Effects of Milk Protein and Vitamin D on Children's Growth and Health

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Bone Health, Muscle Function, Cardiometabolic Health, Appetite Regulation

Intervention / Treatment
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* Dietary Supplement: Milk Protein (high)
* Dietary Supplement: Vitamin D
* Dietary Supplement: Milk Protein (medium)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High protein yoghurt and vitamin D supplement<br>Subjects will receive high protein yoghurt and vitamin D tablets. | Dietary Supplement: Milk Protein (high)<br>* 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.<br>Dietary Supplement: Vitamin D<br>* One daily tablet containing 20 μg of vitamin D3, cholecalciferol.<br>|
| Experimental: High protein yoghurt and placebo supplement<br>Subjects will receive high protein yoghurt and placebo tablets of identical appearance and taste but without vitamin D. | Dietary Supplement: Milk Protein (high)<br>* 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.<br>|
| Experimental: Medium protein yoghurt and vitamin D supplement<br>Subjects will receive medium protein yoghurt and vitamin D tablets. | Dietary Supplement: Vitamin D<br>* One daily tablet containing 20 μg of vitamin D3, cholecalciferol.<br>Dietary Supplement: Milk Protein (medium)<br>* 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.<br>|
| Placebo Comparator: Medium protein yoghurt and placebo supplement<br>Subjects will receive medium protein yoghurt and placebo tablets of identical appearance and taste but without vitamin D. | Dietary Supplement: Milk Protein (medium)<br>* 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.<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Blood pressure |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Child Nutrition, Dietary recommendations, Milk protein, Vitamin D, Bone mineral density, Muscle strength, Immune defence