Trial Outcomes & Findings for Study of Chokeberry to Reduce Cardiovascular Disease Risk in Former Smokers (NCT NCT01541826)

Results Overview

Change in LDL cholesterol from baseline after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

62 participants

Primary outcome timeframe

Baseline, 6 weeks, 12 weeks of intervention

Results posted on

2017-07-11

Participant Flow

Participant milestones

Participant milestones
Measure	Color-matched Rice Powder Pill Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks	Chokeberry Extract Capsule Chokeberry extract capsule Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks. Chokeberry extract capsule, acute: Chokeberry extract capsule, 2 x 250 mg, one-time dose.	Chaokeberry Extract Capsule (Acute) Chokeberry extract capsule, acute: Chokeberry extract capsule, 2 x 250 mg, one-time dose.
Overall Study STARTED	28	28	6
Overall Study COMPLETED	24	25	6
Overall Study NOT COMPLETED	4	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Color-matched Rice Powder Pill Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks	Chokeberry Extract Capsule Chokeberry extract capsule Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks. Chokeberry extract capsule, acute: Chokeberry extract capsule, 2 x 250 mg, one-time dose.	Chaokeberry Extract Capsule (Acute) Chokeberry extract capsule, acute: Chokeberry extract capsule, 2 x 250 mg, one-time dose.
Overall Study Lost to Follow-up	2	3	0
Overall Study Withdrawal by Subject	2	0	0

Baseline Characteristics

Missing value for one participant in acute study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks	Chokeberry Extract Capsule n=25 Participants Chokeberry extract capsule Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Chokeberry Extract Capsule (Acute) n=6 Participants Chokeberry extract capsule, acute: Chokeberry extract capsule, 2 x 250 mg, one-time dose.	Total n=55 Participants Total of all reporting groups
Age, Continuous	37.4 years STANDARD_DEVIATION 14.8 • n=24 Participants	32.6 years STANDARD_DEVIATION 12.7 • n=25 Participants	31.3 years STANDARD_DEVIATION 12.8 • n=6 Participants	34.9 years STANDARD_DEVIATION 13.9 • n=55 Participants
Sex: Female, Male Female	13 Participants n=24 Participants	12 Participants n=25 Participants	3 Participants n=6 Participants	28 Participants n=55 Participants
Sex: Female, Male Male	11 Participants n=24 Participants	13 Participants n=25 Participants	3 Participants n=6 Participants	27 Participants n=55 Participants
Height	1.73 m STANDARD_DEVIATION 0.92 • n=24 Participants	1.71 m STANDARD_DEVIATION 0.83 • n=25 Participants	1.74 m STANDARD_DEVIATION 0.97 • n=6 Participants	1.72 m STANDARD_DEVIATION 0.87 • n=55 Participants
Average years of smoking	14.9 years STANDARD_DEVIATION 11.9 • n=24 Participants • Missing value for one participant in acute study.	8.96 years STANDARD_DEVIATION 6.68 • n=25 Participants • Missing value for one participant in acute study.	4.8 years STANDARD_DEVIATION 3.0 • n=5 Participants • Missing value for one participant in acute study.	11.9 years STANDARD_DEVIATION 10.0 • n=54 Participants • Missing value for one participant in acute study.
Degree of past smoking 3-5 cigarettes/day	2 Participants n=24 Participants • Missing value for one participant in acute study.	4 Participants n=25 Participants • Missing value for one participant in acute study.	1 Participants n=5 Participants • Missing value for one participant in acute study.	7 Participants n=54 Participants • Missing value for one participant in acute study.
Degree of past smoking 6-10 cigarettes/day	4 Participants n=24 Participants • Missing value for one participant in acute study.	7 Participants n=25 Participants • Missing value for one participant in acute study.	1 Participants n=5 Participants • Missing value for one participant in acute study.	12 Participants n=54 Participants • Missing value for one participant in acute study.
Degree of past smoking 11-15 cigarettes/day	4 Participants n=24 Participants • Missing value for one participant in acute study.	4 Participants n=25 Participants • Missing value for one participant in acute study.	2 Participants n=5 Participants • Missing value for one participant in acute study.	10 Participants n=54 Participants • Missing value for one participant in acute study.
Degree of past smoking 16-20 cigarettes/day	11 Participants n=24 Participants • Missing value for one participant in acute study.	6 Participants n=25 Participants • Missing value for one participant in acute study.	0 Participants n=5 Participants • Missing value for one participant in acute study.	17 Participants n=54 Participants • Missing value for one participant in acute study.
Degree of past smoking >20 cigarettes/day	3 Participants n=24 Participants • Missing value for one participant in acute study.	4 Participants n=25 Participants • Missing value for one participant in acute study.	1 Participants n=5 Participants • Missing value for one participant in acute study.	8 Participants n=54 Participants • Missing value for one participant in acute study.
Weight	81.5 kg STANDARD_DEVIATION 17.2 • n=24 Participants	77.2 kg STANDARD_DEVIATION 21.1 • n=25 Participants	72.8 kg STANDARD_DEVIATION 9.5 • n=6 Participants	79.3 kg STANDARD_DEVIATION 19.2 • n=55 Participants
BMI	27.2 kg/m^2 STANDARD_DEVIATION 4.7 • n=24 Participants	25.7 kg/m^2 STANDARD_DEVIATION 5.0 • n=25 Participants	24.1 kg/m^2 STANDARD_DEVIATION 2.3 • n=6 Participants	26.5 kg/m^2 STANDARD_DEVIATION 4.9 • n=55 Participants
Waist circumference	86.0 cm STANDARD_DEVIATION 17.1 • n=24 Participants	90.9 cm STANDARD_DEVIATION 35.1 • n=25 Participants	79.4 cm STANDARD_DEVIATION 8.4 • n=6 Participants	88.5 cm STANDARD_DEVIATION 27.6 • n=55 Participants
Systolic blood pressure	121 mmHg STANDARD_DEVIATION 14 • n=24 Participants	117 mmHg STANDARD_DEVIATION 16 • n=25 Participants	111.3 mmHg STANDARD_DEVIATION 7.7 • n=6 Participants	119 mmHg STANDARD_DEVIATION 15 • n=55 Participants
Diastolic blood pressure	76.0 mmHg STANDARD_DEVIATION 10.4 • n=24 Participants	75.3 mmHg STANDARD_DEVIATION 12.0 • n=25 Participants	73.3 mmHg STANDARD_DEVIATION 4.7 • n=6 Participants	75.6 mmHg STANDARD_DEVIATION 11.0 • n=55 Participants
Total cholesterol	203 mg/dL STANDARD_DEVIATION 36 • n=24 Participants	220 mg/dL STANDARD_DEVIATION 63 • n=25 Participants	160 mg/dL STANDARD_DEVIATION 30 • n=6 Participants	213 mg/dL STANDARD_DEVIATION 51 • n=55 Participants
HDL-cholesterol	28.7 mg/dL STANDARD_DEVIATION 6.1 • n=24 Participants	26.8 mg/dL STANDARD_DEVIATION 7.6 • n=25 Participants	54.8 mg/dL STANDARD_DEVIATION 15.7 • n=6 Participants	27.6 mg/dL STANDARD_DEVIATION 6.9 • n=55 Participants
LDL-cholesterol	158 mg/dL STANDARD_DEVIATION 30 • n=24 Participants	175 mg/dL STANDARD_DEVIATION 54 • n=25 Participants	99.2 mg/dL STANDARD_DEVIATION 19.2 • n=6 Participants	168 mg/dL STANDARD_DEVIATION 44 • n=55 Participants
Triglycerides	82.1 mg/dL STANDARD_DEVIATION 37.3 • n=24 Participants	89.6 mg/dL STANDARD_DEVIATION 45.4 • n=25 Participants	69.2 mg/dL STANDARD_DEVIATION 27.1 • n=6 Participants	86.3 mg/dL STANDARD_DEVIATION 41.0 • n=55 Participants
Total cholesterol/HDL cholesterol	7.3 dimensionless ratio STANDARD_DEVIATION 1.5 • n=24 Participants	8.5 dimensionless ratio STANDARD_DEVIATION 2.7 • n=25 Participants	3.2 dimensionless ratio STANDARD_DEVIATION 0.7 • n=6 Participants	8.0 dimensionless ratio STANDARD_DEVIATION 2.3 • n=55 Participants

PRIMARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks of intervention

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Change in LDL cholesterol from baseline after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
LDL Cholesterol 6 weeks	-12.6 mg/dL Standard Error 5.3	0.9 mg/dL Standard Error 4.2
LDL Cholesterol 12 weeks	-18.5 mg/dL Standard Error 7.8	-0.4 mg/dL Standard Error 5.9

SECONDARY outcome

Timeframe: 6 and 12 weeks after supplementation

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Change in fasting total cholesterol from baseline after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Total Cholesterol Baseline	220 mg/dL Standard Error 13	203 mg/dL Standard Error 7
Total Cholesterol 6 weeks (change from baseline)	1.4 mg/dL Standard Error 2.5	-0.1 mg/dL Standard Error 4.6
Total Cholesterol 12 weeks (change from baseline)	-17.9 mg/dL Standard Error 7.6	-1.3 mg/dL Standard Error 6.4

SECONDARY outcome

Timeframe: 6 and 12 weeks after supplementation

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Change in fasting plasma cholesterol from baseline after chronic supplemenation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
HDL-cholesterol Baseline	26.8 mg/dL Standard Error 1.5	28.8 mg/dL Standard Error 1.3
HDL-cholesterol 6 weeks (change from baseline)	0.2 mg/dL Standard Error 0.8	-0.9 mg/dL Standard Error 1.0
HDL-cholesterol 12 weeks (change from baseline)	0.2 mg/dL Standard Error 0.8	-0.7 mg/dL Standard Error 1.4

SECONDARY outcome

Timeframe: 6 and 12 weeks after supplementation

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Change in fasting plasma triglycerides from baseline after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Triglycerides Baseline	89.6 mg/dL Standard Error 9.0	82.1 mg/dL Standard Error 7.6
Triglycerides 6 weeks (change from baseline)	1.0 mg/dL Standard Error 5.9	-0.6 mg/dL Standard Error 2.7
Triglycerides 12 weeks (change from baseline)	2.0 mg/dL Standard Error 8.5	-1.0 mg/dL Standard Error 5.9

SECONDARY outcome

Timeframe: Baseline, 6 weeks, and 12 weeks following intervention

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Change in resting systolic blood pressure after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Resting Systolic Blood Pressure Baseline	117 mmHg Standard Error 3	121 mmHg Standard Error 3
Resting Systolic Blood Pressure 6 weeks (change from baseline)	2.8 mmHg Standard Error 1.7	-0.8 mmHg Standard Error 1.5
Resting Systolic Blood Pressure 12 weeks (change from baseline)	1.2 mmHg Standard Error 2.4	0.2 mmHg Standard Error 2.9

SECONDARY outcome

Timeframe: Baseline, 6 weeks, and 12 weeks following intervention

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Change in resting diastolic blood pressure after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Resting Diastolic Blood Pressure Baseline	75.3 mmHg Standard Error 2.4	76.0 mmHg Standard Error 2.1
Resting Diastolic Blood Pressure 6 weeks (change from baseline)	5.0 mmHg Standard Error 1.3	-1.2 mmHg Standard Error 2.4
Resting Diastolic Blood Pressure 12 weeks (change from baseline)	2.0 mmHg Standard Error 1.5	-1.1 mmHg Standard Error 1.7

SECONDARY outcome

Timeframe: Baseline and 12 weeks following intervention

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Change in resting urinary F2-isoprostanes after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Urinary F2-isoprostanes Baseline	58.6 ng/mmol creatinine Standard Error 7.0	71.0 ng/mmol creatinine Standard Error 8.1
Urinary F2-isoprostanes 12 weeks	68.4 ng/mmol creatinine Standard Error 9.0	81.6 ng/mmol creatinine Standard Error 7.8

SECONDARY outcome

Timeframe: Baseline, 12 wk

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Monocyte messenger ribonucleic acid (mRNA) expression normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
3-hydroxy-3-methyl-glutaryl Coenzyme A Reductase (HMGR) Baseline	0.91 relative expression (HMGR/GAPDH) Standard Error 0.06	0.90 relative expression (HMGR/GAPDH) Standard Error 0.06
3-hydroxy-3-methyl-glutaryl Coenzyme A Reductase (HMGR) 12 weeks	0.79 relative expression (HMGR/GAPDH) Standard Error 0.12	1.16 relative expression (HMGR/GAPDH) Standard Error 0.28

SECONDARY outcome

Timeframe: Change from baseline at 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Monocyte LDL receptor mRNA normalized to glyceraldehyde-3-phosphate dehydrogenase after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
LDL Receptor (LDLR) Baseline	0.84 relative expression (LDLR/GAPDH) Standard Error 0.07	0.90 relative expression (LDLR/GAPDH) Standard Error 0.07
LDL Receptor (LDLR) 12 weeks	0.88 relative expression (LDLR/GAPDH) Standard Error 0.26	0.93 relative expression (LDLR/GAPDH) Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Monocyte LDL receptor protein by Western blot, normalized to β-actin after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
LDL Receptor (LDLR) Protein Baseline	1.45 relative expression (LDLR/β-actin) Standard Error 0.06	1.71 relative expression (LDLR/β-actin) Standard Error 0.33
LDL Receptor (LDLR) Protein 12 weeks	1.45 relative expression (LDLR/β-actin) Standard Error 0.64	2.47 relative expression (LDLR/β-actin) Standard Error 0.80

SECONDARY outcome

Timeframe: 0, 0.5, 1, 2, 4, 6, 9, 12, and 24 hours following dose

Population: Not determined in chronic arms (Color-matched Rice Powder Pill or Chokeberry Extract Capsule) as this analysis required additional collection time-points that were not utilized in the other arms.

Plasma area under the curve of chokeberry polyphenols and their metabolites. Measurement (time 0) began at study baseline. Not determined in chronic arms (Color-matched Rice Powder Pill or Chokeberry Extract Capsule).

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=6 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Plasma Area Under the Curve of Chokeberry Polyphenols and Their Metabolites. Protocatechuic acid	—	0.054 micrograms x h/mL Standard Error 0.013
Plasma Area Under the Curve of Chokeberry Polyphenols and Their Metabolites. Hippuric acid	—	22.350 micrograms x h/mL Standard Error 4.441
Plasma Area Under the Curve of Chokeberry Polyphenols and Their Metabolites. 3-(4-Hydroxyphenyl)propionic acid	—	2.725 micrograms x h/mL Standard Error 2.391
Plasma Area Under the Curve of Chokeberry Polyphenols and Their Metabolites. Cyanidin-3-O-glucoside	—	0.462 micrograms x h/mL Standard Error 0.170
Plasma Area Under the Curve of Chokeberry Polyphenols and Their Metabolites. Peonidin-3-O-galactoside	—	0.627 micrograms x h/mL Standard Error 0.198

SECONDARY outcome

Timeframe: 0 to 24 h after consumption of extract

Population: Not determined in chronic arms (Color-matched Rice Powder Pill or Chokeberry Extract Capsule) as this analysis required additional collection time-points that were not utilized in the other arms.

Urinary excretion of polyphenols, from 0 to 24 h after consumption of extract, area under the curve (AUC) in Chokeberry Extract Capsule (acute) arm only.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=6 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Urinary Excretion of Polyphenols Protocatechuic acid	—	3.682 mg x h/mg creatinine Standard Error 0.587
Urinary Excretion of Polyphenols 3,4-dihyrdoxyphenylacetic acid	—	11.426 mg x h/mg creatinine Standard Error 0.881
Urinary Excretion of Polyphenols Hippuric acid	—	2429.852 mg x h/mg creatinine Standard Error 360.197
Urinary Excretion of Polyphenols 3-(4-hydroxyphenyl)propionic acid	—	2.299 mg x h/mg creatinine Standard Error 0.715
Urinary Excretion of Polyphenols Cyanidin-3-O-galactoside	—	0.016 mg x h/mg creatinine Standard Error 0.005
Urinary Excretion of Polyphenols Cyanidin-3-O-glucoside	—	0.118 mg x h/mg creatinine Standard Error 0.070
Urinary Excretion of Polyphenols Cyanidin-3-O-arabinoside	—	0.088 mg x h/mg creatinine Standard Error 0.031
Urinary Excretion of Polyphenols Peonidin-3-O-galactoside	—	0.053 mg x h/mg creatinine Standard Error 0.012

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Fasting plasma adiponectin after chronic consumption. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Adiponectin Baseline	12.8 micrograms/mL Standard Error 1.5	13.2 micrograms/mL Standard Error 1.9
Adiponectin 6 weeks	13.8 micrograms/mL Standard Error 1.7	14.2 micrograms/mL Standard Error 2.0
Adiponectin 12 weeks	13.2 micrograms/mL Standard Error 1.5	12.5 micrograms/mL Standard Error 1.6

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Fasting plasma interleukin-1 beta after chronic consumption. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Interleukin-1 Beta Baseline	16.2 pg/mL Standard Error 8.6	9.3 pg/mL Standard Error 2.4
Interleukin-1 Beta 6 weeks	17.0 pg/mL Standard Error 9.7	9.5 pg/mL Standard Error 2.7
Interleukin-1 Beta 12 weeks	14.7 pg/mL Standard Error 7.4	10.1 pg/mL Standard Error 3.0

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Fasting plasma interleukin-6 after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Interleukin-6 Baseline	4.68 pg/mL Standard Error 1.34	1.94 pg/mL Standard Error 0.34
Interleukin-6 6 weeks	5.16 pg/mL Standard Error 1.54	1.87 pg/mL Standard Error 0.38
Interleukin-6 12 weeks	5.34 pg/mL Standard Error 1.52	1.76 pg/mL Standard Error 0.29

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Fasting plasma monocyte chemoattractant protein-1 after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Monocyte Chemoattractant Protein-1 Baseline	133 pg/mL Standard Error 31	97 pg/mL Standard Error 6
Monocyte Chemoattractant Protein-1 6 weeks	167 pg/mL Standard Error 43	96 pg/mL Standard Error 5
Monocyte Chemoattractant Protein-1 12 weeks	141 pg/mL Standard Error 27	91 pg/mL Standard Error 5

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Fasting plasma Tumor necrosis factor-alpha after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Tumor Necrosis Factor-alpha Baseline	5.90 pg/mL Standard Error 1.63	4.36 pg/mL Standard Error 1.83
Tumor Necrosis Factor-alpha 6 weeks	6.44 pg/mL Standard Error 1.83	4.70 pg/mL Standard Error 1.89
Tumor Necrosis Factor-alpha 12 weeks	6.10 pg/mL Standard Error 1.72	4.86 pg/mL Standard Error 1.85

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Fasting plasma C-reactive protein after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
C-reactive Protein Baseline	2.01 pg/mL Standard Error 0.34	2.54 pg/mL Standard Error 0.60
C-reactive Protein 6 weeks	2.32 pg/mL Standard Error 0.39	2.18 pg/mL Standard Error 0.42
C-reactive Protein 12 weeks	2.29 pg/mL Standard Error 0.49	2.24 pg/mL Standard Error 0.38

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Fasting plasma intercellular adhesion molecule 1 after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Intercellular Adhesion Molecule 1 Baseline	96.6 ng/mL Standard Error 5.4	97.1 ng/mL Standard Error 7.2
Intercellular Adhesion Molecule 1 6 weeks	99.4 ng/mL Standard Error 5.7	97.6 ng/mL Standard Error 7.2
Intercellular Adhesion Molecule 1 12 weeks	97.5 ng/mL Standard Error 5.8	100 ng/mL Standard Error 8

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Fasting plasma soluble vascular cell adhesion molecule 1 after chronic consumption. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Soluble Vascular Cell Adhesion Molecule 1 Baseline	601 ng/mL Standard Deviation 31	585 ng/mL Standard Deviation 23
Soluble Vascular Cell Adhesion Molecule 1 6 weeks	622 ng/mL Standard Deviation 31	604 ng/mL Standard Deviation 23
Soluble Vascular Cell Adhesion Molecule 1 12 weeks	599 ng/mL Standard Deviation 27	604 ng/mL Standard Deviation 26

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Fasting plasma P-selectin after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
P-selectin Baseline	124 ng/mL Standard Error 12	130 ng/mL Standard Error 13
P-selectin 6 weeks	127 ng/mL Standard Error 12	111 ng/mL Standard Error 11
P-selectin 12 weeks	145 ng/mL Standard Error 17	131 ng/mL Standard Error 11

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Fasting plasma total antioxidant capacity after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Total Antioxidant Capacity Baseline	208 micrograms vitamin C equivalents/mL Standard Error 3	210 micrograms vitamin C equivalents/mL Standard Error 4
Total Antioxidant Capacity 6 weeks	211 micrograms vitamin C equivalents/mL Standard Error 3	214 micrograms vitamin C equivalents/mL Standard Error 3
Total Antioxidant Capacity 12 weeks	207 micrograms vitamin C equivalents/mL Standard Error 4	209 micrograms vitamin C equivalents/mL Standard Error 4

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Catalase activity after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Catalase Activity 12 weeks	41.2 nmol/min/mL Standard Error 1.8	41.7 nmol/min/mL Standard Error 2.3
Catalase Activity Baseline	41.1 nmol/min/mL Standard Error 2.1	41.7 nmol/min/mL Standard Error 1.4
Catalase Activity 6 weeks	38.7 nmol/min/mL Standard Error 1.5	35.5 nmol/min/mL Standard Error 1.2

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Fasting plasma glutathione peroxidase activity after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Glutathione Peroxidase Activity Baseline	2550 nmol/min/mL Standard Error 140	2550 nmol/min/mL Standard Error 140
Glutathione Peroxidase Activity 6 weeks	2500 nmol/min/mL Standard Error 160	2560 nmol/min/mL Standard Error 130
Glutathione Peroxidase Activity 12 weeks	2650 nmol/min/mL Standard Error 190	2470 nmol/min/mL Standard Error 110

SECONDARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Fasting plasma superoxide dismutase after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Superoxide Dismutase Activity Baseline	1180 units/mL Standard Error 40	1190 units/mL Standard Error 50
Superoxide Dismutase Activity 6 weeks	1160 units/mL Standard Error 40	1190 units/mL Standard Error 50
Superoxide Dismutase Activity 12 weeks	1160 units/mL Standard Error 40	1160 units/mL Standard Error 60

SECONDARY outcome

Timeframe: 12 weeks

Population: Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Overnight urinary polyphenol excretion after chronic supplementation. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=24 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Urinary Polyphenol Excretion Peonidin-3-O-galactoside	0.008 mg/mg creatinine Interval 0.0 to 0.0106	0 mg/mg creatinine Interval 0.0 to 0.0
Urinary Polyphenol Excretion Sum anthocyanins	0.134 mg/mg creatinine Interval 0.028 to 0.442	0.014 mg/mg creatinine Interval 0.0 to 0.091
Urinary Polyphenol Excretion Protocatechuic acid	1.20 mg/mg creatinine Interval 0.64 to 2.03	1.38 mg/mg creatinine Interval 0.94 to 2.08
Urinary Polyphenol Excretion 3,4-dihydroxyphenylacetic acid	4.56 mg/mg creatinine Interval 2.18 to 9.09	5.04 mg/mg creatinine Interval 2.36 to 7.45
Urinary Polyphenol Excretion Hippuric acid	138 mg/mg creatinine Interval 62.0 to 292.0	133 mg/mg creatinine Interval 104.0 to 234.0
Urinary Polyphenol Excretion Ferulic acid	0.71 mg/mg creatinine Interval 0.23 to 3.57	0.68 mg/mg creatinine Interval 0.24 to 1.2
Urinary Polyphenol Excretion 3-(4-hydroxyphenyl)propionic acid	3.36 mg/mg creatinine Interval 0.0 to 9.68	3.91 mg/mg creatinine Interval 0.0 to 9.95
Urinary Polyphenol Excretion Cyanidin-3-O-glucoside	0.00907 mg/mg creatinine Interval 0.0 to 0.1993	0 mg/mg creatinine Interval 0.0 to 0.055
Urinary Polyphenol Excretion Cyanidin-3-O-galactoside	0.00466 mg/mg creatinine Interval 0.0 to 0.0341	0 mg/mg creatinine Interval 0.0 to 0.014
Urinary Polyphenol Excretion Cyanidin-3-O-arabinoside	0 mg/mg creatinine Interval 0.0 to 0.053	0 mg/mg creatinine Interval 0.0 to 0.011

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Survey data were not available for two participants in the "Color-matched rice powder pill" group. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Energy-adjusted intake based on 3-day dietary recalls, determined by the average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=22 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Energy-adjusted Nutrient Intake: Carbohydrate, Protein, Fat, Fiber Carbohydrate	241 g/day Standard Error 9	238 g/day Standard Error 9
Energy-adjusted Nutrient Intake: Carbohydrate, Protein, Fat, Fiber Protein	90.3 g/day Standard Error 3.1	89.2 g/day Standard Error 3.3
Energy-adjusted Nutrient Intake: Carbohydrate, Protein, Fat, Fiber Fat	77.6 g/day Standard Error 29.5	27.8 g/day Standard Error 4.0
Energy-adjusted Nutrient Intake: Carbohydrate, Protein, Fat, Fiber Fiber	21.0 g/day Standard Error 1.5	23.5 g/day Standard Error 1.6

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Survey data were not available for two participants in the "Color-matched rice powder pill" group. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Energy intake reported from 3-day dietary recalls at baseline and 12 weeks, determined by the average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=22 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Energy Intake	1950 kcal/d Standard Error 530	2230 kcal/d Standard Error 735

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Survey data were not available for two participants in the "Color-matched rice powder pill" group. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Energy-adjusted micronutrient intake from 3-day dietary recalls at baseline and 12 weeks. Values reported as the average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=22 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Energy-adjusted Micronutrient Intake Sodium	3480 mg/day Standard Error 150	3490 mg/day Standard Error 160
Energy-adjusted Micronutrient Intake Calcium	1070 mg/day Standard Error 50	947 mg/day Standard Error 58
Energy-adjusted Micronutrient Intake Iron	16.9 mg/day Standard Error 1.2	16.9 mg/day Standard Error 1.3
Energy-adjusted Micronutrient Intake Vitamin D	7.1 mg/day Standard Error 0.8	5.0 mg/day Standard Error 0.9
Energy-adjusted Micronutrient Intake Vitamin C	90.9 mg/day Standard Error 12.1	80.9 mg/day Standard Error 12.9
Energy-adjusted Micronutrient Intake Vitamin E	10.8 mg/day Standard Error 1.1	10.6 mg/day Standard Error 1.1

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Survey data were not available for two participants in the "Color-matched rice powder pill" group. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Energy-adjusted polyphenol intake assessed by 3-day dietary recalls at baseline and 12 weeks, values determined by average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=22 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Polyphenol Intake Isoflavones	8.5 mg/day Standard Error 2.6	3.9 mg/day Standard Error 2.7
Polyphenol Intake Flavanols	81.7 mg/day Standard Error 18.7	73.9 mg/day Standard Error 20.0
Polyphenol Intake Flavones	50.3 mg/day Standard Error 27.2	54.1 mg/day Standard Error 29.1
Polyphenol Intake Flavanones	22.4 mg/day Standard Error 10.7	28.8 mg/day Standard Error 11.4
Polyphenol Intake Flavan-3-ols	26.0 mg/day Standard Error 6.9	20.6 mg/day Standard Error 7.4
Polyphenol Intake Anthocyanins	26.6 mg/day Standard Error 4.8	18.2 mg/day Standard Error 5.2
Polyphenol Intake Proanthocyanidins	418 mg/day Standard Error 150	222 mg/day Standard Error 162

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Survey data were not available for two participants in the "Color-matched rice powder pill" group. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Energy-adjusted intake of dietary antioxidant capacity determined by 3-day dietary recalls at baseline and 12 weeks. Values reported as average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=24 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=22 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Intake of Dietary Antioxidant Capacity	292 Vitamin C equivalents Standard Error 89	417 Vitamin C equivalents Standard Error 95

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Survey data were not available for two participants in the "Color-matched rice powder pill" group. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Energy-adjusted vitamin A intake from 3-day dietary recalls at baseline and 12 weeks. Values reported as the average of baseline and 12 weeks. Not determined in Chokeberry Extract Capsule (Acute) arm as this arm was a one-time dose.

Outcome measures

Outcome measures
Measure	Chokeberry Extract Capsule n=25 Participants Chokeberry Extract: Consumption of 2 x 250 mg chokeberry extract capsules daily for 12 weeks.	Color-matched Rice Powder Pill n=22 Participants Color-matched rice powder pill Placebo capsule: Color-matched rice powder pill, 2 x 250 mg/day for 12 weeks
Energy-adjusted Vitamin A Intake	2690 retinol equivalent mcg/day Standard Error 690	3280 retinol equivalent mcg/day Standard Error 740

Adverse Events

Color-matched Rice Powder Pill

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Chokeberry Extract Capsule

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Chokeberry Extract Capsule (Acute)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Bradley Bolling

University of Wisconsin-Madison, Department of Food Science

Phone: 608-890-0212

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place