The Personalized Nutrition Study

The Personalized Nutrition Study: Evaluation of a Genetically-informed Weight Loss Approach

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04145466

Acronym

POINTS

Enrollment

145

Registered

2019-10-30

Start date

2020-02-27

Completion date

2023-12-30

Last updated

2025-01-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Weight Loss

Brief summary

A person's genetic code is believed to affect how much weight he/she will lose during diets that vary in carbohydrate and dietary fat content. 'Carbohydrate responders' are hypothesized to lose more weight on diets that are high in carbohydrates, as compared to high in fats. 'Fat responders' are hypothesized to lose more weight on diets that are high in dietary fat, as compared to high in carbohydrates. The purpose of the proposed study is to test these hypotheses in a randomized controlled trial.

Detailed description

Obesity and its comorbidities are major public health challenges. To combat the obesity pandemic, many weight-loss strategies have been studied, often emphasizing either high carbohydrate (low fat) diets or high fat (low carbohydrate) diets. Mean weight loss differences between high-carbohydrate and high-fat diets that induce equal caloric deficits have been reported to be small; however, the individual weight loss response varies substantially within diet groups, suggesting that different individuals react differently to high-carbohydrate or high-fat diets. This assumption is supported by retrospective data showing that participants with carbohydrate-responsive polymorphisms lost 2-3 times more weight when assigned to a high-carbohydrate diet compared to a high-fat diet, and vice versa for those with dietary fat-responsive polymorphisms. Conversely, a recent randomized clinical trial aimed to determine the effect of a healthy high-fat diet (high in unsaturated fats) vs. a healthy high-carbohydrate diet (high in whole-grain foods) on 12-month weight change but did not find significant differences between the two groups and failed to find the hypothesized association between genotype patterns and weight loss induced by diets that varied in fat and carbohydrate content. However, an important caveat of their approach is that the single nucleotide polymorphisms selected by the investigators had not been previously associated with obesity or with dietary responses, which may explain their lack of predictive value in identifying differences in inter-individual responses. In addition, the fat composition of the diets was relatively high in both high- and low-fat groups. The inconsistent findings in the literature indicate a need for further research to determine if genetic factors affect weight loss when exposed to diets that vary in carbohydrates and dietary fats. The purpose of this randomized controlled parallel arm trial is to test the following hypotheses. Hypothesis 1 will test if participants assigned to the diet that corresponds to their genotype lose more weight than those assigned to a diet inconsistent with their genotype. Hypothesis 2 will analyze the fat responders and carbohydrate responders separately. * Hypothesis 2a: Fat responders will lose more weight on the high-fat diet vs. the high-carbohydrate diet. * Hypothesis 2b: Carbohydrate responders will lose more weight on the high-carbohydrate diet vs. the high-fat diet. Carbohydrate responders and fat responders will be randomized to one of the following two diets: 1. A high-quality high-carbohydrate diet that is rich in whole-grain foods, or 2. A high-quality high-fat diet that is rich in unsaturated fats and oils

Interventions

BEHAVIORALHigh-fat diet

The high-fat diet will consist of \ 40% energy from fat and \ 45% from carbohydrates. Protein will be 15% of energy. All participants will be assigned an energy intake target that will result in a daily deficit of \ 750 kcal, though no energy intake targets below 1,100 kcal/d (women) and 1,300 kcal/day (men) will be prescribed

BEHAVIORALHigh-carbohydrate diet

The high-carbohydrate diet will consist of \ 20% of energy from fat and \ 65% from carbohydrates. Protein will be 15% of energy. All participants will be assigned an energy intake target that will result in a daily deficit of \ 750 kcal, though no energy intake targets below 1,100 kcal/d (women) and 1,300 kcal/day (men) will be prescribed

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Masking description

Outcome assessors will be blind to diet assignment and genotype pattern. Interventionists will be blind to genotype pattern, but not diet type. To enhance external validity, participants will be told if they are carbohydrate or fat responders.

Intervention model description

Randomized controlled parallel arm trial with 4 groups over 12 weeks 1. Fat responders receiving a high-fat diet (n=52) 2. Fat responders receiving a high-carbohydrate diet (n=52) 3. Carbohydrate responders receiving a high-fat diet (n=25) 4. Carbohydrate responders receiving a high-carbohydrate diet (n=25) The total number per group is an estimate. We will not close cells to enroll this exact number per group, and the total number of people enrolled will not exceed 154.

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Yes

Inclusion criteria

* BMI ≥ 27.0 kg/m2 to \< 47.5 kg/m2 * Completed genealogy test and access to the raw data * Fat responder or Carbohydrate responder, as determined by genetic risk score It is estimated that approximately 1/3 of people are fat responders, 1/3 are carbohydrate responders, and 1/3 are neither or will respond to either diet. Only carbohydrate and fat responders are eligible.

Exclusion criteria

* Current smoker or has smoked in the previous year * For females, pregnant or planned pregnancy during the study duration, or breast-feeding, based on self-report * Conditions, diseases, or medications that affect body weight or metabolism (e.g., certain antipsychotic medications; type 2 diabetes mellitus; heart failure; cancer, excluding certain melanomas; etc.) * Has gained or lost more than 10 pounds in the last 3 months * Currently diagnosed with an eating disorder, major depression, or other condition that, in the judgment of the investigators, could affect the risk to the participant or study completion

Design outcomes

Primary

Measure	Time frame	Description
Weight Change	Baseline to 12 weeks	Weight (kg) at 12 weeks minus weight at baseline (kg)
Percent Weight Change	Baseline to 12 weeks	Weight change (kg) / weight at baseline (kg) \* 100

Secondary

Measure	Time frame	Description
Change in Fat Preference Index	Baseline to 12 weeks	Preference for high- versus low-fat foods is measured with the 74-item Food Preference Questionnaire (FPQ). Individual items in the FPQ measure the preference for either a high fat food or a low fat food on a 9-point Likert scale with the following anchors: 1 = dislike extremely; 5 = neutral, neither like nor dislike; 9 = like extremely. The fat preference index (range: 1/9 - 9) is then calculated as the mean rating for high-fat foods divided by the mean rating for low-fat foods. Values greater than 1.0 reflect a higher fat preference, and values less than 1.0 reflect a lower fat preference. Change in Fat Preference Index is calculated as Fat Preference Index at 12 weeks minus Fat Preference Index at baseline.
Change in Disinhibition	Baseline to 12 weeks	Score on the Disinhibition subscale (16-items) of the 36-item Three-Factor Eating Questionnaire. Items are scored as 'true'=1 or 'false'=0. The Disinhibition score (range: 1-16) is calculated as a sum score of all items within that subscale such that low scores indicate more inhibition while higher scores indicate more disinhibition Change in Disinhibition is calculated as the score on the Disinhibition subscale at 12 weeks minus the score on the Disinhibition subscale at baseline.
Change in Waist Circumference	Baseline to 12 weeks	Waist circumference (cm) at 12 weeks minus waist circumference at baseline (cm)
Change in Cognitive Restraint	Baseline to 12 weeks	Score on the Cognitive Restraint subscale (21 items) of the 36-item Three-Factor Eating Questionnaire. Items are scored as 'true'=1 or 'false'=0. The Cognitive Restraint score (range: 1-21) is calculated as a sum score of all items within that subscale such that low scores indicate less cognitive restraint while higher scores indicate greater cognitive restraint. Change in Cognitive Restraint is calculated as the score on the Cognitive Restraint subscale at 12 weeks minus the score on the Cognitive Restraint subscale at baseline
Change in Hunger	Baseline to 12 weeks	Score on the Hunger subscale (14 items) of the 36-item Three-Factor Eating Questionnaire. Items are scored as 'true'=1 or 'false'=0. The Hunger score (range: 1-14) is calculated as a sum score of all items within that subscale such that low scores indicate a lower tendency to be hungry while higher scores indicate a greater tendency to be hungry. Change in Hunger is calculated as the score on the Hunger subscale at 12 weeks minus the score on the Hunger subscale at baseline.
Change in Food Cravings	Baseline to 12 weeks	Food cravings are assessed via the total score of the 33-item Food Craving Inventory (FCI). The FCI is scaled in a frequency format, assessing the frequency with which an individual experiences a craving for a particular food. All items are scored in the following manner: Never = 1, Rarely = 2, Sometimes = 3, Often = 4, & Always = 5. Responses from all 33 items are then averaged to produce a total score (range 1-5). Lower total scores indicate a low frequency of cravings across several food groups including high fat foods, sweets, carbohydrates, fast food fats, and fruits and vegetables while higher total scores indicate a high frequency of cravings across these food groups. Change in food cravings is calculated as FCI total score at 12 weeks minus FCI total score at baseline.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Fat Responders (1) receiving high-fat diet High-fat diet: The high-fat diet will consist of \ 40% energy from fat and \ 45% from carbohydrates. Protein will be 15% of energy. All participants will be assigned an energy intake target that will result in a daily deficit of \ 750 kcal, though no energy intake targets below 1,100 kcal/d (women) and 1,300 kcal/day (men) will be prescribed	44
Carbohydrate Responders (1) receiving high-fat diet High-fat diet: The high-fat diet will consist of \ 40% energy from fat and \ 45% from carbohydrates. Protein will be 15% of energy. All participants will be assigned an energy intake target that will result in a daily deficit of \ 750 kcal, though no energy intake targets below 1,100 kcal/d (women) and 1,300 kcal/day (men) will be prescribed	21
Fat Responders (2) receiving high-carbohydrate diet High-carbohydrate diet: The high-carbohydrate diet will consist of \ 20% of energy from fat and \ 65% from carbohydrates. Protein will be 15% of energy. All participants will be assigned an energy intake target that will result in a daily deficit of \ 750 kcal, though no energy intake targets below 1,100 kcal/d (women) and 1,300 kcal/day (men) will be prescribed	41
Carbohydrate Responders (2) receiving high-carbohydrate diet High-carbohydrate diet: The high-carbohydrate diet will consist of \ 20% of energy from fat and \ 65% from carbohydrates. Protein will be 15% of energy. All participants will be assigned an energy intake target that will result in a daily deficit of \ 750 kcal, though no energy intake targets below 1,100 kcal/d (women) and 1,300 kcal/day (men) will be prescribed	16
Total	122

Baseline characteristics

Characteristic	Fat Responders (1)	Total	Carbohydrate Responders (2)	Fat Responders (2)	Carbohydrate Responders (1)
Age, Continuous	57.4 years STANDARD_DEVIATION 11.5	54.4 years STANDARD_DEVIATION 13.2	52.4 years STANDARD_DEVIATION 13	54.4 years STANDARD_DEVIATION 14.2	49.8 years STANDARD_DEVIATION 14.1
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	12 Participants	36 Participants	5 Participants	10 Participants	9 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	3 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	30 Participants	83 Participants	10 Participants	31 Participants	12 Participants
Sex: Female, Male Female	37 Participants	102 Participants	13 Participants	35 Participants	17 Participants
Sex: Female, Male Male	7 Participants	20 Participants	3 Participants	6 Participants	4 Participants
Weight	94.2 kg STANDARD_DEVIATION 14	94.3 kg STANDARD_DEVIATION 15.2	95.6 kg STANDARD_DEVIATION 18.1	93.5 kg STANDARD_DEVIATION 14.4	95.2 kg STANDARD_DEVIATION 17.6

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 46	0 / 22	0 / 43	0 / 18
other Total, other adverse events	0 / 46	0 / 22	2 / 43	0 / 18
serious Total, serious adverse events	1 / 46	0 / 22	1 / 43	0 / 18