The Effect of a Meal on Vitamin D Absorption

Study Overview
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Brief Summary
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This study seeks to determine if vitamin D3 absorption in healthy adults will be enhanced in the presence of a meal and if the enhancement will be greater when the meal is low as opposed to high in fat content. The enhancement will result from increased vitamin D absorption. The investigators will test this hypothesis by pursuing the following aims in a 3-mo trial in which up to 70 healthy men and women will be randomized to one of the following meal conditions under which they will take a monthly oral dose of 50,000 IU of vitamin D3: no meal (fasting), a low fat meal, or a high fat meal. The Primary Aim is to identify the meal condition (fasting, low-fat, or high-fat meal) under which the 25OHD3 response to supplemental vitamin D3 is greatest and most consistent. The Secondary Aim is to determine whether vitamin D3 absorption is affected by the meal condition and to determine whether the absorption of vitamin D3 predicts the longer-term 25OHD3 response to supplementation.

Detailed Description
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Vitamin D supplements are increasingly recommended to curb widespread deficiency. Decreasing the variability in 25OHD responses to supplemental vitamin D would make the supplementation process more predictable, and thereby reduce the number of 25OHD measurements and dose adjustments that are needed to achieve the targeted 25OHD level. This study seeks to identify potential sources of variability in the 25OHD3 response to supplemental vitamin D3 that are plausible based on rat studies, but have not been explored in humans. The investigators hypothesize that the serum 25OHD3 response to supplemental vitamin D3 in healthy adults will be enhanced in the presence of a meal and the enhancement will be greater when the meal is low as opposed to high in fat content. The enhancement will result from increased vitamin D absorption. The investigators will test this hypothesis by pursuing the following aims in a 3-mo trial in which up to 70 healthy men and women will be randomized to one of the following meal conditions under which they will take a monthly oral dose of 50,000 IU of vitamin D3: no meal (fasting), a low fat meal, or an iso-caloric high fat meal. Serum 25OHD3 will be measured at baseline and after 1 and 3 mo. A serum vitamin D3 absorption test will be performed in each subject after the first dose of vitamin D. The Primary Aim is to identify the meal condition (fasting, low-fat, or high-fat meal) under which the 25OHD3 response to supplemental vitamin D3 is greatest and most consistent. The Secondary Aim is to determine whether vitamin D3 absorption is affected by the meal condition and to determine whether the absorption of vitamin D3 predicts the longer-term 25OHD3 response to supplementation.

Official Title
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Meal Effects on the 25OHD3 Response to Supplemental Vitamin D3

Conditions
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Vitamin D Deficiency

Intervention / Treatment
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* Dietary Supplement: cholecalciferol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 50 to 69 BMI ≥ 18.5 and ≤ 27.9 kg/m2 those taking ≤ 400 IU/day of vitamin D3 and ≤ 1000 mg calcium/day those who participate must agree not to change their dietary or supplemental vitamin D or calcium intake during the study no use of tanning salons no travel south of latitude 34 degrees north during the study Exclusion Criteria: General: A screening 25OHD level ≤8 or ≥ 25 ng/ml An abnormal serum calcium (reference range is 8.3 -10.2 mg/dl) A screening spot urinary calcium:creatinine ratio > 0.325 Greater than 2 drinks of alcohol a day. BMI <18.5 and >27.9 kg/m2 Menses within the last year (women) Age <50 and > 69 years Allergy to egg A blood donation in the last 2 months (increases likelihood of anemia) Non-English speaking subjects will not be enrolled. Other abnormalities in screening labs, at the discretion of the study physician (PI) Medications: Subjects must agree not to take more than 400 IU per day of vitamin D as supplement or cod liver oil during the study Topical vitamin D preparations Oral estrogen or estrogen patch use in the last 6 months Regular antacid use (>2 times per week) Sucralfate Acarbose/miglitol PPIs - prescription: lansoprazole (Prevacid), omeprazole (Prilosec and Zegerid), esomeprazole (Nexium), rabeprazole (Aciphex), pantoprazole (Protonix); over-the-counter: lansoprazole (Prevacid 24), omeprazole (Prilosec OTC), zegerid OTC (Equate), omeprazole magnesium H2 blockers - prescription: cimetidine (Tagamet), famotidine (Pepsid), nizatidine (Axid), rantidine hydrochloride (Zantac), dexlansoprazole (Kapidex); over the counter: cimetidine (Tagamet-HB, Equate), famotidine (Pepcid-AC, Pepcid Complete), rantidine hydrochloride (Zantac, Wal-Zan, Equate) Drugs that alter fat and cholesterol handling - xenical and alli (Orlistat), cholestyramine (Questran, LoCholest, Prevalite), Zetia Drugs that alter 25OHD metabolism - Antiseizure drugs phenobarbitol and phenytoin (Dilantin), oral glucocorticoids Calcium supplement use >1000 mg/day Diseases: Active parathyroid disease Sarcoidosis Peptic ulcers or esophageal stricture Active malignancy (other than basal cell cancer of the skin) or cancer therapy in the last year Advanced kidney disease (creatinine clearance <30 ml/min calculated from serum creatinine with use of the Modification of Diet in Renal Disease (MDRD) Study equation Kidney stones in the last 5 years. Liver disease Zollinger-Ellison syndrome Known achlorhydria or small bowel overgrowth Malabsorption Diseases associated with fat malabsorption - liver disease, cystic fibrosis, Celiac disease, bariatric surgery, Scleroderma, Crohn's, prior surgery involving the stomach or small bowel (appendectomy okay), gall stones or prior gall bladder surgery, pancreatitis

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low fat meal<br>Those subjects who receive a low fat meal prior to vitamin D3 administration | Dietary Supplement: cholecalciferol<br>* 50,000 IU once per month for 3 months<br>* Other names: vitamin D3;|
| Active Comparator: High fat meal<br>Those subjects who receive a high fat meal prior to vitamin D3 administration | Dietary Supplement: cholecalciferol<br>* 50,000 IU once per month for 3 months<br>* Other names: vitamin D3;|
| Active Comparator: No meal<br>Those subjects who do not receive a meal and continue to fast. They only receive the vitamin D3 dose. | Dietary Supplement: cholecalciferol<br>* 50,000 IU once per month for 3 months<br>* Other names: vitamin D3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 25OHD3 response to supplemental vitamin D3 | To identify the meal condition (fasting, low-fat, or high-fat meal) under which the 25OHD3 response to supplemental vitamin D3 is greatest and most consistent, specifically, to describe and compare changes in serum 25OHD3 concentration across the 3 groups. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in parent vitamin D3 levels | To determine whether vitamin D3 absorption is affected by the meal condition, specifically,a) to describe and compare the change in parent vitamin D3 levels over the 12-hr period following the first dose of vitamin D3 across the 3 groups and b) to determine whether the absorption of vitamin D3 at 12 hours predicts the longer-term 25OHD3 response to supplementation. | 12 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, vitamin D deficiency, vitamin D absorption