Effects of Vitamin D Fortification on Vitamin D Metabolite Profiles and Status in Vitamin D Insufficient Individuals (VITD-2013)

A Double-Blind, Randomized, Control Study to Examine the Effects of Vitamin D Fortification on Vitamin D Metabolite Profiles and Status in Vitamin D Insufficient Individuals.

This is a cross-sectional study designed to compare plasma/serum and urine vitamin D metabolite profiles of vitamin D sufficient and insufficient individuals.

There are two phases of this study.

Phase 1 - Consented study participants will attend a screening visit and provide a fasting blood and urine sample. Those individuals who are vitamin D insufficient based on serum 25(OH)D concentrations will be invited to participate in Phase II

Phase II - is a double-blind, randomized, control study designed to examine vitamin D status in vitamin D insufficient individuals consuming a water-soluble form of vitamin D3. Eligible participants will be asked to consume one of three beverages: i) rooibos iced-tea (control); ii) rooibos iced-tea fortified with 1000 IU of water-soluble vitamin D3; or iii) rooibos iced-tea fortified with 1000 IU of water-soluble vitamin D3 and 360 mg calcium at 240 mL of iced-tea consumed daily for 6 weeks. Participants will attend 6 weekly visits following baseline and provide a fasting blood sample for assessment of serum 25(OH)D concentrations.

Objectives: 1) To investigate plasma/serum and urine vitamin D metabolite profiles in vitamin D sufficient and insufficient individuals; and 2) To determine the effects of vitamin D3 fortification on serum 25-dihydroxy-vitamin D [25(OH)D] concentrations, markers of vitamin D and calcium metabolism, and vitamin D metabolite profile in plasma/serum and urine of vitamin D insufficient individuals.

Study Overview

• Status: Withdrawn
• Conditions: Vitamin D Deficiency
• Intervention / Treatment: Dietary supplement: Rooibos Iced-Tea (Control); Dietary supplement: Rooibos Tea - Vitamin D3; Dietary supplement: Rooibos Tea- Vitamin D3 & Calcium

Detailed Description

Health individuals from the general public will be recruited into this cross-sectional study designed to compare plasma/serum and urine vitamin D metabolite profiles of those identified as vitamin D sufficient and insufficient individuals.

There are two objectives:

Objective 1: To investigate plasma/serum and urine vitamin D metabolite profiles in vitamin D sufficient and insufficient individuals; N=20 and will consist of 10 individuals identified as vitamin D insufficient and 10 individuals identified as vitamin D deficient individuals.

Objective 2: To determine the effects of vitamin D3 fortification on serum 25-dihydroxy-vitamin D [25(OH)D] concentrations, markers of vitamin D and calcium metabolism, and vitamin D metabolite profile in plasma/serum and urine of vitamin D insufficient individuals. N=45.

To achieve the objectives, the study will be conducted in two phases:

Phase 1 - Healthy males or females, ≥19 and ≤50 years of age, will be recruited from the general public. Consented study participants will provide a fasting blood and urine sample for the purpose of determination of vitamin D status (insufficient vs. deficient) based on serum 25(OH)D concentrations. Forty-five (45) individuals identified as vitamin D insufficient (having a serum 25(OH)D concentration ≥30 and ≤75 nmol/L) will proceed to phase II. A N=20 (10 vitamin D insufficient and 10 vitamin D deficient) will also be identified to satisfy objective 1.

Phase II - is a double-blind, randomized, control study designed to examine vitamin D status in vitamin D insufficient individuals consuming a water-soluble form of vitamin D3. Eligible participants will randomized to consume one of three beverages: i) rooibos iced-tea (control); ii) rooibos iced-tea fortified with 1000 IU of water-soluble vitamin D3; or iii) rooibos iced-tea fortified with 1000 IU of water-soluble vitamin D3 and 360 mg calcium at 240 mL of iced-tea consumed daily for 6 weeks. Both researchers and participants will be blinded to the beverage group assigned to each participant. Participants will then attend 6 weekly visits following the baseline visit to provide fasting blood samples for assessment of serum 25(OH)D concentrations.

Analysis of intact-PTH, alkaline-phosphatase, calcium, phosphorus, CRP, TAP and vitamin D metabolite profile and a urine sample will also be obtained for assessment of N-telopeptide and vitamin D metabolite profile will also occur at Baseline and Week 6. Fasting blood samples collected at week 3 will be used for additional assessment of serum alkaline phosphatase, calcium and phosphorus. A 3-day Food Record will be provided at week 3.

Vitamin D insufficient participants will be stratified according to their serum 25(OH)D concentrations (≥30 and ≤50, or >50 and ≤75 nmol/L) after screening and prior to the beverage study to ensure that a range of lower and higher serum 25(OH)D concentrations are represented in each beverage group.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface Hospital, Asper Clinical Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

A. Inclusion Criteria for Objective 1 (Part One):

1. Adult volunteers, male or female, between 19 and 50 years of age;
2. Body mass index (BMI) ≥20 and ≤30 kg/m2 (normal to overweight);
3. Must be on a stable regime for the past three months, if taking vitamin and mineral/dietary/herbal supplements; and
4. Willing to provide informed consent.

B. Inclusion Criteria for Objective 2 (Part Two):

1. Adult volunteers, male or female, between 19 and 50 years of age;
2. Body mass index (BMI) ≥20 and ≤30 kg/m2 (normal to overweight);
3. Must be on a stable regime for the past three months, if taking vitamin and mineral/dietary/herbal supplements;
4. Vitamin D insufficient (serum 25(OH)D concentrations ≥30 and ≤75 nmol/L);
5. Willing to comply with protocol requirements; and
6. Willing to provide informed consent.

Exclusion Criteria:

1. Take a vitamin D or calcium supplement within the last three months before the start date of the study, or during the study;
2. History of vitamin D deficiency (serum 25(OH)D concentration <30 nmol/L);
3. History of hypocalcaemia;
4. Presence of a clinically diagnosed disease affecting the circulatory, respiratory, immune, skeletal, urinary, muscular, endocrine, digestive, nervous or reproductive system that requires medical treatment;
5. Taking any medication (with the exception of birth control);
6. Daily consumption of more than three servings of dairy products;
7. Undergone significant sun exposure one month before start date of the study;
8. Use or have used a tanning booth one month before start date of the study, or during the study;
9. Plan to travel to a sunny climate during the study;
10. Currently smoking or have smoked within the last six months before start date of the study, or during the study;
11. Have allergies to tea products;
12. Pregnant or lactating; and
13. Consume excessive alcohol (>10 drinks/week for women, >15 drinks/week for men).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; Participants will be instructed to consume 240 mL of iced-tea daily for 6 weeks. The iced-tea beverages do not contain added sugar or artificial sweeteners. Beverages will be prepared fresh weekly and picked up by participants during their weekly study visits.	Dietary supplement: Rooibos Iced-Tea (Control); Participants will consume 240 mL of Rooibos iced-tea daily for 6 weeks. The iced-tea beverage will not contain any added sugar or artificial sweeteners. Beverages will be prepared fresh weekly and picked up by participants during their weekly study visits.
Active Comparator: Rooibos Tea - Vitamin D3; Participants will be instructed to consume 240 mL of iced-tea fortified with 1000 IU water-soluable vitamin D3 daily for 6 weeks. The iced-tea beverages do not contain added sugar or artificial sweeteners. Beverages will be prepared fresh weekly and picked up by participants during their weekly study visits.	Dietary supplement: Rooibos Tea - Vitamin D3; Participants will consume 240 mL of Rooibos iced-tea fortified with 1000 IU of water soluable Vitamin D3 daily for 6 weeks. The iced-tea beverage will not contain any added sugar or artificial sweeteners. Beverages will be prepared fresh weekly and picked up by participants during their weekly study visits.
Active Comparator: Rooibos Tea- Vitamin D3 & Calcium; Participants will be instructed to consume 240 mL of Rooibos iced-tea fortified with 1000 IU of water-soluable vitamin D3 and 360 mg of calcium daily for 6 weeks. The iced-tea beverages do not contain added sugar or artificial sweeteners. Beverages will be prepared fresh weekly and picked up by participants during their weekly study visits.	Dietary supplement: Rooibos Tea- Vitamin D3 & Calcium; Participants will consume 240 mL of Rooibos iced-tea fortified with 1000 IU of water soluable Vitamin D3 and 360 mg of Calicum daily for 6 weeks. The iced-tea beverage will not contain any added sugar or artificial sweeteners. Beverages will be prepared fresh weekly and picked up by participants during their weekly study visits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma/Serum and Urine Vitamin D Metabolite Profiles of Vitamin D Sufficient and Insufficient Individuals	To investigate plasma/serum and urine vitamin D metabolite profiles in vitamin D sufficient and insufficient individuals.	Screening Visit (Day 0) - Phase 1
The Effects of Vitamin D Fortification on Serum 25(OH)D in Vitamin D Insufficient Individuals.	To determine the effects of 6 weeks of vitamin D3 fortification on serum 25-dihydroxy-vitamin D [25(OH)D] concentrations of vitamin D insufficient individuals.	6 Weeks (Phase II)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Effects of Vitamin D3 Fortification on markers of vitamin D of vitamin D insufficient individuals	To determine the effects of 6 weeks of vitamin D3 fortification on markers of vitamin D in plasma/serum and urine of vitamin D insufficient individuals.	6 Weeks (Phase II)
The Effects of vitamin D3 Fortification on calcium metabolism of Vitamin D Insufficient Individuals.	To determine the effects of 6 weeks of vitamin D3 fortification on calcium metabolism in plasma/serum and urine of vitamin D insufficient individuals.	6 Weeks (Phase II)
The Effects of Vitamin D3 Fortification on Vitamin D Metabolite Profile of Vitamin D Insufficient Individuals.	Determine the effects of vitamin D3 fortification on the vitamin D metabolite profile in plasma/serum and urine of vitamin D insufficient individuals.	6 Weeks (Phase II)

Collaborators and Investigators

• Sponsor: University of Manitoba
• Collaborators: Canada Manitoba Agri-Food Research and Development Initiative
• Investigators: Principal Investigator: Carla Taylor, PhD, University of Manitoba

Publications and helpful links

General Publications

• Tangpricha V, Koutkia P, Rieke SM, Chen TC, Perez AA, Holick MF. Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health. Am J Clin Nutr. 2003 Jun;77(6):1478-83. doi: 10.1093/ajcn/77.6.1478.
• Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in the United States and Canada: current status and data needs. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1710S-6S. doi: 10.1093/ajcn/80.6.1710S.
• Ding S, Schoenmakers I, Jones K, Koulman A, Prentice A, Volmer DA. Quantitative determination of vitamin D metabolites in plasma using UHPLC-MS/MS. Anal Bioanal Chem. 2010 Sep;398(2):779-89. doi: 10.1007/s00216-010-3993-0. Epub 2010 Jul 14.
• Luque de Castro MD, Fernandez-Romero JM, Ortiz-Boyer F, Quesada JM. Determination of vitamin D3 metabolites: state-of-the-art and trends. J Pharm Biomed Anal. 1999 Jun;20(1-2):1-17. doi: 10.1016/s0731-7085(99)00027-8.
• Stalmach A, Mullen W, Pecorari M, Serafini M, Crozier A. Bioavailability of C-linked dihydrochalcone and flavanone glucosides in humans following ingestion of unfermented and fermented rooibos teas. J Agric Food Chem. 2009 Aug 12;57(15):7104-11. doi: 10.1021/jf9011642.

Helpful Links

• Canadian Centre for Agri-Food Research in Health and Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: February 11, 2015
• First Submitted That Met QC Criteria: April 20, 2015
• First Posted (Estimate): April 21, 2015

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: February 22, 2017
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: calcium; Vitamin D insufficient; rooibos tea
• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin D Deficiency; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: B2013:045 (Other Identifier: University of Manitoba Biomedical Research Ethics Board)