Insulin ResistanceNCT01201603
The Effects of Orange Juice on Insulin Sensitivity and Plasma Lipids
A study testing orange juice in people with Insulin Resistance and Obesity, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
The aim of this study is primarily to investigate the ability of antioxidants found in orange juice (OJ) to increase the body's sensitivity to the hormone insulin. Overweight or mildly obese women, who are otherwise healthy, will be recruited. The time commitment for subjects is ~14wks. Read more about this study
- Who is it for?
- Ages 18 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance, Obesity
- What is being tested?
- orange juice
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 2010to Nov 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- pre-menopausal or post-menopausal and taking HRT
- BMI 27-35kg/m2
- HOMA-IR value > 1.5
- healthy
Who cannot join
- pregnant or breast feeding,
- any metabolic or endocrine abnormalities,
- clinically significant abnormalities on screening,
- fasting glucose > 6.0mmol/l,
- taking medication other than the contraceptive pill or HRT
- herbal supplement use,
- food allergies/intolerances related to the investigational product (citrus juices, fructose)
- daily consumption of >100ml citrus juices
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Nottingham
Nottingham, Notts, NG7 2UH
About this study
The aim of this study is primarily to investigate the ability of antioxidants found in orange juice (OJ) to increase the body's sensitivity to the hormone insulin. Overweight or mildly obese women, who are otherwise healthy, will be recruited. The time commitment for subjects is ~14wks. Subjects will attend the laboratory on 5 occasions after fasting from midnight. The 1st is a medical screening. Laboratory visits 2 \& 5 will take ~5hrs and will be separated by 3 months, during which time subjects will consume 250ml of an orange drink (either OJ or an orange flavoured control drink) once a day. During visits 2 \& 5, subjects will have a scan to assess their %body fat using a low-dose x-ray machine, and have their insulin sensitivity measured using a technique called a 'Glucose Clamp'. During the 3hr glucose clamp, subjects receive an infusion of the hormone insulin and a glucose solution directly into their blood stream, with insulin sensitivity determined from the amount of glucose required to maintain blood glucose at normal levels. In addition, a small sample of fat tissue (about the size of a haricot bean) will be taken from underneath the skin of the belly. Subjects will record their food intake for 3-days in weeks 3, 7 and 11 of consuming the drink, and come to the lab for visits 3\&4 during weeks 4\&8. Laboratory visits 3\&4 repeat measurements taken in the 1st (screening) visit.
Read the detailed description
Background:
Overweight and mild obesity are associated with insulin resistance and mild elevations in lipid risk factors which are not usually sufficiently abnormal to merit treatment. Such people are encouraged to lose weight to reduce their risk of progressing to type 2 diabetes and coronary heart disease, but there is clearly a potential role for dietary modifications to maximize any potential benefit of this weight loss. Flavonoids are known to have vascular effects which might enhance substrate delivery to metabolically active tissues, and thus improve insulin sensitivity. There are many different dietary sources of flavonoids, with fruits such as apples, berries and citrus being rich sources. However, some researchers have expressed concern that a high dietary intake of 100% juice may contribute to the development of insulin resistance, obesity and the Metabolic Syndrome (Bazzano, Li et al. 2008), although this is not universally accepted (Fujioka, Greenway et al. 2006; O'Neil and Nicklas 2008). To date, there have been no studies investigating the effects of citrus fruits on indices of cardio-metabolic health in people who are presently healthy but are at risk of developing some features of the Metabolic Syndrome.
Aims:
To investigate the effects of orange juice (OJ) intake on insulin sensitivity, appetite hormones, blood pressure and plasma lipids. In addition we aim to investigate any gene expression changes associated with OJ consumption, in particular in adipose tissue.
Experimental protocol and methods:
Overweight or obese women (BMI 27-35), who are otherwise healthy, will be recruited onto the study. They will attend the 'David Greenfield Human Physiology' laboratories on 5 convenient mornings, following an overnight fast. The 1st visit is a medical screening and will involve signing a consent form, completing medical screening, food frequency and activity questionnaires, having height, weight, and hip/waist circumference measurements taken and a sample of blood taken for CBC, urea, electrolytes, LFT, TFT, glucose and insulin analysis. Subjects will then be asked to complete a 3-day diet diary for macronutrient assessment and to consume a diet providing 50% of energy as carbohydrate for 3 days prior to the 2nd laboratory visit. This 2nd visit will involve having a DEXA body composition scan, an adipose tissue biopsy and a 3-hr hyperinsulinemic, euglycemic glucose clamp. Starting on the following morning, subjects will then consume an orange drink (either OJ or a carbohydrate matched orange flavoured drink) once a day for 12 wks. A 3-day diet diary for macronutrient assessment will be recorded during wks 3,7and 11 of taking the drink, and measurements made at screening will be repeated on visits 3 and 4 which will take place in weeks 4 and 8. A standardized diet will be consumed for 3 days prior to the final laboratory visit, as before. This 5th visit will be identical to visit 2.
- Conditions
- Insulin Resistance, Obesity
- Being tested
- orange juice
- Keywords
- Women, Orange Juice, Insulin Resistance, Obesity
- Medical subject headings
- Insulin Resistance, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
orange juiceDietary supplement
250ml of orange juice or a sugars matched orange drink
| Study group | Role | What they receive |
|---|---|---|
| Orange Juice | Experimental | Orange Juice reconstituted from frozen concerntrate Receives: Dietary Supplement: orange juice |
| Orange drink | Placebo comparator | Sugars matched orange drink Receives: Dietary Supplement: orange juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity ('M' value)
Insulin sensitivity (mg glucose disposal from the blood/kg body weight/min)calculated from glucose disposal during a hyperinsulinemic, euglycemic glucose clamp
Measured: after 3 months' intervention
Secondary outcomes (4)
Glucose Oxidation rate
Measured by ventilated hood indirect calorimetry
Measured: after 3 months' intervention period
High Density Cholesterol
Serum HDL concentration
Measured: after 3 months' intervention
Low density cholesterol
Serum LDL concentration
Measured: after 3 months' intervention
Gene expression in adipose tissue
Expression of genes related to insulin sensitivity in adipose tissue
Measured: after 3 months' intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2010 (estimated)
- Study startJul 2010
- Primary completionDec 2011
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Collaborators
- Florida Department of Citrus
- Responsible party
- Principal investigator, Elizabeth Simpson, University of Nottingham
- Investigators
- Ian A Macdonald, PhD, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01201603
- Sponsor's protocol ID
- RIS 100058
- Status last verified
- Nov 2025
- First submitted
- 13 Sep 2010
- Last updated
- 28 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Bazzano LA, Li TY, Joshipura KJ, Hu FB. Intake of fruit, vegetables, and fruit juices and risk of diabetes in women. Diabetes Care. 2008 Jul;31(7):1311-7. doi: 10.2337/dc08-0080. Epub 2008 Apr 4.
PubMed 18390796Fujioka K, Greenway F, Sheard J, Ying Y. The effects of grapefruit on weight and insulin resistance: relationship to the metabolic syndrome. J Med Food. 2006 Spring;9(1):49-54. doi: 10.1089/jmf.2006.9.49.
PubMed 16579728O'Neil CE, Nicklas TA. A review of the relationship between 100% fruit juice consumption and weight in children and adolescents. American Journal of Lifestyle Medicine 2(4): 315-354, 2008.
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Orange Juice on Insulin Sensitivity and Plasma Lipids
- ClinicalTrials.gov ID
- NCT01201603
- Acronym / sponsor ID
- RIS 100058
- Conditions
- Insulin Resistance, Obesity
- Keywords
- Women, Orange Juice, Insulin Resistance, Obesity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Collaborators
- Florida Department of Citrus
- Study start
- Jul 2010
- Primary completion
- Dec 2011 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 14 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is primarily to investigate the ability of antioxidants found in orange juice (OJ) to increase the body's sensitivity to the hormone insulin. Overweight or mildly obese women, who are otherwise healthy, will be recruited. The time commitment for subjects is ~14wks. Subjects will attend the laboratory on 5 occasions after fasting from midnight. The 1st is a medical screening. Laboratory visits 2 \& 5 will take ~5hrs and will be separated by 3 months, during which time subjects will consume 250ml of an orange drink (either OJ or an orange flavoured control drink) once a day. During visits 2 \& 5, subjects will have a scan to assess their %body fat using a low-dose x-ray machine, and have their insulin sensitivity measured using a technique called a 'Glucose Clamp'. During the 3hr glucose clamp, subjects receive an infusion of the hormone insulin and a glucose solution directly into their blood stream, with insulin sensitivity determined from the amount of glucose required to maintain blood glucose at normal levels. In addition, a small sample of fat tissue (about the size of a haricot bean) will be taken from underneath the skin of the belly. Subjects will record their food intake for 3-days in weeks 3, 7 and 11 of consuming the drink, and come to the lab for visits 3\&4 during weeks 4\&8. Laboratory visits 3\&4 repeat measurements taken in the 1st (screening) visit.
Detailed description
Background:
Overweight and mild obesity are associated with insulin resistance and mild elevations in lipid risk factors which are not usually sufficiently abnormal to merit treatment. Such people are encouraged to lose weight to reduce their risk of progressing to type 2 diabetes and coronary heart disease, but there is clearly a potential role for dietary modifications to maximize any potential benefit of this weight loss. Flavonoids are known to have vascular effects which might enhance substrate delivery to metabolically active tissues, and thus improve insulin sensitivity. There are many different dietary sources of flavonoids, with fruits such as apples, berries and citrus being rich sources. However, some researchers have expressed concern that a high dietary intake of 100% juice may contribute to the development of insulin resistance, obesity and the Metabolic Syndrome (Bazzano, Li et al. 2008), although this is not universally accepted (Fujioka, Greenway et al. 2006; O'Neil and Nicklas 2008). To date, there have been no studies investigating the effects of citrus fruits on indices of cardio-metabolic health in people who are presently healthy but are at risk of developing some features of the Metabolic Syndrome.
Aims:
To investigate the effects of orange juice (OJ) intake on insulin sensitivity, appetite hormones, blood pressure and plasma lipids. In addition we aim to investigate any gene expression changes associated with OJ consumption, in particular in adipose tissue.
Experimental protocol and methods:
Overweight or obese women (BMI 27-35), who are otherwise healthy, will be recruited onto the study. They will attend the 'David Greenfield Human Physiology' laboratories on 5 convenient mornings, following an overnight fast. The 1st visit is a medical screening and will involve signing a consent form, completing medical screening, food frequency and activity questionnaires, having height, weight, and hip/waist circumference measurements taken and a sample of blood taken for CBC, urea, electrolytes, LFT, TFT, glucose and insulin analysis. Subjects will then be asked to complete a 3-day diet diary for macronutrient assessment and to consume a diet providing 50% of energy as carbohydrate for 3 days prior to the 2nd laboratory visit. This 2nd visit will involve having a DEXA body composition scan, an adipose tissue biopsy and a 3-hr hyperinsulinemic, euglycemic glucose clamp. Starting on the following morning, subjects will then consume an orange drink (either OJ or a carbohydrate matched orange flavoured drink) once a day for 12 wks. A 3-day diet diary for macronutrient assessment will be recorded during wks 3,7and 11 of taking the drink, and measurements made at screening will be repeated on visits 3 and 4 which will take place in weeks 4 and 8. A standardized diet will be consumed for 3 days prior to the final laboratory visit, as before. This 5th visit will be identical to visit 2.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Orange Juice | Experimental | Dietary Supplement: orange juiceOrange Juice reconstituted from frozen concerntrate |
| Orange drink | Placebo comparator | Dietary Supplement: orange juiceSugars matched orange drink |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- pre-menopausal or post-menopausal and taking HRT
- BMI 27-35kg/m2
- HOMA-IR value > 1.5
- healthy
Key exclusion criteria (8 listed)
- pregnant or breast feeding,
- any metabolic or endocrine abnormalities,
- clinically significant abnormalities on screening,
- fasting glucose > 6.0mmol/l,
- taking medication other than the contraceptive pill or HRT
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| orange juice250ml of orange juice or a sugars matched orange drink | Dietary supplement | Orange Juice, Orange drink |
Primary outcome
Insulin sensitivity ('M' value)
Time frame: after 3 months' intervention
Insulin sensitivity (mg glucose disposal from the blood/kg body weight/min)calculated from glucose disposal during a hyperinsulinemic, euglycemic glucose clamp
4 secondary outcomes
Glucose Oxidation rate
Time frame: after 3 months' intervention period
High Density Cholesterol
Time frame: after 3 months' intervention
Low density cholesterol
Time frame: after 3 months' intervention
Gene expression in adipose tissue
Time frame: after 3 months' intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2025.
- Background: PubMed 18390796Bazzano LA, Li TY, Joshipura KJ, Hu FB. Intake of fruit, vegetables, and fruit juices and risk of diabetes in women. Diabetes Care. 2008 Jul;31(7):1311-7. doi: 10.2337/dc08-0080. Epub 2008 Apr 4.
- Background: PubMed 16579728Fujioka K, Greenway F, Sheard J, Ying Y. The effects of grapefruit on weight and insulin resistance: relationship to the metabolic syndrome. J Med Food. 2006 Spring;9(1):49-54. doi: 10.1089/jmf.2006.9.49.
- BackgroundO'Neil CE, Nicklas TA. A review of the relationship between 100% fruit juice consumption and weight in children and adolescents. American Journal of Lifestyle Medicine 2(4): 315-354, 2008.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ian A Macdonald, PhD principal investigator
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing orange juice in people with Insulin Resistance and Obesity, run by University of Nottingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin sensitivity ('M' value) (time frame: after 3 months' intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01201603, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2025; AzTrials last refreshed its copy on 7 Nov 2026.