Assessing the Presence of Casomorphins in Human Plasma After Dairy Ingestion

This purpose of this study is to perform a pilot investigation to determine if opioid peptides such as casomorphin can be detected in human plasma after cheese ingestion.

Study Overview

• Status: Completed
• Conditions: Food Habits
• Intervention / Treatment: Behavioral: cheese ingestion

Detailed Description

Cheese is one of the most commonly craved foods, suggesting the possibility of opiate activity, as has been demonstrated with other craved foods, particularly chocolate. Like other dairy products, cheese contains casein, which is the major protein in cow's milk. This is unlike human milk, in which the primary protein is whey. Casein includes αs1-, αs2-, β- , and κ-casein, with αs1 and β forms predominating. Human and bovine casein molecules are cleaved during digestion to release opioid peptides that are believed to have biological properties relevant to infant physiology and behavior. Specifically, β-casein is cleaved to form β-casomorphins. Like other opiate agonists, β-casomorphins prolong gastrointestinal transit time and have an antidiarrheal effect.

Casomorphin receptor binding has been demonstrated in opiate receptor assays and bioassays. Duodenal aspirates from human volunteers given cow's milk have demonstrated the presence of several casomorphins, particularly β-casomorphin-7. Few studies have assessed the presence or action of casomorphins in humans. The ability of casein-derived opioid peptides to pass into the bloodstream is not well characterized, and is the subject of the present study.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, DC, District of Columbia, United States, 20016-4131
      • Physicians Committee for Responsible Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age greater than 18 years
• Male or female
• Either self-described as having a strong liking for cheese, or have been following a vegan diet for a least the previous six months.

Exclusion Criteria:

• Unstable medical status
• Physical condition affecting eating behavior, digestion, or intestinal absorption
• Dairy allergy or lactose intolerance
• Pregnancy
• History of severe mental illness
• Smoking during the past six months
• Alcohol consumption of more than two drinks per day
• History of substance abuse or dependency followed by any current use
• Inordinate fear of blood draws

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Cheese	Behavioral: cheese ingestion; On study day 1, approximately half of the participants will consume a breakfast of fruits and vegetables, whereas the other half of participants will consume a meal consisting of 9 oz. of cheese. Blood samples will be collected from participants immediately prior to consumption of the meals, and then again at regular intervals for up to 8 hours following the meals. At least 3 days later, participants will return for study Day 2. The participants will receive the second meal. Blood samples will then be collected immediately prior to consumption of the test meal and for up to 8 hours after the meal.
Placebo Comparator: B; Fruits and vegetables	Behavioral: cheese ingestion; On study day 1, approximately half of the participants will consume a breakfast of fruits and vegetables, whereas the other half of participants will consume a meal consisting of 9 oz. of cheese. Blood samples will be collected from participants immediately prior to consumption of the meals, and then again at regular intervals for up to 8 hours following the meals. At least 3 days later, participants will return for study Day 2. The participants will receive the second meal. Blood samples will then be collected immediately prior to consumption of the test meal and for up to 8 hours after the meal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
casomorphin quantification	Measurements will be collected on designated studys within 12-hour time frame

Collaborators and Investigators

• Sponsor: Physicians Committee for Responsible Medicine
• Investigators: Principal Investigator: Neal Barnard, MD, Physicians Committee for Responsible Medicine; Study Director: Hope R Ferdowsian, MD, MPH, Washington Center for Clinical Research

Publications and helpful links

General Publications

• Shah NP. Effects of milk-derived bioactives: an overview. Br J Nutr. 2000 Nov;84 Suppl 1:S3-10. doi: 10.1017/s000711450000218x.
• Meisel H, FitzGerald RJ. Opioid peptides encrypted in intact milk protein sequences. Br J Nutr. 2000 Nov;84 Suppl 1:S27-31. doi: 10.1017/s000711450000221x.
• Brantl V, Teschemacher H, Blasig J, Henschen A, Lottspeich F. Opioid activities of beta-casomorphins. Life Sci. 1981 Apr 27;28(17):1903-9. doi: 10.1016/0024-3205(81)90297-6. No abstract available.
• Svedberg J, de Haas J, Leimenstoll G, Paul F, Teschemacher H. Demonstration of beta-casomorphin immunoreactive materials in in vitro digests of bovine milk and in small intestine contents after bovine milk ingestion in adult humans. Peptides. 1985 Sep-Oct;6(5):825-30. doi: 10.1016/0196-9781(85)90308-0.
• Drewnowski A, Krahn DD, Demitrack MA, Nairn K, Gosnell BA. Taste responses and preferences for sweet high-fat foods: evidence for opioid involvement. Physiol Behav. 1992 Feb;51(2):371-9. doi: 10.1016/0031-9384(92)90155-u.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: August 3, 2006
• First Submitted That Met QC Criteria: August 3, 2006
• First Posted (Estimate): August 7, 2006

Study Record Updates

• Last Update Posted (Estimate): August 7, 2012
• Last Update Submitted That Met QC Criteria: August 6, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: craving; cheese; milk; casein; casomorphin
• Other Study ID Numbers: WCCR-01