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Timby, Niklas
Publications (10 of 16) Show all publications
He, X., Parenti, M., Grip, T., Domellöf, M., Lonnerdal, B., Hernell, O., . . . Slupsky, C. M. (2019). Metabolic phenotype of breast-fed infants, and infants fed standard formula or bovine MFGM supplemented formula: a randomized controlled trial. Scientific Reports, 9, Article ID 339.
Open this publication in new window or tab >>Metabolic phenotype of breast-fed infants, and infants fed standard formula or bovine MFGM supplemented formula: a randomized controlled trial
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 339Article in journal (Refereed) Published
Abstract [en]

Formula-fed (FF) infants exhibit a different metabolic profile than breast-fed (BF) infants. Two potential mechanisms are the higher protein level in formula compared with breast milk and the removal of the milk fat and associated milk fat globule membranes (MFGM) during production of infant formula. To determine whether MFGM may impact metabolism, formula-fed infants were randomly assigned to receive either an MFGM isolate-supplemented experimental formula (EF) or a standard formula (SF) from 2 until 6 months and compared with a BF reference group. Infants consuming EF had higher levels of fatty acid oxidation products compared to infants consuming SF. Although the protein level in the study formula was approximately 12 g/L (lower than most commercial formulas), a metabolic difference between FF and BF remained such that FF infants had higher levels of amino acid catabolism by-products and a low efficiency of amino acid clearance (preference for protein metabolism). BF infants had higher levels of fatty acid oxidation products (preference for fat metabolism). These unique, energy substrate-driven metabolic outcomes did not persist after diet was shifted to weaning foods and appeared to be disrupted by complementary feeding. Our results suggest that MFGM may have a role in directing infant metabolism.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-156312 (URN)10.1038/s41598-018-36292-5 (DOI)000456392400020 ()30674917 (PubMedID)
Available from: 2019-02-21 Created: 2019-02-21 Last updated: 2019-02-21Bibliographically approved
Grip, T., Dyrlund, T. S., Ahonen, L., Domellöf, M., Hernell, O., Hyötyläinen, T., . . . Timby, N. (2018). Serum, plasma and erythrocyte membrane lipidomes in infants fed formula supplemented with bovine milk fat globule membranes. Pediatric Research, 84(5), 726-732
Open this publication in new window or tab >>Serum, plasma and erythrocyte membrane lipidomes in infants fed formula supplemented with bovine milk fat globule membranes
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2018 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 84, no 5, p. 726-732Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Supplementation of formula with bovine milk fat globule membranes has been shown to narrow the gap in immunological and cognitive development between breast-fed and formula-fed infants.

METHOD: In a double-blinded randomized controlled trial 160 formula-fed infants received an experimental formula (EF), supplemented with bovine milk fat globule membranes, or standard formula until 6 months of age. A breast-fed reference group was recruited. Lipidomic analyses were performed on plasma and erythrocyte membranes at 6 months and on serum at 4 and 12 months of age.

RESULTS: At 6 months of age, we observed a significant separation in the plasma lipidome between the two formula groups, mostly due to differences in concentrations of sphingomyelins (SM), phosphatidylcholines (PC), and ceramides, and in the erythrocyte membrane lipidome, mostly due to SMs, PEs and PCs. Already at 4 months, a separation in the serum lipidome was evident where SMs and PCs contributed. The separation was not detected at 12 months.

CONCLUSIONS: The effect of MFGM supplementation on the lipidome is likely part of the mechanisms behind the positive cognitive and immunological effects of feeding the EF previously reported in the same study population.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-155120 (URN)10.1038/s41390-018-0130-9 (DOI)000453019100031 ()30120403 (PubMedID)
Funder
Västerbotten County CouncilVINNOVA
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-02-20Bibliographically approved
Demmelmair, H., Prell, C., Timby, N. & Lönnerdal, B. (2017). Benefits of Lactoferrin, Osteopontin and Milk Fat Globule Membranes for Infants. Nutrients, 9(8), Article ID 817.
Open this publication in new window or tab >>Benefits of Lactoferrin, Osteopontin and Milk Fat Globule Membranes for Infants
2017 (English)In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 9, no 8, article id 817Article, review/survey (Refereed) Published
Abstract [en]

The provision of essential and non-essential amino acids for breast-fed infants is the major function of milk proteins. In addition, breast-fed infants might benefit from bioactivities of milk proteins, which are exhibited in the intestine during the digestive phase and by absorption of intact proteins or derived peptides. For lactoferrin, osteopontin and milk fat globule membrane proteins/lipids, which have not until recently been included in substantial amounts in infant formulas, in vitro experiments and animal models provide a convincing base of evidence for bioactivities, which contribute to the protection of the infant from pathogens, improve nutrient absorption, support the development of the immune system and provide components for optimal neurodevelopment. Technologies have become available to obtain these compounds from cow's milk and the bovine compounds also exhibit bioactivities in humans. Randomized clinical trials with experimental infant formulas incorporating lactoferrin, osteopontin, or milk fat globule membranes have already provided some evidence for clinical benefits. This review aims to compare findings from laboratory and animal experiments with outcomes of clinical studies. There is good justification from basic science and there are promising results from clinical studies for beneficial effects of lactoferrin, osteopontin and the milk fat globule membrane complex of proteins and lipids. Further studies should ideally be adequately powered to investigate effects on clinically relevant endpoints in healthy term infants.

Place, publisher, year, edition, pages
MDPI AG, 2017
Keywords
human milk, bioactive proteins, lactoferrin, osteopontin, milk fat globule membrane
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:umu:diva-139818 (URN)10.3390/nu9080817 (DOI)000408688100025 ()
Available from: 2017-09-25 Created: 2017-09-25 Last updated: 2018-06-09Bibliographically approved
Timby, N., Domellöf, M., Lif Holgerson, P., West, C. E., Lonnerdal, B., Hernell, O. & Johansson, I. (2017). Oral Microbiota in Infants Fed a Formula Supplemented with Bovine Milk Fat Globule Membranes: A Randomized Controlled Trial. PLoS ONE, 12(1), Article ID e0169831.
Open this publication in new window or tab >>Oral Microbiota in Infants Fed a Formula Supplemented with Bovine Milk Fat Globule Membranes: A Randomized Controlled Trial
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0169831Article in journal (Refereed) Published
Abstract [en]

Background In a recent study, supplementation of infant formula with milk fat globule membranes (MFGM) decreased the incidence of otitis media in infants <6 months of age. Objectives The aim of the present study was to characterize the oral microbiota in infants fed MFGM-supplemented formula and compare it to that of infants fed standard formula or breast milk.

Methods In a prospective double-blinded randomized controlled trial, exclusively formula-fed infants <2 months of age were randomized to be fed experimental formula (EF, n = 80) with reduced energy and protein and supplemented with a bovine MFGM concentrate, or standard formula (SF, n = 80) until 6 months of age. A breast-fed reference (BFR, n = 80) group was also recruited. The oral microbiota was analyzed at 4 (n = 124) and 12 (n = 166) months of age using Illumina MiSeq multiplex sequencing and taxonomic resolution against the HOMD 16S rDNA database of oral bacteria.

Results Species richness in the oral samples did not differ between the EF and SF groups, but partial least square modeling identified a few taxa that were significantly associated with being in either group, e.g. lower level of Moraxella catarrhalis in the EF group. Infants in the BFR group had significantly lower species richness at 4 months of age and their microbiota pattern differed markedly from the formula-fed groups.

Conclusions Supplementation of infant formula with MFGM yielded moderate effects on the oral micro biome. Moraxella catarrhalis was less prevalent in infants fed EF than in those fed SF and may be associated with the decrease in otitis media seen in the same group.

National Category
Pediatrics Dentistry
Identifiers
urn:nbn:se:umu:diva-131641 (URN)10.1371/journal.pone.0169831 (DOI)000392380100035 ()28099499 (PubMedID)
Available from: 2017-03-01 Created: 2017-03-01 Last updated: 2018-06-09Bibliographically approved
Timby, N., Domellöf, M., Lonnerdal, B. & Hernell, O. (2017). Supplementation of Infant Formula with Bovine Milk Fat Globule Membranes. Advances in Nutrition, 8(2), 351-355
Open this publication in new window or tab >>Supplementation of Infant Formula with Bovine Milk Fat Globule Membranes
2017 (English)In: Advances in Nutrition, ISSN 2161-8313, Vol. 8, no 2, p. 351-355Article, review/survey (Refereed) Published
Abstract [en]

Studies have shown that supplementation of infant formula with bovine milk fat globule membranes (MFGMs) may substantially narrow the gap in health outcomes between formula-fed and breastfed infants. In one study, consumption of a formula supplemented with a lipid-rich MFGM concentrate between 2 and 6 mo of age improved cognitive performance at 24 wk of age. In another study, a formula supplemented with a protein rich MFGM concentrate given between 2 and 6 mo of age improved cognitive performance at 12 mo of age, decreased infectious morbidity until 6 mo of age, and yielded serum cholesterol concentrations closer to those of breastfed infants. A third study that assessed the safety of supplementing infant formula with a lipid-rich or a protein-rich MFGM concentrate found a noninferior weight gain for both groups compared with a nonsupplemented formula. In this study, there was an increased risk of eczema in the protein-rich group, but no serious adverse events. Infant formulas with supplemental MFGMs have been launched on the market in several countries. However, the evidence base must still be considered quite limited. Based on 3 randomized controlled trials that are not comparable, the intervention seems safe, but there is not enough evidence for a general recommendation on which MFGM fraction to use and at what concentration as formula supplement for a given outcome.

Keywords
MFGM, infant formula, neurodevelopment, cognition, infection, otitis, cholesterol
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-133805 (URN)10.3945/an.116.014142 (DOI)000398109500012 ()28298277 (PubMedID)
Available from: 2017-04-20 Created: 2017-04-20 Last updated: 2019-02-20Bibliographically approved
Hernell, O., Timby, N., Domellöf, M. & Lönnerdal, B. (2016). Clinical Benefits of Milk Fat Globule Membranes for Infants and Children. Journal of Pediatrics, 173, S60-S65
Open this publication in new window or tab >>Clinical Benefits of Milk Fat Globule Membranes for Infants and Children
2016 (English)In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 173, p. S60-S65Article in journal (Refereed) Published
Abstract [en]

The milk fat globule membrane (MFGM) in breast milk contains many bioactive components. Infant formulas traditionally have been devoid of the MFGM fraction, but dairy technology now has made the addition of bovine MFGM technically feasible. We identified 6 double-blinded randomized controlled trials exploring the effects of MFGM supplementation on the diets of infants or children. Results suggest that supplementation is safe and indicate positive effects on both neurodevelopment and defense against infections. MFGM supplementation of infant formula may narrow the gap in cognitive performance and infection rates between breastfed and formula-fed infants. Because of the small number of studies and the heterogeneity of interventions, more high-quality double-blinded randomized controlled trials are needed, with well characterized and clearly defined MFGM fractions, before firm conclusions on the effects of MFGM supplementation on the health and development of infants can be drawn.

National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-122557 (URN)10.1016/j.jpeds.2016.02.077 (DOI)000376533900009 ()27234413 (PubMedID)
Note

Supplement: Emerging Roles of Bioactive Components in Pediatric Nutrition

Available from: 2016-07-27 Created: 2016-06-20 Last updated: 2018-06-07Bibliographically approved
Timby, N., Domellöf, M., Lönnerdal, B. & Hernell, O. (2015). Comment on "Safety and Tolerance Evaluation of Milk Fat Globule Membrane-Enriched Infant Formulas: A Randomized Controlled Multicenter Non-Inferiority Trial in Healthy Term Infants" [Letter to the editor]. Clinical Medicine Insights: Pediatrics, 9, 63-64
Open this publication in new window or tab >>Comment on "Safety and Tolerance Evaluation of Milk Fat Globule Membrane-Enriched Infant Formulas: A Randomized Controlled Multicenter Non-Inferiority Trial in Healthy Term Infants"
2015 (English)In: Clinical Medicine Insights: Pediatrics, ISSN 1179-5565, Vol. 9, p. 63-64Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Sage Publications, 2015
Keywords
allergy prevention, asthma, eczema, Lactobacillus paracasei ssp paracasei F19, nitric oxide
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-118624 (URN)10.4137/CMPed.S27185 (DOI)000215761600009 ()26124694 (PubMedID)
Available from: 2016-03-24 Created: 2016-03-24 Last updated: 2018-06-07Bibliographically approved
Timby, N., Hernell, O., Vaarala, O., Melin, M., Lönnerdal, B. & Domellöf, M. (2015). Infections in infants fed formula supplemented with bovine milk fat globule membranes. Journal of Pediatric Gastroenterology and Nutrition - JPGN, 60(3), 384-389
Open this publication in new window or tab >>Infections in infants fed formula supplemented with bovine milk fat globule membranes
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2015 (English)In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, no 3, p. 384-389Article in journal (Other academic) Published
Abstract [en]

Objectives: Observational studies have shown that even in high-income countries formula-fed infants have a higher incidence of acute otitis media (AGM), and gastrointestinal and respiratory tract infections during the first year of life compared with breast-fed infants. We hypothesized that components of the milk fat globule membrane (MFGM) may be responsible for some of these differences and that supplementation with bovine MFGM would decrease the infectious morbidity in formula-fed infants.

Methods: In a double-blind randomized controlled trial, 160 formula-fed infants received experimental formula (EF) supplemented with bovine MFGM (EF) or unsupplemented standard formula (SF) from <2 months until 6 months of age. A breast-fed reference group consisted of 80 infants. Disease symptoms, health care contacts, and medication were recorded by the parents until 12 months of age. Serum immunoglobulin G for 10 pneumococcal serotypes was analyzed at 6 months of age.

Results: The cumulative incidence of AOM during the intervention was lower in the EF group than in the SF group (1% vs 9%, P = 0.034), and did not differ from the breast-fed reference group (0%, P = 1.0). The incidence (25% vs 43%, P = 0.021) and longitudinal prevalence (P = 0.012) of antipyretic use were significantly lower in the EF group than in the SF group. Serum immunoglobulin G concentrations against pneumococcal serotypes 1, 5, and 14 were lower in the EF group than in the SF group.

Conclusions: Supplementation of formula with bovine MFGM reduces the risk of AOM, decreases antipyretics use in formula-fed infants, and has immunomodulatory effects on humoral response against pneumococcus vaccine.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2015
Keywords
breast-feeding, infant formula, infections, milk fat globule membranes, otitis media
National Category
Pediatrics Nutrition and Dietetics Gastroenterology and Hepatology
Research subject
Pediatrics
Identifiers
urn:nbn:se:umu:diva-88188 (URN)10.1097/MPG.0000000000000624 (DOI)000350527100023 ()25714582 (PubMedID)
Funder
VINNOVA, 2009-00209
Available from: 2014-04-24 Created: 2014-04-24 Last updated: 2018-06-07Bibliographically approved
Timby, N., Lönnerdal, B., Hernell, O. & Domellöf, M. (2014). Cardiovascular risk markers until 12 mo of age in infants fed a formula supplemented with bovine milk fat globule membranes. Pediatric Research, 76(4), 394-400
Open this publication in new window or tab >>Cardiovascular risk markers until 12 mo of age in infants fed a formula supplemented with bovine milk fat globule membranes
2014 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 76, no 4, p. 394-400Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Some of the health advantages of breast-fed as compared to formula-fed infants have been suggested to be due to metabolic programming effects resulting from early nutrition. METHODS: In a prospective double-blinded randomized trial, 160 infants <2 mo of age were randomized to experimental formula (EF) with added milk fat globule membrane (MFGM) or standard formula (SF) until 6 mo of age. A breast-fed reference (BFR) group consisted of 80 infants. Measurements were made at inclusion and at 4, 6, and 12 mo of age. RESULTS: During the intervention, the EF group had higher total serum cholesterol concentration than the SF group, reaching the level of the BFR group. The EF group had a low-density lipoprotein to high-density lipoprotein ratio not significantly different from the SF group but lower than the BFR group. CONCLUSION: Supplementation of infant formula with MFGM modified the fat composition of the formula and narrowed the gap between breast-fed and formula-fed infants with regard to serum lipid status at 12 mo.

Place, publisher, year, edition, pages
Nature Publishing Group, 2014
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-95269 (URN)10.1038/pr.2014.110 (DOI)000342332000010 ()
Available from: 2014-11-04 Created: 2014-10-27 Last updated: 2018-06-07Bibliographically approved
Timby, N. (2014). Effects of feeding term infants low energy low protein formula supplemented with bovine milk fat globule membranes. (Doctoral dissertation). Umeå: Umeå Universitet
Open this publication in new window or tab >>Effects of feeding term infants low energy low protein formula supplemented with bovine milk fat globule membranes
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background Observational studies have shown that early nutrition influences short- and long-term health of infants. Formula-fed infants have higher protein and energy intakes and lower intakes of several biologically active components present in human milk. Some of these are present in the milk fat globule membrane (MFGM). The aim of the present study was to examine the effects of feeding term infants an experimental low energy low protein formula supplemented with bovine milk fat globule membranes. Our hypothesis was that infants fed experimental formula (EF), compared to infants fed standard formula (SF), would have outcomes more similar to a breast-fed reference (BFR) group.

Methods In a double-blinded randomized controlled trial, 160 exclusively formula-fed, healthy, term infants were randomized to receive EF or SF from <2 to 6 months of age. A BFR group consisted of 80 breast-fed infants. Measurements were made at baseline, 4, 6 and 12 months of age. The EF had lower energy (60 vs. 66 kcal/100 mL) and protein (1.20 vs. 1.27 g/100 mL) concentrations, and was supplemented with a bovine MFGM concentrate.

Results At 12 months of age, the EF group performed better than the SF group in the cognitive domain of Bayley Scales of Infant Development, 3rd Ed. During the intervention, the EF group had a lower incidence of acute otitis media than the SF group, less use of antipyretics and the EF and SF groups differed in concentrations of s-IgG against pneumococci. The formula-fed infants regulated their intakes by increasing meal volumes. Thus, there were no differences between the EF and SF groups in energy or protein intakes, blood urea nitrogen, insulin or growth including body fat percent until 12 months of age. Pressure-to-eat score at 12 months of age was reported lower by parents of formula-fed infants than by parents of breast-fed infants, indicating a low level of parental control of feeding in the formula-fed groups. Neither high pressure-to-eat score nor high restrictive score was associated with formula feeding. During the intervention, the EF group gradually reached higher serum cholesterol concentrations than the SF group, and closer to the BFR group. At 4 months of age, there was no significant difference in the prevalence of lactobacilli in saliva between the EF and SF groups.

Conclusions Supplementation of infant formula with a bovine MFGM fraction enhanced both cognitive and immunological development in formula-fed infants. Further, the intervention narrowed the gap in serum cholesterol concentrations between formula-fed and breast-fed infants. The lower energy and protein concentrations of the EF were totally compensated for by a high level of self-regulation of intake which might, at least partly, be explained by a low level of parental control of feeding in the study population. The findings are of importance for further development of infant formulas and may contribute to improved short- and long-term health outcomes for formula-fed infants.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2014. p. 55
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1644
Keywords
infant formula, milk fat globule membranes, energy, protein, growth, cognition, parental control, infection, cholesterol, oral microbiota
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:umu:diva-88192 (URN)978-91-7601-044-0 (ISBN)
Public defence
2014-05-16, Sal E04, Biomedicinarhuset (byggnad R1), Norrlands Universitetssjukhus, Umeå, 13:00 (English)
Opponent
Supervisors
Funder
Vinnova, 2009-00209
Available from: 2014-04-25 Created: 2014-04-24 Last updated: 2018-06-07Bibliographically approved
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