Postprandial Effects of Milk Fats (POEMI)

The Effects of Different Fat Structures on Postprandial Responses in Healthy Subjects

Nowadays, mostly vegetable fat blends are used in infant formula, but the use of bovine milk fat is increasing. In terms of fat structure, bovine milk fat and vegetable fats differ. Bovine milk fat has a higher percentage of palmitic acid attached to the sn-2 position of the glycerol backbone compared to vegetable fat blend. Also bovine milk fat contains milk fat globular membranes, as opposed to vegetable fat. With this study the investigators want to examine the effects of a vegetable fat blend versus bovine milk fat without globular membranes and bovine milk fat with globular membranes on underlying mechanistic, immune and metabolic responses.

Study Overview

• Status: Unknown
• Conditions: Nutrition; Metabolism; Genomics; Postprandial Metabolism
• Intervention / Treatment: Other: 100% vegetable blend; Other: 100% AMF; Other: 100% cream

Detailed Description

Rationale: Human milk is considered as the ideal food for full-term infants. The composition and function of human milk is unique and has provided the basis for the development of modern artificial milk formulas that mimic its complex biological positive effects on infants and can provide an appropriate substitute for non-breastfed infants. An important component in human milk are the lipids, as they deliver 50% of the total energy to infants. Nowadays, mostly vegetable fat blends are used in infant formula, but the use of bovine milk fat is increasing. In terms of fat structure, bovine milk fat and vegetable fats differ. Bovine milk fat has a higher percentage of palmitic acid attached to the sn-2 position of the glycerol backbone compared to vegetable fat blend. Also bovine milk fat contains milk fat globular membranes, as opposed to vegetable fat. Knowledge on how these differences influence underlying mechanistic, immune and metabolic responses is lacking.

Objectives: The primary objective of this study is to determine the effect of three different fat blends on underlying mechanistic and immune responses in the circulation. The secondary objectives of this study are: 1) to examine the effects of the three different fat blends on postprandial triglyceride concentration and other cardio-metabolic markers in the circulation, 2) to investigate the effect of the three different fat blends on postprandial feelings of hunger and satiety, and 3) to investigate how comparable cytokine measurements are in blood samples obtained via a catheter cannula compared to cytokine measurements in dried blood spots obtained via a finger prick.

Study design: The POEMI Study is a double-blind randomized cross-over acute intervention study in which each research subject will visit the university on three separate occasions with a wash-out period of at least one week. At each visit the research subject will undergo one of the three dietary lipid challenge tests (a shake) in a randomized order. On each study day research subjects will be asked to clock in 30 minutes prior to the first data collection points and a catheter cannula will be inserted in a antecubital vein. After the 30 minute rest, blood will be drawn from the catheter cannula and via a finger prick (baseline measurements, t0). After the baseline measurements, the research subjects will have to consume the shake within a time frame of 10 minutes. Blood is again drawn from the catheter cannula at t= 1, 2, 3, 4, 5, 6, 7, and 8 hours after consumption, with an additional finger prick at t=6. A questionnaire on hunger and satiety feelings will be taken after every blood draw.

Study population: The base population will consist of 40 healthy men and women with a BMI ranging from 22 to 27 kg/m2, aged 40 to 70 years old, selected from the surroundings of Wageningen through the mailing list for potential study research subjects of the division of Human Nutrition and health of Wageningen University. If needed, additional recruitment of research subjects will take place by flyers and posters, or advertisements in local newspapers.

Intervention: The dietary lipid challenge tests will be provided in the form of a liquid shake (0.6 L). Each shake will contain 95 gram of fat. The three types of fat that will be tested include: a) 100% vegetable fat blend, b) 100% Anhydrous milk fat (AMF), c) 100% cream (AMF + milk fat globular membranes).

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Wageningen, Gelderland, Netherlands, 6700 EV
      • Recruiting
      • Wageningen University, Division of Human Nutrition
      • Contact: Lydia A Afman, PhD; Phone Number: 0031317485789; Email: lydia.afman@wur.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Apparently healthy man or woman
• Age 40-70y at the time of recruitment
• BMI of 22-27 kg/m2
• Having a Hb value above 8.4 (men) or 7.4 (women) mmol/L (will be checked at the screening visit)
• Having veins suitable for blood sampling via a catheter cannula (judged by study nurse/ medical doctor)
• Having a general practitioner
• Signed informed consent

Exclusion Criteria:

• Any chronic metabolic, gastrointestinal, inflammatory or chronic disease (such as diabetes, anaemia, hepatitis, cardiovascular disease)
• History of gastro-intestinal surgery or having (serious) gastro-intestinal complaints
• Renal or hepatic malfunctioning (pre-diagnosis or determined based on ALAT, ASAT and creatinine values)
• Use of medication that may influence the study results, such as laxatives, stomach protectors and drugs that can affect intestinal motility.
• Donated or intend to donate blood from 2 months before the study until the end of the study
• Reported slimming, medically prescribed or vegan diet
• Unstable body weight (weight gain or loss >5 kg in the past three months)
• Current smokers
• Alcohol on average: more than 2 consumptions/day or more than 14 consumptions/week
• Pregnant, lactating or wishing to become pregnant in the period of the study (self-reported)
• Use of illicit drugs
• Food allergies for products that the investigators use in the study
• Participation in another clinical trial at the same time, or in the month preceding the start of this study
• Inability to understand study information and/or communicate with staff
• Members of the research team
• Working, or doing an internship or thesis at the division "Human Nutrition and Health", Wageningen University

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V-A-C; Order of administration: 100% vegetable fat blend; 100% Anhydrous Milk Fat (AMF); 100% Cream (AMF + milk fat globular membranes)	Other: 100% vegetable blend; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of vegetable fat blend.; Other: 100% AMF; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of anhydrous milk fat.; Other: 100% cream; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of anhydrous milk fat plus milk fat globular membranes.
Experimental: V-C-A; Order of administration: 100% vegetable fat blend; 100% Cream (AMF + milk fat globular membranes); 100% Anhydrous Milk Fat (AMF)	Other: 100% vegetable blend; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of vegetable fat blend.; Other: 100% AMF; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of anhydrous milk fat.; Other: 100% cream; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of anhydrous milk fat plus milk fat globular membranes.
Experimental: A-V-C; Order of administration: 100% Anhydrous Milk Fat (AMF); 100% vegetable fat blend; 100% Cream (AMF + milk fat globular membranes)	Other: 100% vegetable blend; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of vegetable fat blend.; Other: 100% AMF; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of anhydrous milk fat.; Other: 100% cream; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of anhydrous milk fat plus milk fat globular membranes.
Experimental: A-C-V; Order of administration: 100% Anhydrous Milk Fat (AMF); 100% Cream (AMF + milk fat globular membranes); 100% vegetable fat blend	Other: 100% vegetable blend; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of vegetable fat blend.; Other: 100% AMF; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of anhydrous milk fat.; Other: 100% cream; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of anhydrous milk fat plus milk fat globular membranes.
Experimental: C-A-V; Order of administration: 100% Cream (AMF + milk fat globular membranes); 100% Anhydrous Milk Fat (AMF); 100% vegetable fat blend	Other: 100% vegetable blend; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of vegetable fat blend.; Other: 100% AMF; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of anhydrous milk fat.; Other: 100% cream; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of anhydrous milk fat plus milk fat globular membranes.
Experimental: C-V-A; Order of administration: 100% Cream (AMF + milk fat globular membranes); 100% vegetable fat blend; 100% Anhydrous Milk Fat (AMF)	Other: 100% vegetable blend; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of vegetable fat blend.; Other: 100% AMF; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of anhydrous milk fat.; Other: 100% cream; Dietary lipid challenge test: 600 ml skimmed milk plus 95 gram of anhydrous milk fat plus milk fat globular membranes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in transcriptomics from baseline to 6 hours after consumption of the three different fat blends, to elucidate underlying mechanistic responses in the circulation.	By using untargeted whole genome Affymetrix microarray the investigators will measure gene expression in isolated monocytes.	Baseline and 6 hours after consumption of the dietary lipid challenge.
Change in cytokine concentration from baseline and every hour until 8 hours after consumption of the different fat blends, to elucidate the effect on immune responses in the circulation.	Cytokine concentrations in the circulation will be measured via ELISA.	Baseline and every hour until 8 hours after consumption of the dietary lipid challenge.
Change in functional responses to LPS stimulation of isolated monocytes from the circulation from baseline to 6 hours after consumption of the different fat blends.	Cell study with isolated monocytes from the circulation. The cells will be treated with LPS to evaluate functional responses. We will measure fold changes.	Baseline and 6 hours after consumption of the dietary lipid challenge.
Change in sensitivity of isolated monocytes from the circulation.	Cell study with isolated monocytes from the circulation. The cells will be treated with different fat loads and inflammatory stimuli to evaluate the sensitivity of the collected monocytes. We will measure fold changes.	Baseline and 6 hours after consumption of the dietary lipid challenge.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial triacylglycerol changes	TAG concentration in plasma will be measured in a clinical chemical lab.	Baseline and every hour until 8 hours after consumption of the dietary lipid challenge.
Postprandial glucose changes	Cardio-metabolic markers such as glucose (mg/dl) will be measured in the circulation.	Baseline and every hour until 8 hours after consumption of the dietary lipid challenge.
Postprandial adiponectin changes	Cardio-metabolic markers such as adiponectin (pg/ml) will be measured in the circulation.	Baseline and every hour until 8 hours after consumption of the dietary lipid challenge.
Postprandial insulin changes	Cardio-metabolic markers such as insulin (mIU/L) will be measured in the circulation.	Baseline and every hour until 8 hours after consumption of the dietary lipid challenge.
Postprandial (untargeted) protein profile changes	Using untargeted proteomic platforms, the changes in protein profiles in the circulation will be measured.	Baseline and every hour until 8 hours after consumption of the dietary lipid challenge.
Postprandial (targeted) protein profile changes	Using targeted proteomic platforms, the changes in protein profiles in the circulation will be measured.	Baseline and every hour until 8 hours after consumption of the dietary lipid challenge.
Postprandial (untargeted) metabolite profile changes	Using untargeted metabolomic platforms, the changes in protein profiles in the circulation will be measured.	Baseline and every hour until 8 hours after consumption of the dietary lipid challenge.
Postprandial (targeted) metabolite profile changes	Using targeted metabolomic platforms, the changes in protein profiles in the circulation will be measured.	Baseline and every hour until 8 hours after consumption of the dietary lipid challenge.
Postprandial changes in feelings of hunger and satiety	Feelings of hunger and satiety will be measured via a questionnaire using a Visual Analog Scale (VAS), a 100 mm line anchored at each end by descriptors. Research subjects will place a mark on the scale that corresponds to their feelings of hunger and satiety. The distance from the lower end of the scale is then measured and recorded.	Baseline and every hour until 8 hours after consumption of the dietary lipid challenge.
Cytokine concentration comparison	Cytokine concentrations in the circulation obtained via catheter cannula will be measured via ELISA. The investigators will also measure cytokine concentrations in dried blood spots obtained via a finger prick (via a Meso Scale Discovery Electrochemiluminescence platform).	Baseline and 6 hours after consumption of the dietary lipid challenge.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune cell populations	Relative immune cell populations will be determined in whole blood via FACS analysis.	Baseline and 6 hours after consumption of the dietary lipid challenge.
CRP	The CRP value of each research subject will be determined by using a QuikRead CRP test.	Before the start of a study day.
WHR	Both waist and Hip circumference will be measured using a measuring tape.	Baseline
BMI	weight (in kg) and height (in meters) will be measured and combined to report BMI in kg/m^2	Baseline
Habitual intake	As assessed by a validated FFQ.	Baseline
Renal or hepatic malfunctioning	ALAT (IU/L), ASAT (IU/L) will be measured in a clinical chemical lab.	Baseline
Renal malfunctioning	creatinine (mg/dL) will be measured in a clinical chemical lab.	Baseline
Anemia	Hemoglobin will be determined via a finger prick.	Baseline

Collaborators and Investigators

• Sponsor: Wageningen University
• Collaborators: Friesland Campina
• Investigators: Principal Investigator: Lydia Afman, PhD, Wageningen University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 2, 2019
• Primary Completion (Anticipated): February 28, 2020
• Study Completion (Anticipated): February 28, 2020

Study Registration Dates

• First Submitted: August 16, 2019
• First Submitted That Met QC Criteria: November 22, 2019
• First Posted (Actual): November 26, 2019

Study Record Updates

• Last Update Posted (Actual): November 26, 2019
• Last Update Submitted That Met QC Criteria: November 22, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Humans; Nutrition; Clinical Trial; Genomics; Metabolism; Milk fat
• Other Study ID Numbers: NL69492.081.19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Collected data will be coded.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No