Trial Outcomes & Findings for Framingham State Food Study (NCT NCT02068885)

Results Overview

Total energy expenditure (TEE), assessed by indirect calorimetry using stable isotopes Total calories burned: Participants each drank about a cup of water containing special tracers which are measurable when they pass out of the body through urine. They provided a urine sample before they drank the water and then about every other day for the next two (2) weeks. Change: average (midpoint of test phase, end of test phase) - start of trial

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

234 participants

Primary outcome timeframe

Start of Trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Results posted on

2026-01-09

Participant Flow

We recruited participants by posting flyers, newspaper advertisements, and Internet announcements.

We enrolled 234 participants for the run-in phase. Of these, 164 participants achieved at least 10% weight loss and were randomly assigned to one of three diets for the test phase (low-carbohydrate diet, n=57; moderate-carbohydrate diet, n=53; or high-carbohydrate diet, n=54).

Participant milestones

Participant milestones
Measure	Low Carbohydrate Diet Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Overall Study STARTED	57	53	54
Overall Study Provided data at midpoint test phase	56	50	48
Overall Study Provided data at end of test phase	54	48	46
Overall Study Included in intention-to-treat analysis	56	52	54
Overall Study COMPLETED	54	48	46
Overall Study NOT COMPLETED	3	5	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Low Carbohydrate Diet Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Overall Study Withdrew	3	5	8

Baseline Characteristics

Framingham State Food Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Carbohydrate Diet n=57 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Total n=164 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=8 Participants	0 Participants n=7 Participants	0 Participants n=15 Participants	0 Participants n=42 Participants
Age, Categorical Between 18 and 65 years	57 Participants n=8 Participants	53 Participants n=7 Participants	54 Participants n=15 Participants	164 Participants n=42 Participants
Age, Categorical >=65 years	0 Participants n=8 Participants	0 Participants n=7 Participants	0 Participants n=15 Participants	0 Participants n=42 Participants
Age, Continuous	37.1 years STANDARD_DEVIATION 13.3 • n=8 Participants	37.3 years STANDARD_DEVIATION 14.9 • n=7 Participants	39.8 years STANDARD_DEVIATION 15.1 • n=15 Participants	37.8 years STANDARD_DEVIATION 14.4 • n=42 Participants
Sex: Female, Male Female	37 Participants n=8 Participants	36 Participants n=7 Participants	42 Participants n=15 Participants	115 Participants n=42 Participants
Sex: Female, Male Male	20 Participants n=8 Participants	17 Participants n=7 Participants	12 Participants n=15 Participants	49 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=8 Participants	7 Participants n=7 Participants	8 Participants n=15 Participants	25 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants n=8 Participants	46 Participants n=7 Participants	46 Participants n=15 Participants	139 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=8 Participants	0 Participants n=7 Participants	0 Participants n=15 Participants	0 Participants n=42 Participants
Region of Enrollment United States	57 participants n=8 Participants	53 participants n=7 Participants	54 participants n=15 Participants	164 participants n=42 Participants
Total Energy Expenditure	3110 kcal/d STANDARD_DEVIATION 680 • n=8 Participants	3030 kcal/d STANDARD_DEVIATION 788 • n=7 Participants	2915 kcal/d STANDARD_DEVIATION 686 • n=15 Participants	3021 kcal/d STANDARD_DEVIATION 719 • n=42 Participants

PRIMARY outcome

Timeframe: Start of Trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Intention-to-treat analysis

Total energy expenditure (TEE), assessed by indirect calorimetry using stable isotopes Total calories burned: Participants each drank about a cup of water containing special tracers which are measurable when they pass out of the body through urine. They provided a urine sample before they drank the water and then about every other day for the next two (2) weeks. Change: average (midpoint of test phase, end of test phase) - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=52 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Total Energy Expenditure, Assessed by Indirect Calorimetry Using Stable Isotopes Start of Trial	2713 kcal/d Interval 2696.0 to 2730.0	2504 kcal/d Interval 2486.0 to 2522.0	2640 kcal/d Interval 2623.0 to 2657.0
Total Energy Expenditure, Assessed by Indirect Calorimetry Using Stable Isotopes Change	190 kcal/d Interval 109.0 to 270.0	71 kcal/d Interval -12.0 to 155.0	-19 kcal/d Interval -104.0 to 66.0

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Intention-to-treat analysis

Resting energy expenditure, assessed by indirect calorimetry using respiratory gas exchange Calories burned while resting: Participants lied down with head and neck under a clear plastic "bubble," breathing room air. Gases in expired air were collected. Change: average (midpoint of test phase, end of test phase) - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=51 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Resting Energy Expenditure, Assessed by Indirect Calorimetry Using Respiratory Gas Exchange Start of Trial	1615 kcal/d Interval 1609.0 to 1621.0	1576 kcal/d Interval 1569.0 to 1583.0	1603 kcal/d Interval 1597.0 to 1609.0
Resting Energy Expenditure, Assessed by Indirect Calorimetry Using Respiratory Gas Exchange Change	54 kcal/d Interval 32.0 to 76.0	46 kcal/d Interval 23.0 to 69.0	34 kcal/d Interval 10.0 to 57.0

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Intention-to-treat analysis

Actigraph Accelerometer Change: average (midpoint of test phase, end of test phase) - start of trial An Actigraph Accelerometer measures movement, similar to a pedometer. Data are reported as counts (divided by 1,000) per day. Each participant wore the the accelerometer on the right hip for 7 days at each time point.

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=55 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=52 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Physical Activity, Assessed by Accelerometry Start of Trial	495.8 counts/d Interval 489.5 to 502.1	463.8 counts/d Interval 457.0 to 470.6	476.6 counts/d Interval 470.4 to 482.8
Physical Activity, Assessed by Accelerometry Change	-6.9 counts/d Interval -31.0 to 17.1	-42.4 counts/d Interval -67.7 to -17.1	-26.3 counts/d Interval -52.0 to -0.6

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Efficiency is expressed as percentage ratio of power generated during cycle ergometry (with conversion of Watts to kcal/min using a factor of 0.01433) to energy expenditure above resting. Change: end of test phase - start of trial.

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=55 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=51 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Skeletal Muscle Work Efficiency Start of Trial	12.2 % power generated to energy expended Interval 12.1 to 12.3	11.7 % power generated to energy expended Interval 11.6 to 11.8	12.2 % power generated to energy expended Interval 12.1 to 12.3
Skeletal Muscle Work Efficiency Change	0.3 % power generated to energy expended Interval -0.3 to 0.9	-0.0 % power generated to energy expended Interval -0.6 to 0.6	-0.1 % power generated to energy expended Interval -0.8 to 0.5

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss)

Population: Intention-to-treat analysis

Leptin levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)). Changes (see Outcome 6) are expressed in percentage units (100%×(exp(change in log)-1)): average (midpoint of test phase, end of test phase) - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=51 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Leptin (Start of Trial)	9.6 ng/mL Interval 9.2 to 10.0	9.8 ng/mL Interval 9.4 to 10.2	10.9 ng/mL Interval 10.5 to 11.3

SECONDARY outcome

Timeframe: Change through 20 weeks' weight loss maintenance

Population: Intention-to-treat analysis

Leptin levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): average (midpoint of test phase, end of test phase) - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=51 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Leptin (% Change)	17.9 % change Interval 7.7 to 29.1	34.8 % change Interval 22.6 to 48.2	34.2 % change Interval 21.8 to 47.7

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss)

Population: Intention-to-treat analysis

Ghrelin levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)). Changes (see Outcome 8) are expressed in percentage units (100%×(exp(change in log)-1)): average (midpoint of test phase, end of test phase) - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=51 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Ghrelin (Start of Trial)	598.2 pg/mL Interval 586.3 to 610.1	640.1 pg/mL Interval 626.4 to 653.8	693.2 pg/mL Interval 679.5 to 706.9

SECONDARY outcome

Timeframe: Change through 20 weeks' weight loss maintenance

Population: Intention-to-treat analysis

Ghrelin levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): average (midpoint of test phase, end of test phase) - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=51 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Ghrelin (% Change)	-11.8 % change Interval -14.8 to -8.6	-8.7 % change Interval -12.0 to -5.3	-4.9 % change Interval -8.4 to -1.2

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Biomeasure of carbohydrate intake Change, 10 weeks: midpoint of test phase - start of trial Change, 20 weeks: end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=51 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
1,5-Anhydroglucitol Start of Trial	16.7 ug/mL Interval 16.2 to 17.2	17.2 ug/mL Interval 16.7 to 17.7	17.1 ug/mL Interval 16.7 to 17.6
1,5-Anhydroglucitol Change, 10 weeks	-2.5 ug/mL Interval -3.0 to -2.0	-1.2 ug/mL Interval -1.7 to -0.7	0.1 ug/mL Interval -0.4 to 0.6
1,5-Anhydroglucitol Change, 20 weeks	-3.5 ug/mL Interval -4.2 to -2.8	-1.8 ug/mL Interval -2.6 to -1.1	0.6 ug/mL Interval -0.2 to 1.3

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Change, 10 weeks: midpoint of test phase - start of trial. Change, 20 weeks: end of test phase - start of trial.

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=51 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Glycemic Control, Assessed by HgA1c Start of Trial	5.56 % hemoglobin with glucose bound Interval 5.52 to 5.6	5.58 % hemoglobin with glucose bound Interval 5.54 to 5.62	5.61 % hemoglobin with glucose bound Interval 5.57 to 5.65
Glycemic Control, Assessed by HgA1c Change, 10 weeks	0.01 % hemoglobin with glucose bound Interval -0.02 to 0.04	0.03 % hemoglobin with glucose bound Interval 0.0 to 0.06	-0.01 % hemoglobin with glucose bound Interval -0.05 to 0.02
Glycemic Control, Assessed by HgA1c Change, 20 weeks	-0.01 % hemoglobin with glucose bound Interval -0.04 to 0.03	0.00 % hemoglobin with glucose bound Interval -0.03 to 0.04	-0.05 % hemoglobin with glucose bound Interval -0.08 to -0.01

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Triglyceride levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units Change, 10 weeks: midpoint of test phase - start of trial Change, 20 weeks: end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=51 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Triglycerides Start of Trial	77.3 md/dL Interval 71.1 to 84.0	76.5 md/dL Interval 70.2 to 83.3	80.5 md/dL Interval 74.2 to 87.4
Triglycerides Change, 10 weeks	-12.1 md/dL Interval -18.5 to -5.1	8.4 md/dL Interval 0.0 to 17.5	10.9 md/dL Interval 2.3 to 20.2
Triglycerides Change, 20 weeks	-12.8 md/dL Interval -19.8 to -5.2	-0.1 md/dL Interval -8.5 to 9.1	7.5 md/dL Interval -1.7 to 17.6

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Intention-to-treat analysis

Body fat, presented as a % of total mass Participants each had a special scan (x-ray) to measure their amount of body fat. The special x-ray is called "dual-energy x-ray absorptiometry" (DXA). They were asked to lie still on a table for x-ray pictures. Change: end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=52 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Body Composition (DXA) Start of Trial	36.2 % of total body mass Interval 34.6 to 37.9	37.3 % of total body mass Interval 35.1 to 39.5	37.8 % of total body mass Interval 36.2 to 39.4
Body Composition (DXA) Change	-0.3 % of total body mass Interval -0.7 to 0.2	-0.3 % of total body mass Interval -0.7 to 0.1	-0.5 % of total body mass Interval -1.0 to -0.1

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Intention-to-treat analysis

Glucose level, fasting blood draw Change: end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=52 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Glucose Start of Trial	95.1 mg/dL Interval 92.9 to 97.2	94.3 mg/dL Interval 91.9 to 96.8	95.1 mg/dL Interval 92.9 to 97.3
Glucose Change	1.0 mg/dL Interval -0.9 to 2.8	-0.3 mg/dL Interval -2.2 to 1.7	-1.0 mg/dL Interval -3.0 to 0.9

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

Lipoprotein insulin resistance (LPIR) score was calculated from triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P). LPIR score is quantified on a scale of 0-100. Higher scores indicate worse outcome. Change: end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Change in Lipoprotein Particle Subfraction Distribution Start of trial	34.6 score on a scale (0-100) Interval 28.7 to 40.5	31.5 score on a scale (0-100) Interval 26.1 to 36.9	31.4 score on a scale (0-100) Interval 26.9 to 35.9
Change in Lipoprotein Particle Subfraction Distribution Change	-5.3 score on a scale (0-100) Interval -9.2 to -1.5	-0.02 score on a scale (0-100) Interval -4.1 to 4.1	3.6 score on a scale (0-100) Interval -0.6 to 7.7

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

Change: end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Total Cholesterol Change	16.1 mg/dL Interval 11.5 to 20.7	18.5 mg/dL Interval 13.6 to 23.3	16.2 mg/dL Interval 11.2 to 21.1
Total Cholesterol Start of trial	147.5 mg/dL Interval 140.2 to 154.9	145.5 mg/dL Interval 136.1 to 154.8	142.9 mg/dL Interval 135.1 to 150.8

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

High-density lipoprotein cholesterol Change, 10 weeks: midpoint of test phase - start of trial. Change, 20 weeks: end of test phase - start of trial.

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=51 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
HDL-Cholesterol Start of Trial	47.8 md/dL Interval 45.7 to 49.8	49.1 md/dL Interval 47.0 to 51.2	47.6 md/dL Interval 45.5 to 49.6
HDL-Cholesterol Change, 10 weeks	11.1 md/dL Interval 9.4 to 12.8	6.9 md/dL Interval 5.1 to 8.7	4.7 md/dL Interval 2.9 to 6.5
HDL-Cholesterol Change, 20 weeks	13.0 md/dL Interval 11.0 to 15.0	9.7 md/dL Interval 7.6 to 11.8	6.8 md/dL Interval 4.7 to 8.9

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

Calculated by subtracting HDL-cholesterol from total cholesterol. Change: end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Non-HDL-Cholesterol Start of trial	101.5 mg/dL Interval 94.1 to 108.9	99.0 mg/dL Interval 90.6 to 107.5	98.2 mg/dL Interval 91.2 to 105.3
Non-HDL-Cholesterol Change	6.3 mg/dL Interval 1.8 to 10.9	11.0 mg/dL Interval 6.3 to 15.8	9.5 mg/dL Interval 4.6 to 14.4

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

Low-density-lipoprotein cholesterol Change: end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
LDL-Cholesterol Start of trial	80.6 mg/dL Interval 75.1 to 86.1	77.6 mg/dL Interval 70.3 to 84.9	79.5 mg/dL Interval 73.2 to 85.8
LDL-Cholesterol Change	10.0 mg/dL Interval 6.3 to 13.7	11.7 mg/dL Interval 7.8 to 15.7	8.2 mg/dL Interval 4.2 to 12.2

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss)

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

Total and high molecular weight adiponectin Adiponectin levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)). Changes (see Outcome 20) are expressed in percentage units (100%×(exp(change in log)-1)): end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Adiponectin (Start of Trial) Total	4.0 ng/mL Interval 3.0 to 5.9	5.1 ng/mL Interval 3.3 to 7.2	4.9 ng/mL Interval 3.5 to 5.9
Adiponectin (Start of Trial) High Molecular Weight	2.3 ng/mL Interval 1.4 to 3.5	2.8 ng/mL Interval 1.6 to 4.2	2.7 ng/mL Interval 1.9 to 3.6

SECONDARY outcome

Timeframe: Change through 20 weeks' weight loss maintenance

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

Adiponeptin levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Adiponectin (% Change) Total	33.6 % change Interval 24.9 to 42.9	17.4 % change Interval 9.4 to 26.0	23.0 % change Interval 14.5 to 32.3
Adiponectin (% Change) High Molecular Weight	42.9 % change Interval 33.3 to 53.1	27.6 % change Interval 18.6 to 37.2	27.8 % change Interval 18.7 to 37.7

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss)

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

C-reactive protein, marker of inflammation C-reactive protein levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)). Changes (see Outcome 22) are expressed in percentage units (100%×(exp(change in log)-1)): end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
C-reactive Protein (Start of Trial)	1.1 mg/L Interval 0.6 to 2.5	1.5 mg/L Interval 0.7 to 4.6	1.5 mg/L Interval 0.6 to 3.1

SECONDARY outcome

Timeframe: Change through 20 weeks' weight loss maintenance

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

C-reactive protein, marker of inflammation C-reactive protein levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
C-reactive Protein (% Change)	-9.9 % change Interval -24.2 to 7.1	-20.6 % change Interval -33.8 to -4.8	-1.7 % change Interval -18.6 to 18.6

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss)

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

Interleukin-6, marker of inflammation Interleukin-6 levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)). Changes (see Outcome 24) are expressed in percentage units (100%×(exp(change in log)-1)): end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
IL-6 (Start of Trial)	1.4 pg/mL Interval 1.0 to 2.4	1.8 pg/mL Interval 1.1 to 3.3	1.7 pg/mL Interval 1.0 to 2.6

SECONDARY outcome

Timeframe: Change through 20 weeks' weight loss maintenance

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

Interleukin-6, marker of inflammation Interleukin-6 levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
IL-6 (% Change)	-23.6 % change Interval -35.4 to -9.6	-20.1 % change Interval -33.0 to -4.7	-18.3 % change Interval -31.8 to -2.2

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

Systolic and diastolic blood pressure Change: end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Blood Pressure Systolic, Start of trial	117.2 mmHg Interval 114.7 to 119.7	119.2 mmHg Interval 115.9 to 122.5	114.3 mmHg Interval 111.8 to 116.9
Blood Pressure Systolic, Change	-1.5 mmHg Interval -4.4 to 1.5	0.0 mmHg Interval -3.1 to 3.1	1.8 mmHg Interval -1.3 to 5.0
Blood Pressure Diastolic, Start of trial	70.7 mmHg Interval 68.3 to 73.1	73.7 mmHg Interval 71.3 to 76.0	70.5 mmHg Interval 68.3 to 72.7
Blood Pressure Diastolic, Change	2.2 mmHg Interval -0.4 to 4.8	1.4 mmHg Interval -1.3 to 4.1	2.2 mmHg Interval -0.6 to 5.0

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss)

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

Plasminogen activator inhibitor-1 levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)). Changes (see Outcome 27) are expressed in percentage units (100%×(exp(change in log)-1)): end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Plasminogen Activator Inhibitor-1 (Start of Trial)	1.1 ng/mL Interval 0.7 to 2.5	1.5 ng/mL Interval 0.7 to 3.1	1.2 ng/mL Interval 0.6 to 2.1

SECONDARY outcome

Timeframe: Change through 20 weeks' weight loss maintenance

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

Plasminogen activator inhibitor-1 levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Plasminogen Activator Inhibitor-1 (% Change)	7.2 % change Interval -14.7 to 34.8	26.9 % change Interval -0.2 to 61.4	14.9 % change Interval -10.1 to 46.9

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Retention rate was 90%, with 148 of 164 participants completing the study and 147 included in the analysis (after a priori exclusion of one participant who developed hypothyroidism).

Change: end of test phase - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=53 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Fibrinogen Change	-17.0 mg/dL Interval -36.8 to 2.7	-22.4 mg/dL Interval -43.2 to -1.7	-21.7 mg/dL Interval -42.9 to -0.5
Fibrinogen Start of trial	421.1 mg/dL Interval 398.2 to 443.9	461.0 mg/dL Interval 430.7 to 491.4	428.1 mg/dL Interval 400.9 to 455.2

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss)

Population: Descriptive data, reflecting participant flow Pre-weight loss (N=162, minus 1 participant in the Moderate carbohydrate diet group for whom insulin-30 result is missing) Start of trial (N=162) End of test phase (N=148, minus 1 participant in the High carbohydrate diet group for whom insulin-30 result is missing)

Insulin level 30 minutes after consuming 75 grams of glucose

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=52 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Insulin Secretion Determined as Blood Insulin Concentration 30 Minutes After Oral Glucose (Start of Trial) Pre-weight loss	131.4 mIU/L Interval 77.6 to 173.5	116.7 mIU/L Interval 86.8 to 218.5	99.2 mIU/L Interval 73.7 to 153.4
Insulin Secretion Determined as Blood Insulin Concentration 30 Minutes After Oral Glucose (Start of Trial) Start of trial	95.9 mIU/L Interval 55.5 to 131.3	79.9 mIU/L Interval 56.1 to 143.3	68.0 mIU/L Interval 57.0 to 106.6
Insulin Secretion Determined as Blood Insulin Concentration 30 Minutes After Oral Glucose (Start of Trial) End of test phase	96.2 mIU/L Interval 50.5 to 134.0	74.5 mIU/L Interval 51.3 to 135.4	74.8 mIU/L Interval 53.1 to 109.9

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Descriptive data, reflecting participant flow End of test phase (N=148, completers)

thyroid function test

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Thyroxine (T4) Pre-weight loss	85 nmol/L Interval 78.0 to 95.0	86 nmol/L Interval 78.0 to 97.0	90 nmol/L Interval 79.0 to 102.0
Thyroxine (T4) Start of trial	84 nmol/L Interval 75.0 to 96.0	85 nmol/L Interval 80.0 to 93.0	86 nmol/L Interval 78.0 to 96.0
Thyroxine (T4) End of test phase	85 nmol/L Interval 78.0 to 94.0	86 nmol/L Interval 80.0 to 98.0	85 nmol/L Interval 77.0 to 98.0

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Descriptive data, reflecting participant flow End of test phase (N=148, completers)

free thyroxine, thyroid function test

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Free T4 Pre-weight loss	14.3 pmol/L Interval 13.1 to 15.9	15.0 pmol/L Interval 13.9 to 16.4	14.8 pmol/L Interval 13.5 to 16.1
Free T4 Start of trial	14.9 pmol/L Interval 13.6 to 15.9	15.2 pmol/L Interval 15.0 to 16.9	15.0 pmol/L Interval 14.1 to 15.8
Free T4 End of test phase	15.4 pmol/L Interval 14.0 to 16.6	15.7 pmol/L Interval 14.7 to 17.2	15.2 pmol/L Interval 14.0 to 16.1

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Descriptive data, reflecting participant flow End of test phase (N=148, completers)

Produced by the pituitary gland in the brain. Tells the thyroid gland to make thyroid hormones.

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Thyroid Stimulating Hormone Pre-weight loss	2.0 ulU/ml Interval 1.6 to 2.6	1.8 ulU/ml Interval 1.4 to 2.5	2.1 ulU/ml Interval 1.3 to 3.2
Thyroid Stimulating Hormone Start of trial	2.1 ulU/ml Interval 1.5 to 2.9	2.2 ulU/ml Interval 1.5 to 2.7	2.5 ulU/ml Interval 1.7 to 3.0
Thyroid Stimulating Hormone End of test phase	2.0 ulU/ml Interval 1.5 to 2.5	1.7 ulU/ml Interval 1.4 to 2.7	2.1 ulU/ml Interval 1.4 to 3.5

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Descriptive data, reflecting participant flow End of test phase (N=148, completers minus 1 participant in the High carbohydrate diet group for whom reverse T3 result is missing)

thyroid function test, inactive form of triiodothyronine (T3) Lifespan Bio kit was used for analysis. The range of this kit is 250 to 5000 pg/mL, which varies from other commercially available kits (about 10-fold greater values).

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=45 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Reverse T3 Pre-weight loss	1499 pg/mL Interval 1306.0 to 1610.0	1548 pg/mL Interval 1429.0 to 1676.0	1536 pg/mL Interval 1410.0 to 1756.0
Reverse T3 Start of trial	1545 pg/mL Interval 1356.0 to 1687.0	1554 pg/mL Interval 1383.0 to 1768.0	1548 pg/mL Interval 1378.0 to 1733.0
Reverse T3 End of test phase	1557 pg/mL Interval 1375.0 to 1702.0	1572 pg/mL Interval 1404.0 to 1795.0	1546 pg/mL Interval 1332.0 to 1686.0

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Descriptive data, reflecting participant flow End of test phase (N=148, completers)

cortisol (stress hormone) excreted in the urine over a 24-hour period

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Urinary Cortisol Excretion Pre-weight loss	61 μg/d Interval 48.0 to 78.0	59 μg/d Interval 41.0 to 80.0	63 μg/d Interval 45.0 to 91.0
Urinary Cortisol Excretion Start of trial	66 μg/d Interval 48.0 to 83.0	64 μg/d Interval 47.0 to 88.0	63 μg/d Interval 50.0 to 77.0
Urinary Cortisol Excretion End of test phase	78 μg/d Interval 56.0 to 100.0	64 μg/d Interval 50.0 to 94.0	64 μg/d Interval 45.0 to 84.0

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Descriptive data, reflecting participant flow End of test phase (N=148, completers)

catecholamine excreted in the urine over 24 hours, also known as epinephrine

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Urinary Catecholamine - Adrenaline Pre-weight loss	3.1 mcg/day Interval 2.4 to 4.1	3.0 mcg/day Interval 2.2 to 4.2	2.9 mcg/day Interval 2.2 to 3.6
Urinary Catecholamine - Adrenaline Start of trial	3.5 mcg/day Interval 2.7 to 4.7	3.2 mcg/day Interval 2.3 to 4.3	3.0 mcg/day Interval 2.2 to 3.5
Urinary Catecholamine - Adrenaline End of test phase	3.6 mcg/day Interval 2.6 to 5.3	3.4 mcg/day Interval 2.3 to 4.7	3.1 mcg/day Interval 2.3 to 4.1

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Descriptive data, reflecting participant flow End of test phase (N=148, completers)

catecholamine excreted in the urine over 24 hours

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Urinary Catecholamine - Dopamine Pre-weight loss	142.0 mcg/day Interval 105.7 to 187.5	143.2 mcg/day Interval 83.2 to 187.8	117.8 mcg/day Interval 92.7 to 163.6
Urinary Catecholamine - Dopamine Start of trial	112.9 mcg/day Interval 75.1 to 157.6	112.4 mcg/day Interval 85.7 to 135.3	104.7 mcg/day Interval 76.0 to 125.9
Urinary Catecholamine - Dopamine End of test phase	123.0 mcg/day Interval 86.4 to 159.1	112.9 mcg/day Interval 90.5 to 156.6	104.7 mcg/day Interval 83.9 to 141.7

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: Descriptive data, reflecting participant flow End of test phase (N=148, completers)

catecholamine excreted in the urine over 24 hours, also known as norepinephrine

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=48 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=46 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Urinary Catecholamine - Noradrenaline Pre-weight loss	25.8 mcg/day Interval 18.9 to 34.2	23.9 mcg/day Interval 18.9 to 31.6	25.3 mcg/day Interval 19.8 to 31.1
Urinary Catecholamine - Noradrenaline Start of trial	25.2 mcg/day Interval 19.4 to 31.6	25.3 mcg/day Interval 20.1 to 31.7	24.7 mcg/day Interval 17.5 to 30.5
Urinary Catecholamine - Noradrenaline End of test phase	27.4 mcg/day Interval 18.8 to 36.1	26.1 mcg/day Interval 20.6 to 36.9	26.0 mcg/day Interval 19.5 to 32.4

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

California Verbal Learning Test - Second Edition \[CVLT-II\] and Digit Span Test

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Trail Making Test Parts A and B \[TMT-A, TMT-B\]

Outcome measures

Outcome data not reported

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Population: The outcome is "Effect Modification by Insulin Secretion." Thus,participants were divided into tertiles of Insulin-30. Tertile I: Low=17, Moderate=16, High=22 Tertile II: Low=15, Moderate=22, High=17 Tertile III: Low=24, Moderate=14, High=15

Effect modifier: Insulin level 30 minutes into an standard OGTT (Insulin-30) Outcome: Total Energy Expenditure Tertiles: Pre-weight-loss Insulin-30 (Low, Moderate, High) Change: average (midpoint of test phase, end of test phase) - start of trial

Outcome measures

Outcome measures
Measure	Low Carbohydrate Diet n=56 Participants Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	Moderate Carbohydrate Diet n=52 Participants Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum	High Carbohydrate Diet n=54 Participants Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein Feeding study: Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Effect Modification by Insulin Secretion of Metabolic Responses to Diet Start of Trial, Low Insulin-30	2795 kcal/d Interval 2591.0 to 2998.0	2673 kcal/d Interval 2456.0 to 2891.0	2647 kcal/d Interval 2463.0 to 2832.0
Effect Modification by Insulin Secretion of Metabolic Responses to Diet Change, Low Insulin-30	147 kcal/d Interval -1.0 to 295.0	103 kcal/d Interval -44.0 to 250.0	15 kcal/d Interval -119.0 to 148.0
Effect Modification by Insulin Secretion of Metabolic Responses to Diet Start of Trial, Moderate Insulin-30	2816 kcal/d Interval 2597.0 to 3035.0	2563 kcal/d Interval 2377.0 to 2750.0	2782 kcal/d Interval 2571.0 to 2993.0
Effect Modification by Insulin Secretion of Metabolic Responses to Diet Change, Moderate Insulin-30	114 kcal/d Interval -37.0 to 266.0	-5 kcal/d Interval -136.0 to 127.0	-50 kcal/d Interval -200.0 to 101.0
Effect Modification by Insulin Secretion of Metabolic Responses to Diet Start of Trial, High Insulin-30	2643 kcal/d Interval 2461.0 to 2826.0	2281 kcal/d Interval 2053.0 to 2508.0	2544 kcal/d Interval 2331.0 to 2757.0
Effect Modification by Insulin Secretion of Metabolic Responses to Diet Change, High Insulin-30	271 kcal/d Interval 145.0 to 396.0	141 kcal/d Interval -20.0 to 303.0	-37 kcal/d Interval -201.0 to 127.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Start of (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance

Outcome measures

Outcome data not reported

Adverse Events

Run-in Phase

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Low Carbohydrate Diet

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Moderate Carbohydrate Diet

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

High Carbohydrate Diet

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Run-in Phase n=234 participants at risk Pre-randomization: During the run-in phase, energy intake was restricted to promote 12% (within 2%) weight loss over 9-10 weeks.	Low Carbohydrate Diet n=57 participants at risk Feeding study: Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein.	Moderate Carbohydrate Diet n=53 participants at risk Feeding study: Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein.	High Carbohydrate Diet n=54 participants at risk Feeding study: Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein
Surgical and medical procedures Laparoscopic cholecystectomy	0.00% 0/234 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	1.9% 1/54 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Reproductive system and breast disorders Removal of intrauterine device	0.00% 0/234 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	1.9% 1/54 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.

Other adverse events

Additional Information

Cara Ebbeling, PhD, Co-Director, New Balance Foundation Obesity Prevention Center

Boston Children's Hospital

Phone: 617-919-3457

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Run-in Phase n=234 participants at risk Pre-randomization: During the run-in phase, energy intake was restricted to promote 12% (within 2%) weight loss over 9-10 weeks.	Low Carbohydrate Diet n=57 participants at risk Feeding study: Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein.	Moderate Carbohydrate Diet n=53 participants at risk Feeding study: Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein.	High Carbohydrate Diet n=54 participants at risk Feeding study: Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein
Gastrointestinal disorders Constipation	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Immune system disorders Food allergy, aversion or intolerance	1.7% 4/234 • Number of events 4 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	3.5% 2/57 • Number of events 2 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	3.8% 2/53 • Number of events 2 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	1.9% 1/54 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Gastrointestinal disorders Gastroenteritis	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
General disorders Mood changes	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Metabolism and nutrition disorders Increased blood cholesterol	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
General disorders Possible gall bladder disease	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Endocrine disorders Possible hypoglycemia	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
General disorders Hematoma	1.3% 3/234 • Number of events 3 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Nervous system disorders Vasovagal reaction	1.7% 4/234 • Number of events 4 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	1.8% 1/57 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	1.9% 1/53 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
General disorders Vomiting	0.85% 2/234 • Number of events 2 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
General disorders Lightheadedness	0.00% 0/234 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	1.9% 1/53 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
General disorders Migraine	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Musculoskeletal and connective tissue disorders Bone fracture	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	1.9% 1/53 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Vascular disorders High blood pressure	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Musculoskeletal and connective tissue disorders Ankle sprain	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Surgical and medical procedures Tested to rule out meningitis	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Metabolism and nutrition disorders Possible post-viral lactose intolerance	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
General disorders Food intolerance	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
General disorders Hypertension (new prescription medication)	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Renal and urinary disorders Urinary tract infection	0.43% 1/234 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/234 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	3.5% 2/57 • Number of events 2 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/53 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.
Infections and infestations Pericarditis	0.00% 0/234 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/57 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	1.9% 1/53 • Number of events 1 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.	0.00% 0/54 • Adverse event data were collected throughout the run-in diet (~12 weeks) and the test diet (20 weeks) periods of the study, a total of ~32 weeks.