Cardiovascular Health, Chronic Stress, Immune System, Stress
Conditions
Keywords
peanut, stress, immune function, cardiovascular health, chronic stress, pss10, inflammation, gut microbiota
Brief summary
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.
Detailed description
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.
Interventions
OTHERPeanuts, roasted, salted with skins
42g roasted salted peanuts with skins consumed daily
OTHERIsocaloric food
Corn chips (45g)
Sponsors
USDA, Western Human Nutrition Research Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in psychosocial stress over time | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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. |
| Change from baseline of allostatic load following dietary interventions | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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). |
| Change from baseline of monocyte gene expression | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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. |
| Change from baseline of cytokine and interferon production in PBMCs | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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. |
| Change from baseline of cytotoxicity of peripheral natural killer cells | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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. |
| Change from baseline of interferon-gamma | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of tumor necrosis factors alpha and beta | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of interleukins | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of fibroblast growth factor | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of granulocyte-macrophage colony-stimulating factor | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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: |
| Change from baseline of thymus and activation-regulated chemokine | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of macrophage inflammatory proteins-1 alpha and beta | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of macrophage-derived chemokine | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of monocyte chemoattractant proteins-1 and -4 | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of interferon gamma-induced protein-10 | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of eotaxin and eotaxin-3 | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of C-reactive protein | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of intercellular adhesion molecule-1 | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of placental growth factor | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of serum amyloid A | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of angiopoietin-1 receptor | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of vascular cell adhesion molecule-1 | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of vascular endothelial growth factors A, C, and D | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of vascular endothelial growth factor receptor-1 | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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 |
| Change from baseline of monocyte phenotype | Baseline, 4 weeks, 8 weeks, 12 weeks | 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. |
| Change from baseline of monocyte functional profile | Baseline, 4 weeks, 8 weeks, 12 weeks | 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). |
| Change from baseline of natural killer cell phenotype | Baseline, 4 weeks, 8 weeks, 12 weeks | Natural killer (NK) cells will be identified by CD45+, cluster of differentiation 56+ (CD56+), and lin-CD3/CD66b/CD14/CD19 using flow cytometry. |
| Change from baseline of natural killer cell functional profile | Baseline, 4 weeks, 8 weeks, 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in stool consistency | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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. |
| Changes in stool metrics | Baseline, 4 weeks, 8 weeks, and 12 weeks | Participants will provide stool samples at 4 times throughout the study. Stool samples will be used to determine the whole stool weight. |
| Changes in bowel movement frequency | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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. |
| Changes in gut transit time | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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. |
| Changes in Gastrointestinal (GI) symptoms | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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. |
| Changes in gut microbial diversity | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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. |
| Changes in stool short chain fatty acids | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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). |
| Changes in gut inflammatory markers | Baseline, 4 weeks, 8 weeks, and 12 weeks | Participants will provide stool samples at 4 times throughout the study. Stool samples will be used to measure the inflammatory marker, fecal calprotectin. |
| Change in salivary cortisol | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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. |
| Change in urinary cortisol levels | Baseline, 4 weeks, 8 weeks, and 12 weeks | Before and after each intervention, 12-hour overnight urinary cortisol will be measured. |
| Change in urinary epinephrine levels | Baseline, 4 weeks, 8 weeks, and 12 weeks | Before and after each intervention, 12-hour overnight urinary epinephrine levels will be measured. |
| Change in urinary norepinephrine levels | Baseline, 4 weeks, 8 weeks, and 12 weeks | Before and after each intervention, 12-hour overnight urinary norepinephrine levels will be measured. |
| Change in urinary creatinine levels | Baseline, 4 weeks, 8 weeks, and 12 weeks | Before and after each intervention, 12-hour overnight urinary creatinine levels will be measured. |
| Change in resting blood pressure | Baseline, 4 weeks, 8 weeks, and 12 weeks | Research team will collect resting blood pressure (systolic and diastolic) in mmHg (millimeters of mercury). |
| Change in dietary intake | Baseline, 4 weeks, 8 weeks, and 12 weeks | 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. |
| Change in Body Weight | Baseline, 4 weeks, 8 weeks, and 12 weeks | Research team will collect weight in kg. |
| Change in white blood cell count | Baseline, 4 weeks, 8 weeks, and 12 weeks | White blood cell (WBC) count will be measured by a DxH 520 Hematology analyzer. |
| Change in lymphocyte count | Baseline, 4 weeks, 8 weeks, and 12 weeks | Lymphocyte (LY) count will be measured by a DxH 520 Hematology analyzer. |
| Change in monocyte count | Baseline, 4 weeks, 8 weeks, and 12 weeks | Monocyte (MO) count will be measured by a DxH 520 Hematology analyzer. |
| Change in neutrophil granulocyte count | Baseline, 4 weeks, 8 weeks, and 12 weeks | Neutrophil granulocyte (NE) count will be measured by a DxH 520 Hematology analyzer. |
| Change in eosinophil count | Baseline, 4 weeks, 8 weeks, and 12 weeks | Eosinophil (EO) count will be measured by a DxH 520 Hematology analyzer. |
| Change in basophil count | Baseline, 4 weeks, 8 weeks, and 12 weeks | Basophil (BA) count will be measured by a DxH 520 Hematology analyzer. |
| Change in levels of triglycerides | Baseline, 4 weeks, 8 weeks, and 12 weeks | Lipid-related markers including triglycerides will be measured by auto-analyzer, Cobas Integra 400+ instrument. |
| Change in levels of total cholesterol | Baseline, 4 weeks, 8 weeks, and 12 weeks | Lipid-related markers including total cholesterol will be measured by auto-analyzer, Cobas Integra 400+ instrument. |
| Change in levels of HDL-cholesterol | Baseline, 4 weeks, 8 weeks, and 12 weeks | Lipid-related markers including HDL-cholesterol (HDL-C) will be measured by auto-analyzer, Cobas Integra 400+ instrument. |
| Change in levels of LDL-cholesterol | Baseline, 4 weeks, 8 weeks, and 12 weeks | Lipid-related markers including LDL-cholesterol (LDL-C) will be measured by auto-analyzer, Cobas Integra 400+ instrument. |
| Change in levels of glucose | Baseline, 4 weeks, 8 weeks, and 12 weeks | Plasma glucose will be measured by auto-analyzer, Cobas Integra 400+ instrument. |
Countries
United States
Contacts
CONTACTEllen Bonnel, PhD
CONTACTIone Summers, BSc
PRINCIPAL_INVESTIGATORRyan Snodgrass, PhD
United States Department of Agriculture - Western Human Nutrition Research Center
Outcome results
None listed