Developing Biomarkers of Dietary Intake

NCT01237093 | Completed Phase 1

• 2 other identifiers: 99991101811-DK-N018
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Researchers who study health and nutrition are interested in developing more accurate methods of determining what people eat from day to day and how it affects their general health. In particular, better methods are needed to determine if people are accurately remembering what they ate. One possible method involves the use of biomarkers, or indicators in urine, blood, saliva, fat, and hair, which are related to the intake of a particular food in a consistent way. One set of biomarkers in blood samples and hair may be used to determine the relative amount of meat, fish, and soda (corn/sugar cane) in a person s diet. However, more research is needed to study the effectiveness of using these biomarkers to accurately track dietary intake. Objectives: \- To validate the use of biomarkers as representative of specific dietary intake patterns (meat/fish/soda). Eligibility: \- Healthy, nondiabetic men between 18 and 65 years of age. Design:

• This study involves an initial screening visit and a 12-13 week inpatient dietary study period.
• Participants will be screened with a medical history and physical examination, as well as blood and urine samples and a glucose tolerance test to exclude individuals who have diabetes.
• After 3 days of a standard weight-maintaining diet, participants will have a glucose tolerance test and a body fat scan; provide hair, blood, and fat tissue samples; and complete questionnaires and performance tests.
• Participants will spend one day in a metabolic chamber to measure their energy expenditure and general metabolism.
• Participants will then be randomized into one of eight carefully designed diets for 12 weeks. The diets will differ in the amount of meat, fish, and soda, including one diet where none of the three biomarker-related foods will be permitted. Blood samples will be collected throughout the study diet period.
• At the end of the 12-week study diet period, participants will provide additional hair, blood, and fat tissue samples, and will have a second metabolism assessment in the metabolic chamber.

Conditions

Healthy Volunteers; Diet Therapy

Keywords

Fish Diet; Meat Diet; Biomarkers; Stable Isotopes; Dietary Intake

Outcome Measures

Primary Outcomes (2)

• Change in NIR

  Change in nitrogen stable isotope rations (N15/N14)

  Weeks 0, 2, 4, 6, 8, 10, 12

• Change in CR

  Change in carbon stable isotope ratios (13C/12C)

  Weeks 0, 2, 4, 6, 8, 10, 12

Secondary Outcomes (4)

• Performance tests

  Weeks 0 and 12

• OGTT

  Weeks 0 and 12

• Lipid panel

  Weeks 0 and 12

• Respiratory quotient (RQ)

  Weeks 0 and 12

Study Arms (8)

1. Meat, no fish or soda

EXPERIMENTAL

weight maintaining diet with meat but no fish or soda for 12 weeks

Other: 1. Meat, no fish or soda

2. Meat and soda, no fish

EXPERIMENTAL

weight maintaining diet with meat and soda but no fish for 12 weeks

Other: 2. Meat and soda, no fish

4. Meat and fish and soda

EXPERIMENTAL

weight maintaining diet with meat, fish, and soda for 12 weeks

Other: 4. Meat and fish and soda

5. Fish, no meat or soda

EXPERIMENTAL

weight maintaining diet with meat, fish, and soda for 12 weeks

Other: 5. Fish, no meat or soda

6. Fish and soda, no meat

EXPERIMENTAL

weight maintaining diet with fish and soda but no meat for 12 weeks

Other: 6. Fish and soda, no meat

7. No meat, fish, or soda

EXPERIMENTAL

no fish, and no soda (vegetarian) for 12 weeks

Other: 7. No meat, fish or soda

8. Soda, no meart or fish

EXPERIMENTAL

weight maintaining diet with soda but no meat or fish (vegetarian + soda) for 12 weeks

Other: 8. Soda, no meat or fish

Meat and fish, no soda

EXPERIMENTAL

weight maintaining diet with meat and fish but no soda for 12 weeks

Other: 3. Meat and fish, no soda

Interventions

3. Meat and fish, no soda OTHER

weight maintaining diet with meat and fish but no soda

Meat and fish, no soda

4. Meat and fish and soda OTHER

weight maintaining diet with meat, fish and soda

4. Meat and fish and soda

5. Fish, no meat or soda OTHER

weight maintaining diet with fish but no meat or soda

5. Fish, no meat or soda

6. Fish and soda, no meat OTHER

weight maintaining diet with fish and soda but no meat

6. Fish and soda, no meat

7. No meat, fish or soda OTHER

weight maintaining diet with no meat, no fish, and no soda (vegetarian)

7. No meat, fish, or soda

8. Soda, no meat or fish OTHER

weight maintaining diet with soda but no meat or fish (vegetarian + soda)

8. Soda, no meart or fish

1. Meat, no fish or soda OTHER

weight maintaining diet with meat but no fish or soda

1. Meat, no fish or soda

2. Meat and soda, no fish OTHER

weight maintaining diet with meat and soda but no fish

2. Meat and soda, no fish

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body mass index less than or equal to 35 kg/m(2) to minimize the impact of body size on isotope measurements.
• Males 18-65 years old will be recruited for this study. Minors under the age of 18 will be excluded because the time requirements of the study are such that they would interfere with school schedules.
• Healthy, as determined by medical history, physical examination, and laboratory tests.

You may not qualify if:

• Current smoking
• Female sex
• Baldness or hair less than 2 cm in length
• Medically- or self-imposed dietary restrictions that would limit a participant s ability/willingness to consume the diet to which they are randomized.
• Type 2 diabetes (according to the World Health Organization diagnostic criteria)
• Endocrine disorders (Cushing s Disease, pituitary disorders, and hypo- and hyperthyroidism)
• Chronic pulmonary disorders, including chronic obstructive pulmonary disease, that would limit ability to follow the protocol (investigator judgment) and obstructive sleep apnea syndrome; only subjects with mild or exercise-induced asthma on no medications or on beta-adrenergic agonists only (such as albuterol) will be allowed to enter the study (provided use of these agents is not required for one week before study entry).
• Cardiovascular diseases (coronary heart disease, heart failure, arrhythmias, and peripheral artery disease)
• Hypertension (blood pressure measurement higher than 140/90 mm Hg on two or more occasions or use of anti-hypertensive medications)
• Diagnosed gastrointestinal diseases, including inflammatory bowel diseases (e.g., Crohn s disease and ulcerative colitis), malabsorption syndromes (e.g., celiac disease), gastric ulcer (active); only subjects with gastro-esophageal reflux will be allowed to enter the study
• Presence of a pacemaker or other implantable devices
• Liver disease (cirrhosis, active hepatitis B or C, and AST or ALT greater than or equal to 1.5 x normal)
• Renal disease (serum creatinine concentrations greater than or equal to 1.5 mg/dl and/or greater than 100mg/dl of protein based on urine dipstick)
• Central nervous system disease (cerebrovascular accidents, dementia, and neurodegenerative disorders)
• Cancer requiring treatment in the past five years, except for non-melanoma skin cancers or cancers that have clearly been cured or in the opinion of the investigator carry an excellent prognosis

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

NIDDK, Phoenix

Phoenix, Arizona, 85014, United States

Location

Related Publications (10)

• Kipnis V, Subar AF, Midthune D, Freedman LS, Ballard-Barbash R, Troiano RP, Bingham S, Schoeller DA, Schatzkin A, Carroll RJ. Structure of dietary measurement error: results of the OPEN biomarker study. Am J Epidemiol. 2003 Jul 1;158(1):14-21; discussion 22-6. doi: 10.1093/aje/kwg091.

  PMID: 12835281 BACKGROUND

• Subar AF, Kipnis V, Troiano RP, Midthune D, Schoeller DA, Bingham S, Sharbaugh CO, Trabulsi J, Runswick S, Ballard-Barbash R, Sunshine J, Schatzkin A. Using intake biomarkers to evaluate the extent of dietary misreporting in a large sample of adults: the OPEN study. Am J Epidemiol. 2003 Jul 1;158(1):1-13. doi: 10.1093/aje/kwg092.

  PMID: 12835280 BACKGROUND

• Tarasuk V, Beaton GH. The nature and individuality of within-subject variation in energy intake. Am J Clin Nutr. 1991 Sep;54(3):464-70. doi: 10.1093/ajcn/54.3.464.

  PMID: 1877501 BACKGROUND

• Johnson JJ, Ghosh S, Shaw PA, Neuhouser ML, Lampe JW, Tinker LF, Prentice RL, Tasevska N, Freedman LS, Boyer BB, Hopkins SE, Nash SH, Votruba SB, Krakoff J, O'Brien DM. The carbon isotope ratio of alanine is a biomarker of added sugar and sugar-sweetened beverage intakes: a pooled analysis of 4 studies. Am J Clin Nutr. 2025 Dec;122(6):1769-1777. doi: 10.1016/j.ajcnut.2025.09.049. Epub 2025 Oct 3.

  PMID: 41047130 DERIVED

• Mitchell CM, Oxtoby LE, Shaw PA, Budge SM, Wooller MJ, Cabeza de Baca T, Krakoff J, Votruba S, O'Brien DM. Carbon Isotope Ratios of Plasma and RBC Fatty Acids Identify Meat Consumers in a 12-Week Inpatient Feeding Study of 32 Men. J Nutr. 2023 Jan 14;152(12):2847-2855. doi: 10.1093/jn/nxac213.

  PMID: 36095134 DERIVED

• Johnson JJ, Shaw PA, Wooller MJ, Venti CA, Krakoff J, Votruba SB, O'Brien DM. Amino Acid Nitrogen Isotope Ratios Respond to Fish and Meat Intake in a 12-Week Inpatient Feeding Study of Men. J Nutr. 2022 Sep 6;152(9):2031-2038. doi: 10.1093/jn/nxac101.

  PMID: 35511610 DERIVED

• Mitchell CM, Piaggi P, O'Brien DM, Krakoff J, Votruba SB. Metabolic Characterization of Meat, Fish, and Soda Intake in Males: Secondary Results from a Randomized Inpatient Pilot Study. Obesity (Silver Spring). 2021 Jun;29(6):995-1002. doi: 10.1002/oby.23167. Epub 2021 May 3.

  PMID: 33938613 DERIVED

• Johnson JJ, Shaw PA, Oh EJ, Wooller MJ, Merriman S, Yun HY, Larsen T, Krakoff J, Votruba SB, O'Brien DM. The carbon isotope ratios of nonessential amino acids identify sugar-sweetened beverage (SSB) consumers in a 12-wk inpatient feeding study of 32 men with varying SSB and meat exposures. Am J Clin Nutr. 2021 May 8;113(5):1256-1264. doi: 10.1093/ajcn/nqaa374.

  PMID: 33676366 DERIVED

• Votruba SB, Shaw PA, Oh EJ, Venti CA, Bonfiglio S, Krakoff J, O'Brien DM. Associations of plasma, RBCs, and hair carbon and nitrogen isotope ratios with fish, meat, and sugar-sweetened beverage intake in a 12-wk inpatient feeding study. Am J Clin Nutr. 2019 Dec 1;110(6):1306-1315. doi: 10.1093/ajcn/nqz208.

  PMID: 31515553 DERIVED

• Stinson EJ, Graham AL, Thearle MS, Gluck ME, Krakoff J, Piaggi P. Cognitive dietary restraint, disinhibition, and hunger are associated with 24-h energy expenditure. Int J Obes (Lond). 2019 Jul;43(7):1456-1465. doi: 10.1038/s41366-018-0305-9. Epub 2019 Jan 16.

  PMID: 30651576 DERIVED

MeSH Terms

Interventions

In Situ Hybridization, Fluorescence

Intervention Hierarchy (Ancestors)

In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Cytogenetic Analysis; Genetic Techniques; Nucleic Acid Hybridization

Study Officials

• Susanne M Votruba, Ph.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2010
• First Posted: November 9, 2010
• Study Start: October 24, 2010
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: May 5, 2026

Record last verified: 2026-03-16

Locations

US (1)