved dietary patterns were maintained for up to two years post-intervention.</p></div><div><h3>Trial registration</h3><p>The protocol was registered under the EU Clinical Trials Register, <span><span>https://www.clinicaltrials","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0261561424002310/pdfft?md5=5ca4610e582dfcbebc20d585c4d2ba02&pid=1-s2.0-S0261561424002310-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.1016/j.clnu.2024.07.001
Background and aims
While clinical studies indicate that dietary protein may benefit glucose homeostasis in type 2 diabetes (T2D), the impact of dietary protein, including whether the protein is of animal or plant origin, on the risk of T2D is uncertain. We conducted a systematic review and meta-analysis to evaluate the associations of total, animal, and plant protein intakes with the risk of T2D.
Methods
A systematic search was performed using multiple data sources, including PubMed/Medline, ISI Web of Science, Scopus, and Google Scholar, with the data cut-off in May 2023. Our selection criteria focused on prospective cohort studies that reported risk estimates for the association between protein intake and T2D risk. For data synthesis, we calculated summary relative risks and 95% confidence intervals for the highest versus lowest categories of protein intake using random-effects models. Furthermore, we conducted both linear and non-linear dose-response analyses to assess the dose-response associations between protein intake and T2D risk.
Results
Sixteen prospective cohort studies, involving 615,125 participants and 52,342 T2D cases, were identified, of which eleven studies reported data on intake of both animal and plant protein. Intakes of total (pooled effect size: 1.14, 95% CI: 1.04–1.24) and animal (pooled effect size: 1.18, 95% CI: 1.09–1.27) protein were associated with an increased risk of T2D. These effects were dose-related – each 20-g increase in total or animal protein intake increased the risk of T2D by ∼3% and ∼7%, respectively. In contrast, there was no association between intake of plant protein and T2D risk (pooled effect size: 0.98, 95% CI: 0.89–1.08), while replacing animal with plant protein intake (per each 20 g) was associated with a reduced risk of T2D (pooled effect size: 0.80, 95% CI: 0.76–0.84).
Conclusions
Our findings indicate that long-term consumption of animal, but not plant, protein is associated with a significant and dose-dependent increase in the risk of T2D, with the implication that replacement of animal with plant protein intake may lower the risk of T2D.
{"title":"Association between total, animal, and plant protein intake and type 2 diabetes risk in adults: A systematic review and dose-response meta-analysis of prospective cohort studies","authors":"","doi":"10.1016/j.clnu.2024.07.001","DOIUrl":"10.1016/j.clnu.2024.07.001","url":null,"abstract":"<div><h3>Background and aims</h3><p>While clinical studies indicate that dietary protein may benefit glucose homeostasis in type 2 diabetes (T2D), the impact of dietary protein, including whether the protein is of animal or plant origin, on the risk of T2D is uncertain. We conducted a systematic review and meta-analysis to evaluate the associations of total, animal, and plant protein intakes with the risk of T2D.</p></div><div><h3>Methods</h3><p>A systematic search was performed using multiple data sources, including PubMed/Medline, ISI Web of Science, Scopus, and Google Scholar, with the data cut-off in May 2023. Our selection criteria focused on prospective cohort studies that reported risk estimates for the association between protein intake and T2D risk. For data synthesis, we calculated summary relative risks and 95% confidence intervals for the highest versus lowest categories of protein intake using random-effects models. Furthermore, we conducted both linear and non-linear dose-response analyses to assess the dose-response associations between protein intake and T2D risk.</p></div><div><h3>Results</h3><p>Sixteen prospective cohort studies, involving 615,125 participants and 52,342 T2D cases, were identified, of which eleven studies reported data on intake of both animal and plant protein. Intakes of total (pooled effect size: 1.14, 95% CI: 1.04–1.24) and animal (pooled effect size: 1.18, 95% CI: 1.09–1.27) protein were associated with an increased risk of T2D. These effects were dose-related – each 20-g increase in total or animal protein intake increased the risk of T2D by ∼3% and ∼7%, respectively. In contrast, there was no association between intake of plant protein and T2D risk (pooled effect size: 0.98, 95% CI: 0.89–1.08), while replacing animal with plant protein intake (per each 20 g) was associated with a reduced risk of T2D (pooled effect size: 0.80, 95% CI: 0.76–0.84).</p></div><div><h3>Conclusions</h3><p>Our findings indicate that long-term consumption of animal, but not plant, protein is associated with a significant and dose-dependent increase in the risk of T2D, with the implication that replacement of animal with plant protein intake may lower the risk of T2D.</p></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141707018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1016/j.clnu.2024.07.003
{"title":"Further insight into the association of Growth differentiation factor 15 (GDF15) levels and malnutrition in acutely admitted older adults","authors":"","doi":"10.1016/j.clnu.2024.07.003","DOIUrl":"10.1016/j.clnu.2024.07.003","url":null,"abstract":"","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141714959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1016/j.clnu.2024.06.036
Martha Guevara-Cruz , Karla G. Hernández-Gómez , Citlally Condado-Huerta , Luis E. González-Salazar , Ana Karen Peña-Flores , Edgar Pichardo-Ontiveros , Aurora E. Serralde-Zúñiga , Mónica Sánchez-Tapia , Otoniel Maya , Isabel Medina-Vera , Lilia G. Noriega , Adriana López-Barradas , Oscar Rodríguez-Lima , Irma Mata , Viridiana Olin–Sandoval , Nimbe Torres , Armando R. Tovar , Laura A. Velázquez-Villegas
Background
Mitochondrial dysfunction occurs in monocytes during obesity and contributes to a low-grade inflammatory state; therefore, maintaining good mitochondrial conditions is a key aspect of maintaining health. Dietary interventions are primary strategies for treating obesity, but little is known about their impact on monocyte bioenergetics. Thus, the aim of this study was to evaluate the effects of calorie restriction (CR), intermittent fasting (IF), a ketogenic diet (KD), and an ad libitum habitual diet (AL) on mitochondrial function in monocytes and its modulation by the gut microbiota.
Methods and findings
A randomized controlled clinical trial was conducted in which individuals with obesity were assigned to one of the 4 groups for 1 month. Subsequently, the subjects received rifaximin and continued with the assigned diet for another month. The oxygen consumption rate (OCR) was evaluated in isolated monocytes, as was the gut microbiota composition in feces and anthropometric and biochemical parameters. Forty-four subjects completed the study, and those who underwent CR, IF and KD interventions had an increase in the maximal respiration OCR (p = 0.025, n2p = 0.159 [0.05, 0.27] 95% confidence interval) in monocytes compared to that in the AL group. The improvement in mitochondrial function was associated with a decrease in monocyte dependence on glycolysis after the IF and KD interventions. Together, diet and rifaximin increased the gut microbiota diversity in the IF and KD groups (p = 0.0001), enriched the abundance of Phascolarctobacterium faecium (p = 0.019) in the CR group and Ruminococcus bromii (p = 0.020) in the CR and KD groups, and reduced the abundance of lipopolysaccharide (LPS)-producing bacteria after CR, IF and KD interventions compared to the AL group at the end of the study according to ANCOVA with covariate adjustment. Spearman's correlation between the variables measured highlighted LPS as a potential modulator of the observed effects. In line with this findings, serum LPS and intracellular signaling in monocytes decreased with the three interventions (CR, p = 0.002; IF, p = 0.001; and KD, p = 0.001) compared to those in the AL group at the end of the study.
Conclusions
We conclude that these dietary interventions positively regulate mitochondrial bioenergetic health and improve the metabolic profile of monocytes in individuals with obesity via modulation of the gut microbiota. Moreover, the evaluation of mitochondrial function in monocytes could be used as an indicator of metabolic and inflammatory status, with potential applications in future clinical trials.
Trial registration
This trial was registered with ClinicalTrials.gov (NCT05200468).
{"title":"Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial","authors":"Martha Guevara-Cruz , Karla G. Hernández-Gómez , Citlally Condado-Huerta , Luis E. González-Salazar , Ana Karen Peña-Flores , Edgar Pichardo-Ontiveros , Aurora E. Serralde-Zúñiga , Mónica Sánchez-Tapia , Otoniel Maya , Isabel Medina-Vera , Lilia G. Noriega , Adriana López-Barradas , Oscar Rodríguez-Lima , Irma Mata , Viridiana Olin–Sandoval , Nimbe Torres , Armando R. Tovar , Laura A. Velázquez-Villegas","doi":"10.1016/j.clnu.2024.06.036","DOIUrl":"https://doi.org/10.1016/j.clnu.2024.06.036","url":null,"abstract":"<div><h3>Background</h3><p>Mitochondrial dysfunction occurs in monocytes during obesity and contributes to a low-grade inflammatory state; therefore, maintaining good mitochondrial conditions is a key aspect of maintaining health. Dietary interventions are primary strategies for treating obesity, but little is known about their impact on monocyte bioenergetics. Thus, the aim of this study was to evaluate the effects of calorie restriction (CR), intermittent fasting (IF), a ketogenic diet (KD), and an ad libitum habitual diet (AL) on mitochondrial function in monocytes and its modulation by the gut microbiota.</p></div><div><h3>Methods and findings</h3><p>A randomized controlled clinical trial was conducted in which individuals with obesity were assigned to one of the 4 groups for 1 month. Subsequently, the subjects received rifaximin and continued with the assigned diet for another month. The oxygen consumption rate (OCR) was evaluated in isolated monocytes, as was the gut microbiota composition in feces and anthropometric and biochemical parameters. Forty-four subjects completed the study, and those who underwent CR, IF and KD interventions had an increase in the maximal respiration OCR (p = 0.025, n<sup>2</sup>p = 0.159 [0.05, 0.27] 95% confidence interval) in monocytes compared to that in the AL group. The improvement in mitochondrial function was associated with a decrease in monocyte dependence on glycolysis after the IF and KD interventions. Together, diet and rifaximin increased the gut microbiota diversity in the IF and KD groups (p = 0.0001), enriched the abundance of <em>Phascolarctobacterium faecium</em> (p = 0.019) in the CR group and <em>Ruminococcus bromii</em> (p = 0.020) in the CR and KD groups, and reduced the abundance of lipopolysaccharide (LPS)-producing bacteria after CR, IF and KD interventions compared to the AL group at the end of the study according to ANCOVA with covariate adjustment. Spearman's correlation between the variables measured highlighted LPS as a potential modulator of the observed effects. In line with this findings, serum LPS and intracellular signaling in monocytes decreased with the three interventions (CR, p = 0.002; IF, p = 0.001; and KD, p = 0.001) compared to those in the AL group at the end of the study.</p></div><div><h3>Conclusions</h3><p>We conclude that these dietary interventions positively regulate mitochondrial bioenergetic health and improve the metabolic profile of monocytes in individuals with obesity via modulation of the gut microbiota. Moreover, the evaluation of mitochondrial function in monocytes could be used as an indicator of metabolic and inflammatory status, with potential applications in future clinical trials.</p></div><div><h3>Trial registration</h3><p>This trial was registered with ClinicalTrials.gov (NCT05200468).</p></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0261561424002280/pdfft?md5=7ba698b0593dda4148cecf3784309dbc&pid=1-s2.0-S0261561424002280-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141607044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarcopenic obesity (SO) and dynapenic obesity (DO) represent two manifestations of excessive fat accumulation concurrent with compromised muscle mass and function, thereby necessitating an examination of their implications for health. This study aims to investigate the relationship between SO/DO and mortality, taking into account various adiposity measures and existing sarcopenia criteria, with further stratified analyses based on age and gender.
Methods
The study sample comprised 1779 older adults residing in the community from the I-Lan Longitudinal Aging Study (ILAS). Body composition was assessed via dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was adhered to the 2019 consensus of the Asian Working Group for Sarcopenia, while adiposity was measured by waist circumference (WC), body mass index (BMI), and fat percentage. SO/DO was defined as the coexistence of sarcopenia/dynapenia and obesity. Multivariate Cox proportional hazard regression models were adopted to examine the association between SO or DO, defined by WC, BMI, fat percentage, and mortality.
Results
This 11-year follow-up study of 1779 participants aged 63.9 ± 9.2 years involved 15,068 person-years and 229 deaths. WC-defined SO (HR 1.9, 95% CI 1.1–3.3, p = 0.021) and WC-defined DO (HR 1.4, 95% CI 1.1–1.9, p = 0.022) significantly increased mortality risk, whereas definitions employing alternative adiposity metrics exhibited no statistical significance. WC-defined SO was associated with increased risk of mortality among middle-aged adults, while WC-defined DO was associated with increased risk of mortality among older adults. In sex-specific analysis, WC-defined DO was also associated with increased risk of mortality in men (HR 1.6, 95% CI 1.1–2.4, p = 0.019), while defined by other measurements showed no associations in both sexes.
Conclusions
The study identified a significant link between SO/DO, defined by WC, and an 11-year mortality risk, advocating for WC-defined adiposity as an obesity measure and personalized interventions considering SO and DO's distinct impacts on mortality in middle-aged and older adults.
背景与目的：肌肉疏松性肥胖症（Sarcopenic obesity，SO）和动态性肥胖症（Dynapenic obesity，DO）是脂肪堆积过多同时肌肉质量和功能受损的两种表现形式，因此有必要研究它们对健康的影响。本研究旨在根据不同的脂肪测量方法和现有的肌肉疏松症标准，并进一步根据年龄和性别进行分层分析，探讨SO/DO与死亡率之间的关系：研究样本包括伊兰老龄化纵向研究（ILAS）中居住在社区的 1779 名老年人。身体成分通过双能 X 光吸收测定法进行评估。对 "肌肉疏松症 "的诊断符合亚洲 "肌肉疏松症工作组 "2019 年的共识，而对 "肥胖症 "的测量则采用腰围（WC）、体重指数（BMI）和脂肪百分比。SO/DO被定义为同时存在肌少症/动态肌无力症和肥胖症。采用多变量考克斯比例危险回归模型来研究以腹围、体重指数、脂肪百分比定义的SO或DO与死亡率之间的关系：这项为期 11 年的随访研究有 1779 名参与者参加，年龄为 63.9 ± 9.2 岁，共研究了 15,068 人/年，229 人死亡。WC定义的SO（HR 1.9，95% CI 1.1-3.3，p = 0.021）和WC定义的DO（HR 1.4，95% CI 1.1-1.9，p = 0.022）显著增加了死亡风险，而采用其他脂肪指标的定义则没有统计学意义。WC定义的SO与中年人死亡风险增加有关，而WC定义的DO与老年人死亡风险增加有关。在性别特异性分析中，WC 定义的 DO 也与男性死亡风险增加有关（HR 1.6，95% CI 1.1-2.4，p = 0.019），而根据其他测量方法定义的 DO 在两性中均无相关性：该研究发现，以腹围定义的SO/DO与11年的死亡风险之间存在重要联系，因此主张将以腹围定义的脂肪作为肥胖测量指标，并考虑SO和DO对中老年人死亡率的不同影响，采取个性化干预措施。
{"title":"The distinct impacts of sarcopenic and dynapenic obesity on mortality in middle-aged and older adults based on different adiposity metrics: Results from I-Lan Longitudinal Aging Study","authors":"Li-Yen Tseng , Chih-Kuang Liang , Li-Ning Peng , Ming-Hsien Lin , Ching-Hui Loh , Wei-Ju Lee , Fei-Yuan Hsiao , Liang-Kung Chen","doi":"10.1016/j.clnu.2024.06.035","DOIUrl":"10.1016/j.clnu.2024.06.035","url":null,"abstract":"<div><h3>Background & aims</h3><p>Sarcopenic obesity (SO) and dynapenic obesity (DO) represent two manifestations of excessive fat accumulation concurrent with compromised muscle mass and function, thereby necessitating an examination of their implications for health. This study aims to investigate the relationship between SO/DO and mortality, taking into account various adiposity measures and existing sarcopenia criteria, with further stratified analyses based on age and gender.</p></div><div><h3>Methods</h3><p>The study sample comprised 1779 older adults residing in the community from the I-Lan Longitudinal Aging Study (ILAS). Body composition was assessed via dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was adhered to the 2019 consensus of the Asian Working Group for Sarcopenia, while adiposity was measured by waist circumference (WC), body mass index (BMI), and fat percentage. SO/DO was defined as the coexistence of sarcopenia/dynapenia and obesity. Multivariate Cox proportional hazard regression models were adopted to examine the association between SO or DO, defined by WC, BMI, fat percentage, and mortality.</p></div><div><h3>Results</h3><p>This 11-year follow-up study of 1779 participants aged 63.9 ± 9.2 years involved 15,068 person-years and 229 deaths. WC-defined SO (HR 1.9, 95% CI 1.1–3.3, p = 0.021) and WC-defined DO (HR 1.4, 95% CI 1.1–1.9, p = 0.022) significantly increased mortality risk, whereas definitions employing alternative adiposity metrics exhibited no statistical significance. WC-defined SO was associated with increased risk of mortality among middle-aged adults, while WC-defined DO was associated with increased risk of mortality among older adults. In sex-specific analysis, WC-defined DO was also associated with increased risk of mortality in men (HR 1.6, 95% CI 1.1–2.4, p = 0.019), while defined by other measurements showed no associations in both sexes.</p></div><div><h3>Conclusions</h3><p>The study identified a significant link between SO/DO, defined by WC, and an 11-year mortality risk, advocating for WC-defined adiposity as an obesity measure and personalized interventions considering SO and DO's distinct impacts on mortality in middle-aged and older adults.</p></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1016/j.clnu.2024.06.037
Pamela N. Klassen , Vera C. Mazurak , Vickie Baracos , Lisa Martin , Sunita Ghosh , Jessica Kasnik , Michael B. Sawyer
Background & aims
Exocrine pancreatic insufficiency (EPI) contributes to malnutrition, marked by muscle loss during chemotherapy for advanced pancreatic cancer (aPC). Pancreatic enzyme replacement therapy (PERT) is recommended for patients with EPI; however, it's efficacy for attenuating muscle loss has not been demonstrated. We aimed to delineate the impact of PERT dose on muscle loss using a 7-year population-based cohort with aPC who were provided PERT at the discretion of their oncologist or dietitian according to clinical indications of EPI.
Methods
All patients treated with chemotherapy for aPC from 2013 to 2019 in Alberta, Canada (population ∼4.3 million) were included if they had computed tomography (CT) scans both prior to and 12 ± 4 weeks after chemotherapy initiation. Change in muscle area (cm2) was measured at 3rd lumbar level on repeated CT scans. Muscle loss was defined by measurement error (loss >2.3 cm2). Clinical and pharmaceutical data were retrieved from provincial registries. For patients who were dispensed PERT -8 to +6 weeks from chemo start (PERT users), estimated dose consumed per day was calculated as: (total dose dispensed) / (days, first to last dispensation). PERT users were categorized as high dose or low dose users according to the median estimated dose consumed. Non-users were classified as No PERT. Association between PERT use and muscle loss was analyzed with multivariable logistic regression.
Results
Among 210 patients, 81 (39%) were PERT users. Median estimated dose consumed per day of 75 000 USP lipase units defined the cutoff between low dose and high dose uses. There were no significant differences in baseline characteristics between high dose and low dose groups. Muscle loss was more prevalent among low dose compared to both high dose and No PERT groups (88% vs. 58% and 67%, p < 0.05). In the multivariable model predicting muscle loss, low dose PERT was independently associated with greater odds of muscle loss (OR 5.4, p = 0.004) vs. high dose, independent of tumour response, disease stage, and chemotherapy regimen.
Conclusion
In patients with clinical indications of EPI during chemotherapy for aPC, low doses of PERT were insufficient to prevent muscle loss. Patients with EPI consuming higher doses of PERT had similar odds of muscle maintenance to patients without clinical indications of EPI. Provider education for optimal PERT dosing in patients with EPI should be prioritized, and resources must be allocated to support dose titration.
{"title":"Dose optimization of pancreatic enzyme replacement therapy is essential to mitigate muscle loss in patients with advanced pancreatic cancer and exocrine pancreatic insufficiency","authors":"Pamela N. Klassen , Vera C. Mazurak , Vickie Baracos , Lisa Martin , Sunita Ghosh , Jessica Kasnik , Michael B. Sawyer","doi":"10.1016/j.clnu.2024.06.037","DOIUrl":"10.1016/j.clnu.2024.06.037","url":null,"abstract":"<div><h3>Background & aims</h3><p>Exocrine pancreatic insufficiency (EPI) contributes to malnutrition, marked by muscle loss during chemotherapy for advanced pancreatic cancer (aPC). Pancreatic enzyme replacement therapy (PERT) is recommended for patients with EPI; however, it's efficacy for attenuating muscle loss has not been demonstrated. We aimed to delineate the impact of PERT dose on muscle loss using a 7-year population-based cohort with aPC who were provided PERT at the discretion of their oncologist or dietitian according to clinical indications of EPI.</p></div><div><h3>Methods</h3><p>All patients treated with chemotherapy for aPC from 2013 to 2019 in Alberta, Canada (population ∼4.3 million) were included if they had computed tomography (CT) scans both prior to and 12 ± 4 weeks after chemotherapy initiation. Change in muscle area (cm<sup>2</sup>) was measured at 3rd lumbar level on repeated CT scans. Muscle loss was defined by measurement error (loss >2.3 cm<sup>2</sup>). Clinical and pharmaceutical data were retrieved from provincial registries. For patients who were dispensed PERT -8 to +6 weeks from chemo start (PERT users), estimated dose consumed per day was calculated as: (total dose dispensed) / (days, first to last dispensation). PERT users were categorized as high dose or low dose users according to the median estimated dose consumed. Non-users were classified as No PERT. Association between PERT use and muscle loss was analyzed with multivariable logistic regression.</p></div><div><h3>Results</h3><p>Among 210 patients, 81 (39%) were PERT users. Median estimated dose consumed per day of 75 000 USP lipase units defined the cutoff between low dose and high dose uses. There were no significant differences in baseline characteristics between high dose and low dose groups. Muscle loss was more prevalent among low dose compared to both high dose and No PERT groups (88% vs. 58% and 67%, <em>p</em> < 0.05). In the multivariable model predicting muscle loss, low dose PERT was independently associated with greater odds of muscle loss (OR 5.4, <em>p</em> = 0.004) vs. high dose, independent of tumour response, disease stage, and chemotherapy regimen.</p></div><div><h3>Conclusion</h3><p>In patients with clinical indications of EPI during chemotherapy for aPC, low doses of PERT were insufficient to prevent muscle loss. Patients with EPI consuming higher doses of PERT had similar odds of muscle maintenance to patients without clinical indications of EPI. Provider education for optimal PERT dosing in patients with EPI should be prioritized, and resources must be allocated to support dose titration.</p></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0261561424002292/pdfft?md5=5d829eb88b14522b3ccd961448f85f8a&pid=1-s2.0-S0261561424002292-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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