Effects of Milk Protein and Vitamin D on Children's Growth and Health (D-pro)

Effects of Milk Protein and Vitamin D on Children's Growth and Health (D-pro)

The purpose of D-pro is to investigate the combined and separate effects of milk protein and vitamin D on bone health, growth, muscle function, body composition and cardiometabolic health in 6-8-year-old children.

Study Overview

• Status: Completed
• Conditions: Appetite Regulation; Muscle Function; Cardiometabolic Health; Bone Health
• Intervention / Treatment: Dietary supplement: Milk Protein (high); Dietary supplement: Vitamin D; Dietary supplement: Milk Protein (medium)

Detailed Description

The D-pro study investigates the effects of high or medium intakes of milk protein, and vitamin D supplements or placebo, in healthy 6-8 year-old Danish children. The study is a 2×2-factorial randomized controlled trial with 4 study arms. The subjects will be randomly allocated to receive yoghurt products with either high or medium protein content (300g/day, 6 days/week) and to receive tablets with either vitamin D (20 μg/day) or placebo for 24 weeks. Measurements and biological sampling will be performed at baseline and at the end of the intervention.

The primary outcome will be bone mineral density (BMD). The investigators will also measure effects on children's muscle function, cardiometabolic health, body composition, growth and growth factors, nutrient status, immune defence and risk of acute respiratory tract infections, as well as appetite hormones. The investigators will also assess potential sex-specific effects and the potential modifying effect of genotype.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Frederiksberg, Denmark
    • Department of Nutrition, Exercise and Sports, University of Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 8 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Children must:

• Be 6-8 years of age at the start of the intervention
• Be healthy
• Have a frequent intake of milk and yoghurt products, corresponding to at least ¼ liter a day
• Like yoghurt and high protein yoghurt ("skyr")
• Be of white, Danish or European origin

Moreover:

• The family must not be planning a winter vacation south of a latitude of 50° North
• The child must speak and understand Danish in order to understand the study procedures
• At least one parent must read, speak and write Danish

Exclusion Criteria:

• Known or suspected allergy or intolerance to milk or milk components
• Chronic illness or disease that may affect study outcomes
• Chronic intake of medicine that may affect study outcomes
• Use of vitamin D-containing supplements >3 days/week the 2 last months and use of any vitamin D-containing supplements the last 1 month before intervention start
• Concomitant participation in other studies involving dietary supplements or blood sampling
• Living in a household with another participating child

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High protein yoghurt and vitamin D supplement; Subjects will receive high protein yoghurt and vitamin D tablets.	Dietary supplement: Milk Protein (high); High protein yoghurt which contains approx. 10 g protein per 100 g. Participants will be asked to consume 300 g (=3 dl) 6 days a week.; Dietary supplement: Vitamin D; One daily tablet containing 20 μg of vitamin D3, cholecalciferol.
Experimental: High protein yoghurt and placebo supplement; Subjects will receive high protein yoghurt and placebo tablets of identical appearance and taste but without vitamin D.	Dietary supplement: Milk Protein (high); High protein yoghurt which contains approx. 10 g protein per 100 g. Participants will be asked to consume 300 g (=3 dl) 6 days a week.
Experimental: Medium protein yoghurt and vitamin D supplement; Subjects will receive medium protein yoghurt and vitamin D tablets.	Dietary supplement: Vitamin D; One daily tablet containing 20 μg of vitamin D3, cholecalciferol.; Dietary supplement: Milk Protein (medium); Ordinary yoghurt containing approx. 3.3 g protein per 100 g. Participants will be asked to consume 300 g (=3 dl) 6 days a week.
Placebo Comparator: Medium protein yoghurt and placebo supplement; Subjects will receive medium protein yoghurt and placebo tablets of identical appearance and taste but without vitamin D.	Dietary supplement: Milk Protein (medium); Ordinary yoghurt containing approx. 3.3 g protein per 100 g. Participants will be asked to consume 300 g (=3 dl) 6 days a week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Mineral Density (BMD)	Measured by dual energy x-ray absorptiometry (DXA)	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure		24 weeks
Bone Mineral Content (BMC)	by DXA	24 weeks
Fat mass index	by DXA	24 weeks
Fat free mass index	by DXA	24 weeks
Bone area	by DXA	24 weeks
Height	by stadiometer	24 weeks
Waist circumference		24 weeks
Insulin-like Growth Factor 1 (IGF-1)	by fasting blood sample	24 weeks
Insulin-like growth factor-binding protein 3 (IGFBP-3)	by fasting blood sample	24 weeks
Serum calcium	by fasting blood sample	24 weeks
Osteocalcin	by fasting blood sample	24 weeks
Parathyroid hormone (PTH)	by fasting blood sample	24 weeks
Bone-specific alkaline phosphatase	by fasting blood sample	24 weeks
C-terminal telopeptide of type 1 collagen in serum (s-CTX)	by fasting blood sample	24 weeks
Maximal leg press strength	Measured by isometric leg press	24 weeks
Maximal jumping height	Measured by squat jump with linear encoder	24 weeks
Maximal jumping length	Measured by standing long jump	24 weeks
Maximal grip strength	Measured by hand grip dynamometer	24 weeks
Muscle endurance	Measured by 30 sec. sit-to-stand	24 weeks
Hemoglobin A1c (HbA1c)	by fasting blood sample	24 weeks
Glucose	by fasting blood sample	24 weeks
Insulin	by fasting blood sample	24 weeks
Total cholesterol	by fasting blood sample	24 weeks
High density lipoprotein cholesterol (HDL cholesterol)	by fasting blood sample	24 weeks
Low density lipoprotein cholesterol (LDL cholesterol)	by fasting blood sample	24 weeks
Triacylglycerol (TG)	by fasting blood sample	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical activity	by accelerometry	24 weeks
C-peptide	by fasting blood sample	24 weeks
Vitamin D binding protein	by fasting blood sample	24 weeks
Serum 25(OH) vitamin D	by fasting blood sample	24 weeks
1,25(OH)2vitamin D	by fasting blood sample	24 weeks
Urea	by fasting blood sample	24 weeks
Interleukin-6 (IL-6)	by fasting blood sample	24 weeks
Interleukin-1β (IL-1β)	by fasting blood sample	24 weeks
Tumor necrosis factor a (TNF-a)	by fasting blood sample	24 weeks
Leptin	by fasting blood sample	24 weeks
Adiponectin	by fasting blood sample	24 weeks
High sensitivity C-reactive protein (hsCRP)	by fasting blood sample	24 weeks
Immune cell counts	by fasting blood sample	24 weeks
Immuno-active peptides in nasal fluid	by nasal fluid sample	24 weeks
Immuno-active peptides in blood	by fasting blood sample	24 weeks
Respiratory tract infections	by questionnaires	24 weeks
Dietary intake	By 4-day dietary record	24 weeks
Vitamin D and calcium intake	By food frequency questionnaire	24 weeks

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: University of Aarhus; Arla Foods; Arla Foods Ingredients
• Investigators: Principal Investigator: Camilla T Damsgaard, Assoc Prof, Department of Nutrition, Exercise and Sports, University of Copenhagen; Study Chair: Christian Mølgaard, Prof, Department of Nutrition, Exercise and Sports, University of Copenhagen; Study Chair: Mette Hansen, Assoc Prof, Institute of Public Health, Aarhus University, Denmark

Publications and helpful links

General Publications

• Thams L, Hvid LG, Stounbjerg NG, Brond JC, Molgaard C, Damsgaard CT, Hansen M. Vitamin D supplementation and increased dairy protein intake do not affect muscle strength or physical function in healthy 6-8-year-old children: the D-pro randomized trial. Eur J Nutr. 2022 Oct;61(7):3613-3623. doi: 10.1007/s00394-022-02912-0. Epub 2022 May 28.
• Thams L, Stounbjerg NG, Hvid LG, Molgaard C, Hansen M, Damsgaard CT. Effects of high dairy protein intake and vitamin D supplementation on body composition and cardiometabolic markers in 6-8-y-old children-the D-pro trial. Am J Clin Nutr. 2022 Apr 1;115(4):1080-1091. doi: 10.1093/ajcn/nqab424.
• Stounbjerg NG, Thams L, Hansen M, Larnkjaer A, Clerico JW, Cashman KD, Molgaard C, Damsgaard CT. Effects of vitamin D and high dairy protein intake on bone mineralization and linear growth in 6- to 8-year-old children: the D-pro randomized trial. Am J Clin Nutr. 2021 Dec 1;114(6):1971-1985. doi: 10.1093/ajcn/nqab286.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2019
• Primary Completion (Actual): April 3, 2020
• Study Completion (Actual): April 3, 2020

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 16, 2019
• First Posted (Actual): May 21, 2019

Study Record Updates

• Last Update Posted (Actual): April 15, 2020
• Last Update Submitted That Met QC Criteria: April 14, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Vitamin D; Muscle strength; Bone mineral density; Dietary recommendations; Child Nutrition; Milk protein; Immune defence
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Vitamins; Bone Density Conservation Agents; Chelating Agents; Sequestering Agents; Vitamin D; Caseins
• Other Study ID Numbers: D224

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No