SSPSM: Nutrient Intake (2014)

Citation:

Metz JA, Stern JS, Kris-Etherton P, Reusser ME, Morris CD, Hatton DC, Oparil S, Haynes RB, Resnick LM, Pi-Sunyer FX, Clark S, Chester L, McMahon M, Snyder GW, McCarron DA. A randomized trial of improved weight loss with a prepared meal plan in overweight and obese patients:  impact on cardiovascular risk reduction. Arch Intern Med. 2000; 160: 2,150-2,158.  

PubMed ID: 10904458
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To assess the long-term effects of a prepackaged, nutritionally complete, prepared meal plan compared with a usual-care diet (UCD) on weight loss and cardiovascular risk factors in overweight and obese persons.
Inclusion Criteria:
  • 25 to 70 years
  • BMI of 42 or less
  • One of these diagnostic measures: Hypertension/dyslipidemia or Type 2 diabetes mellitus.
Exclusion Criteria:
  • Insulin treatment
  • Substance abuse
  • Any serious health problems, as noted on history or physical examination that would interfere with study participation
  • For this sub-group analysis of the original study, participants with a baseline BMI of 25 or less were excluded.
Description of Study Protocol:

Recruitment

Adult men and women with hypertension or dyslipidemia or with type 2 diabetes mellitus, who had been advised by their physicians or nurses to follow special diets to manage their conditions, were recruited through outpatient clinics and advertisements.

Design

  • Randomized controlled trial
  • Multicenter
  • Two cohorts (hypertension and dyslipidemia; type 2 diabetes).

Individuals in each cohort were randomized separately to the prepared meal plan or the UCD, stratified by clinic site. Randomization was done by the study coordinating center at Oregon Health Sciences University after documentation that the subject met all the inclusion and exclusion criteria. The randomization scheme was computer-generated, with assignments by a locked computer file at the cooridinating center. Randomization was done following the participant's second clinic visit during the baseline period and assignments were conveyed to the respective clinic sites by telephone and facsimile.

Blinding Used

All measurements were performed by study nurses unaware of the treatment assignment to maintain blinding; only the dietitian at each site was aware of the randomization group.

Intervention

  • Prepared meal plan
  • Usual-care diet plan.

Statistical Analysis

  • Had 80% power, with a two-sided alpha error level of 5% to detect differences between treatment groups of approximately two mmHg in systolic blood pressure, 0.10mmol per L (four mg per dL) in plasma cholesterol level and 0.2% difference in HbA1c level, with at least 80 persons per group
  • All baseline data except weight were averaged during the baseline period when multiple measures were available; baseline weight was recorded at the last visit before the intervention
  • The blood pressure and lipoprotein level were averaged at Weeks 10 and 12, 24 and 26, and 50 and 52, respectively
  • A repeated-measures analysis of variance model was used to analyze differences between baseline and treatment periods for each cohort; this allowed computation of the effect of diet between periods and of the differential effect of the diets
  • An intention-to-treat approach was used
  • For analysis of the proportion of participants meeting dietary complicance criteria and the proportion of participants achieving 5% weight loss, chi-square tests were used to detect independence of categorical factors
  • Additional analyses of quality-of-life data included computation of a responsiveness index for each reported score. This was calculated by dividing the change score between baseline and each week by the mean within-person SD of change between two measures during baseline. A score of 0.3 was a priori selected as a conservative estimate of clinical importance.
Data Collection Summary:

Timing of Measurements

  • A four-week baseline period preceded the 52-week treatment period
  • At zero, 10, 12, 24, 26, 50 and 52 weeks.

Dependent Variables

Primary outcome: Weight change

Secondary outcomes

  • Lipid levels: Total cholesterol by colorimetric enzymatic end-point method; HDL-cholesterol by heparin-manganese method; LDL-cholesterol calculated using the Friedewald algorithm
  • Blood pressure: Standardized across centers by a studywide training session
  • Glycemic control: Insulin by radioimmunoassay; glucose measured by SmithKline Beecham Clinical Laboratories
  • Nutrient intake: Four-day food records at Weeks 12, 26 and 52
    • Analysed using the Nutrition Coordinating Center database of the University of Minnesota, supplemented by the product content of meals provided by the Campbell Soup Company
    • Dietary compliance was calculated based on the percentage of energy from fat, saturated fat and cholesterol to assess achievement of guidelines for American Heart Association Step I and Step II diets.
  • Quality of life: Self-administered questionnaires that measured health- and nutrition-related quality of life
    • Mental Health Inventory and the General Perceived Health, Daily Activities, Work Performance and Satisfaction and Sexual Function scales
    • Nutrition-related measures addressed nutritional health perception, hassles, affect, social function and satisfaction.

Independent Variables

  • Prepared meal plan: Comprised seven breakfast, 13 lunch, 12 dinner and eight snack selections
    • The meals were formulated to provide recommended levels of sodium, total and saturated fat, cholesterol and fiber; and were fortified to meet at least 100% of the recommended dietary allowance for 22 essential vitamins and minerals
    • Prepared meal plan participants ordered their meal choices every two weeks by telephone and the foods were delivered to their homes
    • Pariticpants were instructed to consume one breakfast, lunch and dinner, supplemented with one serving each of fruit, vegetable and low-fat diary products daily. They could also select one item per day from a "bonus list" (in quantities equivalent to approximately 420kJ), including vegetable oils, alcoholic beverages or the energy equivalent in fruits, vegetables or low-fat dairy products. If needed, prepared snacks were used to meet prescribed energy needs.
  • Usual-care diet plan: Prescribed a macronutrient-equivalent diet based on the exchange-list system of the American Dietetic and American Diabetes Associations; the number of servings from each exchange list was determined by the individual's nutrition prescription. These participants could also select one serving daily from the bonus list. To balance provision of the foods to the Prepared Meal Plan Group, persons consuming the UCD recieved monetary compensation in the clinic at Weeks Zero, 12, 26 and 52.
  • Adherence to the prepared meal plan was monitored by reports at clinic visits and by the patterns of ordering the prepared meals. Program adherence was defined as follows and pertains to food ordering patterns between the Week 12 and the Week 52 visits
    • Full program adherence, 21 meals per week
    • Partial adherence, averaged to less than 21 meals per week
    • Off the program, did not oreder any prepared meals.
  • For each participant, a nutrition prescription (energy intake) was calculated during baseline using the Harris-Benedict equation and an activity factor to estimate individual energy needs. All participants were prescribed hypoenergetic nutrition prescriptions with weight loss not to exceed 90kg per week for the intervention. The prescriptions targeted an 835.8-J range, the lowest being 5,040.0 to 5,875.8kJ per day. Participants received their nutrition prescriptions and instructions for their use at Week Zero, along with their randomization assignment.
Description of Actual Data Sample:

Initial N

  • 330 were randomized into the study
  • 302 met the criterion for overweight or obesity and were included in this study.

Attrition (Final N)

  • Prepared Meal Plan: 120
  • Usual-Care Plan: 130
  • Intent-to-treat analysis was used.

Age and Sex

  • Participants with hypertension or dyslipidemia
    • Prepared meal plan (N=93): 54.5±9.0; 43 male, 50 female
    • Usual care diet (N=90): 54.4±9.5; 40 male, 50 female.
  • Participants with type 2 diabetes
    • Prepared meal plan (N=56): 54.6±9.0; 25 male, 31 female
    • Usual care diet (N=63): 54.0±9.9; 25 male, 38 female.

Ethnicity

  • Participants with hypertension or dyslipidemia
    • Prepared-meal plan (N=93): White, 86; African-American, five; Other, two
    • Usual-care diet (N=90): White, 77; African-American, seven; Other, six.
  • Participants with type 2 diabetes
    • Prepared-meal plan (N=56): White, 47; African-American, four; Other, five
    • Usual-care diet (N=63): White, 48; African-American, nine, Other, six.

Other Relevant Demographics
None given.

Anthropometrics

  • Participants with hypertension or dyslipidemia
  • Prepared meal plan
    • BMI: 33.0±4.9
    • Overweight: 30 (32%)
    • Obese: 63 (68%).
  • Usual-care diet
    • BMI: 32.0±4.2
    • Overweight: 32 (36%)
    • Obese: 58 (64%).
  • Participants with type 2 diabetes
  • Prepared meal plan
    • BMI: 33.0±4.4
    • Overweight: 17 (30%)
    • Obese: 39 (70%).
  • Usual-care diet
    • BMI: 34.5±4.5
    • Overweight: 12 (19%)
    • Obese: 51 (81%).
  • Overweight was defined as a BMI between 25.0 and 29.9. Obesity was defined as a BMI of 30 or greater.

Location

Five university-based medical centers: Oregon Health Sciences University, Portland; Pennsylvania State University, University Park; St Luke's Roosevelt Hospital, New York, NY; University of Alabama at Birmingham; and University of California at Davis.

Summary of Results:

Table Two: Diet Effects on Outcome Measures

[Reviewers note: Because of space and ease of reading, only significant results are shown. The first table is for the Prepared Meal Plan Group; the second table is for the Usual-Care Diet Group.]

Prepared meal plan

Outcome Measure

Baseline

12-Week Change

26-Week Change

52-Week Change

Participants with Hypertension/Dyslipidemia

N=93 N=90

N=86

N=79
SBP, mmHg* 145.0±10 12.2±10.6 -12.9±10.2 -11.9±11.7
Cholesterol, mmol/L (mg/dL)* 6.03±0.74 (233.0±28.0) -0.48±0.67 (-18.5±25.9) -0.10±0.70 (-4.0±27.1) -0.16±0.77 (-6.3±29.9)
HDL cholesterol, mmol/L (mg/dL)* 1.22±0.38 (47.0±14.5) -0.06±0.15 (-2.2±5.8) 0.04±0.15 (1.7±6.0) 0.06±0.17 (2.1±6.5)

Glucose, mmol/L (mg/dL)*

5.1±0.9 (92.8±16.6)

-0.2±0.8 (-2.9±13.6)

-0.1±1.0 (-2.6±17.9) 

-0.2±0.9 (-4.3±15.4)
HbA1c, %** 5.65±0.42 -0.01±0.30 0.05±0.33 0.05±0.33
 

Participants with Type 2 Diabetes Mellitus

N=56

N=54 

N=43 

N=41
Cholesterol, mmol/L (mg/dL)* 5.38±1.0 (208.8±39.0) -0.28±0.62 (-10.7±23.9) 0.39±0.40 (3.2±30.0) 0.16±0.76 (6.2±29.2)
Glucose, mmol/L (mg/dL)* 10.5±2.8 (189.0±49.7) -2.1±2.6 (-38.7±47.0) -1.7±3.0 (-30.9±54.7) -0.6±3.3 (-11.2±59.8)
HbA1c, %* 8.76±1.43 -1.04±1.03 -0.87±1.29 -0.24±1.52

Usual-Care Diet

Outcome Measure

Baseline

12-Week Change

26-Week Change

52-Week Change

Participants with Hypertension/Dyslipidemia

N=90 N=85

N=82

N=79
SBP, mmHg* 145.0±10.8 -9.2±9.6 -9.0±11.0 -10.5±13.2
Cholesterol, mmol/L (mg/dL)* 6.05±0.75 (234.0±29.0) -0.21±0.56 (-7.9±21.7) -0.19±0.69 (-7.2±26.8) -0.22±0.66 (-8.5±25.6)
HDL cholesterol, mmol/L (mg/dL)* 1.17±0.30 (45.3±11.6) -0.05±0.12 (-1.8±4.5) 0.01±0.10 (0.5±3.8) 0.00±0.13 (0.1±5.0)

Glucose, mmol/L (mg/dL)*

5.1±1.0 (92.2±17.9) 

0.1±0.8 (1.8±14.3)

0.2±0.9 (2.8±16.9)

0.0±0.9 (0.8±16.1)
HbA1c, %** 5.63±0.46 0.03±0.31 0.13±0.31 0.16±0.31
 

Participants with Type 2 Diabetes Mellitus

 N=56

N=54 

N=43 

N=41
Cholesterol, mmol/L (mg/dL)* 5.28±0.87 (204.4±34.0) -0.06±0.46 (-2.3±17.9) 0.70±0.53 (0.9±26.1) 0.03±1.08 (1.0±41.7)
Glucose, mmol/L (mg/dL)* 11.1±2.6 (199.4±47.2) -0.6±2.3 (-10.7±42.0) -0.5±2.7 (-8.2±49.5) -0.6±3.4 (-10.9±61.6)
HbA1c, %* 8.82±1.24 -0.31±1.07 -0.22±1.30 -0.20±1.30

Data are given as mean ±SD. SBP indicates systolic blood pressure.
*P<0.05 for the difference between diets over time.

Table Three: Changes in Reported Macronutrient Intake
[Reviewers' note: In interest of space, energy is reported only in kcal per day.]

Participants with hypertension or dyslipidemia

Macronutrient Intake

Baseline

Week 52

Change

Energy (kcal/d) Prepared meal plan N=98 N=72 N=72
2,154±677 1,602±456 -550±681
Usual-care diet N=90 N=78 N=78
2,214±619 1,793±551 -460±504
Energy from Protein, % Prepared meal plan 16.5±3.4 18.4±3.0 1.7±3.9
Usual-care diet 15.8±3.3 17.3±3.2 1.7±3.7
Energy from Carbohydrate, %* Prepared meal plan

50.6±8.3

58.4±7.5 8.0±8.3
Usual-care diet 51.5±8.1 52.9±8.9 1.1±7.7
Energy from Fat, %* Prepared meal plan 32.7±7.1 23.3±6.5 -9.6±8.1
Usual-care diet 32.6±6.9 29.9±7.4 -2.7±6.9
Energy from Saturated Fat, %* Prepared meal plan 11.0±2.8 7.9±2.6 -3.2±3.0
Usual-care diet 10.8±3.2 9.9±3.3 -0.9±2.8
Cholesterol, mg* Prepared meal plan 285±148 150±94 -135±147
Usual-care diet 271±123 235±154 -36±154

Participants with Type 2 Diabetes Mellitus

Macronutrient Intake

Baseline

Week 52

Change

Energy (kcal/d) Prepared meal plan N=56 N=39 N=39
2,132±722 1,533±484 -521±563
Usual-care diet N=63 N=47 N=47
2,198±618 1,863±1019 -327±863
Energy from Protein, % Prepared meal plan 17.5±4.0 19.3±3.4 1.3±3.4
Usual-care diet 17.0±3.5 18.4±4.3 1.2±3.7
Energy from Carbohydrate, %* Prepared meal plan

48.5±8.2

54.0±9.1 5.9±10.2
Usual-care diet 47.9±7.1 49.8±9.7 1.6±10.0
Energy from Fat, %* Prepared meal plan 35.2±7.2 27.6±8.6 -7.4±9.0
Usual-care diet 35.4±6.5 32.3±8.5 -2.8±8.3
Energy from Saturated Fat, %* Prepared meal plan 11.8±2.9 9.0±2.8 -2.6±3.5
Usual-care diet 11.4±2.6 10.6±3.6 -0.6±3.5
Cholesterol, mg* Prepared meal plan 306±155 181±124 -114±179
Usual-care diet 318±120 269±120 -30±231

*P<0.001 for the difference in the nutrient change over time between diets.

Other Findings

The ordering patterns of participants with hypertension or dyslipidemia and of those with type 2 diabetes mellitus were as follows at Week 26: Full program, 49% and 53%; partial program, 45% and 44%; off the program, 6% and 2%, respectively. At Week 52, these respective proportions were as follows: Full program, 33% and 39%; partial program, 56% and 38%; off the program, 11% and 29%.

Diet-related adverse effects in the prepared meal plan vs. the UCD Group were reported by 10% vs. 1% of participants with hypertension or dyslipidemia (P<0.05) and 6% vs. 2% of participants with type 2 diabetes mellitus. Three symptoms accounted for these differences: Flatulence, 2% vs 0% for hypertension or dyslipidemia and 3% vs. 0% for diabetes; abdominal pain, 3% vs. 0% for hypertension or dyslipidemia and none for type 2 diabetes mellitus; diarrhea, 3% vs. 0% for hypertension or dyslipidemia and none for type 2 diabetes mellitus. With few exceptions, symptoms were reported at only one visit, were self-limiting and thus did not affect program adherence.

Hypertension or Dyslipidemia Group

  • Weight loss for prepared meal plan was greater than the UCD during the 52-week study period (P<0.001)
  • Prepared meal plan weight loss: At 12 weeks, 6.9±4.0kg; 26 weeks, 7.8±6.3kg; 52 weeks, 5.8±6.8kg; participants maintained 74% of their Week 26 weight loss by the end of the study
  • Usual Care Diet Group weight loss: At 12 weeks, 2.3±3.6kg; 26 weeks, 2.4±5.4kg; 52 weeks, 1.7±6.5kg; participants maintained 71% of their Week 26 weight loss
  • Weight loss of at least 5% was achieved by 45 (57%) of 79 prepared meal plan participants, compared with 15 (19%) of 79 UCD participants (P<0.001)
  • Throughout the intervention period, the Prepared Meal Plan Group reported greater compliance with American Heart Association Step I and Step II dietary recommendations, compared with the UCD Group (P<0.001). At baseline, 29% of both dietary groups reported compliance with Step I recommendations; 5% of the Prepared Meal Plan Group and 12% of the UCD Group met Step II guidelines. Compliance with Step I recommendations across the weeks of study was achieved by the following proportions of the Prepared Meal Plan Group, compared with the UCD Group: 92% vs. 14% at Week 12, 75% vs. 37% at Week 26 and 74% vs. 37% at Week 52. The proportions compliant with Step II guidelines were as follows: 72% vs. 19% at Week 12, 56% vs. 19% at Week 26 and 43% vs. 17% at Week 52.
  • During the intervention period, participants in the Prepared Meal Plan Group reported significantly greater improvements in quality of life compared with UCD participants on the following scales: Mental Health Inventory (P<0.01), General Health Perceptions (P<0.001), Daily Activities (P<0.001), Work Performance (P<0.02), Nutritional Hassles (P<0.001), Nutritional Health Perceptions (P<0.001), Nutrition and Social Function (P<0.045), Nutrition and Affect (P<0.001) and Satisfaction with Diet (P<0.001).

Type 2 Diabetes Mellitus Group

  • Weight loss greater with the Prepared Meal Plan Group than with UCD (P<0.001)
  • Prepared Meal Plan Group weight loss: At 12 weeks, 4.7±4.0kg; 26 weks, 5.5±6.4kg; 52 weeks, 3.0±5.4kg; participants maintained 55% of their Week 26 weight loss by the end of the study
  • UCD Group weight loss: At 12 weeks, 1.3±2.5kg; 26 weeks, 1.5±3.2kg; 52 weeks, 1.0±3.8kg; participants maintained 67% of their Week 26 weight loss
  • Weight loss of at least 5% was achieved by 12 (29%) of 41 prepared meal plan participants, compared with five (10%) of 51 UCD participants (P<0.03)
  • At Weeks 12 and 26, the Prepared Meal Plan Group was more compliant with American Heart Association Step I and Step II dietary recommendations, compared with the UCD Group (P<0.001). At baseline, 16% of the Prepared Meal Plan Group and 11% of the UCD Group were compliant with Step I recommendations; 4% of the Prepared Meal Plan Group and 5% of the UCD group met Step II guidelines. Compliance with Step I recommendations across the weeks of the study was achieved by the following proportions of the Prepared Meal Plan Group, compared with the UCD Group: 87% vs. 31% at Week 12, 68% vs. 33% at Week 26 and 56% vs. 36% at Week 52. The proportions compliant with Step II guidelines were as follows: 64% vs. 12% at Week 12, 39% vs. 11% at Week 26 and 31% vs. 15% at Week 52.
  • During the intervention period, participants in the Prepared Meal Plan Group reported significantly greater improvements in quality of life, compared with UCD participants on the following scales: Mental Health Inventory (P<0.04), Daily Activities (P<0.03), Nutritional Hassles (P<0.01), Nutritional Health Perceptions (P<0.0001), Nutrition and Affect (P<0.01) and Satisfaction with Diet (P<0.001).
Author Conclusion:
  • The enhanced quality of life reported with the prepared meal plan may be essential to the success of this program
  • The prepared meal plan promoted and sustained long-term weight loss and reduced cardiovascular risk. The simplicity, variety, portion control and nutrient composition necessary to enhance and maintain long-term dietary compliance while concomitantly improving quality of life were critical to achieving these outcomes.
Funding Source:
Industry:
Campbells Soup Company
Food Company:
Reviewer Comments:
  • The only source of funding listed is from the Campbell's Center for Nutrition & Wellness, Campbell Soup Company; thus an apparent conflict of interest cannot be completely ruled out
  • However, in this reviewer's opinion, this was a well-designed and conducted study that does not appear to be affected by the source of funding.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? ???
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? ???