The Efficacy of Individualized Dietary Advice in Improving Diet Quality and Cardiovascular Health
Phase: NA
Conditions: Cardiovascular Diseases
Sponsor: Queen's University, Belfast

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Title: To evaluate the effects of personalized dietary advice on improving diet quality and 
cardiometabolic health 
 
 
Aim:  
To evaluate the effects of personalised dietary advice, tailored to both individual biomarker profiles 
and a diet quality assessment (assessed using PDQS questionnaire), on improving diet quality and 
cardiometabolic health, compared with conventional dietary advice, in adults at risk of 
cardiovascular disease (CVD) on the island of Ireland. These objectives will be assessed in an adult 
population who are overweight, consume a poor quality diet and who have one or more other risk 
factors for CVD, on the island of Ireland. This will be a dual-centre study completed at both Queen’s 
University Belfast and University College Dublin. Ethical approval will be obtained separately 
through the two institutions to cover each recruitment site. 
 
Objectives: 
 
Conduct a 6-month randomized trial among participants at risk of cardiovascular disease (CVD) 
living in Northern Ireland to examine the effects of a dietary intervention, tailored to both 
individuals’ food biomarker profiles and a diet quality assessment (assessed using PDQS 
questionnaire) compared with conventional dietary advice. 
 
• 
Primary outcome: change in overall diet quality assessed using the Prime Diet Quality 
Score (PDQS) 
• 
Secondary outcomes: cardiometabolic outcomes (i.e., blood pressure, lipid profile and 
metabolic markers (e.g. HbA1c), and body composition and body weight), change in biomarkers of 
diet quality, physical activity levels, habitual dietary intake and demographic/lifestyle information. 
• 
Exploratory outcome: changes in gut microbiota compositions and functionality.  
 
 
Background  
 
A healthy dietary pattern, in which saturated fat, sugar and salt are within recommended ranges 
and intake of fibre, fruit and vegetables is high, is known to reduce the risk of non-communicable 
diseases (NCDs)(1-5). However, global burden of NCDs has continued to rise in recent decades, with 

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71% of worldwide deaths attributable to NCDs6. It is thought that up to 80% of cardiovascular 
diseases and over one third of cancers could be prevented by modifying behaviours such as 
smoking, diet, alcohol consumption and physical activity7. As cardiovascular diseases account for 
the majority of NCD deaths, more must be done to determine how best to encourage populations 
to adopt and maintain healthy behaviours to reduce risk of CVD incidence and improve outcomes.  
 
In the context of these rising rates of NCDs, the effectiveness of a personalised nutrition approach 
has been examined in recent years.  Promising evidence from a European dietary intervention has 
suggested that personalised dietary advice, based on individual baseline diet assessed via food 
frequency questionnaire, is more effective than conventional dietary advice in producing positive 
changes in dietary behaviour8. Interestingly, in this trial, it was reported that the inclusion of 
phenotypic or phenotypic plus genotypic information in the generation of personalised dietary 
advice did not enhance the effectiveness of the intervention when compared with advice based on 
individual dietary data alone8. 
 
Although the research in this area is promising, the use of dietary data to tailor personalised dietary 
advice is limited by the self-reported nature of these methodologies and the substantial 
measurement error associated with food frequency questionnaires, 24-hour recalls and food 
diaries9. Food biomarkers are, however, able to objectively assess diet without reliance on self-
reported dietary intake and although further research is needed to discover, validate and examine 
novel biomarkers for foods and/or food groups, it is an area of significant potential in the area of 
personalised nutrition. 
 
The aim of the current project is to examine whether novel food biomarkers, in combination with a 
diet quality assessment (measured using PDQS questionnaire), can be used to deliver precision 
nutrition advice and substantially improve cardiometabolic health. This idea is supported by 
research previously conducted by the research team10 and will be evaluated for the first time in this 
trial. 
 
Plan of Investigation    
 
Participants 
In total n=134 participants will be recruited, n=85 will be recruited by a research team at Queen’s 
University Belfast. 49 participants will be recruited in UCD.  
 
Population characteristics: Participants who are 18 years or over, overweight, consume a poor 
quality diet and have one or more other risk factors for cardiovascular disease. Recruitment will 
take place over a 12-month period. 
 
Participants will be considered eligible to enrol in the study if they are: 

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• 
g18 years AND 
• 
     Overweight or obese (BMI >25 kg/m2 and <45 kg/m2) AND 
• 
have a low diet quality assessed using Prime Diet Quality Score (PDQS) (f21) AND 
one or more of the following risk factors for CVD:  
• 
current smoker  
• 
hypertension (whether pharmacologically managed or not) 
• 
hypercholesterolaemia (whether pharmacologically managed or not) 
 
 
Exclusion criteria:  
 
Participants will be ineligible to enrol in the study if they have: 
 
• 
established CVD (i.e. MI, angina, heart failure, stroke, TIA, peripheral arterial disease or 
aortic disease) 
• 
a medical condition which would substantially limit ability to complete study requirements 
(i.e. follow dietary advice and attend study site for data collection). 
• 
following a medically prescribed diet or have a dietary restriction(s) that would substantially 
limit ability to complete study requirements (e.g. following a diet for management of Type 1 or 
Type 2 diabetes, weight loss, Coeliac Disease, Inflammatory Bowel Disease, food allergies or any 
other condition requiring significant dietary management). 
• 
excessive alcohol consumption (>28 units/week for men or >21 units/week for women) 
• 
     currently pregnant 
• 
no internet/email access (as this would impact on intervention delivery). 
• 
unable to provide informed consent. 
 
Recruitment 
Participants will be recruited from the general population via established recruitment mechanisms. 
An electronic recruitment poster,email, and/or flyers will be circulated to workplaces and online 
notification systems e.g. church online bulletins, local online newspapers, online community notices 
(e.g. University of the Third Age) and social media outlets such as Twitter, Facebook and Instagram. 
A pop-up banner of the recruitment poster will also be produced and placed in entrance halls of 
public spaces/workplaces with appropriate permissions obtained. Contact details of the research 
team will be published on all study advertisements. Managerial permission will be obtained, where 
relevant, before any online advertisements are circulated or placed within workplace spaces. 
Recruitment will take place over a 12-month period. 
   

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The Belfast site will recruit n=85 participants according to the inclusion and exclusion criteria.  The 
UCD site will recruit 49 participants.  
 
Those who are interested in taking part in the study after reading the study advertisement will be 
directed to make contact with the research team. The initial screening process will involve asking 
participants to complete a screening questionnaire (incorporating all aspects of inclusion/exclusion 
criteria and collection of contact details) via telephone with the researcher. The screening process 
will rely on self-reported information obtained from the participant and should take approximately 
20-30 minutes to complete. After the telephone call, researchers will review responses within the 
screening questionnaire and email a link to the Participant Information Sheet   to those identified 
as potentially eligible to take part.  
 
After being given at least 48 hours to read the Participant Information Sheet, the researcher will 
telephone the participant to discuss the research in further detail and ensure the participant fully 
understands the study information, implications of involvement and answer any questions they 
might have. If the participant agrees to participate, they will be invited to complete their consent 
online and attend the Centre for Public Health for baseline data collection.  
 
Study design and assessments 
 
This is a single-blind randomised controlled parallel group dietary intervention, conducted over 6 
months in participants at high risk of cardiovascular disease living on the island of Ireland, to 
evaluate the efficacy of personalised dietary advice, based on both food biomarkers and a diet 
quality assessment, in improving diet quality and cardiometabolic outcomes. 
 
Study randomisation will be conducted centrally for both sites (Northern Ireland and Republic of 
Ireland). Once participants have completed their baseline visit, they will be randomized 
(randomization scheme generated using www.randomization.com with random block sizes) to 
either control or intervention group. Participants will be stratified by gender and diet quality. 
Participants will be unaware of which group they have been randomised to. Control participants will 
be offered personalised dietary advice at the end of the intervention: 
 
1) Control – participants will be given conventional dietary advice based on current regional 
population dietary recommendations via email to encourage dietary change towards a better quality 
diet. Participants will be given the dietary advice at baseline (4 messages) and month 3 (4 
messages) of the intervention. Control participants will be offered personalised dietary advice at 
the end of the intervention. 
 
2) Personalized dietary advice – participants will be encouraged to make dietary change using 
individualized recommendations incorporating both food biomarkers and diet quality assessment 

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(assessed using PDQS questionnaire). Based on these biomarker data and the diet quality 
assessment, a system of categorization will be developed and decision trees created to ensure 
standardized delivery of advice within this intervention arm. In this way, the intervention will be 
standardised across sites. Relevant behaviour change techniques (BCT), i.e. the BCT framework 
and the CALOR-E diet and physical activity-specific taxonomy11,12 have been integrated into the 
intervention development.  Dietary advice will be delivered via email in both groups.  
 
Participants will commence on the intervention within one month of their baseline visit. This will 
enable researchers to collect, process and analyse urine samples to help inform the dietary advice 
given as part of the intervention. 
 
Dietary advice will be delivered via email. Both groups will receive dietary advice at baseline and 
month 3. Both groups will receive contact from the research team at months 0, 1, 3 and 6 months 
via email. The control group will be offered personalised dietary advice at the end of the 
intervention. As such, the frequency and duration of contact will be similar in both groups. 
 
 
Outcome measures:  
Outcomes will be assessed during a study visit at 0, 3, and 6 months and maintenance data will be 
collected online at 12 months for the primary outcome.  
 
Primary outcome: 
• 
Change in dietary quality assessed by Prime Diet Quality Score (PDQS). This will also be 
assessed six months after the intervention completes, to determine whether the intervention 
influences longer term adherence to a better quality diet. (assessed at 0, 3, 6 and 12 months. 
The 12 month PDQS (6 months post intervention) will be collected online). 
 
Secondary Outcomes: 
1. Change in markers of cardiometabolic risk including: 
o 
 Blood pressure (measured twice from the non-dominant arm, using automated Omron 
sphygmomanometer, with the participant sitting quietly for at least five minutes. 
(assessed at 0, 3 and 6 months). 

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o 
Lipid profile (fasting blood samples will be drawn from the antecubital vein and 
immediately separated into plasma/serum for the proposed assays detailed below. It will 
be stored at -70°C until analysis (assessed at 0, 3 and 6 months). 
o 
Other metabolic markers (e.g. HbA1c) (blood sample as above) (assessed at 0, 3 and 6 
months). 
o 
Anthropometric measurements (weight (kg), height (m), measured using calibrated 
scales and stadiometer, respectively, BMI (kg/m2), waist and hip circumference and body 
composition measured by bioelectrical impedance (Bodystat 1500) (assessed at 0, 3 and 
6 months) 
2. Demographic/lifestyle information (e.g. alcohol consumption, medication use assessed via 
questionnaire) (assessed at 0 months; shortened change in medication/lifestyle 
questionnaire administered at 3 and 6 months). 
3. Change in biomarkers of diet quality, including food biomarker-based diet quality score 
(fasting morning urine sample stored at -70ºC until analysis; further details below) 
(assessed at 0, 3 and 6 months). 
4. Physical activity using a 7-day pedometer and Global Physical Activity Questionnaire (GPAQ) 
(assessed at 0, 3 and 6 months). 
5. Habitual dietary intake assessed using the EPIC Food Frequency Questionnaire (assessed at 
0, 3 and 6 months). 
All questionnaires will be administered via the online survey software Qualtrics. 
Exploratory outcome: 
• 
Gut microbiota composition and functionality.  Faecal samples will be collected from 
participants who consent to contribute to this optional element of the study for exploratory 
analyses. As faecal samples are required from a large proportion (n=70; n=35 in each study 
arm) of the n=85 participants we intend to recruit at the QUB site, all participants recruited 
at QUB will be asked to consider consenting to the provision of faecal samples). Participants 
will be given a faecal sample home collection kit and instructed to collect a sample during 
the week following the month 0 and month 6 study visits. Full instructions and a postage 
box will be provided within the faecal sample collection kit so participants can easily return 
sample to researchers via post.  

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Laboratory methodology 
All methods utilised are routinely used in the participating laboratories and are performed with 
careful attention to quality control and with participation in external quality control schemes where 
available. All laboratory analyses will be conducted blind, i.e., the analyst will not know to which 
intervention the participant has been assigned.  
 
 
Biomarkers of cardiometabolic risk: 
Serum lipids (total cholesterol, HDL-C, and TG) whole blood HbA1c will be assessed by enzymatic 
assays (Randox Ltd, Crumlin, NI and Glen Bio, Antrim, NI) on a Randox auto-analysern I-Lab 600 
auto-analyzer. LDL-C will be calculated.  
 
Biomarkers of diet quality: 
The following biomarkers will be used :  
• 
red meat (methylhistidinescarnosine)  
• 
white meat (guanidoacetate, anserine)  
• 
fruit and vegetables (proline betaine, isothiocyanates, S-methyl-L-cysteine sulfoxide, and 
tartaric acid)  
• 
wholegrains (alkylresorcinols)  
• 
coffee (phenolic acids, N-methylpyridinium, trigonelline, 2-furoylglycine; SSBs --formate, 
citrulline, taurine, and isocitrate)  
• 
fish (omega-3 index (20:5n-3 and 22:6n-3; % of total fatty acids).  
Others will be added as they emerge in the literature. 
 
Gut microbiome composition and functionality (exploratory): 
Faecal samples will be collected via home collection kits, posted back to researchers and stored at 
Queen’s University Belfast in preparation for shipment to US partner laboratories for analyses.  
 
Power 

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Based on published US data, with a standard deviation (SD) of PDQS of 2.3, as previously seen13, 
and an assumption of a difference in increase in PDQS of 5 between the personalized dietary advice 
and control groups, then, if we have 60 participants in each group, the study would have over 90% 
power to detect this difference in mean PDQS as statistically significant, at the α=0.05 level. We 
will recruit 134 participants in total to allow for approximately 10% drop-out. For the health 
outcomes, and, based on what was observed in a dietary intervention study on improving diet 
quality in similar, high CVD risk participants14, if we have 60 participants in each group, and we 
assume that (i) the SD of the change in diastolic blood pressure (DBP) is 9 mmHg at the end of the 
study; (ii) a difference in DBP of 4.5 mmHg between the personalized dietary advice and control 
groups; then the study would have 80% power to detect, as statistically significant at the 5% level, 
these differences in mean change between the two groups. We will have similar levels of power 
(~80%) to detect effect sizes of similar magnitude in total cholesterol, HbA1c, and body weight. 
The analysis of gut microbiota composition and functionality will be exploratory in nature. 
 
 
Statistical analysis 
 
The repeated end-point measures generated by the study design will be analyzed with techniques 
appropriate for longitudinal data using the xt panel study procedures available in Stata release 11 
(College Station, TX). Initial examination of the correlation structure of the repeated measures 
will help guide model fitting. The influence of the dietary intervention under study will be assessed 
by comparing the means of changes in measurements from baseline to 6 months between the 
personalised dietary advice and control groups. This difference in means will provide an estimate 
of the effect of intervention and 95% confidence limits will be calculated to indicate its precision. If 
appropriate, measurements will be logarithmically transformed prior to analysis and interpretation 
will be made in ratio terms on the original scale. Compositional analysis of whole metagenome and 
metatranscriptome datasets will be performed using the read-based bioinformatics analysis suite, 
including the HUMAnN2158 analysis network15, MetaPhlAn2 profiler16 and KneadDATA pipeline, 
developed in the Huttenhower laboratory at Harvard T.H. Chan School of Public Health. Testing for 
differences in microbial features between intervention and control groups will be performed with 
the MaAsLin sparse regression method17. It is unknown whether men and women respond 
differently to the same diet, in terms of food biomarker profiles and CHD risk. In previous cohort 
studies conducted by the research teams, similar associations of various diet quality indices were 
observed with risk of chronic diseases between men and women18-21. In the current study, we 
consider both men and women, and whenever appropriate, we will perform gender-specific 
analyses to assess gender difference. We will combine the data of men and women when the test 
for interactions by gender is not significant, and gender will be adjusted as a covariate. 
 
 

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Process Evaluation 
A process evaluation will be conducted at the end of the 6-month study to help elucidate if, how 
and why the intervention worked. A process evaluation framework for the PAD-Q trial has been 
developed based on both the Medical Research Council guidance22 and RE-AIM framework23.  
 
A large proportion of data for process evaluation will be naturally collected as part of the trial 
process (receipt of delivery of dietary reports, number of participants making contact with the 
research team to ask further questions) but to address the outstanding aspects, the research team 
has developed a brief process evaluation questionnaire (to be administered online) and a guide for 
a semi-structured follow-up interview to be conducted via telephone. These additional aspects of 
data collection are optional and will therefore involve a separate Participant Information Sheet and 
Consent From. The purpose of the online questionnaire is to collect data from participants on 
intervention fidelity, dose, acceptability, reach, context, mechanisms of impact and contamination, 
as per MRC framework. In order to allow participants to elaborate further on the aspects reported 
within the questionnaire, a follow-up phone call will also be an option, which would be expected to 
last approximately 30 minutes. The phone call will be conducted by a researcher and audio tape-
recorded to enable transcription for subsequent analyses. Participants will be reminded that the 
data collection process will be fully anonymized and that they have the option to ask the research 
to omit any aspects of the conversation which they do not wish to be transcribed at the end of the 
phone call. 
 
 In order to collect these data, we plan to circulate an email to all participants (both those 
randomized to the invention or control groups) at the end of the 6-month trial with an Information 
Sheet attached, specific to process evaluation, to gauge interest in completing the optional process 
evaluation questionnaire or follow-up phone-call. If a participant expresses interest, researchers 
will email a link to an electronic consent form. Once consent is completed, researchers will then 
circulate a link to the process evaluation questionnaire (via Qualtrics survey software) and arrange 
a follow-up phone call to those who provide consent. Participants will be offered the option to 
complete either the questionnaire or phone call, or both.  
 
Project timetable, including who will carry out which parts of the project 
June 2021-September 2021 
Project planning, preparation of study documentation, intervention delivery preparation, 
development of personalised messaging templates and logistical organisation will be carried out by 
a Research Fellow and PhD student.  
 
September 2021-September 2023 

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The recruitment period is expected to last 12 months and commence in September 2021. It is 
expected that recruitment, randomisation, intervention delivery and data collection will be 
implemented on a rolling basis between Belfast and Dublin sites. The intervention will be 6 months 
in duration and the primary outcome will also be collected 6 months post-intervention to determine 
maintenance.   The day-to-day management of the study and all data collection procedures will be 
undertaken by a Research Fellow and a PhD student.  
 
September 2023-May 2024 
Project data analyses, write-up and dissemination. 
 
Data protection issues  
Data collected in association with this study will be pseudonymised. Consent and online 
questionnaire data will be pseudonymised and stored within password-protected databases within 
secure university OneDrive servers. Only researchers will have access to these data.. All biological 
samples collected will be pseudonymised and stored within secure -80oC freezers at Queen’s 
University Belfast site. Urine samples will be shipped to University College Dublin for analyses and 
a Material Transfer Agreement will be in place. Faecal samples, which are an optional element of 
the study, will be stored at Queen’s University Belfast and shipped to partner laboratory in United 
States for analyses and a Material Transfer Agreement will be in place.  Study measurement records 
(height, height, blood pressure) completed at study visits will be the only hard copy data collected 
and will be pseudonymised and stored within lockable researcher filing cabinets within the Centre 
for Public Health. Data will be made available for secondary research in a timely and responsible 
manner following requests made to and approved by the study research team. 
 
Ethical issues and safety 
Participants will be fully informed about the requirements of the study before they provide consent. 
If a participant feels uncomfortable about providing any of the information, they can withdraw at 
any time without giving a reason. This trial involves promotion of healthy behaviours tailored to an 
individual’s biomarker profile, where indicated. These purposeful changes in behaviour are healthy 
behaviours and therefore intended to be of benefit to the participant in terms of their health. Control 
group participants will be offered the personalised feedback at the end of the intervention.  
Biological samples collected as part of this study will not be used in future research unless specific 
consent is obtained and this is clearly outlined within the Participant Information Sheet. All 
biological samples will be collected, handled and stored in accordance with Human Tissue Act 2004, 
where relevant e.g. HcA1C sample; whereby all relevant documentation with regards to the Human 
Tissue Authority will be in place. 

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Participants will be informed that if, during the process of data collection, any incidental findings 
with regards to health (newly concerning lipid profile, HbA1C outside of the normal range, elevated 
blood pressure measurement) are identified, participants will be informed. Specific consent with 
regards to contacting the participant’s General Practitioner in these instances will be obtained.  •
 
With regards to HbA1C, people previously diagnosed with type 2 diabetes will be excluded 
from the trial. However, if a HbA1C blood test level of 48mmol/mol or above is detected as a result 
of 
this 
study 
(https://cks.nice.org.uk/topics/diabetes-type-2/diagnosis/diagnosis-in-adults/), 
researchers will ask participant permission to contact their GP. If participant does not consent, they 
will be encouraged to make contact with their GP themselves.  With regards to lipid profile, if a 
participant has a total cholesterol reading of 5mmol/L or above, triglycerides 2.3mmol/L or above, 
or HDL 1mmol/L or below (LDL cholesterol will be calculated from these values with a criteria of 
3mmol/L or above) researchers will ask participant permission to contact their GP. If participant 
does not consent, they will be encouraged to make contact with their GP themselves. With regards 
to blood pressure, an average of 3 blood pressure measurements will be recorded at each timepoint. 
Researchers will ask permission to contact a participant’s GP if an average blood pressure 
measurement of 140/90mmHg or higher is recorded 
Please note that an elevated blood 
pressure measure of concern will be immediately apparent to the researcher in terms of making 
contact with the participant’s GP, however, HBA1C and lipid profile will not be measured until the 
end of the intervention due to research practicalities such as the need to analyse bloods in batches.   
 
 
 
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10, doi doi: 10.1017/cts.2021.789).   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PAD-Q Study: Intervention Protocol 
14 
Woodside  
PAD-Q Intervention Protocol  
V4: 01.09.22 
Figure 1: Summary flow chart of study visits 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participants screened based on inclusion/exclusion criteria (n=85 QUB site, 49 UCD) 
Consented participants will be randomized (randomization scheme generated 
using www.randomization.com with random block sizes): 
 
Personalized dietary advice:  
emailed to participant at baseline 
and month 3 (6 month 
intervention) 
 
Control: emailed at baseline and 
month 3 (6 month intervention) 
0 months 
3 months 
6 months 
Primary outcome PDQS score                                                                                         
Secondary outcomes: Change in markers of cardiometabolic risk including: Blood 
pressure, lipid profile, HbA1c, weight (kg), height (m), BMI (kg/m2), waist and hip 
circumference and body composition measured by bioelectrical impedance, 
demographic/lifestyle information, change in biomarkers of diet quality, physical activity 
(7-day pedometer and GPAQ), dietary intake (EPIC FFQ) 
Exploratory outcome: gut microbiota composition and functionality (optional) 
Primary outcome PDQS score                                                                                          
Secondary outcomes: Change in markers of cardiometabolic risk including: Blood 
pressure, lipid profile, HbA1c, weight (kg), height (m), BMI (kg/m2), waist and hip 
circumference and body composition measured by bioelectrical impedance, 
demographic/lifestyle information, change in biomarkers of diet quality, physical activity (7-
day pedometer and GPAQ), dietary intake (EPIC FFQ). 
 
Primary outcome PDQS score                                                                                         
Secondary outcomes: Change in markers of cardiometabolic risk including: Blood 
pressure, lipid profile, HbA1c, weight (kg), height (m), BMI (kg/m2), waist and hip 
circumference and body composition measured by bioelectrical impedance, 
demographic/lifestyle information, change in biomarkers of diet quality, physical activity 
(7-day pedometer and GPAQ), dietary intake (EPIC FFQ). 
Exploratory outcome: gut microbiota composition and functionality (optional) 
Process Evaluation (optional) online questionnaire only or questionnaire and follow-up 
phone call. 
Primary outcome: PDQS score will also be assessed 6 months post-intervention in both 
intervention and control groups to assess maintenance of dietary changes.