Effects of Antioxidant Sugar vs Granulated Sugar on Metabolic Outcomes in Healthy and Cardio Metabolic Subjects

Study Overview
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Brief Summary
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Study 1: To investigate the effects of antioxidant-rich sugar as alternative compared to granulated sugar on gene expression and other metabolic parameters in healthy subjects. The hypotheses is antioxidant-rich sugar have positive effects on reducing inflammatory cytokines, oxidative stress biomarkers and other metabolic parameters in intervention group compared to control group. Study 2: To evaluate the effectiveness of a nutrition education module in modifying sugar consumption and other CMR-related outcomes in individuals with cardiometabolic risk. The hypotheses is the nutrition education module significantly improves the sugar consumption and other CMR-related outcomes in the intervention groups compared to the control group

Detailed Description
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Study 1: After being informed about the study and potential risks, written informed consent will be obtained from all subjects involved in the study. Respondents will be interviewed at Nutritional Status Assessments Lab at University of Putra, Malaysia (UPM) to obtain socio-demographic data, medical status, nutritional status, lifestyle practices and daily dietary intake. This study will be conducted for a period of 8 weeks. The study design is single-blinded parallel-randomized controlled trial (n=80), with 40 subjects in each group (one intervention and one control group). The participants will be selected based on the inclusion and exclusion criteria. Study 2: After being informed about the study and potential risks, written informed consent will be obtained from all subjects involved in the study prior to commencing the study. Respondents will be screened at Nutritional Status Assessments Lab at UPM for mental health status, daily sugar intake, cardiometabolic risk factors (waist circumference, blood pressure, fasting blood glucose, triglyceride and high-density lipoprotein cholesterol) where blood pressure and blood sample will be taken by the phlebotomist. Female candidates will be screened for pregnancy or breast feeding. Those who meet the inclusion/exclusion criteria will be selected. They will be informed via communication application whether they are eligible for the study. This study will be conducted for a period of 6 months.

Official Title
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1: Effects of Antioxidant-rich Sugar as Alternative Compared to Granulated Sugar on Gene Expression and Other Metabolic Parameters in Healthy Subjects 2: Effectiveness of Education Module to Modify Sugar Consumption Among Individuals With Cardio Metabolic Risk

Conditions
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Gene Expression, Cardiometabolic Risk, Metabolic Syndrome

Intervention / Treatment
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* Other: Study 1: MRBS
* Other: Study 2: White sugar & education module
* Other: Study 2: MRBS & education module


Participation Criteria
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Eligibility Criteria
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Study 1: Inclusion Criteria: Willingness to adhere to study protocol Healthy adults to be aged between 18 and 60 years in both genders Being non-smoker Body mass index (BMI) between 23 - 26.9 kg/m2 (overweight). Exclusion Criteria: Present of any kidney, liver and/or inflammatory disease (inflammatory bowel disease, Rheumatoid arthritis and etc.), thyroid disorder, diabetes (Type 1 & Type 2), cardiovascular or metabolic disease Individuals with impaired glucose tolerance or with fasting blood glucose level that more than 5.2 mmol/L Pregnancy or lactation Alcohol consumption, food allergy Individuals who are on regular antioxidant, anti-inflammatory and /or anti-obesity drugs, receiving any glucose lowering and/or lipid lowering medications Change in the diet and physical activity (significant weight changes during study period) Subjects who habitually consumed beverages rich in sugar such as milo, Teh tarik more than 500 ml, (as tested with the FFQ) Study 2: Candidates will be screened for: Cardiometabolic risk factors (waist circumference, blood pressure, fasting blood glucose, triglyceride and high-density lipoprotein cholesterol) Pregnancy or breast feeding Mental health status Daily total sugar intake Inclusion Criteria: Malaysian, aged ≥18-59 years old Able to read, write and communicate well either in Malay or English Attained at least formal education level (secondary school and above) Able to use the gadgets and have access to the internet Presence with Cardiometabolic risk defines at least any of three out of five risk factors are present and the risk factors are:waist circumference (men: ≥90cm, women:≥80 cm); blood pressure (≥130/85 mmHg); having diabetes mellitus or fasting blood sugar (≥5.6mmol/L); triglyceride (≥1.7 mmol/L) or high-density lipoprotein (men: <1.03 mmol/L, women: <1.3 mmol/L). Daily free sugar intake ≥10% of the daily energy intake Exclusion Criteria: Unstable mental health referring to the DASS-21 score for Depression score ≥5; Anxiety score ≥4 and Stress score ≥8 (Ramli, Salmiah, Nurul Ain 2009) Uncontrolled type 2 diabetes defines as HbA1c of more than 8% or hypertriglyceridemia of > 10 mmol/L Presence with chronic diseases-related complications such as liver disease or stage 3 chronic kidney disease Reported abnormal thyroid stimulating hormones On current dietary program or medication for weight loss On cancer therapy Having physical disabilities Pregnancy or the desire to become pregnant in the next 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Study 1: The study will be using a two-arm single-blinded RCT with 40 subjects in each of the intervention and control groups. Study 2: The study will be using a three-arm RCT with 23 subjects in each groups (two interventions and one control groups).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Study 1: Normal sugar<br>Control group will be required to continue consuming normal sugar intake for 8 weeks. | |
| Experimental: Study 1:Minimally refined brown sugar (MRBS)<br>Intervention group will be required to consume MRBS as added sugar based on their habitual diet for 8 weeks intervention. | Other: Study 1: MRBS<br>* MRBS as added sugar based on their habitual diet<br>* Other names: Food-based and gene expression;|
| No Intervention: Study 2: Normal sugar intake<br>- The control group will have no intervention and will continue with their normal daily intake for six months. | |
| Experimental: Study 2: White sugar<br>Intervention group I will be advised to reduce sugar intake to no more than 10% from total energy intake. Intervention group I will be given white sugar for daily usage. Participants in this group will be exposed to the nutrition education module (45 minutes per session, once a week) for six months, attend lecture classes and communicate with health educators through communication applications. For the first three months, one-to-one diet counseling will be conducted. Participants' intake of free sugar, as well as other nutrients (carbohydrate, protein, fats, fibre and others) will be closely monitored to ensure compliance to dietary recommendations. | Other: Study 2: White sugar & education module<br>* White sugar for daily usage (<10% daily energy intake)<br>* Other names: Food-based and nutrition education study;|
| Experimental: Study 2: MRBS<br>Intervention group II will be advised to reduce sugar intake to no more than 10% from total energy intake. Intervention group II will be given MRBS for daily usage. Participants in this group will be exposed to the nutrition education module (45 minutes per session, once a week) for six months, attend lecture classes and communicate with health educators through communication applications. For the first three months, one-to-one diet counseling will be conducted. Participants' intake of free sugar, as well as other nutrients (carbohydrate, protein, fats, fibre and others) will be closely monitored to ensure compliance to dietary recommendations. | Other: Study 2: MRBS & education module<br>* MRBS for daily usage (<10% daily energy intake)<br>* Other names: Food-based and nutrition education study;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study 1: Gene expression of inflammation biomarkers (interleukin-6) | Change from baseline in gene expression of interleukin-6 in micrograms at 8th weeks. | 8 weeks | 
| Study 1: Gene expression of inflammation biomarkers (TNF-α) | Change from baseline in gene expression of TNF-α in picograms per milliliter at 8th weeks. | 8 weeks | 
| Study 1: Gene expression of inflammation biomarkers (CPR) | Change from baseline in gene expression of CPR in milligram per liter at 8th weeks. | 8 weeks | 
| Study 1: Gene expression of oxidative stress biomarkers (MDA) | Change from baseline in gene expression of MDA in millimolar at 8th weeks. | 8 weeks | 
| Study 1: Gene expression of oxidative stress biomarkers (SOD) | Change from baseline in gene expression of SOD in Units per milliliter at 8th weeks. | 8 weeks | 
| Study 1: Gene expression of oxidative stress biomarkers (CAT) | Change from baseline in gene expression of CAT in nanomoles at 8th weeks. | 8 weeks | 
| Study 2: Change from baseline in sugar consumption | Dietary sugar intake will be determined using a 3-day food record and semi-quantitative FFQ of added sugar intake. Total sugar (grams per day) in foods will be calculated using formula [(total sugar (grams) - natural sugar (grams)]. The total added sugar intake will be divided into four centiles i.e., 25th percentile [<10.3g (2 tsps.)], 50th percentile [10.3-23.8g (2-5 tsps.)], 75th percentile [23.8-47.0g (5-9 tsps.)] and 100th percentiles [>47g (9 tsps.)]. | 3 months | 
| Study 2: Change from baseline in sugar consumption | Dietary sugar intake will be determined using a 3-day food record and semi-quantitative FFQ of added sugar intake. Total sugar (grams per day) in foods will be calculated using formula [(total sugar (grams) - natural sugar (grams)]. The total added sugar intake will be divided into four centiles i.e., 25th percentile [<10.3g (2 tsps.)], 50th percentile [10.3-23.8g (2-5 tsps.)], 75th percentile [23.8-47.0g (5-9 tsps.)] and 100th percentiles [>47g (9 tsps.)]. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study 1: Inflammation biomarkers (interleukin-6) | Change from baseline in interleukin-6 in micrograms at 8th weeks. | 8 weeks | 
| Study 1: Inflammation biomarkers (TNF-α) | Change from baseline in TNF-α in picograms per milliliter at 8th weeks. | 8 weeks | 
| Study 1: Inflammation biomarkers (CPR) | Change from baseline in CPR in milligram per liter at 8th weeks. | 8 weeks | 
| Study 1: Oxidative stress biomarkers (MDA) | Change from baseline in MDA in millimolar at 8th weeks. | 8 weeks | 
| Study 1: Oxidative stress biomarkers (SOD) | Change from baseline in SOD in Units per milliliter at 8th weeks. | 8 weeks | 
| Study 1: Oxidative stress biomarkers (CAT) | Change from baseline in CAT in nanomoles at 8th weeks. | 8 weeks | 
| Study 1: TAC | Change from baseline in TAC in millimolar at 8th weeks. | 8 weeks | 
| Study 1: Blood pressure | Change from baseline in blood pressure in mmHg at 8th weeks. | 8 weeks | 
| Study 1: Lipid profile | Change from baseline in total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides in mmol/L at 8th weeks. | 8 weeks | 
| Study 1: Glucose profile | Change from baseline in fasting glucose in mmol/L at 8th weeks. | 8 weeks | 
| Study 1: Anthropometric measurements (height) | Change from baseline in height in meters at 8th weeks. | 8 weeks | 
| Study 1: Anthropometric measurements (weight) | Change from baseline in weight in kilograms at 8th weeks. | 8 weeks | 
| Study 1: Anthropometric measurements (waist circumference) | Change from baseline in waist circumference in centimeters at 8th weeks. | 8 weeks | 
| Study 1: Anthropometric measurements (hip circumference) | Change from baseline in hip circumference in centimeters at 8th weeks. | 8 weeks | 
| Study 1: Body mass index | Weight (kg) and height (m) will be combined to report body mass index in kg/m2. | 8 weeks | 
| Study 1: Waist hip ratio | Waist (cm) and hip circumference (cm) will be combined to report waist hip ratio | 8 weeks | 
| Study 1: Change from baseline in sugar consumption at 8th weeks | Dietary sugar intake will be determined using a 3-day food record and semi-quantitative FFQ of added sugar intake. Total sugar (grams per day) in foods will be calculated using formula [(total sugar (grams) - natural sugar (grams)]. The total added sugar intake will be divided into four centiles i.e., 25th percentile [<10.3g (2 tsps.)], 50th percentile [10.3-23.8g (2-5 tsps.)], 75th percentile [23.8-47.0g (5-9 tsps.)] and 100th percentiles [>47g (9 tsps.)]. | 8 weeks | 
| Study 1: Change from baseline in physical activity level at 8th weeks | - Physical activity level will be measured using International Physical Activity Questionnaire (IPAQ) and results will be categorized as low, moderate and high physical activity. | 8 weeks | 
| Study 1: Change from baseline in intensity of physical activity at 8th weeks | Metabolic Equivalent Task (minutes/week) will be used to assess the intensity of physical activity. | 8 weeks | 
| Study 2: Change from baseline in anthropometric measurements (height) | Height in meters will be taken. | 3 months | 
| Study 2: Change from baseline in anthropometric measurements (weight) | Weight in meters will be taken. | 3 months | 
| Study 2: Change from baseline in anthropometric measurements (waist circumference) | Waist circumference in centimeters will be taken. | 3 months | 
| Study 2: Change from baseline in anthropometric measurements (hip circumference) | Hip circumference in centimeters will be taken. | 3 months | 
| Study 2: Change from baseline in body mass index | Weight (kg) and height (m) will be combined to report body mass index in kg/m2. | 3 months | 
| Study 2: Change from baseline in waist hip ratio | Waist (cm) and hip circumference (cm) will be combined to report waist hip ratio. | 3 months | 
| Study 2: Change from baseline in blood pressure | Blood pressure in mmHg will be taken. | 3 months | 
| Study 2: Change from baseline in lipid profile | Total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides in mmol/L will be measured. | 3 months | 
| Study 2: Change from baseline in sugar profile | Fasting glucose in mmol/L will be measured. | 3 months | 
| Study 2: Change from baseline in antioxidant activity | Antioxidant activity in mmol/L will be measured. | 3 months | 
| Study 2: Change from baseline in 24-hour urinary sucrose/fructose | Urinary sucrose (mg/day) and fructose (mg/day) will be combined to report 24-hour urinary sucrose/fructose. | 3 months | 
| Study 2: Change from baseline in knowledge level | Knowledge level of healthy diet and sugar will be tested using Knowledge Assessment Questionnaire. The score will be presented in percentage. | 3 months | 
| Study 2: Change from baseline in health belief | Health belief model construct will be determined using Health Belief Model questionnaire. Five subscales: perceived susceptibility, perceived severity, perceived benefits, perceived barriers and perceived self-efficacy will be measured and the scores will be presented in percentage. | 3 months | 
| Study 2: Change from baseline in mental health | Mental health status will be measured using DASS-21 questionnaire, measuring depression (normal cut-off point: 0-4), anxiety (normal cut-off point: 0-3) and stress (normal cut-off point: 0-7). | 3 months | 
| Study 2: Change from baseline in physical activity level | Physical activity level will be measured using International Physical Activity Questionnaire (IPAQ) and results will be categorized as low, moderate and high physical activity. | 3 months | 
| Study 2: Change from baseline in intensity of physical activity | Metabolic Equivalent Task (minutes/week) will be used to assess the intensity of physical activity. | 3 months | 
| Study 2: Change from baseline in anthropometric measurements (weight) | Weight in meters will be taken. | 6 months | 
| Study 2: Change from baseline in anthropometric measurements (height) | Height in meters will be taken. | 6 months | 
| Study 2: Change from baseline in anthropometric measurements (waist circumference) | Waist circumference in centimeters will be taken. | 6 months | 
| Study 2: Change from baseline in anthropometric measurements (hip circumference) | Hip circumference in centimeters will be taken. | 6 months | 
| Study 2: Change from baseline in body mass index | Weight (kg) and height (m) will be combined to report body mass index in kg/m2. | 6 months | 
| Study 2: Change from baseline in waist hip ratio | Waist (cm) and hip circumference (cm) will be combined to report waist hip ratio. | 6 months | 
| Study 2: Change from baseline in blood pressure | Blood pressure in mmHg will be taken. | 6 months | 
| Study 2: Change from baseline in lipid profile | Total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides in mmol/L will be measured. | 6 months | 
| Study 2: Change from baseline in sugar profile | Fasting glucose in mmol/L will be measured. | 6 months | 
| Study 2: Change from baseline in antioxidant activity | Antioxidant activity in mmol/L will be measured. | 6 months | 
| Study 2: Change from baseline in 24-hour urinary sucrose/fructose | Urinary sucrose (mg/day) and fructose (mg/day) will be combined to report 24-hour urinary sucrose/fructose. | 6 months | 
| Study 2: Change from baseline in knowledge level | Knowledge level of healthy diet and sugar will be tested using Knowledge Assessment Questionnaire. The score will be presented in percentage. | 6 months | 
| Study 2: Change from baseline in health belief | Health belief model construct will be determined using Health Belief Model questionnaire. Five subscales: perceived susceptibility, perceived severity, perceived benefits, perceived barriers and perceived self-efficacy will be measured and the scores will be presented in percentage. | 6 months | 
| Study 2: Change from baseline in mental health | Mental health status will be measured using DASS-21 questionnaire, measuring depression (normal cut-off point: 0-4), anxiety (normal cut-off point: 0-3) and stress (normal cut-off point: 0-7). | 6 months | 
| Study 2: Change from baseline in physical activity level | Physical activity level will be measured using International Physical Activity Questionnaire (IPAQ) and results will be categorized as low, moderate and high physical activity. | 6 months | 
| Study 2: Change from baseline in intensity of physical activity | Metabolic Equivalent Task (minutes/week) will be used to assess the intensity of physical activity. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antioxidant sugar, Gene Expression, Cardio metabolic risks, Education tool