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This study is conducted to investigate if vitamin E status in healthy individuals and individuals with metabolic syndrome can be improved by dairy fat. The investigators hypothesize that full-fat dairy will substantially increase the bioavailability of alpha-tocopherol, a form of vitamin E. The results of this study will contribute to the application of dairy fat as a simple and effective strategy for improving vitamin E status, which is partly due to poor vitamin E intake. By completing this study, the investigators anticipate developing new dietary recommendations to achieve adequate vitamin E status through the regular consumption of dairy fat paired with foods containing vitamin E.
Nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome and affects >70 million Americans. Weight loss and vitamin E supplementation are leading strategies for preventing and/or treating NASH. However, the long-term success of weight loss is limited and >92% of Americans fail to meet dietary recommendations for vitamin E. Thus, the objective is to define the extent to which dairy fat facilitates adequate vitamin E status in individuals with metabolic syndrome, a population at high-risk for NASH, by improving α-tocopherol bioavailability. The central hypothesis is that full-fat dairy will substantially increase alpha-tocopherol (a-T) bioavailability to the extent needed to facilitate production of alpha-carboxyethyl-hydroxy-chromanol (a-CEHC), a metabolite of a-T that predict a-T status. The will therefore complete the following specific aims: 1) define milk fat-mediated improvements in a-T bioavailability, and 2) define dairy fat-mediated improvements in a-T status. This study involves a randomized crossover study design where healthy adults and those with metabolic syndrome (n = 10/group) will ingest deuterium-labeled a-T (15 mg) with 1 cup of either fat-free milk, low-fat milk, whole milk, or soy milk. Urine and blood samples will be collected at timed intervals prior to and following milk consumption. Blood will be collected at timed intervals over 72 h, and plasma will be analyzed by liquid chromatography with mass spectrometry to determine pharmacokinetic parameters by measuring labeled and unlabeled a-T and a-CEHC. Risk to participants is expected to be minimal and will be outlined in the informed consent form in clear and simple terms. Upon successful completion of this study, it is expected to show that a-T bioavailability increases in a milk fat-dependent manner and that dairy milk compared with soy milk significantly improves a-T bioavailability. The results are expected to provide timely evidence demonstrating the amount and type of fat needed to achieve optimal vitamin E status specifically in a population of significant public health concern. Overall, these studies will fill a substantial knowledge gap regarding the importance of dairy fat in contributing to optimal health and provide a simple dietary approach to ameliorate poor vitamin E status among a significant proportion of Americans.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acute Fat-Free Milk Ingestion | Experimental | Participants will ingest 1 cup of fat-free milk with 15 mg deuterium-labeled alpha-tocopherol. |
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| Acute Low-Fat Milk Ingestion | Experimental | Participants will ingest 1 cup of low-fat milk with 15 mg deuterium-labeled alpha-tocopherol. |
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| Acute Full-Fat Milk Ingestion | Experimental | Participants will ingest 1 cup of full-fat milk with 15 mg deuterium-labeled alpha-tocopherol. |
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| Acute Soy Milk Ingestion | Experimental | Participants will ingest 1 cup of soy milk with 15 mg deuterium-labeled alpha-tocopherol. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fat-Free Milk | Other | Fat-free milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve 0-72 h (Deuterium Labeled Alpha-tocopherol) | 0, 3, 6, 9, 12, 24, 36, 48, and 72 h post test meal | |
| Cmax | Maximal plasma concentration of deuterium labelled alpha-tocopherol | 0-72 h post-meal |
| Tmax | Time to maximal plasma concentration of deuterium labelled alpha-tocopherol | 0-72 h post-meal |
| Elimination Rate | Rate of plasma elimination of deuterium labelled alpha-tocopherol | 0-72 h post-meal |
| Estimated Absorption (% Dose) | Absorption of deuterium labelled alpha-tocopherol | 0-72 h post-meal |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Richard Bruno, PhD, RD | Ohio State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ohio State University | Columbus | Ohio | 43210 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26447154 | Result | Mah E, Sapper TN, Chitchumroonchokchai C, Failla ML, Schill KE, Clinton SK, Bobe G, Traber MG, Bruno RS. alpha-Tocopherol bioavailability is lower in adults with metabolic syndrome regardless of dairy fat co-ingestion: a randomized, double-blind, crossover trial. Am J Clin Nutr. 2015 Nov;102(5):1070-80. doi: 10.3945/ajcn.115.118570. Epub 2015 Oct 7. | |
| 28077381 |
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Data will be shared when it becomes available
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| ID | Title | Description |
|---|---|---|
| FG000 | Acute Fat-Free Milk Ingestion First | Participants ingested fat-free milk first and then the remaining three milks in a randomized order: low-fat milk, full-fat milk, and soy milk. Participants will ingest 1 cup of fat-free milk with 15 mg deuterium-labeled alpha-tocopherol. Fat-Free Milk: Fat-free milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. |
| FG001 | Acute Low-Fat Milk Ingestion First | Participants ingested low-free milk first and then the remaining three milks in a randomized order: fat-fat milk, full-fat milk, and soy milk. Participants will ingest 1 cup of low-fat milk with 15 mg deuterium-labeled alpha-tocopherol. Low-Fat Milk: Low-fat milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. |
| FG002 | Acute Full-Fat Milk Ingestion First | Participants ingested full-free milk first and then the remaining three milks in a randomized order: low-fat milk, low-fat milk, and soy milk. Participants will ingest 1 cup of full-fat milk with 15 mg deuterium-labeled alpha-tocopherol. Full-Fat Milk: Full-fat milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. |
| FG003 | Acute Soy Milk Ingestion First | Participants ingested soy milk first and then the remaining three milks in a randomized order: low-fat milk, full-fat milk, and fat-free milk. Participants will ingest 1 cup of soy milk with 15 mg deuterium-labeled alpha-tocopherol. Soy Milk: Soy milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 (Cross-over Arm 1) |
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| Period 2 (Cross-over Arm 2) |
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| Period 3 (Cross-over Arm 3) |
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| Period 4 (Cross-over Arm 4) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Participants | As a randomized crossover study design, participants were stratified by health status (healthy versus metabolic syndrome) and received fat-free milk, low-fat milk, full-fat milk, and soy milk in a randomized order. |
| BG001 | Metabolic Syndrome Participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Curve 0-72 h (Deuterium Labeled Alpha-tocopherol) | Posted | Mean | Standard Error | umol/L x h | 0, 3, 6, 9, 12, 24, 36, 48, and 72 h post test meal |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Acute Fat-Free Milk Ingestion | Participants will ingest 1 cup of fat-free milk with 15 mg deuterium-labeled alpha-tocopherol. Fat-Free Milk: Fat-free milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Richard S. Bruno, PhD, RD | The Ohio State University | 614-292-1698 | bruno.27@osu.edu |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| D024821 | Metabolic Syndrome |
| D008107 | Liver Diseases |
| D005234 | Fatty Liver |
| ID | Term |
|---|---|
| D004066 | Digestive System Diseases |
| D007333 | Insulin Resistance |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
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| ID | Term |
|---|---|
| D018752 | Diet, Fat-Restricted |
| D041942 | Soy Milk |
| ID | Term |
|---|---|
| D004035 | Diet Therapy |
| D044623 | Nutrition Therapy |
| D013812 | Therapeutics |
| D004032 | Diet |
| D009747 |
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| Low-Fat Milk | Other | Low-fat milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. |
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| Full-Fat Milk | Other | Full-fat milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. |
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| Soy Milk | Other | Soy milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. |
|
| Traber MG, Mah E, Leonard SW, Bobe G, Bruno RS. Metabolic syndrome increases dietary alpha-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial. Am J Clin Nutr. 2017 Mar;105(3):571-579. doi: 10.3945/ajcn.116.138495. Epub 2017 Jan 11. |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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As a randomized crossover study design, participants were stratified by health status (healthy versus metabolic syndrome) and received fat-free milk, low-fat milk, full-fat milk, and soy milk in a randomized order. |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Body mass index | Mean | Standard Deviation | kg/m2 |
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| Glucose | Mean | Standard Deviation | mg/dL |
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| Systolic Blood Pressure | Mean | Standard Deviation | mmHg |
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| Diastolic Blood Pressure | Mean | Standard Deviation | mmHg |
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| Waist Circumference | Mean | Standard Deviation | cm |
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| Triglyceride | Mean | Standard Deviation | mg/dL |
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| HDL cholesterol | Mean | Standard Deviation | mg/dL |
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| alpha-tocopherol | Mean | Standard Deviation | umol/L |
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| alpha-tocopherol | Mean | Standard Deviation | umol/mmol lipid |
|
| Acute Full-Fat Milk Ingestion |
Participants will ingest 1 cup of full-fat milk with 15 mg deuterium-labeled alpha-tocopherol. Full-Fat Milk: Full-fat milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. |
| OG003 | Acute Soy Milk Ingestion | Participants received 1 cup of soy milk with deuterium labeled alpha-tocopherol |
|
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| Primary | Cmax | Maximal plasma concentration of deuterium labelled alpha-tocopherol | Posted | Mean | Standard Error | umol/L | 0-72 h post-meal |
|
|
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| Primary | Tmax | Time to maximal plasma concentration of deuterium labelled alpha-tocopherol | Posted | Mean | Standard Error | h | 0-72 h post-meal |
|
|
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| Primary | Elimination Rate | Rate of plasma elimination of deuterium labelled alpha-tocopherol | Posted | Mean | Standard Error | mmol/L/h | 0-72 h post-meal |
|
|
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| Primary | Estimated Absorption (% Dose) | Absorption of deuterium labelled alpha-tocopherol | Posted | Mean | Standard Error | % dose | 0-72 h post-meal |
|
|
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| 0 |
| 20 |
| 0 |
| 20 |
| EG001 | Acute Low-Fat Milk Ingestion | Participants will ingest 1 cup of low-fat milk with 15 mg deuterium-labeled alpha-tocopherol. Low-Fat Milk: Low-fat milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. | 0 | 20 | 0 | 20 |
| EG002 | Acute Full-Fat Milk Ingestion | Participants will ingest 1 cup of full-fat milk with 15 mg deuterium-labeled alpha-tocopherol. Full-Fat Milk: Full-fat milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. | 0 | 20 | 0 | 20 |
| EG003 | Acute Soy Milk Ingestion | Participants will ingest 1 cup of soy milk with 15 mg deuterium-labeled alpha-tocopherol. Soy Milk: Soy milk ingestion with 15 mg deuterium-labeled alpha-tocopherol. | 0 | 20 | 0 | 20 |
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| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D041941 | Milk Substitutes |
| D001628 | Beverages |
| D045730 | Soy Foods |
| D000067075 | Vegetable Products |
| D014675 | Vegetables |
| D005502 | Food |
| D019602 | Food and Beverages |
| Metabolic Syndrome |
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| Metabolic Syndrome |
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| Metabolic Syndrome |
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| Metabolic Syndrome |
|