Publications by authors named "K Hettinga"

82 Publications

Effects of microfiltration combined with ultrasonication on shelf life and bioactive protein of skim milk.

Ultrason Sonochem 2021 Jul 17;77:105668. Epub 2021 Jul 17.

State Key Laboratory of Food Science and Technology, Jiangnan University, 214122 Wuxi, Jiangsu Province, China; International Joint Research Laboratory for Functional Dairy Protein Ingredients, Jiangnan University, 214122 Wuxi, Jiangsu Province, China. Electronic address:

To extend the shelf life and retain bioactive proteins in milk, this study utilized microfiltration (MF) combined with ultrasonication to treat skim milk and investigated its efficiency in removing bacteria and retaining bioactive proteins compared with HTST pasteurization and microfiltration alone. Results showed that microfiltration combined with ultrasonication at 1296 J/mL could completely remove the bacteria in skim milk. Ultrasonication further extended the shelf life (4 °C) of microfiltered skim milk, which could reach at least 40 days when MF was combined with ˃1296 J/mL ultrasonication. In addition, ELISA showed that HTST pasteurization significantly decreased the levels of IgG by ~30%, IgA by ~ 50%, IgM by ~60%, and lactoferrin by ~40%, whereas the activity of the enzymes lactoperoxidase and xanthine oxidase were also decreased by ~ 20%. Compared with HTST, MF alone or combined with ultrasonication retained these bioactive proteins to a larger degree. On the other hand, proteomics indicated both damage to casein micelle and fat globule structures in milk when ultrasonication at >1296 J/mL was applied, as shown by increases in caseins and milk fat globular proteins. Simultaneously, this ultrasound intensity also decreased levels of bioactive proteins, such as complement factors. Taken together, this study provided new insights that may help to implement this novel combination of non-thermal technologies for the dairy industry aimed at improving milk quality and functionality.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105668DOI Listing
July 2021

Micronutrient deficiencies in critical illness.

Clin Nutr 2021 Jun 11;40(6):3780-3786. Epub 2021 May 11.

Department of Intensive Care Medicine, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716 RP, Ede, the Netherlands; Division of Human Nutrition and Health, Wageningen University & Research, HELIX (Building 124), Stippeneng 4, 6708 WE, Wageningen, the Netherlands. Electronic address:

Background & Aims: Low micronutrient levels in critical illness have been reported in multiple studies. Because of the antioxidant properties of various micronutrients, micronutrient deficiency may augment oxidative stress in critical illness. However, it remains unclear whether micronutrient concentrations in ICU patients are different from those in healthy age-matched controls. It is also unclear whether micronutrient deficiency develops, worsens, or resolves during ICU admission without supplementation.

Methods: We prospectively studied a cohort of adult critically ill patients. Micronutrient levels, including selenium, β-carotene, vitamin C, E, B and B were measured repeatedly during the first week of ICU admission. We compared the micronutrient concentrations at ICU admission to those of healthy age-matched controls. In addition, associations between micronutrient concentrations with severity of illness, inflammation and micronutrient intake were investigated.

Results: Micronutrient blood concentrations were obtained from 24 critically ill adults and 21 age-matched healthy controls. The mean micronutrient levels at admission in the ICU patients were: selenium 0.52 μmol/l, β-carotene 0.17 μmol/l, vitamin C 21.5 μmol/l, vitamin E 20.3 μmol/l, vitamin B 129.5 nmol/l and vitamin B 41.0 nmol/l. In the healthy controls micronutrient levels of selenium (0.90 μmol/l), β-carotene (0.50 μmol/l), vitamin C (45 μmol/l) and vitamin E (35.5 μmol/l) were significantly higher, while vitamin B (122 nmol/l) and B (44 nmol/l) were not significantly different between patients and controls. Selenium, vitamin B and vitamin B levels remained stable during ICU admission. Vitamin C levels dropped significantly until day 5 (p < 0.01). Vitamin E and β-carotene levels increased significantly on days 5-7 and day 7, respectively (p < 0.01). Micronutrient levels were not associated with severity of illness, CRP or micronutrient intake during the admission.

Conclusions: At admission, ICU patients already had lower plasma levels of selenium, β-carotene, vitamin C and vitamin E than healthy controls. Vitamin C levels dropped significantly during the first days of ICU admission, while β-carotene and vitamin E levels increased after 5-7 days. No association between micronutrient levels and severity of illness, C-reactive protein (CRP) or micronutrient intake was found. Progressive enteral tube feeding containing vitamins and trace elements does not normalize plasma levels in the first week of ICU stay. This was a hypothesis generating study and more investigation in a larger more diverse sample is needed.
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http://dx.doi.org/10.1016/j.clnu.2021.05.003DOI Listing
June 2021

Human Milk from Previously COVID-19-Infected Mothers: The Effect of Pasteurization on Specific Antibodies and Neutralization Capacity.

Nutrients 2021 May 13;13(5). Epub 2021 May 13.

Department of Pediatrics, Amsterdam UMC, Vrije Universiteit, University of Amsterdam Emma Children's Hospital, 1105 AZ Amsterdam, The Netherlands.

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), many put their hopes in the rapid availability of effective immunizations. Human milk, containing antibodies against syndrome coronavirus 2 (SARS-CoV-2), may serve as means of protection through passive immunization. We aimed to determine the presence and pseudovirus neutralization capacity of SARS-CoV-2 specific IgA in human milk of mothers who recovered from COVID-19, and the effect of pasteurization on these antibodies.

Methods: This prospective case control study included lactating mothers, recovered from (suspected) COVID-19 and healthy controls. Human milk and serum samples were collected. To assess the presence of SARS-CoV-2 antibodies we used multiple complementary assays, namely ELISA with the SARS-CoV-2 spike protein (specific for IgA and IgG), receptor binding domain (RBD) and nucleocapsid (N) protein for IgG in serum, and bridging ELISA with the SARS-CoV-2 RBD and N protein for specific Ig (IgG, IgM and IgA in human milk and serum). To assess the effect of pasteurization, human milk was exposed to Holder (HoP) and High Pressure Pasteurization (HPP).

Results: Human milk contained abundant SARS-CoV-2 antibodies in 83% of the proven cases and in 67% of the suspected cases. Unpasteurized milk with and without these antibodies was found to be capable of neutralizing a pseudovirus of SARS-CoV-2 in (97% and 85% of the samples respectively). After pasteurization, total IgA antibody levels were affected by HoP, while SARS-CoV-2 specific antibody levels were affected by HPP. Pseudovirus neutralizing capacity of the human milk samples was only retained with the HPP approach. No correlation was observed between milk antibody levels and neutralization capacity.

Conclusions: Human milk from recovered COVID-19-infected mothers contains SARS-CoV-2 specific antibodies which maintained neutralization capacity after HPP. All together this may represent a safe and effective immunization strategy after HPP.
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http://dx.doi.org/10.3390/nu13051645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152997PMC
May 2021

Perspective: A Legal and Nutritional Perspective on the Introduction of Quinoa-Based Infant and Follow-on Formula in the EU.

Adv Nutr 2021 Apr 15. Epub 2021 Apr 15.

Law Group, Wageningen University and Research, Wageningen, The Netherlands.

Infants are vulnerable consumers and highly depend on dietary proteins for growth and development during their first months of life. Infant formula (IF) and follow-on formula (FOF) have been developed to meet these requirements, although few protein sources are currently allowed to be used. At the same time, allergies to these available protein sources are becoming more frequent. There is thus a need to explore alternative protein sources for infant nutrition. One alternative could be quinoa, which is a pseudocereal that is naturally free from gluten and has a high protein content and quality. This review assessed the composition, nutritional properties, and applicability of quinoa proteins for IF and FOF as well as the legal framework for their use in the European Union (EU). The protein quality of isolated quinoa proteins (IQPs) is relatively high compared with other plant-based proteins like rice. Besides, during the protein isolation process, unfavorable compounds are mostly removed, ensuring that the final product can comply with the maximum residue concentrations allowed. Overall, IF and FOF are strictly regulated under the Foods for Specific Groups (FSG) Regulation (EU) No 609/2013 and more research is needed before the introduction of IQP in such products is considered, but this review shows it has several promising features that warrant further investigation.
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http://dx.doi.org/10.1093/advances/nmab041DOI Listing
April 2021

Enhanced Uptake of Processed Bovine β-Lactoglobulin by Antigen Presenting Cells: Identification of Receptors and Implications for Allergenicity.

Mol Nutr Food Res 2021 04 10;65(8):e2000834. Epub 2021 Mar 10.

Cell Biology & Immunology, Wageningen University & Research Centre, Wageningen, the Netherlands.

Scope: β-lactoglobulin (BLG) is a major cow milk allergen encountered by the immune system of infants fed with milk-based formulas. To determine the effect of processing on immunogenicity of BLG, this article characterized how heated and glycated BLG are recognized and internalized by APCs. Also, the effect of heat-induced structural changes as well as gastrointestinal digestion on immunogenicity of BLG is evaluated.

Methods And Results: The binding and uptake of BLG from raw cow milk and heated either alone (BLG-H) or with lactose/glucose (BLG-Lac and BLG-Glu) to the receptors present on APCs are analyzed by ELISA and cell-binding assays. Heated and glycated BLG is internalized via galectin-3 (Gal-3)and scavenger receptors (CD36 and SR-AI) while binding to the receptor for advanced glycation end products (R AGE) does not cause internalization. Receptor affinity of BLG is dependent on increased hydrophobicity, β-sheet exposure and aggregation. Digested glycated BLG maintained binding to sRAGE and Gal-3 but not to CD36 and SR-AI, and is detected on the surface of APCs. This suggests a mechanism via which digested glycated BLG may trigger innate (via RAGE) and adaptive immunity (via Gal-3).

Conclusions: This study defines structural characteristics of heated and glycated BLG determining its interaction with APCs via specific receptors thus revealing enhanced immunogenicity of glycated versus heated BLG.
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http://dx.doi.org/10.1002/mnfr.202000834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244112PMC
April 2021
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