This study uses a bone labeling calcium tracer methodology to compare the dose-response
      effect of blueberry consumption on calcium retention and bone loss. Post-menopausal women
      will receive food or beverage products containing freeze-dried blueberries in the amount
      equivalent to 0.75 (low), 1.5 (medium), and 3 cups (high) of fresh blueberries per day over a
      42-day period. The hypothesis is that the polyphenolics found in blueberries will reduce
      calcium loss from bones.

Effect of Blueberries on Bone Turnover

Osteoporosis, Postmenopausal

Bone Loss, Age-related

Participants will be dosed with Ca-41, a rare long-lived radioisotope of calcium. After the
      equilibration of tracer in the body and its deposition in bones (150 days), subjects will be
      randomized to one of 6 dose sequences, all of which will begin with a 42-day baseline period.
      During baseline, 24-hour urine will be collected every 14 days. Following baseline, subjects
      will enter a 42-day intervention period with one of three doses of blueberries equivalent to
      0.75 (low), 1.5 (medium), and 3 cups (high) of blueberries per day. Each dose will be
      provided in the form of freeze-dried blueberry powder incorporated in 2-4 foods or beverages
      per day. During the intervention, 24-hour urine will be collected weekly for 6 weeks except
      week 1. After intervention, subjects will enter a 42-day washout period, during which 24-hour
      urine will be collected every 3 weeks. The entire study duration will be 444 days for
      subjects who have not been dosed with Ca-41 previously. In a crossover design, all subjects
      will complete three 42-day intervention periods corresponding to the three doses of
      blueberries (low, medium, and high), each followed by a 42-day washout period. The
      dose-response effect of continuous blueberry consumption over a 42-day period on bone
      resorption in healthy post-menopausal women will be studied by measuring the loss of Ca-41 in
      urine by Accelerator Mass Spectrometry.

Blueberry Baseline

Blueberry Low

Blueberry Medium

Blueberry High

Berries and Bones: The Effect of Polyphenolic Metabolites From Blueberries on Bone Turnover

Urinary Ca-41 excretion will be expressed as Ca-41/Ca ratio, which is unit-less, and converted to a percent change from the baseline value.
24-hour urine will be collected approximately every 2 weeks during baseline (week 0, 2, 4, and 6), weekly (except for week 1) during the low, medium, and high blueberry dose interventions completed in a randomized order (weeks 8-12, 20-24, 32-36) and every 3 weeks during the washout periods (weeks 15, 18, 27, 30, 39, 42). Ca-41/Ca ratios will be measured by Accelerator Mass Spectrometry.

Research Scientist - Study Director

Polyphenol concentrations in urine and serum will be expressed in molar units and compared against reference values and across the study periods. Polyphenolic metabolites will be measured by LC-MSMS.
Fasting blood and urine will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).

Calcium concentration in urine and serum will be expressed in mg/L and measured by Atomic Absorption Spectrophotometry.
Fasting blood and urine will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).

IGF-1 will be expressed in ng/mL and measured by ELISA.
Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).

Osteoprotegerin will be expressed in pmol/L and measured by ELISA.
Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).

RANK-L will be expressed in pmol/L and measured by ELISA.
Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).

25(OH) Vitamin D will be expressed in ng/mL and measured by LC/MS.
Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).

Sclerostin will be expressed in ng/mL and measured by ELISA.
Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).

NTX will be expressed in ng/mL and measured by ELISA.
Fasting urine will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).

PINP will be will be expressed in ug/L and measured by ELISA.
Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).

No blueberry products provided as part of the usual dietary intake

One blueberry product per day containing an equivalent of 0.75 cups of fresh blueberries provided as part of usual dietary intake for 42 days

Two blueberry products per day containing an equivalent of 1.5 cups of fresh blueberries provided as part of usual dietary intake for 42 days

Four blueberry products per day containing an equivalent of 3 cups of fresh blueberries provided as part of usual dietary intake for 42 days

Effect of Blueberries on Bone Turnover

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Trial Timing

What is this trial about?

What are the participation requirements?