Impact of Peanut Consumption on Stress, Immune Function, Inflammation, and Cardiovascular Health in High-Stress Individuals

USDA, Western Human Nutrition Research Center70 enrolled

Overview

The purpose of this research is to determine whether peanut consumption improves indicators of cardiovascular disease (CVD) risk in human subjects following the consumption of study foods.

The overall goal of the proposed study is to determine whether peanut consumption improves indices of cardiovascular disease (CVD) risk in human subjects with high levels of perceived chronic stress. Chronic stress is a growing public health concern and is associated with adverse health outcomes, including CVD. Stress, experienced when a person feels that environmental, physiological, or psychosocial demands tax or exceed their adaptive capacity, triggers a coordinated response from the sympathetic nervous system (SNS) and hypothalamic- pituitary- adrenal (HPA) axis increasing blood pressure, driving systemic inflammation, and affecting the immune system by accelerating the output of disease-promoting immune cells from bone marrow.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Immune System Stress Chronic Stress Cardiovascular Health

Interventions

Peanuts, roasted, salted with skinsOTHER

42g roasted salted peanuts with skins consumed daily

Isocaloric foodOTHER

Corn chips (45g)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Males and females * 18-65 years old * BMI ≥ 18.5 kg/m2 and ≤ 39.9 kg/ m2 * Recruitment will be based on Perceived Stress Scale - 4 (PSS-4) score Exclusion Criteria: * Less than 18 and over 65 years old * Pregnant or lactating women * Adults who rely on prescription medication that may influence study variables, apart from birth control * BMI \< 18.5 kg/m2 and \> 39.9 kg/m2 * Smokers who currently use tobacco- or marijuana-containing products including e-cigarettes, vape pens, pod mods, tanks, and electronic nicotine delivery devices (ENDS) * Habitual consumption of nuts, nut butters, nut powders, nut side dishes, nut bars or other nut products * Known food allergies (milk, eggs, fish, shellfish, tree nuts, peanuts, wheat, soybeans, sesame, corn) due to samples not prepared in a hypoallergenic environment * Currently living in close contact with individuals who have an allergy to peanuts, in order to avoid exposing these individuals to an allergen * Self-reported history of difficulties with blood drawing procedures including prior fainting or dizziness, or veins assessed as not suitable for four separate venipunctures by licensed phlebotomist * Diagnosed active chronic diseases for which the individual is currently taking daily medication, including but not limited to: * Diabetes mellitus, cardiovascular disease, cancer, gastrointestinal disorders, kidney disease, liver disease, bleeding disorders, asthma, autoimmune disorders, hypertension, osteoporosis * Recent minor surgery (within 4 weeks) or major surgery (within 16 weeks) * Known gallbladder disease or history of cholecystectomy * History of gastrointestinal surgery, including gastric bypass surgery or resection * Diagnosis of irritable bowel syndrome * Recent antibiotic therapy (within 4 weeks) * Recent hospitalization (within 4 weeks) * Current participation in another research study * Has HIV/AIDS, hepatitis, or another disease that affects the immune system * Gives regular blood donations and is unwilling to stop during the study * Blood Pressure ≥ 140 mmHg systolic or 90 mmHg diastolic * Current diagnoses of an eating disorder (ex. anorexia, bulimia, etc.) * High - very high triglyceride levels: ≥ 300 mg/dL * Adults who are unable to consent, individuals who are not yet adults (infants, children and teenagers), pregnant women and prisoners will be excluded from participation in the study * Participants who are unwilling to collect and transport urine, stool and saliva samples * Abnormal hemoglobin and/or hematocrit levels * Abnormal liver function (defined as liver enzymes that are \>200% of upper limit (ALT upper limit is 43 U/L or Aspartate transaminase (AST) upper limit is 54 U/L) * Unwillingness to discontinue probiotic, prebiotic, fiber, or other supplements (except RDA-level vitamin and mineral supplements) during the study * Unwilling to consume study foods * Alcohol consumption \> 20 g/day

Locations (1)

Western Human Nutrition Research Center

Davis, California, United States

RECRUITING

Outcomes

Primary Outcomes

Change in psychosocial stress over time

The PSS-10 will be administered 4 times during the study. The 10-item Perceived Stress Scale (PSS-10) is a validated, standard instrument used to assess subjective perceptions of chronic psychological stress (i.e., excessive demands, insufficient coping resources, and a perceived lack of control). The minimum score is 0 and the maximum score is 40. Higher scores indicate greater severity of psychosocial stress.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of allostatic load following dietary interventions

Before and after each intervention, cumulative physiological stress load, also referred to as allostatic load (AL), will be calculated. AL will be derived from 12-h overnight urinary cortisol, norepinephrine, and epinephrine levels (corrected for urinary creatinine levels), resting systolic and diastolic blood pressure, and overnight fasted waist-to-hip ratio, fasting serum levels of high-sensitivity C-reactive protein (hs-CRP), cholesterol, HDL-cholesterol, fasting plasma dehydroepiandrosterone sulfate (DHEA-S), and whole blood glycohemoglobin (HbA1c).

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of monocyte gene expression

Total monocytes isolated from human peripheral blood mononuclear cells (PBMCs) at baseline and post-intervention will be collected, and their global gene expression will be analyzed by ribonucleic acid (RNA) sequencing.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of cytokine and interferon production in PBMCs

Monocytes isolated from human peripheral blood mononuclear cells (PBMCs) will be challenged with and without toll-like receptor ligands to assess cytokine and interferon production in low- and high-stress subjects at baseline and after intervention.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of cytotoxicity of peripheral natural killer cells

Central Contacts

Ellen Bonnel, PhD

CONTACT

530-752-4184 elbonnel@ucdavis.edu

Ione Summers, BSc

CONTACT

530-754-8544 iosummerssteffes@ucdavis.edu

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

The cytotoxicity of peripheral natural killer (NK) cells isolated from subject's peripheral blood mononuclear cells (PBMCs) of low- and high-stress individuals at baseline and after intervention will be assessed using an ex vivo cytotoxicity assay with human erythroleukemic cell line (K562) target cells.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of interferon-gamma

Interferon-gamma (IFN-γ) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of tumor necrosis factors alpha and beta

Tumor necrosis factors alpha and beta (TNF-α, TNF-β) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of interleukins

A panel of interleukins: (IL) (IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of fibroblast growth factor

Fibroblast growth factor (FGF) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of granulocyte-macrophage colony-stimulating factor

Granulocyte-macrophage colony-stimulating factor (GM-CSF) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery:

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of thymus and activation-regulated chemokine

Thymus and activation-regulated chemokine (TARC). will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of macrophage inflammatory proteins-1 alpha and beta

Macrophage inflammatory proteins-1 alpha and beta (MIP-1α, MIP-1β) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of macrophage-derived chemokine

Macrophage-derived chemokine (MDC) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of monocyte chemoattractant proteins-1 and -4

Monocyte chemoattractant proteins-1 and -4 (MCP-1, MCP-4) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of interferon gamma-induced protein-10

Interferon gamma-induced protein-10 (IP-10) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of eotaxin and eotaxin-3

Eotaxin and eotaxin-3 will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of C-reactive protein

C-reactive protein (CRP) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of intercellular adhesion molecule-1

Intercellular adhesion molecule-1 (ICAM-1) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of placental growth factor

Placental growth factor (PlGF) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of serum amyloid A

Serum amyloid A (SAA) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of angiopoietin-1 receptor

Angiopoietin-1 receptor (Tie-2) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of vascular cell adhesion molecule-1

Vascular cell adhesion molecule-1 (VCAM-1) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of vascular endothelial growth factors A, C, and D

Vascular endothelial growth factors A, C, and D (VEGF-A, VEGF-C, VEGF-D) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of vascular endothelial growth factor receptor-1

Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1) will be measured before and after each intervention using the V-PLEX Human Biomarker 40-Plex Kit from Meso Scale Discovery

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change from baseline of monocyte phenotype

Classical monocytes, intermediate monocytes, and non-classical monocytes, will be identified by leukocyte common antigen (CD45+), Low-density lipoprotein receptor-related protein 1 (CD91+), cluster of differentiation 14 (CD14), cluster of differentiation 16 (CD16), and cluster of differentiation 3 (lin-CD3)/cluster of differentiation 66b (CD66b)/neural cell adhesion molecule (CD56)/cluster of differentiation 19 (CD19) using flow cytometry.

Time frame: Baseline, 4 weeks, 8 weeks, 12 weeks

Change from baseline of monocyte functional profile

Cellular activation of classical monocytes, intermediate monocytes, and non-classical monocytes will be assessed by expression of cluster of differentiation 11b (CD11b) and cluster of differentiation 163 (CD163).

Time frame: Baseline, 4 weeks, 8 weeks, 12 weeks

Change from baseline of natural killer cell phenotype

Natural killer (NK) cells will be identified by CD45+, cluster of differentiation 56+ (CD56+), and lin-CD3/CD66b/CD14/CD19 using flow cytometry.

Time frame: Baseline, 4 weeks, 8 weeks, 12 weeks

Change from baseline of natural killer cell functional profile

Natural killer (NK) cell maturation status and cytotoxic potential via CD16, cluster of differentiation 57 (CD57), killer cell lectin-like receptor K1 (NKG2D), and cluster of differentiation 159 (NKG2A) will be analyzed using flow cytometry.

Time frame: Baseline, 4 weeks, 8 weeks, 12 weeks

Secondary Outcomes

Changes in stool consistency

Participants will provide stool samples at 4 times throughout the study. Stool samples will be used to confirm the stool consistency reported by the study subject.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Changes in stool metrics

Participants will provide stool samples at 4 times throughout the study. Stool samples will be used to determine the whole stool weight.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Changes in bowel movement frequency

During the week prior to each intervention and the final week of each intervention, participants will maintain a stool diary for recording frequency of bowel movements.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Changes in gut transit time

During the week prior to each intervention and the final week of each intervention, participants will consume a muffin containing blue food dye. Participants will log the date and time of consumption, and will log each bowel movement until stool color changes. This will be used to measure gut transit time.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Changes in Gastrointestinal (GI) symptoms

During the week prior to each intervention and the final week of each intervention, a short GI Symptoms Questionnaire will be administered via Qualtrics to record occurrence of gastric symptoms.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Changes in gut microbial diversity

Participants will provide stool samples at 4 times throughout the study. Stool samples will be used to determine the microbial community composition by 16-subunit ribosomal ribonucleic acid (16S rRNA) amplicon sequence analysis.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Changes in stool short chain fatty acids

Participants will provide stool samples at 4 times throughout the study. Stool samples will be used to measure the amount of fecal short chain fatty acids (SCFAs).

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Changes in gut inflammatory markers

Participants will provide stool samples at 4 times throughout the study. Stool samples will be used to measure the inflammatory marker, fecal calprotectin.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in salivary cortisol

To assess waking and diurnal cortisol fluctuations, saliva will be collected at home at selected times upon waking and before bedtime. The waking saliva sample must be collected within 10-15 minutes of waking. Following the waking sample, participants will be asked to collect additional saliva samples at 15, 30, 45, and 60 minutes after the waking sample, as well as a saliva sample before bedtime. In total, participants will return 24 saliva samples (6 per visit) throughout the study.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in urinary cortisol levels

Before and after each intervention, 12-hour overnight urinary cortisol will be measured.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in urinary epinephrine levels

Before and after each intervention, 12-hour overnight urinary epinephrine levels will be measured.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in urinary norepinephrine levels

Before and after each intervention, 12-hour overnight urinary norepinephrine levels will be measured.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in urinary creatinine levels

Before and after each intervention, 12-hour overnight urinary creatinine levels will be measured.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in resting blood pressure

Research team will collect resting blood pressure (systolic and diastolic) in mmHg (millimeters of mercury).

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in dietary intake

Dietary intake will be assessed by using the Automated Self-Administered 24-hour (ASA24®) dietary assessment tool, a web-based tool that enables multiple, automatically coded, self-administered 24-hour recalls. Three dietary recalls will be conducted in the week preceding and the final week of each intervention period, for a total of 12, 24-hour dietary recalls.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in Body Weight

Research team will collect weight in kg.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in white blood cell count

White blood cell (WBC) count will be measured by a DxH 520 Hematology analyzer.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in lymphocyte count

Lymphocyte (LY) count will be measured by a DxH 520 Hematology analyzer.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in monocyte count

Monocyte (MO) count will be measured by a DxH 520 Hematology analyzer.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in neutrophil granulocyte count

Neutrophil granulocyte (NE) count will be measured by a DxH 520 Hematology analyzer.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in eosinophil count

Eosinophil (EO) count will be measured by a DxH 520 Hematology analyzer.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in basophil count

Basophil (BA) count will be measured by a DxH 520 Hematology analyzer.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in levels of triglycerides

Lipid-related markers including triglycerides will be measured by auto-analyzer, Cobas Integra 400+ instrument.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in levels of total cholesterol

Lipid-related markers including total cholesterol will be measured by auto-analyzer, Cobas Integra 400+ instrument.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in levels of HDL-cholesterol

Lipid-related markers including HDL-cholesterol (HDL-C) will be measured by auto-analyzer, Cobas Integra 400+ instrument.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in levels of LDL-cholesterol

Lipid-related markers including LDL-cholesterol (LDL-C) will be measured by auto-analyzer, Cobas Integra 400+ instrument.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks

Change in levels of glucose

Plasma glucose will be measured by auto-analyzer, Cobas Integra 400+ instrument.

Time frame: Baseline, 4 weeks, 8 weeks, and 12 weeks