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Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

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Appendix E

Key Questions and Eligibility Criteria

Key Question: What is the association between body mass index (BMI) and chronic disease, including all-cause mortality?

Population	Human only General population (not existing disease state)
Interventions/exposures and comparators	Body weight category (by BMI, Z-score): overweight, obese, underweight, normal weight
Study designs (of primary studies included within the systematic reviews)	Include: Longitudinal studies Exclude: Cross-sectional studies Systematic reviews must include a meta-analysis
Timing	No minimum “treatment” or exposure duration required No minimum follow-up duration (to when outcome is measured)
Setting	Restrict to high- and upper middle-income countries Restrict to systematic reviews published 2017 or later

Page 256 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

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Outcomes

Incident cardiovascular disease/coronary heart disease
Incident type 2 diabetes
Incident cancer
Incident hypertension
Incident hip fracture
All-cause mortality
Pregnancy-related
Maternal mortality
Preeclampsia
Infant mortality
Premature delivery
Pediatric
Growth

Key Question: What is the effect of BMI (and other measures of adiposity) on energy balance or energy expenditure?

Population	Human only Allow focus on health conditions: obesity, type 2 diabetes Exclude focus on other health conditions Allow focus on other population groups: High physical activity Diet type Subgroups of interest Age/life stage Sex Race/ethnicity
Interventions/exposures and comparators	Body weight category (by BMI, Z-score): overweight, obese, underweight, normal weight Other measures of adiposity Exclude any cointerventions/coexposures (e.g., low fat + vitamin B₁₂ vs. high fat; physical activity)
Study designs (of primary studies included within the systematic reviews)	Include: Randomized crossover trials Randomized clinical trials (parallel) Nonrandomized comparative studies, multivariable adjusted Association analyses (e.g., regression models, predictors, risk factors), multivariable adjusted Exclude: Nonrandomized comparative studies, unadjusted Single group (noncomparative between interventions/exposures) Association analyses (e.g., models, predictors, risk factors), univariate, unadjusted Other study designs
Timing	No minimum “treatment” or exposure duration required No minimum follow-up duration (to when outcome is measured)

Page 257 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

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Setting

Restrict to high- and upper middle-income countries
Restrict to studies published 2000 or later

Outcomes

Energy balance/imbalance/excess/deficit
- Energy intake
- Energy expenditure (TEE, REE, BMR, BEE, RMR)
- Body weight
- BMI
Energy utilization
- Fat/carbohydrate/protein oxidation
- Body fat
- Body weight
Energy metabolism/metabolic efficiency/metabolic flexibility
Obesity risk
- Body weight
- BMI
- Body fat %
- Waist circumference
- Visceral fat
Type 2 diabetes mellitus risk
- Body weight
- BMI
- Body fat %
- Waist circumference
- Visceral fat
- Glucose
- Insulin
- HOMA-IR
Cardiovascular Disease risk

NOTE: BEE = basal energy expenditure; BMI = body mass index; BMR = basal metabolic rate; HOMA-IR = Homeostatic Model Assessment of Insulin Resistance; REE = resting energy expenditure; RMR = resting metabolic rate.

Key Question: What is the association of body composition with metabolic efficiency (energy usage/expenditure)?

Page 258 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

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Population	Human only Exclude focus on other health conditions (e.g., malnourished population) Allow focus on other population groups: High physical activity Diet (e.g., vegetarian, vegan) Others (determined on a case-by-case basis) Subgroups of interest Age/life stage Sex Race/ethnicity Study must provide separate results data by sex (or be specific to one sex)
Interventions/exposures and comparators	Exposure: fat mass vs. fat-free mass measured within the same individual Within the exposure of interest, consider studies using DLW, DXA, and/or underwater weighing to estimate FM and FFM Allow any cointerventions/coexposures (e.g., low fat + vitamin B₁₂ vs. high fat; physical activity)
Study designs (of primary studies included within the systematic reviews)	Include: Randomized crossover trials (including N-of-1) Randomized clinical trials (parallel) Single group (noncomparative between interventions/exposures) Nonrandomized comparative studies, multivariable adjusted Exclude: Nonrandomized comparative studies, unadjusted Association analyses (e.g., regression models, predictors, risk factors), multivariable adjusted Association analyses (e.g., models, predictors, risk factors), univariate, unadjusted Other study designs
Timing	No minimum “treatment” or exposure duration required No minimum follow-up duration (to when outcome is measured)
Setting	Restrict to high- and upper middle-income countries Restrict to studies published 2000 or later
Outcomes	Usage/expenditure must be measured (e.g., DLW, direct and indirect calorimetry) 24-hour energy expenditure Resting or basal metabolic rate Energy cost of physical activity Thermic effect of food Metabolic adaptation (mitochondria dynamics)

NOTE: DLW = doubly labeled water; DXA = dual-energy X-ray absorptiometry; FFM = fat-free mass; FM = fat mass.

Page 259 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

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Key Question: How does the increase in tissue deposition associated with growth during infancy, childhood, adolescence, pregnancy, and lactation influence, affect, or contribute to energy requirements?

Population	Human only Do not allow focus on health conditions or other population groups Study must provide separate results data by sex (or be specific to one sex) Study must provide separate results data by age group (or be specific to one age group or life stage) Subgroups of interest Age/life stage Sex
Interventions/exposures and comparators	The life stage of infancy, childhood, adolescence, pregnancy, and lactation
Study designs	Include: Randomized clinical trials Nonrandomized comparative studies, unadjusted Single group (noncomparative between interventions/exposures) Nonrandomized comparative studies, multivariable adjusted Longitudinal studies Systematic reviews Exclude: Association analyses (e.g., regression models, predictors, risk factors), multivariable adjusted Association analyses (e.g., models, predictors, risk factors), univariate, unadjusted
Timing	No minimum “treatment” or exposure duration required No minimum follow-up duration (to when outcome is measured)
Setting	Restrict to high- and upper middle-income countries Restrict to studies published 1980 or later

Page 260 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

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Outcomes

Energy usage or energy expenditure
- Measured by DLW, direct or indirect calorimetry
Growth during infancy, childhood, or adolescence
- Measured by weight gain (anthropometry) and composition of gain (body composition techniques), energetic efficiency (encompassed by DLW; also estimated by theoretical biochemical efficiencies)
Pregnancy
- Measured by rate of weight gain per trimester (anthropometry) and composition of gain (body composition techniques); energy efficiency (encompassed by DLW)
Lactation
- Measured by volume of milk production and proximate analysis of milk (fat, protein, carbohydrate) or energy content of milk (bomb calorimetry); energy efficiency (encompassed by DLW)

NOTE: DLW = doubly labeled water

Key Question: What is the impact of race or ethnicity on energ expenditure?

Population	Human only Subgroups of interest Age/life stage Sex
Interventions/exposures and comparators	Race or ethnic group
Study designs (of primary studies included within the systematic reviews and primary studies)	Randomized clinical trials Nonrandomized comparative studies, unadjusted Single group (noncomparative between interventions/exposures) Nonrandomized comparative studies, multivariable adjusted Association analyses (e.g., regression models, predictors, risk factors), multivariable adjusted Association analyses (e.g., models, predictors, risk factors), univariate, unadjusted Other study designs
Timing	No minimum “treatment” or exposure duration required No minimum follow-up duration (to when outcome is measured)
Setting	Restrict to high- and upper middle-income countries Restrict to systematic reviews published 2012 or later Restrict to primary studies published 1980 or later

Page 261 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

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Outcomes

BMR
RMR
BEE
REE
Energy metabolism
Energy expenditure
Energy balance
Caloric expenditure

NOTE: BEE = basal energy expenditure; BMR = basal metabolic rate; REE = resting energy expenditure; RMR = resting metabolic rate.

Key Question: What is the association of macronutrient composition of the diet on metabolic efficiency (energy usage/expenditure)?

Population

Human only
Allow focus on health conditions: obesity or type 2 diabetes
- Exclude focus on other health conditions
Allow focus on other population groups:
- High physical activity
- Diet (e.g., vegetarian, vegan)
- Others (determined on a case-by-case basis)
Subgroups of interest
- Age/life stage
- Sex
- Race/ethnicity

Interventions/exposures and comparators

Diets with different macronutrient composition

High fat vs. low protein (holding carbohydrates stable with comparator)
High fat vs. low carbohydrate (holding protein stable with comparator)
Low fat vs. high protein (holding carbohydrates stable with comparator)
Low fat vs. high carbohydrate (holding protein stable with comparator)
High protein vs. low carbohydrate (holding fat stable with comparator)
Low protein vs. high carbohydrate (holding fat stable with comparator)
Within the intervention/exposure of interest, exclude if diets not isocaloric

Page 262 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

×

Study designs (of primary studies included within the systematic reviews)	Include: Randomized crossover trials (including N-of-1) Randomized clinical trials (parallel) Single group (noncomparative between interventions/exposures) Nonrandomized comparative studies, multivariable adjusted Exclude: Nonrandomized comparative studies, unadjusted Association analyses (e.g., regression models, predictors, risk factors), multivariable adjusted Association analyses (e.g., models, predictors, risk factors), univariate, unadjusted Other study designs
Timing	No minimum “treatment” or exposure duration required No minimum follow-up duration (to when outcome is measured)
Setting	Restrict to high- and upper middle-income countries Restrict to studies published 2000 or later
Outcomes	Usage/expenditure must be measured (e.g., DLW, direct and indirect calorimetry) 24-hour energy expenditure Resting or basal metabolic rate Energy cost of physical activity Thermic effect of food Metabolic adaptation (mitochondria dynamics)

NOTE: DLW = doubly labeled water.

Key Question: In the U.S. and Canadian free-living population, what is the degree of systematic bias or random error of energy intake as assessed by diet records, 24-hour recalls, food frequency questionnaires, compared to doubly labeled water? Does the bias differ by age group, sex, body weight status, body mass index (BMI), social economic status, race, ethnicity, presence of chronic disease, or physical activity level?

Population

Human only
Allow focus on health conditions: obesity, type 2 diabetes
Allow focus on other population groups:
- High physical activity
- Diet (e.g., vegetarian, vegan)
Subgroups of interest
- Age/life stage
- Sex
- Race/ethnicity
Study must provide separate results data by age group (or be specific to one age group/life stage).

Page 263 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

×

Interventions/exposures and comparators	Participation in a doubly labeled water study measuring usual dietary intake
Study designs (of primary studies included within the systematic reviews)	Randomized clinical trials Nonrandomized comparative studies, unadjusted Single group (noncomparative between interventions/exposures) Nonrandomized comparative studies, multivariable adjusted Association analyses (e.g., regression models, predictors, risk factors), multivariable adjusted Association analyses (e.g., models, predictors, risk factors), univariate, unadjusted Other study designs
Timing	No minimum “treatment” or exposure duration required No minimum follow-up duration (to when outcome is measured)
Setting	Restrict to high-income countries Restrict to systematic reviews published 2012 or later
Outcomes	Percent of misreporting of energy intakes

Key Question: How do physical activity and energy expenditure change across the life span?

Population

Human only
Allow focus on health conditions: obesity, type 2 diabetes
- Exclude focus on other health conditions
Allow focus on other population groups:
- High physical activity
- Diet (e.g., vegetarian, vegan)
Subgroups of interest
- Age/life stage
- Sex
- Race/ethnicity

Interventions/exposures and comparators

Different age or age categories

Study designs (of primary studies included within the systematic reviews)

Include:

Randomized clinical trials
Nonrandomized comparative studies, multivariable adjusted
Association analyses (e.g., regression models, predictors, risk factors), multivariable adjusted

Exclude:

Nonrandomized comparative studies, unadjusted
Single group (noncomparative between interventions/exposures)
Association analyses (e.g., models, predictors, risk factors), univariate, unadjusted

Page 264 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

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Timing	No minimum “treatment” or exposure duration required No minimum follow-up duration (to when outcome is measured)
Setting	Restrict to high- and upper middle-income countries Restricted to studies published 2000 or later
Outcomes	Physical activity Kcals METs Physical activity intensity (light, moderate, vigorous) Sedentary behaviors Steps Total activity counts Volume Activity type Behavior Energy expenditure Total energy expenditure Net energy expenditure Activity energy expenditure Energy cost of physical activity Type of measurement Doubly labeled water Accelerometer Wearable sensors Questionnaire Objective Subjective Indirect calorimetry Room calorimeter Free living Obesity risk Body weight BMI Body fat % Waist circumference Visceral fat

NOTE: BMI = body mass index; kcals = kilocalories; METs = metabolic equivalent of task.

Page 265 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

×

Key Question: What is the relationship between different measurements of physical activity and energy expenditure?

Population	Human only Allow focus on health conditions: obesity, type 2 diabetes Exclude focus on other health conditions Allow focus on other population groups: High physical activity Diet (e.g., vegetarian, vegan) Subgroups of interest Age/life stage Sex Race/ethnicity
Interventions/exposures and comparators	Physical activity measurement method
Study designs (of primary studies included within the systematic reviews)	Include: Randomized clinical trials Nonrandomized comparative studies, multivariable adjusted Association analyses (e.g., regression models, predictors, risk factors), multivariable adjusted Exclude: Nonrandomized comparative studies, unadjusted Single group (noncomparative between interventions/exposures) Association analyses (e.g., models, predictors, risk factors), univariate, unadjusted
Timing	No minimum “treatment” or exposure duration required No minimum follow-up duration (to when outcome is measured)
Setting	Restrict to high- and upper middle-income countries Restrict to studies published 2000 or later
Outcomes	Physical activity Kcals METs Physical activity intensity (light, moderate, vigorous) Sedentary behaviors Steps Total activity counts Volume Activity type Behavior

Page 266 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

×

Energy expenditure
- Total energy expenditure
- Net energy expenditure
- Activity energy expenditure
- Energy cost of physical activity
Type of measurement
- Doubly labeled water
- Accelerometer
- Wearable sensors
- Questionnaire
- Objective
- Subjective
- Indirect calorimetry
- Room calorimeter
- Free living
Obesity risk
- Body weight
- BMI
- Body fat %
- Waist circumference
- Visceral fat

NOTE: BMI = body mass index; kcals = kilocalories; METs = metabolic equivalent of task.

Key Question: What is the association between weight change an chronic disease outcomes?

Population	Human only General population (not existing disease state) Adults, including postpartum women (lactating or not) as a subpopulation of interest Children
Interventions/exposures and comparators	Body weight change (weight cycling, weight gain, weight loss, postpartum weight gain/retention). May include weight maintenance or slowed weight gain Weight must be measured (not self-reported) Exclude studies focused on unintentional weight loss and studies of bariatric surgery outcomes
Study designs (of primary studies included within the systematic reviews)	Include: Longitudinal studies (adults) Cohort studies (adults) Randomized clinical trials of weight loss interventions Exclude: Cross-sectional studies
Timing	Cohort studies: at least 12 months of follow-up Randomized clinical trials: at least 3 months of intervention
Setting	Restrict to high- and upper middle-income countries Restrict to systematic reviews published 2017 or later

Page 267 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

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Outcomes

Incident cardiovascular disease/coronary heart disease
Incident type 2 diabetes
All-cause mortality
Incident hypertension
Incident cancer (adults)
Incident hip fracture (adults)
Dementia (adults)
cardiovascular disease risk factors (children)
Metabolic syndrome or prediabetes (children)

Key Question: What is the effect or association of weight cycling on metabolic efficiency (energy usage/expenditure) and health outcomes?

Population	Human only Allow focus on health conditions: obesity, type 2 diabetes Exclude focus on other health conditions Allow focus on other population groups: High physical activity Diet type Subgroups of interest Age/life stage Sex Race/ethnicity
Interventions/exposures and comparators	Weight cycling Exclude any cointerventions/coexposures (e.g., low fat + vitamin B₁₂ vs. high fat; physical activity)
Study designs (of primary studies included within the systematic reviews)	Include: Randomized crossover trials (including N-of-1) Randomized controlled trials (parallel) Nonrandomized comparative studies, multivariable adjusted Association analyses (e.g., regression models, predictors, risk factors), multivariable adjusted Exclude: Nonrandomized comparative studies, unadjusted Single group (noncomparative between interventions/exposures) Association analyses (e.g., models, predictors, risk factors), univariate, unadjusted Other study designs
Timing	No minimum “treatment” or exposure duration required No minimum follow-up duration (to when outcome is measured)
Setting	Restrict to high- and upper middle-income countries Restrict to studies published 2000 or later

Page 268 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

×

Outcomes

Energy balance/imbalance/excess/deficit
- Energy intake
- Energy expenditure (TEE, REE, BMR, BEE, RMR)
- Body weight
- BMI
Energy utilization
- Fat/carbohydrate/protein oxidation
- Body fat
- Body weight
Body composition
- Lean mass
- Fat mass
- Body fat %
- Body weight
Energy metabolism/metabolic efficiency/metabolic flexibility
Obesity risk
- Body weight
- BMI
- Body fat %
- Waist circumference
- Visceral fat
Type 2 diabetes mellitus risk
- Body weight
- BMI
- Body fat %
- Waist circumference
- Visceral fat
- Glucose
- Insulin
- HOMA-IR

NOTE: BEE = basal energy expenditure; BMI = body mass index; BMR = basal metabolic rate; HOMA-IR = Homeostatic Model Assessment of Insulin Resistance; REE = resting energy expenditure; RMR = resting metabolic rate.

Page 269 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

×

Key Questions:

What level of calorie intake is needed to produce weight gain in individuals with underweight? What amount of calorie intake (deficit) is necessary to produce weight loss in individuals with overweight or obesity? What level of calorie intake is needed to maintain weight across the weight spectrum?

Population	Human only Allow focus on health conditions: obesity, type 2 diabetes Allow focus on other population groups: High physical activity Diet (e.g., vegan, vegetarian) Subgroups of interest Age/life stage Sex Race/ethnicity
Interventions/exposures and comparators	Measure of caloric intake Exclude any cointerventions/coexposures (e.g., low fat + vitamin B₁₂ vs. high fat; physical activity)
Study designs (of primary studies included within the systematic reviews)	Include: Randomized crossover trials Randomized clinical trials Nonrandomized comparative studies, multivariable adjusted Association analyses (e.g., regression models, predictors, risk factors), multivariable adjusted Exclude: Nonrandomized comparative studies, unadjusted Single group (noncomparative between interventions/exposures) Association analyses (e.g., models, predictors, risk factors), univariate, unadjusted Other study designs
Timing	No minimum “treatment” or exposure duration required No minimum follow-up duration (to when outcome is measured)
Setting	Restrict to high- and upper middle-income countries Restrict to studies published 2000 or later

Page 270 Cite

Suggested Citation:"Appendix E: Key Questions and Eligibility Criteria." National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference Intakes for Energy. Washington, DC: The National Academies Press. doi: 10.17226/26818.

×

Outcomes

Energy balance/imbalance/excess/deficit
- Energy intake
- Energy expenditure (TEE, REE, BMR, BEE, RMR)
- Body weight
- BMI
Energy use
- Fat/carbohydrate/protein oxidation
- Body fat
- Body weight
Energy metabolism/metabolic efficiency/metabolic flexibility
Obesity risk
- Body weight
- BMI
- Body fat %
- Waist circumference
- Visceral fat
Type 2 diabetes mellitus risk
- Body weight
- BMI
- Body fat %
- Waist circumference
- Visceral fat
- Glucose
- Insulin
- HOMA-IR

NOTE: BEE = basal energy expenditure; BMI = body mass index; BMR = basal metabolic rate; HOMA-IR = Homeostatic Model Assessment of Insulin Resistance; REE = resting energy expenditure; RMR = resting metabolic rate.