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| Name | Class |
|---|---|
| General Mills | INDUSTRY |
| Tufts Medical Center | OTHER |
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The purpose of this study is to determine if substituting whole grains for refined grains in the diets of healthy adults over a period of 6 weeks alters the composition of the bacteria in the gut, and has beneficial effects on immune function, digestive health, cardiovascular health, regulation of body weight and composition, and vitamin K status.
The investigators hypothesize that whole grain consumption over a period of 6 weeks will alter the gut microflora toward a more beneficial bacterial profile, improve the immune response while reducing oxidative stress and inflammatory markers, have favorable effects on factors influencing the regulation of body weight and composition,increase bacterial vitamin K synthesis, and beneficially effect surrogate markers of cholesterol synthesis/absorption, vitamin D concentrations, and whole genome DNA methylation patterns. In statin users it is hypothesized that, consumption of whole grains will alter statin pharmacokinetics by decreasing rate of statin absorption, resulting in more sustained plasma concentrations.
This study is a randomized parallel-arm trial using a six-week dietary intervention following a 2 week run-in period. Healthy volunteers will be randomized to two groups (n=40/group), and consume either a diet rich in whole grains or a diet rich in refined grains provided at estimated energy requirements for 6 weeks. Outcomes will be measured during the run-in period and at week 6 of the intervention. To control for variation in microbiota an additional 10 volunteers will serve as "negative controls" and not undergo any diet intervention.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Whole grain rich diet | Experimental | Participants in the whole grain (WG) group will receive a diet providing 100% of energy requirements in a diet rich in whole grains. |
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| Refined grain rich diet | Placebo Comparator | Participants in the refined grain (RG) group will receive a diet providing 100% of energy requirements in a diet rich in refined grains. |
|
| Negative control | No Intervention | Subjects randomized to the negative control group will consume their own usual diet (i.e. not receive foods and beverages from the study). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Whole grains | Other | Following completion of the baseline period (a 2-week run-in phase), participants in the WG group will receive a diet providing 100% of energy requirements in a diet rich in whole grains and the RG group will be provided with 100% of energy requirements in a diet rich in refined grains but otherwise similar to the WG diet for 6 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| change in T Cell-mediated immunity | Delayed-type hypersensitivity (DTH) and lymphocyte proliferation will be measured at baseline (week 2 of washout period) and at week-6 of the diet intervention to assess adaptive immune function, specifically T cell-mediated immunity. | week 2 of washout diet and week 6 of diet intervention |
| change in Lymphocyte proliferation | Whole blood collected at baseline (week 2 of washout period) and at week-6 of the diet intervention will be investigated for the ability of lymphocytes to proliferate by quantifying the incorporation of tritium following mitogen stimulation. | week 2 of washout diet and week 6 of diet intervention |
| change in Natural Killer Function | The ability of peripheral blood mononuclear cells to bind and kill leukemia cells will be measured at baseline (week 2 of washout period) and at week-6 of the diet intervention | week 2 of washout diet and week 6 of diet intervention |
| change in Cytokines | Peripheral blood and stool samples will be analyzed at baseline (week 2 of washout diet) and week-6 of diet intervention for cytokines. | week 2 of washout diet and week 6 of diet intervention |
| change in Salivary immunoglobulin A (IgA) | Salivary IgA will be analyzed at baseline (week 2 of washout period) and at week-6 of the diet intervention. | week 2 of washout diet and week 6 of intervention diet |
| Measure | Description | Time Frame |
|---|---|---|
| change in gut microbiota composition | Phylogenetic composition and relative abundance of bacteria in stool will be analyzed from 24-hour fresh sample collected at baseline (week 2 of washout diet) and at week 6 of intervention diet | week 2 of washout diet and week 6 of intervention diet |
| change in cardiovascular health risk factors |
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Subjects Inclusion Criteria
Healthy male and female subjects aged 40-65 y (women must be > 1 year postmenopausal or had both ovaries removed, if premenopausal).
Body mass index (BMI) 20-35 kg/m.2
Pass screening blood and urine tests
Must be willing to be randomized.
Those randomized to either the WG or RG groups must be willing to consume only study foods and beverages provided.
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Simin N Meydani, DVM, PhD | Human Nutrition Research Center on Aging | Principal Investigator |
| Junaidah B Barnett, MCH(N), PhD | Human Nutrition Research Center on Aging | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HNCRA at Tufts University | Boston | Massachusetts | 02111 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28814395 | Derived | Karl JP, Meydani M, Barnett JB, Vanegas SM, Barger K, Fu X, Goldin B, Kane A, Rasmussen H, Vangay P, Knights D, Jonnalagadda SS, Saltzman E, Roberts SB, Meydani SN, Booth SL. Fecal concentrations of bacterially derived vitamin K forms are associated with gut microbiota composition but not plasma or fecal cytokine concentrations in healthy adults. Am J Clin Nutr. 2017 Oct;106(4):1052-1061. doi: 10.3945/ajcn.117.155424. Epub 2017 Aug 16. | |
| 28179226 |
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| ID | Term |
|---|---|
| D000067348 | Whole Grains |
| ID | Term |
|---|---|
| D002523 | Edible Grain |
| D018556 | Crops, Agricultural |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
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| Refined grains | Other | Following completion of the baseline period (a 2-week run-in phase), participants in the WG group will receive a diet providing 100% of energy requirements in a diet rich in whole grains and the RG group will be provided with 100% of energy requirements in a diet rich in refined grains but otherwise similar to the WG diet for 6 weeks. |
|
Consumption of the whole grain (WG) diet will be beneficial for multiple outcomes of cardiovascular health including a favorable blood lipid profile (low density lipoprotein, very low-density lipoprotein, high density lipoprotein, total cholesterol and triglycerides), and a decrease in blood pressure, and in oxidative stress status (secondary hypothesis). |
| week 2 of washout diet and week 6 of intervention diet |
| change in vitamin K status | Fecal menaquinones concentrations; Fasting serum phylloquinone and menaquinones concentration from 72-hour stool collected at baseline (week 2 of washout diet) and at week 6 of intervention diet | week 2 of washout diet and week 6 of intervention diet |
| change in body composition | Fat and fat free mass; waist and hip circumference | week 2 of washout diet and week 6 of intervention diet |
| change in appetite | Visual analog scales to assess hunger, fullness and satisfaction while on the study diet | Weekly for 8 weeks |
| change in fasting gut hormone concentration | Plasma glucagon-like peptide-1 and peptide-YY will be measured from blood samples collected at baseline (week 2 of washout diet) and week 6 of intervention diet | week 2 of washout diet and week 6 of intervention diet |
| change in fasting serum leptin | week 2 of washout diet and week 6 of intervention diet |
| change in glycemic regulation | 48 hr continuous glucose monitoring; fasting serum glucose; fasting serum insulin; HOMA-IR | week 2 of washout diet and week 6 of intervention diet |
| change in resting energy metabolism | Resting energy expenditure; substrate oxidation at rest | week 2 of washout diet and week 6 of intervention diet |
| change in eating behaviors | Questionnaires will be administered at baseline (week 2 of washout diet) and week 6 of intervention diet | week 2 of washout diet and week 6 of intervention diet |
| change in quality of life | Questionnaires will be administered at baseline (week 2 of washout diet) and week 6 of intervention diet | week 2 of washout diet and week 6 of intervention diet |
| change in breath hydrogen and methane | week 2 of washout diet and week 6 of intervention diet |
| change in stool pH | Will be measured from 72-hour stool sample collected at baseline (week 2 of washout diet) and week 6 of intervention diet | week 2 of washout diet and week 6 of intervention diet |
| change in 72hr fecal weight | Will be measured from 72-hour stool sample collected at baseline (week 2 of washout diet) and week 6 of intervention diet | week 2 of washout diet and week 6 of intervention diet |
| change in stool water content | Will be measured from 72-hour stool sample collected at baseline (week 2 of washout diet) and week 6 of intervention diet | week 2 of washout diet and week 6 of intervention diet |
| change in total stool anaerobic and aerobic bacterial counts | Will be measured from 72-hour stool sample collected at baseline (week 2 of washout diet) and week 6 of intervention diet | week 2 of washout diet and week 6 of intervention diet |
| change in stool energy content | Will be measured from 72-hour stool sample collected at baseline (week 2 of washout diet) and week 6 of intervention diet | week 2 of washout diet and week 6 of intervention diet |
| change in DNA methylation | week 2 of washout diet and week 6 of intervention diet |
| change in concentrations of the cholesterol synthesis (squalene, desmosterol, lathosterol) and absorption (campesterol, sitosterol, cholestanol) markers | Plasma squalene, desmosterol, lathosterol), campesterol, sitosterol, and cholestanol concentrations will be measured at baseline (week 2 of washout diet) and week 6 of intervention diet | week 2 of washout diet and week 6 of intervention diet |
| change in serum vitamin D | week 2 of washout diet and week 6 of intervention diet |
| Derived |
| Vanegas SM, Meydani M, Barnett JB, Goldin B, Kane A, Rasmussen H, Brown C, Vangay P, Knights D, Jonnalagadda S, Koecher K, Karl JP, Thomas M, Dolnikowski G, Li L, Saltzman E, Wu D, Meydani SN. Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults. Am J Clin Nutr. 2017 Mar;105(3):635-650. doi: 10.3945/ajcn.116.146928. Epub 2017 Feb 8. |
| 28179223 | Derived | Karl JP, Meydani M, Barnett JB, Vanegas SM, Goldin B, Kane A, Rasmussen H, Saltzman E, Vangay P, Knights D, Chen CO, Das SK, Jonnalagadda SS, Meydani SN, Roberts SB. Substituting whole grains for refined grains in a 6-wk randomized trial favorably affects energy-balance metrics in healthy men and postmenopausal women. Am J Clin Nutr. 2017 Mar;105(3):589-599. doi: 10.3945/ajcn.116.139683. Epub 2017 Feb 8. |
| D010829 |
| Physiological Phenomena |
| D012639 | Seeds |
| D019602 | Food and Beverages |