Brain Insulin Sensitivity, Brain Vascular Function, Cerebral Blood Flow, Cognitive Function, Satiety
Conditions
Brief summary
Protein-rich foods may improve brain insulin-sensitivity, which is important for cognitive and metabolic health, and may also translate into an improved food intake regulation. It is therefore pertinent to delineate the effects of plant-derived proteins, which are a more sustainable alternative to animal-derived proteins, on brain insulin-sensitivity and related functional benefits. The hypothesis is that daily plant-derived or animal-derived protein supplementation improves brain vascular function and insulin-sensitivity, thereby improving cognitive performance and appetite control in overweight or obese older men and women. The primary objective is to investigate in overweight or obese older adults the effect of daily protein supplementation for two weeks with either a plant-derived protein or an animal-derived protein on vascular function and insulin-sensitivity in the brain, while changes in cognitive performance and appetite-related brain reward activity will also be evaluated (secondary study objectives). Cerebral blood flow responses before (brain vascular function) and after the administration of intranasal insulin spray (brain insulin-sensitivity) will be quantified by the gold standard magnetic resonance imaging (MRI)-perfusion method Arterial Spin Labeling (ASL).
Interventions
DIETARY_SUPPLEMENTProtein supplementation with an animal-based protein isolate
Study participants will consume, in random order, twice daily (2 x \ 20 g) a plant protein (fava bean protein isolate), animal protein (milk protein isolate) or control (cornstarch providing no extra protein)
DIETARY_SUPPLEMENTProtein supplementation with a plant-based protein isolate
Study participants will consume, in random order, twice daily (2 x \ 20 g) a plant protein (fava bean protein isolate), animal protein (milk protein isolate) or control (cornstarch providing no extra protein)
OTHERControl arm - cornstarch
Study participants will consume, in random order, twice daily (2 x \ 20 g) a plant protein (fava bean protein isolate), animal protein (milk protein isolate) or control (cornstarch providing no extra protein)
Sponsors
Cosun
Maastricht University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women, aged between 60-75 years (older adults) * BMI between 25-35 kg/m2 (overweight or obese) * Fasting plasma glucose \< 7.0 mmol/L * Fasting serum total cholesterol \< 8.0 mmol/L * Fasting serum triacylglycerol \< 4.5 mmol/L * Systolic blood pressure \< 160 mmHg and diastolic blood pressure \< 100 mmHg * Stable body weight (weight gain or loss \< 3 kg in the past three months) * Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study * No difficult venipuncture as evidenced during the screening visit
Exclusion criteria
* Intolerant to milk products or fava bean allergy * Vegetarians * Left-handedness * Current smoker, or smoking cessation \< 12 months * Diabetic patients * Familial hypercholesterolemia * Abuse of drugs * More than 3 alcoholic consumptions per day * Use of products or dietary supplements known to interfere with the main outcomes as judged by the principal investigators * Use medication to treat blood pressure, lipid, or glucose metabolism * Use of an investigational product within another biomedical intervention trial within the previous 1-month * Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases, and rheumatoid arthritis * Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident * Contra-indications for MRI imaging (e.g., pacemaker, surgical clips/material in body, metal splinter in eye, claustrophobia)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cerebral blood flow responses before (brain vascular function) and after the administration of intranasal insulin spray (brain insulin-sensitivity) | Measured after 2 weeks of supplementation with protein isolate or control |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive performance | Measured after 2 weeks of supplementation with protein isolate or control | Cognitive performance will be assessed with a neuropsychological test battery |
| Appetite-related brain reward activity | Measured after 2 weeks of supplementation with protein isolate or control | Blood oxygenation level-dependent (BOLD)-functional MRI (fMRI) response to food cues |
Other
| Measure | Time frame | Description |
|---|---|---|
| Metabolic risk markers - Fasting lipids | Measured at baseline and after two weeks of supplementation with protein isolate or control | Fasting lipids: * Fasting serum triacylglycerol (TAG) concentrations in mmol/L will be measured * Fasting serum total cholesterol (TC) and HDL-C in mmol/L will be measured |
| Metabolic risk markers - glucose and insulin | Measured at baseline and after two weeks of supplementation with protein isolate or control | Fasting glucose and insulin: * Fasting plasma glucose concentrations in mmol/L will be measured * Fasting serum insulin concentrations in mmol/L will be measured |
| Metabolic risk markers - Low-grade systemic inflammation and microvascular function | Measured at baseline and after two weeks of supplementation with protein isolate or control | Low-grade systemic inflammation and microvascular function: * Fasting hemostatic factors and plasma markers related to systemic inflammation will be measured to assess low-grade systemic inflammatory responses (e.g. CRP) * Fasting plasma markers related to microvascular function will be measured to determine microvascular responses |
| Transcranial Doppler ultrasound | Measured after 2 weeks of supplementation with protein isolate or control | Blood flow velocity in the MCA |
| Perceived hunger and satiety | Measured after 2 weeks of supplementation with protein isolate or control | Visual analogue scale (VAS) questionnaires will be used to assess perceived feelings of hunger, fullness, desire to eat, and prospective food consumption. |
| Anthropometric measurements | Measured at baseline and after two weeks of supplementation with protein isolate or control | At all test days, anthropometric measurements (weight, length, waist and hip circumferences as indirect measures of fat distribution, and skinfold measurements) will be measured |
| Dietary intake | Measured after 2 weeks of supplementation with protein isolate or control | At the end of both interventions, food intake will be measured using a validated food frequency questionnaire (FFQ) |
| Single nucleotide polymorphisms (SNPs) | Measured once during the start of the study | Leucocytes will be isolated from EDTA blood. DNA will be isolated from these leucocytes according to standard procedures. DNA will be used for analyzing the presence of known SNPs in genes encoding proteins known to play a role in cholesterol metabolism. |
| Blood pressure | Measured at baseline and after two weeks of supplementation with protein isolate or control | Office BP (SBP and DBP) measured in mmHg |
| Heart rate | Measured at baseline and after two weeks of supplementation with protein isolate or control | Heart rate (HR) measured in beats/min |
Countries
Netherlands
Outcome results
None listed