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Article ; Online: Effects of L-citrulline supplementation and watermelon consumption on longer-term and postprandial vascular function and cardiometabolic risk markers: A meta-analysis of randomized controlled trials in adults.

Smeets, Ellen T H C / Mensink, Ronald P / Joris, Peter J

2021 , Page(s) 1–34

Abstract: L-citrulline may improve non-invasive vascular function and cardiometabolic risk markers ... through increases in L-arginine bioavailability and nitric oxide synthesis. A meta-analysis ... of randomized controlled trials (RCTs) was performed to examine longer-term and postprandial effects of L-citrulline ...

Abstract	L-citrulline may improve non-invasive vascular function and cardiometabolic risk markers through increases in L-arginine bioavailability and nitric oxide synthesis. A meta-analysis of randomized controlled trials (RCTs) was performed to examine longer-term and postprandial effects of L-citrulline supplementation and watermelon consumption on these markers for cardiovascular disease in adults. Summary estimates of weighted mean differences (WMDs) in vascular function and cardiometabolic risk markers with accompanying 95% confidence intervals (CIs) were calculated using random or fixed-effect meta-analyses. Seventeen RCTs were included involving an L-citrulline intervention, of which six studied postprandial and twelve longer-term effects. Five studies investigated longer-term effects of watermelon consumption and five assessed effects during the postprandial phase. Longer-term L-citrulline supplementation improved brachial artery flow-mediated vasodilation (FMD) by 0.9 %-point (95 % CI: 0.7 to 1.1, P < 0.001). Longer-term watermelon consumption improved pulse wave velocity by 0.9 m/s (95% CI: 0.1 to 1.5, P < 0.001), while effects on FMD were not studied. No postprandial effects on vascular function markers were found. Postprandial glucose concentrations decreased by 0.6 mmol/L (95% CI: 0.4 to 0.7, P < 0.001) following watermelon consumption, but no other longer-term or postprandial effects were observed on cardiometabolic risk markers. To conclude, longer-term L-citrulline supplementation and watermelon consumption may improve vascular function, suggesting a potential mechanism by which increased L-citrulline intake beneficially affects cardiovascular health outcomes in adults. No effects on postprandial vascular function markers were found, while more research is needed to investigate effects of L-citrulline and watermelon on risk markers related to cardiometabolic health.
Language	English
Publishing date	2021-12-06
Publishing country	England
Document type	Journal Article
ZDB-ID	280396-3
ISSN	1475-2662 ; 0007-1145
ISSN (online)	1475-2662
ISSN	0007-1145
DOI	10.1017/S0007114521004803
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Article ; Online: Effects of Beetroot Powder with or without L-Arginine on Postprandial Vascular Endothelial Function: Results of a Randomized Controlled Trial with Abdominally Obese Men.

Smeets, Ellen T H C / Mensink, Ronald P / Hoeks, Joris / de Vogel-Van den Bosch, Johan / Hageman, Robert J J / Joris, Peter J

Nutrients

2020 Volume 12, Issue 11

Abstract: ... improved after the intake of a high amount of nitrate or L-arginine, but decreased after the intake ... of a high-fat meal. Therefore, we compared the effects of beetroot powder with or without L-arginine ... of beetroot powder providing 200 mg nitrate, beetroot with 0.8 g of L-arginine, beetroot with 1.5 g of L ...

Abstract	Background: Through effects on nitric oxide bioavailability, vascular endothelial function is improved after the intake of a high amount of nitrate or L-arginine, but decreased after the intake of a high-fat meal. Therefore, we compared the effects of beetroot powder with or without L-arginine on postprandial brachial artery flow-mediated vasodilation (FMD) after consumption of a high-fat mixed-meal. Methods: Eighteen abdominally obese men completed this randomized, double-blinded, cross-over trial. The study consisted of five test days, each separated by a wash-out period of at least one week. Participants received in random order, a blended meal with a control or nutritional supplement consisting of beetroot powder providing 200 mg nitrate, beetroot with 0.8 g of L-arginine, beetroot with 1.5 g of L-arginine, or 3.0 g of L-arginine. Participants then fasted and 2 h postprandial FMD measurements were performed. Results: No significant differences between meals were observed for postprandial FMD ( Conclusion: This trial could not provide evidence for beneficial additive effects of a single dose of beetroot powder combined with L-arginine on postprandial endothelial function in abdominally obese men.
MeSH term(s)	Aged ; Arginine/administration & dosage ; Beta vulgaris/chemistry ; Blood Flow Velocity/drug effects ; Blood Flow Velocity/physiology ; Blood Glucose ; Brachial Artery/physiopathology ; Cross-Over Studies ; Dietary Supplements ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/physiopathology ; Food ; Humans ; Insulin/blood ; Male ; Middle Aged ; Nitric Oxide/blood ; Obesity, Abdominal/physiopathology ; Postprandial Period ; Powders ; Triglycerides/blood ; Vascular Stiffness/drug effects ; Vasodilation/drug effects
Chemical Substances	Blood Glucose ; Insulin ; Powders ; Triglycerides ; Nitric Oxide (31C4KY9ESH) ; Arginine (94ZLA3W45F)
Language	English
Publishing date	2020-11-16
Publishing country	Switzerland
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu12113520
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Article ; Online: Reply: Measurement of regional rates of protein synthesis in human brain in vivo with L-[1-11C]-leucine PET.

Smeets, Joey S J / van Loon, Luc J C

Brain : a journal of neurology

2018 Volume 141, Issue 7, Page(s) e52

MeSH term(s)	Brain ; Carbon Radioisotopes ; Humans ; Leucine ; Protein Biosynthesis
Chemical Substances	Carbon Radioisotopes ; Carbon-11 ; Leucine (GMW67QNF9C)
Language	English
Publishing date	2018-05-03
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awy119
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Article ; Online: Effects of tree nut and groundnut consumption compared with those of l-arginine supplementation on fasting and postprandial flow-mediated vasodilation: Meta-analysis of human randomized controlled trials.

Smeets, Ellen T H C / Mensink, Ronald P / Joris, Peter J

Clinical nutrition (Edinburgh, Scotland)

2020 Volume 40, Issue 4, Page(s) 1699–1710

Abstract: Introduction: l-arginine supplementation may improve vascular endothelial function. As tree nuts ... and groundnuts are a source of the amino acid l-arginine, we performed a meta-analysis of human ... randomized controlled trials (RCTs) to compare effects of tree nut and groundnut consumption with those of l-arginine ...

Abstract	Introduction: l-arginine supplementation may improve vascular endothelial function. As tree nuts and groundnuts are a source of the amino acid l-arginine, we performed a meta-analysis of human randomized controlled trials (RCTs) to compare effects of tree nut and groundnut consumption with those of l-arginine supplementation on fasting and postprandial endothelial function as assessed by flow-mediated vasodilation of the brachial artery (FMD). Methods: Summary estimates of weighted mean differences (WMDs) in FMD and 95% confidence intervals (CIs) were calculated using random-effect meta-analyses. Results: A total of thirteen RCTs focusing on tree nut and groundnut consumption and nineteen RCTs investigating effects of l-arginine supplementation were included. Longer-term consumption of tree nuts and groundnuts increased fasting FMD by 1.09 %-point (PP) (95% CI: 0.49, 1.69, P < 0.001; I Conclusion: Longer-term consumption of tree nuts and groundnuts, as well as l-arginine supplementation did improve fasting endothelial function, as assessed by FMD. However, the positive effects of tree nuts and groundnuts could not be fully explained by the amount of l-arginine in these nuts. Only l-arginine supplementation did improve postprandial FMD, but effects were not different from those of tree nuts and groundnuts. Future studies should focus on the identifications of the bioactive nutrients in tree nuts and groundnuts and mechanistic pathways behind differences in postprandial and longer-term fasting changes in FMD.
MeSH term(s)	Arginine/pharmacology ; Diet/methods ; Dietary Supplements ; Fasting/physiology ; Humans ; Nuts ; Postprandial Period/physiology ; Randomized Controlled Trials as Topic ; Vasodilation/physiology
Chemical Substances	Arginine (94ZLA3W45F)
Language	English
Publishing date	2020-09-15
Publishing country	England
Document type	Comparative Study ; Journal Article ; Meta-Analysis
ZDB-ID	604812-2
ISSN	1532-1983 ; 0261-5614
ISSN (online)	1532-1983
ISSN	0261-5614
DOI	10.1016/j.clnu.2020.09.015
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Article: Effects of tree nut and groundnut consumption compared with those of l-arginine supplementation on fasting and postprandial flow-mediated vasodilation: Meta-analysis of human randomized controlled trials

Smeets, Ellen T.H.C / Mensink, Ronald P / Joris, Peter J

Clinical nutrition. 2020 Sept. 09,

2020

Abstract: l-arginine supplementation may improve vascular endothelial function. As tree nuts and groundnuts ... are a source of the amino acid l-arginine, we performed a meta-analysis of human ... randomized controlled trials (RCTs) to compare effects of tree nut and groundnut consumption with those of l-arginine ...

Abstract	l-arginine supplementation may improve vascular endothelial function. As tree nuts and groundnuts are a source of the amino acid l-arginine, we performed a meta-analysis of human randomized controlled trials (RCTs) to compare effects of tree nut and groundnut consumption with those of l-arginine supplementation on fasting and postprandial endothelial function as assessed by flow-mediated vasodilation of the brachial artery (FMD).Summary estimates of weighted mean differences (WMDs) in FMD and 95% confidence intervals (CIs) were calculated using random-effect meta-analyses.A total of thirteen RCTs focusing on tree nut and groundnut consumption and nineteen RCTs investigating effects of l-arginine supplementation were included. Longer-term consumption of tree nuts and groundnuts increased fasting FMD by 1.09 %-point (PP) (95% CI: 0.49, 1.69, P < 0.001; I²: 76.7%, P < 0.001), while l-arginine supplementation (daily range: 3–21 g) increased fasting FMD by 0.53 PP (95% CI: 0.12, 0.93; P = 0.012; I²: 91.6%, P < 0.001). Effects between treatments were not statistically different (P = 0.31). Tree nut and groundnut consumption did not affect postprandial FMD responses (1.25 PP, 95% CI: −0.31, 2.81, P = 0.12; I²: 91.4%, P < 0.001), whereas l-arginine supplementation (range: 3–15 g) improved FMD during the postprandial phase by 2.02 PP (95% CI: 0.92, 3.13, P < 0.001; I²: 99.1%, P < 0.001). However, treatment effects did not differ significantly (P = 0.60). Overall, these results derive from high-quality evidence.Longer-term consumption of tree nuts and groundnuts, as well as l-arginine supplementation did improve fasting endothelial function, as assessed by FMD. However, the positive effects of tree nuts and groundnuts could not be fully explained by the amount of l-arginine in these nuts. Only l-arginine supplementation did improve postprandial FMD, but effects were not different from those of tree nuts and groundnuts. Future studies should focus on the identifications of the bioactive nutrients in tree nuts and groundnuts and mechanistic pathways behind differences in postprandial and longer-term fasting changes in FMD.
Keywords	arginine ; clinical nutrition ; confidence interval ; humans ; meta-analysis ; nutrients ; peanuts ; randomized clinical trials ; vasodilation
Language	English
Dates of publication	2020-0909
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-light ; Pre-press version
ZDB-ID	604812-2
ISSN	1532-1983 ; 0261-5614
ISSN (online)	1532-1983
ISSN	0261-5614
DOI	10.1016/j.clnu.2020.09.015
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Selective laser-melted fully biodegradable scaffold composed of poly(d,l-lactide) and β-tricalcium phosphate with potential as a biodegradable implant for complex maxillofacial reconstruction: In vitro and in vivo results.

Smeets, Ralf / Barbeck, Mike / Hanken, Henning / Fischer, Horst / Lindner, Markus / Heiland, Max / Wöltje, Michael / Ghanaati, Shahram / Kolk, Andreas

Journal of biomedical materials research. Part B, Applied biomaterials

2016 Volume 105, Issue 5, Page(s) 1216–1231

Abstract: Objectives: Scaffolds (SC) composed of poly(d,l-lactide) and β-tricalcium phosphate of variable ...

Abstract	Objectives: Scaffolds (SC) composed of poly(d,l-lactide) and β-tricalcium phosphate of variable pore structures were manufactured by selective laser melting (SLM), which allowed the production of porous interconnected structures promoting cellular adhesion and vascular proliferation. Biocompatibility, rate of osseointegration and new bone formation (NB) were analyzed. Material and methods: Powder based on the material composition was selective melted by a laser beam allowing layer-by-layer production. Pore size and biocompatibility were tested with mesenchymal stem cells (rMSC) and Saos 2 cells that were cultivated on SCs showing better proliferation, without toxicity, than controls. SCs with a 600- to 700-µm pore diameter proved ideal for fast and reliable cellular and vascular supply throughout the interconnecting pore system. Jaw and calvarial critical-size defects (CSD) with diameters of 5 or 16 mm were drilled in rats and either SLM test SCs (pore diameter 600 µm) or the previously removed autologs bone as controls were (re-) implanted. Results: The SC in vivo led to complete bone ingrowth with minimal inflammatory reaction adjacent to and within the CSD as compared with controls. The SC promoted the differentiation of rMSC into osteoblasts, revealing osteoinductive properties. Promising NB ingrowth of the material was also obtained in the animal study. Conclusion: The SC showed complete bony replacement within 30 days in all rats; this ingrowth was significantly superior to that of controls and revealed no signs of significant foreign body reaction. Because of continuous replacement by bone this material composition is ideal for SCs fitting 3D bone defects. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1216-1231, 2017.
MeSH term(s)	Absorbable Implants ; Animals ; Calcium Phosphates/chemistry ; Calcium Phosphates/pharmacology ; Humans ; Lasers ; Materials Testing ; Mesenchymal Stem Cells/metabolism ; Orthognathic Surgical Procedures ; Polyesters/chemistry ; Polyesters/pharmacology ; Rats ; Rats, Inbred Lew ; Reconstructive Surgical Procedures
Chemical Substances	Calcium Phosphates ; Polyesters ; beta-tricalcium phosphate ; poly(lactide) (459TN2L5F5)
Language	English
Publishing date	2016-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2099992-6
ISSN	1552-4981 ; 1552-4973 ; 0021-9304
ISSN (online)	1552-4981
ISSN	1552-4973 ; 0021-9304
DOI	10.1002/jbm.b.33660
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Article ; Online: A novel hemostatic delivery device for thrombin: biodegradable poly(D,L-lactide-co-glycolide) 50:50 microspheres.

Smeets, Ralf / Gerhards, Frank / Stein, Jamal M / Stein, Jamal / Paz, Rui Miguel Pereira / Vogt, Stephan / Pautke, Christoph / Weitz, Jochen / Kolk, Andreas

Journal of biomedical materials research. Part A

2011 Volume 96, Issue 1, Page(s) 177–185

Abstract: ... related surgery, for example, in dental surgery. Thrombin-loaded poly(D,L-lactide-co-glycolide ...

Abstract	Topical thrombins are locally active hemostatic agents that can be used to minimize blood loss during any surgery. The aim of this study was to design and investigate a thrombin-containing biodegradable hemostyptic device with an optimized drug release profile to promote local blood clot formation. It is effective with ongoing systemic antithrombotic therapy and can be used in all types of bone-related surgery, for example, in dental surgery. Thrombin-loaded poly(D,L-lactide-co-glycolide) microspheres were synthesized by means of complex (w/o/w) emulsion evaporation method. The resulting enzyme activity of the serine-protease thrombin was verified by the specific chromogenic substrate S-2238. The thrombin release profile depended on four factors: (1) thrombin dosage, (2) polymer concentration in the o-phase, (3) phase quotient w1:0 in the primary emulsion, and (4) the addition of pore-introducing agents. A collagenous sponge containing thrombin-loaded microspheres by means of lyophilization was developed. The impact of several production factors of the (w1/o/w2) solvent evaporation method to optimize thrombin encapsulation, morphology of the spheres, and desired drug release profile have been investigated. The in vitro thrombin release was dependent on the polymer-to-oil phase ratio, the polymer concentration, and the type of solvent and polymer. The porosity of the spheres and release rate of the active agent were enhanced by increasing the inner aqueous w1 phase. With this study, a new biodegradable hemostyptic device could be verified and established for a potentially safe and locally controlled thrombin release to manage postsurgical hemorrhage in patients undergoing anticoagulant therapy.
MeSH term(s)	Absorbable Implants ; Biocompatible Materials/chemistry ; Biocompatible Materials/metabolism ; Drug Carriers/chemical synthesis ; Drug Carriers/chemistry ; Drug Carriers/metabolism ; Hemostatics/chemistry ; Hemostatics/metabolism ; Humans ; Hydrogen-Ion Concentration ; Lactic Acid/chemistry ; Materials Testing ; Microscopy, Electron, Scanning ; Microspheres ; Particle Size ; Polyglycolic Acid/chemistry ; Solvents ; Thrombin/chemistry ; Thrombin/metabolism
Chemical Substances	Biocompatible Materials ; Drug Carriers ; Hemostatics ; Solvents ; polylactic acid-polyglycolic acid copolymer ; Polyglycolic Acid (26009-03-0) ; Lactic Acid (33X04XA5AT) ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2011-01
Publishing country	United States
Document type	Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2099989-6
ISSN	1552-4965 ; 1549-3296 ; 0021-9304
ISSN (online)	1552-4965
ISSN	1549-3296 ; 0021-9304
DOI	10.1002/jbm.a.32970
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Article: Relation between in vitro lipid digestion and beta-carotene bioaccessibility in beta-carotene-enriched emulsions with different concentrations of L-alpha-phosphatidylcholine

Verrijssen, T. A. J. / Smeets, K. H. G. / Christiaens, S. / Palmers, S. / Van Loey, A. M. / Hendrickx, M. E.

Food research international

2015 Volume 67, Issue -, Page(s) 60

Language	English
Document type	Article
ZDB-ID	1111695-x
ISSN	0963-9969
Database	Current Contents Nutrition, Environment, Agriculture

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Conference proceedings: Ein neuer Weg der lokalen Hämostaseförderung? Thrombinbeladene resorbierare poly (D,L-lactide-co-glycolide) 50:50 Mikrosphären

Smeets, R. / Gerhards, F. / Heiland, M. / Paz, R. M.

2012 , Page(s) 12dgpw44

Event/congress	50. Jahrestagung der Deutschen Gesellschaft für Plastische und Wiederherstellungschirurgie (DGPW); Hannover; Deutsche Gesellschaft für Plastische und Wiederherstellungschirurgie; 2012
Keywords	Medizin, Gesundheit
Publishing date	2012-12-04
Publisher	German Medical Science GMS Publishing House; Düsseldorf
Document type	Conference proceedings
DOI	10.3205/12dgpw44
Database	German Medical Science

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Article: Relation between in vitro lipid digestion and Î²-carotene bioaccessibility in Î²-carotene-enriched emulsions with different concentrations of l-Î±-phosphatidylcholine

Verrijssen, Tina A.J / Karen H.G. Smeets / Stefanie Christiaens / Stijn Palmers / Ann M. Van Loey / Marc E. Hendrickx

Food research international. 2015 Jan., v. 67

2015

Abstract: ... concentrations (1â2â3â4%) of l-Î±-phosphatidylcholine (PHC), as an emulsifier. The lipid digestion ...

Abstract	In view of consumer health, it is desirable to promote the bioaccessibility of lipid-soluble compounds like carotenoids, while limiting the lipid intake. The objective of this work was to examine the relation between in vitro lipid digestion and Î²-carotene bioaccessibility of carrot-based model food emulsions containing water, 5% olive oil enriched with Î²-carotene (from carrots) and different concentrations (1â2â3â4%) of l-Î±-phosphatidylcholine (PHC), as an emulsifier. The lipid digestion (hydrolysis of triacylglycerols (TAGS) and incorporation of free fatty acids (FFAs) and monoacylglycerols (MAGs) in the micelles) and the Î²-carotene bioaccessibility (incorporation of Î²-carotene in the micelles) were studied after an in vitro digestion procedure wherein the stomach phase was mimicked for 2.0h (37Â°C) and the small intestinal phase was mimicked for 1.0h, 1.5h and 2.0h (37Â°C) (both end-over-end rotations). As a consequence, not only the influence of the emulsifier concentration, but also the influence of the duration in the small intestinal phase was investigated in this study. The oil droplet size distributions of the emulsions at different stages of digestion were shown to be dependent on the phosphatidylcholine concentration, but independent on the duration in the small intestinal phase (1.0hâ2.0h). Furthermore, all TAGs were already hydrolysed into FFAs and MAGs after 1.0h small intestinal phase and the incorporation of FFAs and MAGs into micelles seemed to reach a maximum for all emulsions (approximately 26.5%), independent on the phoshpatidylcholine concentration and thus on the particle size distributions. Finally, the Î²-carotene bioaccessibility increased with increasing phosphatidylcholine concentration, ranging from 33.2% to 79.8% for a 1% and 4% PHC emulsion respectively. No significant differences in Î²-carotene bioaccessibility were however noticed for the different durations in the small intestinal phase tested. In conclusion, a higher phosphatidylcholine concentration in emulsions leads to higher Î²-carotene bioaccessibility while the incorporation of lipids into micelles did not increase.
Keywords	beta-carotene ; bioavailability ; carrots ; digestion ; droplet size ; emulsifiers ; emulsions ; fat intake ; free fatty acids ; hydrolysis ; in vitro digestion ; lipid metabolism ; micelles ; monoacylglycerols ; olive oil ; particle size distribution ; phosphatidylcholines ; stomach ; triacylglycerols
Language	English
Dates of publication	2015-01
Size	p. 60-66.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1111695-x
ISSN	1873-7145 ; 0963-9969
ISSN (online)	1873-7145
ISSN	0963-9969
DOI	10.1016/j.foodres.2014.10.024
Database	NAL-Catalogue (AGRICOLA)

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