Efficacy of Vitamin D Supplementation in Bariatric Surgery Patients

The prospective pilot study is designed to evaluate vitamin D status pre-operatively and
post-operatively in 37 female patients undergoing either Roux-en Y gastric bypass or sleeve
gastrectomy at The Methodist Hospital with 32 patients expecting to complete the 12 week
trial. Women scheduled for either of these two types of bariatric surgery will be considered
for inclusion in the pilot study. Based on previous research experience at The Methodist
Hospital, the majority of bariatric patients are women. No children are treated at the
Methodist Hospital bariatric center.

Subjects will be excluded if they have evidence of vitamin D deficiency (25(OH)D <20 ng/mL),
hypercalcemia (calcium > 2.63 mmol/L), hypocalcemia (calcium < 1.75 mmol/L), renal
insufficiency (GFR < 50 ml/min), or a history of primary hyperparathyroidism or renal tubular
acidosis. Participants will be excluded if they take medications that interfere with vitamin
D metabolism, have significant sun exposure, plan to travel to sunny climates during the
study, or a history of hypercalcemia.

Baseline measures of serum 25(OH)D, PTH, calcium and phosphorus will be obtained. Values will
be determined one week prior to surgery and during the follow-up visit at 12 weeks
postoperatively. In addition, 25(OH)D will be measured at the 4th week post-operative clinic
visit. Baseline information obtained will include age, height (centimeter), weight
(kilogram), body mass index, sex, and race or ethnicity. A full medication list and medical
history to identify any co-morbid conditions will be collected. Participants will be
instructed to avoid traveling to sunny locations during the 12 week study.

Laboratory measurements pre-operative: 25(OH)D, PTH, CBC/Diff, glucose, calcium, albumin,
total protein, sodium, potassium, CO2, BUN, creatinine, ALP, ALT, AST, bilirubin, lipid
panel, ferritin, folate, iron, total iron binding capacity, hemoglobin A1c, insulin, vitamin
B12, PT/PTT, TSH, HCG, C-reactive protein.

Laboratory measurements at week 4: 25(OH)D

Laboratory measurements at week 12: 25(OH)D, PTH, CBC/Diff, glucose, calcium, albumin, total
protein, sodium, potassium, CO2, BUN, creatinine, ALP, ALT, AST, bilirubin, lipid panel,
ferritin, folate, total iron binding capacity, vitamin B12, and TSH.

Nutrient intake assessments: Dietary intake of macronutrients, vitamin D, calcium, and other
micronutrients will be assessed using the University of Minnesota 2010 Nutrition Data System
for Research (NDSR) program. NDSR is a comprehensive nutrient calculation software program
used for research purposes. The NDSR database contains values for 160 nutrients and includes
more than 18,000 foods.

Participants' baseline laboratory will be used to measure the response to vitamin D and
calcium supplementation over the course of 12 weeks. Bariatric patients participating in the
study will be instructed to take a total of 1500 mg of calcium (as calcium citrate) plus 1000
IU of vitamin D3 as three chewable tablets (Celebrate ®). An addition 1000 IU of vitamin D3
per day will be taken as two chewable multi-vitamin bariatric supplements (Celebrate ®).
Supplement compliance will be assessed by daily written records and inspection of supplement
bottle containers at each clinic visit.

Serum 25(OH)D will be measured by ARUP Laboratories (Salt Lake City, UT, USA) using a
chemiluminescent immunoassay. Serum calcium and phosphorus will be determined by The
Methodist Hospital Clinical Chemistry Department as part of the standard bariatric protocol
comprehensive metabolic panel. Intact PTH (iPTH) assays will be performed using the ADVIA
Centaur ® XP Immunoassay System.

Vitamin D deficiency will be defined as 25(OH)D levels less than 20 ng/mL (50 nmol/L) and
vitamin D insufficiency as 21 to 29 ng/mL (50 to 80 nmol/L). Secondary hyperparathyroidism
will be defined as iPTH ≥ 70 ng/L. An increase in serum intact PTH level will be taken to be
indicative of a possible negative calcium balance or a vitamin D deficiency (or both).
Hypercalcemia will be defined as calcium > 2.63 mmol/L.

Statistical analysis:

Primary Hypothesis: Daily supplementation with 2,000 IU of vitamin D3 for 12 weeks will
significantly increase mean serum 25(OH)D levels in obese subjects following bariatric
surgery compared to baseline levels.

Secondary Hypothesis: The percent response above baseline to daily supplementation with 2,000
IU of vitamin D3 will significantly differ between Roux-en Y and sleeve gastrectomy patients.

Subject Withdrawal:

Participants will be withdrawn from the study if serum 25(OH)D levels are identified as
within the deficient range so that the patient can receive needed treatment. A vitamin D
deficiency will be defined as 25(OH)D concentrations less than 20 ng/mL (50 nmol/L) and
vitamin D insufficiency as 21 to 29 ng/mL. In addition, if an abnormally high level of
25(OH)D is obtained (200 ng/mL or 500 nmol/L), we will have the 25(OH)D measurement repeated.
If the second test is confirmed to be high, then we will withdraw that particular patient
from the study for medical follow-up. If we find a trend of excess vitamin D among
participants, however, we will re-evaluate and consider termination of the study.

Inclusion Criteria: Adult female obese patients undergoing either Roux-en Y gastric bypass
or sleeve gastrectomy at The Methodist Hospital may participate in the study. Obese
patients with a body mass index (BMI) > 40 or BMI >35 with a co-morbidity will be eligible.

Exclusion Criteria:Subjects will be excluded if they have evidence of vitamin D deficiency
(< 20 ng/mL), hypercalcemia (calcium > 2.63 mmol/L), hypocalcemia (calcium < 1.75 mmol/L),
renal insufficiency (GFR < 50 ml/min), or a history of primary hyperparathyroidism or renal
tubular acidosis.Participants will be excluded if they take medications that interfere with
vitamin D metabolism, have significant sun exposure, plan to travel to sunny climates
during the study, or a history of hypercalcemia.