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OBES SURG (2008) 18:145–150

DOI 10.1007/s11695-007-9315-8

RESEARCH ARTICLE

Prevalence of Vitamin D Insufficiency and Deficiency


in Morbidly Obese Patients: A Comparison
with Non-Obese Controls
Whitney S. Goldner & Julie A. Stoner & Jon Thompson &
Karen Taylor & Luann Larson &
Judi Erickson & Corrigan McBride

Received: 30 August 2007 / Accepted: 27 September 2007 / Published online: 4 January 2008
# Springer Science + Business Media B.V. 2007

Abstract corrected for albumin, and creatinine were not significantly


Background Vitamin D deficiency is common in patients different between the groups, but mean albumin levels were
after bariatric surgery. However, obesity itself has also been significantly lower among surgery patients.
associated with decreased vitamin D. The prevalence of Conclusion Vitamin D deficiency is common in obese
vitamin D deficiency in obese persons has not previously patients at the time of bariatric surgery and is also
been compared to non-obese controls when controlling for accompanied by secondary hyperparathyroidism approxi-
factors that could affect vitamin D status. mately half the time. These findings suggest that vitamin D
Methods We evaluated 25 hydroxy vitamin D, iPTH, deficiency after bariatric surgery is multifactorial and in part
calcium, albumin, and creatinine in 41 patients undergoing caused by preoperative vitamin D deficiency rather than
Roux-en-Y gastric bypass. We then compared them to postoperative malabsorption alone. In this study, increased
healthy non-obese controls matched for age, sex, race/ vitamin D deficiency in obese persons cannot be explained by
ethnicity, and season of vitamin D measurement. a difference in calcium/vitamin D intake or sunlight exposure.
Results Ninety percent of the pre-bariatric surgery patients
had 25-OH-D levels <75 nmol/l, and 61% had 25-OH-D Keywords Vitamin D deficiency . Vitamin D insufficiency .
levels <50 nmol/l versus 32 and 12% in controls, respectively. Obesity . Bariatric surgery . Secondary hyperparathyroidism
Additionally, 49% of the pre-bariatric surgery patients had
secondary hyperparathyroidism versus 2% of controls. These
differences persisted after controlling for sunlight exposure
Introduction
and dietary intake of calcium and vitamin D. Mean calcium,
Vitamin D deficiency is increasingly recognized as being
W. S. Goldner (*) : J. Erickson common in many groups [1] especially after bariatric
Department of Internal Medicine, Section of Diabetes, surgery. Vitamin D deficiency has been documented in
Endocrinology, and Metabolism, University of Nebraska 50–80% of patients after Roux-en-Y gastric bypass or
Medical Center, Omaha, NE 68198-3020, USA
biliopancreatic diversion [2–5]. Extreme cases of severe
e-mail: wgoldner@unmc.edu
vitamin D deficiency, secondary hyperparathyroidism, met-
J. A. Stoner abolic bone disease, hypocalcemia, and chronic pain syn-
Department of Biostatistics, College of Public Health, dromes have also been reported as late complications after
University of Nebraska Medical Center, Omaha, NE, USA
bariatric surgery [6, 7]. It has previously been hypothesized
J. Thompson : K. Taylor : C. McBride that the mechanism for vitamin D deficiency after bariatric
Department of Surgery, University of Nebraska Medical Center, surgery was postoperative malabsorption, decreased nutri-
Omaha, NE, USA ent and calcium and vitamin D intake, or all of these.
Recent evidence suggests that obesity itself is an indepen-
L. Larson
Department of Internal Medicine, Clinical Research Center, dent risk factor for vitamin D deficiency and body fat is
University of Nebraska Medical Center, Omaha, NE, USA inversely proportional to 25 hydroxy vitamin D (25-OH-D)
146 OBES SURG (2008) 18:145–150

concentrations [8, 9]. Unfortunately, there has not been a phosphatase, 25-OH-D, intact PTH (iPTH), and a spot urine
consistent definition for vitamin D deficiency and assays calcium/creatinine ratio. 25-OH-D was performed by ARUP
variably recognize vitamin D forms. Using a variety of Laboratories, (Salt Lake City, UT) using a chemiluminescent
25-OH-D thresholds, vitamin D deficiency has been reported immunoassay. Serum calcium, albumin, phosphorus, creat-
in 21–81% of obese populations [10–13]. Factors such as inine, alkaline phosphatase and spot urine calcium/creatinine
dietary intake of vitamin D, sunlight exposure, latitude, ratio were all performed at the Clinical Laboratory of
season, age, and skin color can all affect 25-OH-D levels the Nebraska Medical Center using the VITROS\ assay
[14–17]. None of the previous studies have compared (Ortho-Clinical Diagnostics, Inc., Rochester, NY). Intact
prevalence of vitamin D deficiency in obese persons to non- PTH assay was performed at the Clinical Laboratory at the
obese persons matched for all of the variables that can affect Nebraska Medical Center using the Immulite\ 1000 assay
vitamin D status. Therefore, we sought to evaluate the preva- (DPC\ Diagnostic Products Corporation, Los Angeles, CA).
lence of vitamin D deficiency and secondary hyperparathy- Serum calcium was adjusted for serum albumin using two
roidism in obese persons at the time of bariatric surgery and separate equations. The first calculated the corrected calcium
compare them to non-obese controls matched for age, sex, by subtracting the albumin level from 4.44, multiplying the
race/ethnicity, and season of vitamin D measurement. difference by 0.75, and adding the product to the measured
calcium level. The second formula for corrected calcium
subtracted albumin from 4.0 and multiplied the difference by
Materials and Methods 0.8, then added the product to the measured calcium level.
Both formulas were used when comparing the measured
Patient population As part of a larger pilot study to assess calcium to corrected calcium for albumin.
optimal dosing of vitamin D after bariatric surgery, 45 Vitamin D deficiency was defined as 25-OH-D
patients planning to undergo Roux-en-Y gastric bypass <50 nmol/l (<20 ng/ml), and vitamin D insufficiency was
were studied. All of the participants needed to be older than defined as 25-OH-D 50-75 nmol/l (20–30 ng/ml). Second-
19 and have plans to undergo Roux-en-Y gastric bypass. ary hyperparathyroidism was defined as iPTH≥70 pg/ml.
Participants were excluded if they planned to undergo
another form of bariatric surgery, had evidence of hyper- Statistical analysis Descriptive statistics (mean±SD) were
calcemia (calcium>10.5 mg/dl), hypocalcemia (calcium< used to summarize the baseline lab values and patient
7.0 mg/dl), or renal insufficiency (GFR<50 ml/min), or if characteristics distributions. A two-sample t test was used
they had a history of primary hyperparathyroidism, renal to compare the mean values between bariatric surgery
tubular acidosis, sarcoidosis, granulomatous diseases, or patients and control patients, and a chi-square test or
malignancy. Four patients who had baseline lab draws for Fishers exact test was used to compare the distribution of
calcium, creatinine, and albumin after bariatric surgery or categorical endpoints between the bariatric surgery and
had baseline lab draws for 25-OH-D or PTH more than control patients. A chi-square test for trend was used for
3 days after bariatric surgery were excluded resulting in a ordered categorical responses. Proportions were estimated
sample size of 41 surgery patients. Additional information for the following endpoints: the proportion of subjects with
obtained included age, height (cm), weight (kg), body mass vitamin D levels <75 nmol/l, the proportion of subjects with
index (BMI; kg/m2), sex, race/ethnicity, and season of vitamin D levels <50 nmol/l, and the proportion of subjects
vitamin D measurement. Full medication list, medical with iPTH values ≥70 pg/ml. The association between two
history detailing comorbid conditions, and assessment of continuous measures was summarized using a Spearman’s
daily intake of calcium and vitamin D and history of rank correlation coefficient. A logistic regression modeling
sunlight exposure was also obtained at baseline. Omaha procedure was used to compare the odds of low 25-OH-D
Nebraska is located at latitude 41.3N. levels between surgery and control patients while adjusting
A non-obese control group (BMI<30 kg/m2) of similar for calcium and vitamin D intake. A value of p<0.05 was
age, sex, race/ethnicity, and season of vitamin D measure- considered significant.
ment was identified. Season of measurement was divided
into summer (April through September) and winter (October
through March). Similar diet, physical, and laboratory Results
information were obtained from the controls as the study
group. The protocol was approved by the Institutional The bariatric surgery group and the control group were well
Review Board at the University of Nebraska Medical Center. matched and had a mean age of 46.9±10.0 years in the pre-
bariatric surgery group and 46.3±8.3 years in the control
Laboratory testing The baseline labs obtained included group (Table 1). Fifty-four percent of patients were enrolled
serum calcium, albumin, phosphorus, creatinine, alkaline during the summer months (April through September), and
OBES SURG (2008) 18:145–150 147

Table 1 Summary of patient demographic and clinical characteristics

Measurement Subject group P value

Bariatric surgery patients (n=41) Controls (n=41)

Range Mean SD Range Mean SD

Age at screening (years) 25–73 46.9 10.0 27–65 46.3 8.3 0.8
Height (cm) 117.0–198.2 165.2 17.9 149–190 167.8 8.8 0.4
Weight (kg) 109.4–223.0 150.9 30.2 53.6–96.6 70.8 11.7 <0.0001
BMI (kg/m2) 41.8–88.2 56.4 12.3 20.0–29.1 24.7 2.7 <0.0001

Sex 0.8
Male 8 (20%) 9 (22%)
Female 33 (80%) 32 (78%)
Race >0.9
Black/African American 1 (2%) 1 (2%)
White 38 (93%) 40 (98%)
Not provided 2 (5%)

46% were enrolled in the winter months (October through difference between the groups for 25-OH-D and iPTH (data
March) in both groups. As designed, there was a statistical not shown).
difference between BMI for the bariatric surgery group Among the bariatric surgery patients, 61% had 25-OH-D
versus controls. Mean BMI for the bariatric surgery group levels <50 nmol/l (vitamin D deficiency) compared with
was 56.4±12.3 kg/m2, and control group BMI mean was 12% of the controls (p<0.0001; Table 4). Similarly, when
24.7±2.7 kg/m2 (p<0.0001; Table 1). evaluating vitamin D insufficiency and deficiency (25-OH-
Overall, the Vitamin D levels were significantly lower, D <75 nmol/l), 90% of surgery patients had levels
and the iPTH values were significantly higher in the <75 nmol/l compared to 32% of controls (p<0.0001;
bariatric surgery group (Table 2). Mean 25-OH-D in the Table 3). Intact PTH values were elevated ≥70 pg/ml in
bariatric surgery group was 47.7 nmol/l (19.2 ng/ml) versus 49% of the bariatric surgery patients compared with 2% of
90.8 nmol/l (36.3 ng/ml) in controls (p<0.0001). Mean the controls (p<0.0001; Table 4).
iPTH in the bariatric surgery group was 87.6 pg/ml versus Serum creatinine was normal in both groups and did not
controls at 39.8 pg/ml (p<0.0001). The bariatric surgery differ significantly between the surgery and control groups
group was also evaluated according to time of lab draw in (Table 2). Serum albumin was also within the normal range
relation to day of surgery. The pre-surgery labs were com- in both groups, but significantly lower in the surgery group
pared with post-surgery labs, and there was not a significant compared with controls (p<0.0001). Mean albumin in the

Table 2 Summary of patient laboratory characteristics

Measurement Subject group P value

Bariatric surgery patients (n=41) Controls (n=41)

Range Mean SD Range Mean SD

25-OH-D (nmol/l) 12.5–129.8 47.7 24.7 32.4–177.2 90.8 34.2 <0.0001


PTH (ng/l) 20.0–284.0 87.6 54.3 3.0–97.0 39.8 18.3 <0.0001
Serum Calcium (mmol/l) 2.3–2.4 2.3 0.08 2.1–2.5 2.3 0.1 <0.0001
Corrected calcium for albumina (mmol/l) 2.1–2.5 2.3 0.08 2.2–2.6 2.4 0.08 0.1
Corrected calcium for albuminb (mmol/l) 2.0–2.4 2.2 0.08 2.8–2.5 2.3 0.08 0.1
Albumin (g/l) 35–46 41.0 3 37–49 43 3 <0.0001
Creatinine (μmol/l) 53.0–106.1 79.6 17.7 53.0–114.9 79.6 17.7 0.3
a
Corrected calcium (formula 1)=(44.4−serum albumin)×0.75+serum calcium.
b
Corrected calcium (formula 2)=(40.0−serum albumin)×0.8+serum calcium.
148 OBES SURG (2008) 18:145–150

Table 3 Summary of dietary calcium and vitamin D intake

Variable count (column %) Surgery patients (n=38) Controls (n=41) P value

How much milk do you drink? 0.3


>2 8 oz glasses/day 3 (8%) 6 (15%)
1 glass per day 12 (32%) 13 (32%)
1 glass every other day 3 (8%) 9 (22%)
<3 glasses/week 12 (34%) 4 (10%)
None 7 (18%) 9 (22%)
How much cheese, cottage cheese, yogurt, calcium and vitamin D enriched orange 0.1
juice do you eat/drink?
>2 servings/day 4 (10%) 3 ( 8%)
1 serving per day 10 (26%) 21 (54%)
1 serving every other day 9 (24%) 7 (18%)
<3 servings/week 14 (37%) 6 (15%)
None 1 (3%) 2 (5%)
How much spinach, broccoli, or other green leafy vegetables do you eat? <0.0001
>2 servings/day 0 (0%) 11 (27%)
1 serving per day 6 (16%) 11 (27%)
1 serving every other day 8 (21%) 11 (27%)
<3 servings/week 20 (53%) 6 (15%)
None 4 (10%) 1 (3%)

bariatric surgery group was 4.1 g/dl versus 4.3 g/dl in the bariatric surgery group reported consuming at least one
control group (Table 2). serving per day, less than one serving per day, or no spinach,
Mean serum calcium was also significantly lower for the broccoli, and green leafy vegetables, respectively, compared
surgery group when compared with controls (9.0 versus with 55, 43, and 2% of controls, respectively (p<0.0001).
9.3 mg/dl, p<0.0001), but this difference did not persist There was also a significant difference between reported
after correction of calcium for albumin using both equa- medication administration of calcium and vitamin D
tions (Table 2). between the two groups. Forty-nine percent of controls
BMI was inversely correlated to 25-OH-D levels (r=−0.3, reported taking calcium and/or vitamin D and only 2% of
p=0.06), but no other associations to BMI were significant the bariatric surgery patients reported taking calcium and or
in the bariatric surgery group. There was no significant vitamin D (p<0.0001; Table 5). All patients who reported
correlation between BMI and any of the other variables in calcium supplementation were taking less than 2,000 mg of
the control group (data not shown). calcium per day. Most patients could not quantify the
Reported dietary intake of milk, cheese, cottage cheese, amount of vitamin D they ingested per day; however, all
yogurt, and calcium, and vitamin-D-enriched orange juice patients reporting vitamin D supplementation received it as
was not significantly different between the bariatric surgery part of their calcium supplementation. None took vitamin D
group and the controls. However, there was a significant as a separate supplement. Hence, the likely maximum
difference between reported intake of vegetables containing supplementation dose of vitamin D was 800 IU/day. The
vitamin D (Table 3). Sixteen percent, 74 and 10% of the

Table 5 Supplements and medications


Table 4 Summary of vitamin D deficiency, vitamin D insufficiency,
Medication type count Surgery patients Controls P value
and elevated iPTH
(column %) (n=41) (n=41)
Variable count Surgery patients Controls P value
(column %) (n=41) (n=41) Calcium/vitamin D 1 (2%) 20 (49%) <0.0001
Antihypertensive 13 (32%) 4 (10%) 0.01
25 OH Vitamin D agents
<50 nmol/l 25 (61%) 5 (12%) <0.0001 Estrogen replacement 4 (10%) 10 (24%) 0.08
<75 nmol/l 37 (90%) 13 (32%) <0.0001 therapy
PTH Diabetes medicationsa 6 (15%) 0 0.03
≥70 pg/ml 20 (49%) 1 (2%) <0.0001 a
Includes oral diabetes medications and insulin.
OBES SURG (2008) 18:145–150 149

Table 6 Association between 25-OH D and season Discussion


Variable count Surgery patients Controls P value
(column %) Rates of obesity in the USA have steadily increased over
the last two decades. It is well known that obesity is
Summer (n=22) (n=22) associated with diabetes mellitus, coronary artery disease,
25 OH Vitamin D
hyperlipidemia, and osteoarthritis. It is now clear that
<50 nmol/l 12 (55%) 1 (5%) 0.0003
Vitamin D deficiency is also associated with obesity.
<75 nmol/l 19 (86%) 3 (14%) <0.0001
Before global screening for vitamin D deficiency after
Winter (n=19) (n=19) bariatric surgery, vitamin D deficiency was only rarely
25 OH Vitamin D reported many years after bariatric surgery [6, 7], so was
<50 nmol/l 13 (68%) 4 (21%) 0.003
thought to be a rare long-term complication of bariatric
<75 nmol/l 18 (95%) 10 (53%) 0.003
surgery. Recent studies have shown that obesity itself is
associated with vitamin D deficiency, and BMI is inversely
correlated with vitamin D levels and positively correlated
bariatric surgery patients also had significantly higher usage with iPTH, which our study confirmed [8, 9]. Ybarra et al.
of anti-hypertensive drugs and diabetes medications, but [12] demonstrated that the rates of vitamin D deficiency in
the controls reported significantly higher usage of estrogen obese populations before and after bariatric surgery were
therapy (Table 5). After adjusting for the reported calcium/ not significantly different, suggesting both pre- and
vitamin D intake, the surgery patients were still at increased postoperative factors contribute to vitamin D deficiency
risk for vitamin D deficiency (25-OH-D <50 nmol/l; OR= after bariatric surgery. Vitamin D deficiency is known to
11.1, 95%CI 2.8–43.4, p=0.0006). Similarly, when com- contribute to metabolic bone disease. Additionally, vitamin
bining vitamin D deficiency with vitamin D insufficiency D deficiency has been associated with autoimmune disease,
(25-OH-D <75 nmol/l), the surgery patients were also still at certain cancers, insulin resistance, and cardiovascular
increased risk for low 25-OH-D (OR=19.0, 95%CI 4.9–73.6, disease [1, 8–20]. This raises the question of a possible
p<0.0001). association between obesity, vitamin D deficiency, and the
There was no significant difference in the amount of occurrence of these other medical conditions.
reported sunlight exposure between the groups (p=0.08), The prevalence of vitamin D deficiency (25-OH-D
with approximately 60% of subjects in each group <50 nmol/l) in obese patients was 61% and combined
receiving less than 30 min of sun exposure per day. We vitamin D deficiency and insufficiency (25-OH-D
also evaluated the patients according to the season in which <75 nmol/l) was 90%. This is consistent with previous
they were studied (Table 6). In each season and for each studies showing rates of vitamin D deficiency of 21–81%
endpoint, bariatric surgery patients were more likely to before bariatric surgery [10–13]. A possible explanation for
have low vitamin D levels. When evaluating both vitamin the discrepant range in previous studies could be the
D deficiency and insufficiency (25-OH-D<75 nmol/l), inconsistent vitamin D threshold to define vitamin D
significantly more controls had low vitamin D levels in deficiency. Many of the previous reports used much lower
winter (53%) compared with summer (14%; p=0.008). cutoffs ranging from 25 to 50 nmol/l (10–20 ng/ml) to
There was no significant difference in winter and summer define vitamin D deficiency, which could result in a lower
rates when comparing the outcomes using the vitamin D reported incidence of vitamin D deficiency in those studies.
deficiency cutoff (25-OH-D<50 nmol/l); however, there In this study, we used a threshold of 75 nmol/l (30 ng/ml) to
were only four patients in the deficiency category. The define vitamin D sufficiency, which is consistent with
summer and winter rates did not differ for either vitamin D recently published consensus recommendations [21]. We
deficiency or combined vitamin D deficiency and vitamin D also found that approximately half of the patients with low
insufficiency in the bariatric surgery group (p>0.4 for each). vitamin D levels also had evidence of secondary hyper-
When comparing symptoms before bariatric surgery parathyroidism, consistent with previous reports [2].
versus controls, there were significantly more patients who Serum 25-OH-D is affected by a number of variables,
reported muscle aches in the bariatric surgery group (61%) including vitamin D intake, sunlight exposure, and season.
compared with controls (10%; p<0.0001). The bariatric To evaluate for these potential confounders, we evaluated
surgery patients also reported more nausea or vomiting and reported dietary and medication intake of calcium and
watery stools or diarrhea pre-surgery. Eighteen percent of vitamin D. The controls consumed significantly more
the surgery patients reported nausea or vomiting compared calcium and vitamin D via medication supplements and
with none of the controls (p=0.003), and 37% of bariatric more vitamin-D-containing vegetables. However, after
surgery patients reported diarrhea versus 7% of controls adjusting for calcium and vitamin D intake, the risk for
(p=0.001). vitamin D deficiency and combination vitamin D deficiency
150 OBES SURG (2008) 18:145–150

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