Effects of Glycoxidative Stress on Human Aging

NCT00579774 | Completed

• 2 other identifiers: GCO 03-01165R37AG023188
• Study Type: interventional
• Target: 438
• Locations: 1 country
• Sites: 1

Brief Summary

Advanced glycation products or AGEs are a heterogeneous group of molecules formed by exposure of tissue constituents to high levels of reducing sugars, e.g. glucose. The interaction of these compounds with extra- and intra-cellular components may account in part for several conditions related to aging. It has recently been recognized that AGEs are also formed during the preparation of food by heating, are absorbed into the circulation and become largely incorporated into tissue components. Accumulation of these exogenous substances over time may, together with those generated endogenously, contribute to the clinical manifestations and complications of aging. This is an interventional-randomized study in which we are trying to determine whether a diet low in AGE can effectively reduce circulating AGE levels, with or without altering oxidation or inflammatory markers, in a subset of both young and older subjects , over a period of 4 months. If positive results are obtained, longer-term prospective studies will be designed to determine if this intervention can affect disease outcomes in older age subjects. The study design is very simple and consists initially of obtaining a dietary history, a blood sample, 24-hour urine collection and, subsequently, of determining the effects of a low-AGE diet for 4 months on the plasma levels of these compounds in a group of healthy subjects.

Conditions

Aging

Keywords

Aging; oxidative stress; glycoxidative stress; glycation; inflammation; nutrition; low AGE intake; dietary AGEs

Outcome Measures

Primary Outcomes (1)

• Levels of AGE

  Monthly

Secondary Outcomes (1)

• Side Effect Measurement

  Monthly

Study Arms (2)

1 - Low AGE Diet

EXPERIMENTAL

Low Age Diet

Other: Low AGE Diet

2 - Regular Diet

ACTIVE COMPARATOR

Regular Diet

Other: Regular Diet

Interventions

Low AGE Diet OTHER

Diet

1 - Low AGE Diet

Regular Diet OTHER

Diet

2 - Regular Diet

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adult subjects of any gender or race between the ages of 18 and 35 or older than 60 years

You may not qualify if:

• Diagnosis of diabetes (absence of diabetes will be defined as a negative history of diabetes in combination with a HgbA1c \< 6% at the time of recruitment)
• Any major cardiovascular event (myocardial infarction, stroke, PTCA or coronary artery bypass) within the preceding 3 months
• Smokers
• Glucocorticoid, anticoagulant (except for aspirin) or antioxidant therapy
• Serum creatinine greater than 2 mg/dl
• Inability to understand or unwillingness to follow study diets
• Any severe illness with an expected patient survival less than 1 year
• Patients who have initiated therapy with ACE inhibitors, lipid lowering medications or hormone replacement within the previous 3 months. Patients on stable doses of these medications will be included
• Before randomization all subjects will be screened with a 3-day food record to determine their average spontaneous daily intake of AGEs. Only those subjects whose daily intake is on the upper half of normal (greater than 14 AGE Eq/day) will participate in the study. This value of 14 E/day corresponds to the median daily AGE intake estimated in a large number of healthy subjects.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Related Publications (7)

• Cai W, Uribarri J, Zhu L, Chen X, Swamy S, Zhao Z, Grosjean F, Simonaro C, Kuchel GA, Schnaider-Beeri M, Woodward M, Striker GE, Vlassara H. Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans. Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):4940-5. doi: 10.1073/pnas.1316013111. Epub 2014 Feb 24.

  PMID: 24567379 RESULT

• Uribarri J, Cai W, Pyzik R, Goodman S, Chen X, Zhu L, Ramdas M, Striker GE, Vlassara H. Suppression of native defense mechanisms, SIRT1 and PPARgamma, by dietary glycoxidants precedes disease in adult humans; relevance to lifestyle-engendered chronic diseases. Amino Acids. 2014 Feb;46(2):301-9. doi: 10.1007/s00726-013-1502-4. Epub 2013 May 1.

  PMID: 23636469 RESULT

• Uribarri J, Cai W, Ramdas M, Goodman S, Pyzik R, Chen X, Zhu L, Striker GE, Vlassara H. Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: potential role of AGER1 and SIRT1. Diabetes Care. 2011 Jul;34(7):1610-6. doi: 10.2337/dc11-0091.

  PMID: 21709297 RESULT

• Beeri MS, Moshier E, Schmeidler J, Godbold J, Uribarri J, Reddy S, Sano M, Grossman HT, Cai W, Vlassara H, Silverman JM. Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals. Mech Ageing Dev. 2011 Nov-Dec;132(11-12):583-7. doi: 10.1016/j.mad.2011.10.007. Epub 2011 Nov 3.

  PMID: 22079406 RESULT

• Vlassara H, Cai W, Goodman S, Pyzik R, Yong A, Chen X, Zhu L, Neade T, Beeri M, Silverman JM, Ferrucci L, Tansman L, Striker GE, Uribarri J. Protection against loss of innate defenses in adulthood by low advanced glycation end products (AGE) intake: role of the antiinflammatory AGE receptor-1. J Clin Endocrinol Metab. 2009 Nov;94(11):4483-91. doi: 10.1210/jc.2009-0089. Epub 2009 Oct 9.

  PMID: 19820033 RESULT

• Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, Yong A, Striker GE, Vlassara H. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010 Jun;110(6):911-16.e12. doi: 10.1016/j.jada.2010.03.018.

  PMID: 20497781 RESULT

• Vlassara H, Uribarri J, Ferrucci L, Cai W, Torreggiani M, Post JB, Zheng F, Striker GE. Identifying advanced glycation end products as a major source of oxidants in aging: implications for the management and/or prevention of reduced renal function in elderly persons. Semin Nephrol. 2009 Nov;29(6):594-603. doi: 10.1016/j.semnephrol.2009.07.013.

  PMID: 20006791 RESULT

MeSH Terms

Conditions

Inflammation

Interventions

Diet

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Helen Vlassara, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 24, 2007
• Study Start: January 1, 2007
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2011
• Last Updated: April 9, 2014

Record last verified: 2014-04

Locations

US (1)