AJCN Tufts Nutrition Symposium, Boston & Online Sept 2009
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Supplemental data
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Aasheim, E. T
Right arrow Articles by Bøhmer, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aasheim, E. T
Right arrow Articles by Bøhmer, T.
Agricola
Right arrow Articles by Aasheim, E. T
Right arrow Articles by Bøhmer, T.
American Journal of Clinical Nutrition, Vol. 87, No. 2, 362-369, February 2008
© 2008 American Society for Nutrition

ORIGINAL RESEARCH COMMUNICATION

Vitamin status in morbidly obese patients: a cross-sectional study1,2,3

Erlend T Aasheim, Dag Hofsø, Jøran Hjelmesæth, Kåre I Birkeland and Thomas Bøhmer

1 From the Departments of Medicine (ETA and TB) and Endocrinology (KIB), Aker University Hospital, Oslo, Norway; Faculty Division Aker University Hospital, University of Oslo, Oslo, Norway (ETA, KIB, and TB); and Morbid Obesity Center, Vestfold Hospital Trust, Tønsberg, Norway (DH and JH)

2 Supported by a research fellowship grant from Eastern Norway Regional Health Authority (to ETA).

3 Reprints not available. Address correspondence to ET Aasheim, Aker University Hospital Research Center, Building 80, Trondheimsvn. 235, 0514 Oslo, Norway. E-mail: e.t.aasheim{at}medisin.uio.no.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background:Morbid obesity is associated with low circulating concentrations of 25-hydroxyvitamin D. Few data on the concentrations of other vitamins in morbidly obese patients are available.

Objective:The objective was to compare serum and blood vitamin concentrations in morbidly obese patients with those in healthy subjects.

Design:In 2 public hospital departments (southeast Norway), we prospectively examined 110 consecutive patients (76 women) and 58 healthy controls (30 women) not taking multivitamin supplements. Patients and controls did not differ significantly in age or ethnicity. The mean (±SD) body mass index (in kg/m2) was 45 ± 7 in the patients and was 24 ± 3 in the controls. Patients with vitamin concentrations lower than 2 SD below the sex-specific mean in controls were considered to have inadequate vitamin status.

Results:The morbidly obese women and men had significantly lower concentrations of vitamin B-6, vitamin C, 25-hydroxyvitamin D, and lipid-standardized vitamin E than did the healthy controls (P < 0.01 for each). The status of these vitamins was inadequate in a substantial proportion of the patients (11–38%). The status of vitamins A, B-1, B-2, and B-12 and of folic acid was adequate in most of the patients (95–100%). A moderately elevated C-reactive protein concentration was associated with lower vitamin A, B-6, and C concentrations. In a multiple regression analysis, concentrations of alkaline phosphatase (inverse relation) and vitamin C were the strongest determinants of serum vitamin B-6 concentrations.

Conclusions:Low concentrations of vitamin B-6, vitamin C, 25-hydroxyvitamin D, and vitamin E adjusted for lipids are prevalent in morbidly obese Norwegian patients seeking weight-loss treatment.

Key Words: Morbid obesity • body mass index • vitamin deficiency • vitamin B-1 • riboflavin • pyridoxal phosphate • ascorbic acid • retinol • {alpha}-tocopherol • 25-hydroxyvitamin D


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Morbid obesity, which is defined as a body mass index (BMI; in kg/m2) >40 or >35 with a weight related comorbidity, impairs quality of life (1), increases the risk of coronary heart disease (2), and shortens life expectancy (3). Currently, an estimated 7% of adult women in the United States have a BMI >40 (4). Although morbidly obese persons have greater intakes than do nonobese persons, morbidly obese persons may have nutritional deficiencies. The most common vitamin deficiency associated with obesity seems to be low concentrations of 25-hydroxyvitamin D (5, 6), which is associated with an increased risk of diabetes and other cardiovascular disease risk factors (7, 8) and depression (9). Few data about other possible vitamin deficiencies in morbidly obese patients are available (10), although their dietary habits obviously deviate from those of nonobese individuals (11).

Bariatric surgery is used with increasing frequency and is the therapeutic option that offers patients with morbid obesity the most pronounced and lasting weight reduction (12). However, bariatric surgical procedures may induce malabsorption and frequently result in nutritional deficiencies (13). The combination of a low preoperative vitamin concentration and the malabsorption that often follows bariatric surgery may render these patients prone to severe vitamin deficiencies.

Observational studies in the general population have shown associations between vitamin status and morbidity, beyond the traditional vitamin deficiency disorders. Low vitamin B-6 concentrations have been linked with symptoms of depression (14) and increased risk of stroke (15) and colorectal neoplasia (16). A low vitamin C concentration in plasma may be associated with increased all-cause mortality (17), risk of myocardial infarction (18), and gallbladder disease (19). The aim of the present study was to assess concentrations of vitamins A, B-1, B-2, B-6, C, D, and E in morbidly obese patients seeking weight reduction and to compare the concentrations with those observed in a healthy control group.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
The study took place in 2 public hospitals in southeast Norway with departments specialized in the treatment of morbid obesity by intensive lifestyle treatment, bariatric surgery, or both. The Regional Ethics Committees for Medical Research approved the study protocol, and all participants gave informed written consent before enrollment.

Patients
Patients were referred from primary or secondary care and were offered an appointment if they had a BMI (in kg/m2) >40 or >35 in patients with obesity-related conditions associated with a high cardiovascular disease risk (such as sleep apnea or diabetes mellitus) or induce physical problems that interfere with lifestyle (joint disorders or body size problems interfering with employment, family function, or ambulation), in accordance with criteria commonly used when considering weight-loss surgery (20). Between December 2005 and April 2006, 132 patients seeking weight reduction were prospectively examined at their first visit. Patients were excluded if they used multivitamin supplements (n = 10), refused to comply with study procedures (n = 2), were >60 y of age (n = 5), were currently being treated for a severe psychiatric disorder (n = 2), had an alcohol intake >50 g/d (n = 2), or had thyroid abnormalities (n = 1, excessive thyroxine substitution). Ten patients undergoing thyroxine substitution who had normal serum concentrations of thyroid-stimulating hormone (TSH) and thyroxine were included. The final study sample consisted of 110 patients.

The medical history of the enrolled patients included depression (n = 52), diabetes (n = 29), previous cholecystectomy (n = 7), and a reversed gastric banding procedure (n = 3). Drugs currently being used by the subjects included blood pressure–lowering agents (n = 36), analgesics (n = 18), antidepressants (n = 16), metformin (n = 15), insulin (n = 3), aspirin (n = 9), antacids (n = 8), oral contraceptives (n = 6), sibutramin (n = 1), and orlistat (n = 1). Four patients not taking thyroxine had elevated concentrations of TSH (concentrations between 5.9 and 15.0 mU/L) and thyroxine concentrations in the normal range.

Controls
Healthy controls were recruited via local advertisements at Aker University Hospital. Between January and May 2007, 58 nonobese subjects (30 women) aged 19–59 y were examined. Exclusion criteria included chronic disease and regular medication or multivitamin supplement use. Subjects using contraceptive medication (n = 10) or thyroxine substitution (n = 4) were allowed to participate.

Clinical characteristics
Demographic data, medical history, and the use of tobacco, alcohol, and vitamin supplements were recorded on standardized forms. Height and weight were measured while the participants were wearing light clothing without shoes. Waist and hip circumferences were assessed with a tape measure at the midpoint between the lowest rib margin and the iliac crest and at the level of the major trochanter, respectively. Blood pressure was measured while the subjects were sitting after they had rested for 5 min. Patients with a history of diabetes (n = 20) or with a fasting plasma glucose concentration ≥7.0 mmol/L (n = 9) were classified as having diabetes. The homeostasis model assessment of insulin resistance was calculated in participants without diabetes from fasting concentrations of glucose and insulin by using the calculator from the Diabetes Trials Unit (Internet: http://www.dtu.ox.ac.uk; accessed 23 November 2006).

Preparation of blood samples
Blood was collected by venipuncture after an overnight fast. Samples clotted 30 min at room temperature, and serum was separated by centrifugation at 1700 x g for 10 min. Aliquots were immediately stored at –20 °C (–80 °C for assays of vitamin B-2, vitamin C, and 25-hydroxyvitamin D). Samples prepared at Vestfold Hospital were kept on dry ice (–57 °C) for up to 16 h during transportation to Aker University Hospital. Laboratory assays were performed within 10 d of blood sampling, except for vitamin B-2 (within 90 d) and 25-hydroxyvitamin D (within 1 y). We previously performed extensive assessment of protocols for preparing specimens for vitamin C analysis with respect to deterioration of ascorbic acid concentrations at different storage conditions. The results are highly reliable when serum aliquots are frozen at –80 °C within 2 h of blood sampling and analyzed within 2 wk.

Laboratory analysis
Routine laboratory analyses were performed in blood, serum, or plasma (eg, homocysteine) with a Hitachi 717 Modular multianalyzer (Boehringer Mannheim, Mannheim, Germany) in the Department of Clinical Chemistry at Aker University Hospital and with a Vitros 950 Chemistry System (Ortho-Clinical Diagnostics, Rochester, NY) at Vestfold Hospital. Data on folic acid, vitamin B-12, and homocysteine were only available for participants at Aker University Hospital. The assays for C-reactive protein (CRP) have detection limits of <1 and <7 mg/L at Aker and Vestfold, respectively; both assays were calibrated by using European Community Bureau of Reference Certified Reference Material 470 (CRM470). A reference population for the assessment of 25-hydroxyvitamin D status in our laboratory was described previously (21).

HPLC was used to assay vitamin B-1 (thiamine pyrophosphate in heparinized blood) (22), vitamin B-2 (flavin mononucleotide in EDTA-blood; Chromsystems, Munich, Germany), vitamin B-6 (pyridoxal-5'-phosphate in serum; Chromsystems), vitamin A (retinol in serum; Bio-Rad Laboratories, Munich, Germany), and vitamin E ({alpha}-tocopherol in serum; Bio-Rad Laboratories). Serum samples were analyzed for vitamin C (ascorbic acid) in an environment acidified with ortho-phosphoric acid according to the method of Zannoni (23). Serum was also analyzed for 25-hydroxyvitamin D (the sum of 25-hydroxyvitamin D2 and 25-hydroxyvitaminD3) and 1,25-hydroxyvitamin D by radioimmunoassay (DiaSorin, Stillwater, MN), intact parathyroid hormone by chemiluminoimmunometric assay (Diagnostic Products Corporation, Los Angeles, CA), and ionized calcium with a Rapidlab 348 analyzer (Instru-Med Inc, Atlanta, GA). The interassay CVs with these methods in our laboratories ranged from 3% to 9%, except for 25-hydroxyvitamin D (14%), based on an analysis of ≥12 replicate samples on 2 different days. Ascorbic acid and 25-hydroxyvitamin D were analyzed in duplicate, and the analysis of 25-hydroxyvitamin D was performed on the same day for patients and controls. All vitamin assays included quality controls with high and low concentrations supplied by the manufacturers plus internal controls. For vitamins B-1 and C, external controls were unavailable and standards were prepared from dry substances (Sigma-Aldrich, St Louis, MO). We observed no significant laboratory drift within the study period when reviewing the results of the quality controls.

Sample size and statistical analysis
The primary objective was to estimate the prevalence of inadequate vitamin concentrations in morbidly obese patientsseeking weight-loss treatment. Reference intervals for each vitamin were calculated separately for women and men based on the mean ± 2 SD in the control group. (Reference intervals for vitamins with a log normal distribution were obtained by calculating the mean ± 2 SD of log-transformed values and back-transforming the result). Vitamin inadequacy was defined as a vitamin concentration below the reference interval. Assuming vitamin inadequacy rates of 2.5% in the control group and 10% in the obese patients, we used an exact binomial test with a 0.05 significance level to estimate that a sample size of 110 patients would give 93% power to detect a difference between the groups.

Data are presented as means ± SDs unless otherwise noted. Skewed data were log transformed when appropriate for further statistical analysis (ie, for the comparison of means or calculation of reference intervals). A Fisher's exact test or chi-square test was used to compare categorical data between groups, a Student's t test or Mann-Whitney U test was used to compare continuous data between groups, and Spearman's rank correlation was calculated to explore relations between continuous variables. The degree of association between vitamin B-6 (log µmol/L) and various clinical variables was determined by linear regression models that included dichotomous and continuous predictor variables. Covariates were variables known to influence vitamin B-6 concentrations and significant predictors in univariate analyses. The final model was obtained using a backward stepwise method. No significant interactions between the remaining variables were identified. The level of significance was P < 0.05, and all P values are 2-tailed. No adjustment was made for multiple testing. Statistical analyses were done in SPSS 14.0 (SPSS Inc, Chicago, IL) for WINDOWS.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
All participants were of Europoid origin, except for 4 patients and 1 control subject of Indian subcontinent origin. Mean age was not significantly different in the patient and control groups, who had mean BMIs of 45 ± 7 and 24 ± 3, respectively. The patients had a higher mean systolic blood pressure level and a less favorable lipid profile than did the controls (Table 1Go).


View this table:
[in this window]
[in a new window]

  		TABLE 1. Clinical status of morbidly obese patients and healthy controls

 
Vitamin status
Overall, vitamin status in the morbidly obese patients was strikingly different from that in the healthy control group, and significant differences were observed in 6 of 9 vitamins assayed. Compared with controls, the obese patients had significantly lower mean serum concentrations of vitamins A, B-6, C, 25-hydroxyvitamin D, and lipid-standardized vitamin E. Conversely, the patients had higher mean blood concentrations of vitamin B-1 than did the controls. These observations were consistent in both women and men (Table 2Go). Moreover, a substantial proportion of patients (11–38%) were considered to have an inadequate vitamin B-6, vitamin C, 25-hydroxyvitamin D, and lipid-standardized vitamin E status (Figure 1Go; see Supplemental Table 1 under "Supplemental data" in the issue online at www.ajcn.org). Female patients had a significantly higher risk of inadequate vitamin C concentrations and a lower risk of inadequate 25-hydroxyvitamin D concentrations than did male patients (P < 0.001 for both), whereas inadequacy rates for other vitamins were not significantly different between men and women (P values not shown). Most patients (95–100%) had adequate concentrations of vitamins A, B-1, B-2, and B-12 and folic acid (see Supplemental Table 1 under "Supplemental data" in the issue online at www.ajcn.org).


View this table:
[in this window]
[in a new window]

  		TABLE 2. Vitamin concentrations in morbidly obese patients and healthy controls

 

Figure 1
View larger version (19K):
[in this window]
[in a new window]

  		FIGURE 1.. Vitamin status in morbidly obese women and men. Horizontal bars indicate the lower limit of the normal reference interval. Reference intervals were derived from the mean ± 2 SD of healthy individuals (n = 30 women and 28 men) who did not use multivitamin supplements. Vitamin concentrations were not normally distributed for vitamins B-6 and D; reference intervals for these vitamins were obtained by calculating the mean ± 2 SD of log-transformed values and backtransforming the result. For exact intervals, see Supplemental Table 1 under "Supplemental data" in the issue online at www.ajcn.org. B-6, serum pyridoxal-5'-phosphate; C, serum ascorbic acid; D, serum 25-hydroxyvitamin D; E/Lipids, serum {alpha}-tocopherol/(cholesterol + triacylglycerols). A female patient with an exceedingly high vitamin B-6 concentration (220 nmol/L) was omitted from the graph.

 
Vitamin concentrations in patients related to BMI and vitamin B-6 status
Patients with a BMI above the median of 45 had significantly lower concentrations of vitamins B-6 and 25-hydroxyvitamin D than did patients with a BMI <45 (Table 3Go). Inadequate vitamin B-6 status was associated with lower concentrations of several other vitamins (Table 3Go) and higher alkaline phosphatase concentrations: 98 ± 25 compared with 76 ± 19 U/L (P < 0.001). Antidepressant medication use was more frequent among female patients (n = 15, 20%) than among male patients (n = 1; 3%; P = 0.020). Women using antidepressants had a lower mean vitamin B-6 concentration than did the women not taking such drugs: 17 ± 7 compared with 32 ± 32 nmol/L (P = 0.018).


View this table:
[in this window]
[in a new window]

  		TABLE 3. Vitamin concentrations in morbidly obese patients related to BMI, vitamin B-6 status, and C-reactive protein (CRP)1

 
Vitamin concentrations related to inflammation
Whereas all control subjects had CRP concentrations <8 mg/L, 65 patients (59%) had moderately elevated CRP concentrations, with concentrations ranging from 8 to 69 mg/L. This finding was more frequent in women (n = 52; 68%) than in men (n = 13; 38%) (P = 0.003). Patients with moderately elevated CRP concentrations had significantly lower mean concentrations of vitamins A, B-6, and C than did patients with lower CRP concentrations (Table 3Go).

Vitamin concentrations related to other patient characteristics
Homocysteine concentrations (Table 2Go) were negatively correlated with folic acid concentrations (rank correlation: –0.38, P = 0.006) and not significantly correlated with vitamin B-2, B-6, or B-12 concentrations (data not shown). Parathyroid hormone concentrations were negatively correlated with 25-hydroxyvitamin D concentrations (rank correlation: –0.32, P = 0.001). All patients had normal concentrations of ionized calcium (n = 51) and 1,25-hydroxyvitamin D (data not shown).

Vitamin concentrations were not significantly associated with age and were not different between groups according to smoking habit or diabetes status. However, in patients without diabetes, vitamin B-6, vitamin C, and 25-hydroxyvitamin D were all negatively correlated with insulin resistance estimated by the homeostasis model assessment (rank correlations: –0.28, –0.34, and –0.28, respectively; P ≤ 0.01 for each). Patients consuming alcohol (range: 1–14 g/d) had significantly higher concentrations of vitamins B-6 and C than did nonconsumers (data not shown).

Determinants of vitamin B-6 concentrations
Determinants of serum vitamin B-6 concentrations in the obese patients were evaluated in multiple linear regression models. The initial model included variables previously reported to be associated with vitamin B-6 concentrations (sex, age, smoking habit, alcohol intake, and concentrations of alkaline phosphatase, phosphate, albumin, creatinine, CRP, and vitamin B-2) and variables that were significant predictors of inadequate vitamin B-6 concentrations in a univariate analysis (BMI, antidepressant medication use, and concentrations of vitamin C and hemoglobin-adjusted vitamin B-1). The variable with the highest P value was removed stepwise until all remaining variables had P values <0.05. Of the remaining variables, the strongest determinants of vitamin B-6 concentrations were alkaline phosphatase (inverse relation) and vitamin C concentrations (Table 4Go). The procedure was then repeated with sex forced to be kept in the model. The results were essentially the same as those in Table 4Go, except that, in the new model, antidepressant use was nearly significant (P = 0.066; sex: P = 0.507). Finally, we tested the model including females only. Results were again consistent with those reported in Table 4Go (R2 = 0.54; antidepressant use: P = 0.037).


View this table:
[in this window]
[in a new window]

  		TABLE 4. Multiple regression analysis of determinants of serum vitamin B-6 concentrations (log µmol/L) in 120 patients1

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The major novel finding of this study of 110 morbidly obese patients referred for weight-loss treatment was a high prevalenceof low vitamin B-6, C, D, and E concentrations, ranging from 11% to 38% of patients. Furthermore, the most obese patients had the most pronounced reductions in vitamin concentrations, antidepressant medication use was associated with lower vitamin B-6 concentrations in women, and lower concentrations of 25-hydroxyvitamin D were associated with higher concentrations of parathyroid hormone. Few patients had low vitamin B-1 concentrations; rather, the patients had somewhat higher mean concentrations of vitamin B-1 than did the controls. The reason for this is not known.

The study included consecutive patients who visited 2 public healthcare institutions and whose characteristics were comparable with those of large populations of candidates for bariatric surgery (12). Vitamin concentrations in erythrocytes or serum are routinely used as indicators of tissue stores (vitamins A, B-1, B-6, D, and E) or recent intakes (vitamin C). Because obese persons often underreport their energy intakes (24), vitamin status was only assessed in blood. In general, care must be taken in interpreting vitamin status assessed by blood concentration measurements because external quality assurance schemes and control materials with defined values are not always available (25). Serum concentrations of 25-hydroxyvitamin D may be lower during the winter season at our latitude (60° N). In the present study, vitamin concentrations in the obese patients were compared with findings in individuals not different in age or ethnicity and examined in the same laboratory during the same season. If the reference interval normally used for 25-hydroxyvitamin D in our laboratory (37–131 nmol/L) had been applied, 55% of patients would have had inadequate vitamin D status (Figure 1Go). Patients and controls were examined 1 y apart and laboratory drift was therefore a potential confounder; however, we found no evidence of such a problem in reviewing the laboratory quality controls for the 2 periods.

Most former studies of vitamin status in obesity have not focused on severe obesity but included subjects with a wide range of BMIs. Vitamin B-6 status was adequate in some (26, 27), but not all (28), reports. An increase in BMI was associated with lower concentrations of vitamins A, C, and E in the United States (29), Western Europe (30-33), and elsewhere (26, 27, 34). In contrast with 2 previous reports (10, 35), low concentrations of vitamin B-1 were rare in our study. However, a comparison of these findings is difficult because the analytic methods were not described. Vitamin B-2 status was normal in obese Polish (26) and Thai (27) subjects. Vitamin D deficiency and secondary hyperparathyroidism are known to be prevalent in obesity (5, 6). Thus, our findings are generally consistent with previous reports and add knowledge regarding several vitamins in patients with morbid obesity.

The low vitamin concentrations observed in the morbidly obese patients could have been caused by several mechanisms. Dietary and lifestyle habits may be the most important contributors. A low intake of fruit, vegetables, and alcohol has been described in severe obesity (11). Current smoking was more frequent in the obese patients than in the control group, and this might in part explain their lower concentrations of ascorbic acid in serum (30). Body composition may also influence vitamin status; low plasma vitamin C concentrations have been related to a central fat distribution independent of BMI (33), and the low serum concentrations of 25-hydroxyvitamin D in obesity may partly be a result of sequestration in adipose tissue (36, 37). Obese individuals have elevated amounts of total body water, and the extracellular compartment is relatively more expanded than the intracellular compartment (38). Possibly, this leads to dilution effects on extracellular vitamin concentrations; the obese patients generally had lower serum vitamin concentrations, whereas blood (erythrocyte) concentrations were not different from, or higher than, those in controls (Table 2Go). No patient had a clinical condition associated with malabsorption, and only one patient currently used orlistat, which may induce malabsorption. Alkaline phosphatase hydrolyzes pyridoxal-5'-phosphate and is a major determinant of vitamin B-6 concentrations in serum (39). Elevated concentrations of alkaline phosphatase have also been reported in obese patients (40).

Importantly, systemic inflammation is associated with reduced serum concentrations of vitamins A (41), B-2 (42), B-6 (42, 43), and C (44), owing to reduced liver production of transport proteins (such as albumin), increased turnover of antioxidant vitamins, or a shift in tissue distribution. A low serum vitamin concentration in inflammation does not necessarily indicate that body stores are depleted (41). Obesity is associated with chronic low-grade inflammation (45). Previous studies have also found moderately elevated CRP concentrations to be more common in women with morbid obesity than in men (46). However, we also observed low concentrations of vitamins B-6, C, and D in patients with lower CRP concentrations. In an animal model, vitamin B-6–deficient rats had increased liver oxidative stress (47), and if also present in humans, such a mechanism could partly explain the relation between serum concentrations of vitamins B-6 and C in our patients.

Morbidly obese individuals have an increased prevalence of several diseases that have been related to a suboptimal status of vitamins B-6, C, and D in other populations, including cardiovascular disease (18, 48), colorectal neoplasia (16, 49), and depression (9, 14). The optimal serum concentration of 25-hydroxyvitamin D may be >75 nmol/L (49, 50). Such a concentration was found in only 4% of the morbidly obese patients (Figure 1Go). An inverse association between serum concentrations of 25-hydroxyvitamin D and diabetes has been reported (7). This agrees with our finding of a negative correlation between the magnitude of insulin resistance and 25-hydroxyvitamin D concentrations.

Future research
Cross-sectional studies such as the present study are important in generating knowledge for further research but cannot establish cause-and-effect relations, and most knowledge regarding vitamin status and disease risk comes from observational studies, which are often limited by confounders. Randomized trials are therefore necessary to evaluate whether morbidly obese patients with low vitamin concentrations benefit from supplementation. It is notable that vitamin B-6 concentrations were normal at baseline in a controlled trial in which supplementation provided no benefit (51). Possibly, patients with a low baseline concentration have a greater potential for benefit. After bariatric surgery, the low vitamin concentrations observed in our study may potentially be further reduced and cause severe adverse reactions (13). This highlights the importance of controlled trials to determine appropriate monitoring and supplementation for such patients.

Conclusion
We compared vitamin status in patients with clinically severe obesity with that in healthy controls. Selection bias was minimized by studying consecutive patients visiting public healthcare services. The limited size of the control group was a weakness of the study, and care should be taken in generalizing our findings to regions with differences in lifestyle and dietary habits. We conclude that morbidly obese Norwegian patients seeking weight loss may have low circulating concentrations of several vitamins, including 25-hydroxyvitamin D, vitamin B-6, vitamin C, and lipid-adjusted vitamin E.


   ACKNOWLEDGMENTS
 
We thank Berit Falch, Anne Hove, and Merete Pettersen for performing the vitamin analyses; Ann Steen, Sigrun Henjum, Hanne Aspaas, Åse Halsne, and Gøril Vinje for helping with the data collection; Egil Haug for contributing to the study design; and Karl G Blaasaas for statistical advice.

The authors' responsibilities were as follows—ETA (guarantor): initiated and organized the study, analyzed and cross-checked the data, and wrote the manuscript; ETA, KIB, and TB: contributed to the study design; TB obtained funding; ETA and DH: helped conduct the study; and KIB and TB: supervised the study. All authors helped plan the study, interpret the data, and revise the manuscript. None of the authors had a personal or financial conflict of interest.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Karlsson J, Taft C, Sjöström L, Torgerson JS, Sullivan M. Psychosocial functioning in the obese before and after weight reduction: construct validity and responsiveness of the Obesity-related Problems scale. Int J Obes Relat Metab Disord 2003;27:617–30.[Medline]
  2. McTigue K, Larson JC, Valoski A, et al. Mortality and cardiac and vascular outcomes in extremely obese women. JAMA 2006;296:79–86.[Abstract/Free Full Text]
  3. Adams KF, Schatzkin A, Harris TB, et al. Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. N Engl J Med 2006;355:763–78.[Abstract/Free Full Text]
  4. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 2006;295:1549–55.[Abstract/Free Full Text]
  5. Hypponen E, Power C. Vitamin D status and glucose homeostasis in the 1958 British Birth Cohort: the role of obesity. Diabetes Care 2006;29:2244–6.[Abstract/Free Full Text]
  6. Carlin AM, Rao DS, Meslemani AM, et al. Prevalence of vitamin D depletion among morbidly obese patients seeking gastric bypass surgery. Surg Obes Relat Dis 2006;2:98–103.[Medline]
  7. Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 2004;27:2813–8.[Abstract/Free Full Text]
  8. Martins D, Wolf M, Pan D, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2007;167:1159–65.[Abstract/Free Full Text]
  9. Kalueff AV, Tuohimaa P. Neurosteroid hormone vitamin D and its utility in clinical nutrition. Curr Opin Clin Nutr Metab Care 2007;10:12–9.[Medline]
  10. Flancbaum L, Belsley S, Drake V, Colarusso T, Tayler E. Preoperative nutritional status of patients undergoing Roux-en-Y gastric bypass for morbid obesity. J Gastrointest Surg 2006;10:1033–7.[Medline]
  11. Lissner L, Lindroos AK, Sjostrom L. Swedish obese subjects (SOS): an obesity intervention study with a nutritional perspective. Eur J Clin Nutr 1998;52:316–22.[Medline]
  12. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292:1724–37.[Abstract/Free Full Text]
  13. Fujioka K. Follow-up of nutritional and metabolic problems after bariatric surgery. Diabetes Care 2005;28:481–4.[Abstract/Free Full Text]
  14. Hvas AM, Juul S, Bech P, Nexo E. Vitamin B6 level is associated with symptoms of depression. Psychother Psychosom 2004;73:340–3.[Medline]
  15. Kelly PJ, Shih VE, Kistler JP, et al. Low vitamin B6 but not homocyst(e)ine is associated with increased risk of stroke and transient ischemic attack in the era of folic acid grain fortification. Stroke 2003;34:51e–4.[Abstract/Free Full Text]
  16. Wei EK, Giovannucci E, Selhub J, Fuchs CS, Hankinson SE, Ma J. Plasma vitamin B6 and the risk of colorectal cancer and adenoma in women. J Natl Cancer Inst 2005;97:684–92.[Abstract/Free Full Text]
  17. Khaw KT, Bingham S, Welch A, et al. Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition. Lancet 2001;357:657–63.
  18. Nyyssonen K, Parviainen MT, Salonen R, Tuomilehto J, Salonen JT. Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland. BMJ 1997;314:634–8.[Abstract/Free Full Text]
  19. Simon JA, Hudes ES. Serum ascorbic acid and gallbladder disease prevalence among US adults: the Third National Health and Nutrition Examination Survey (NHANES III). Arch Intern Med 2000;160:931–6.[Abstract/Free Full Text]
  20. Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement. Am J Clin Nutr 1992;55(suppl):615S–9S.[Medline]
  21. Meyer HE, Falch JA, Sogaard AJ, Haug E. Vitamin D deficiency and secondary hyperparathyroidism and the association with bone mineral density in persons with Pakistani and Norwegian background living in Oslo, Norway: the Oslo Health Study Bone 2004;35:412–7.
  22. Tallaksen CM, Bohmer T, Bell H, Karlsen J. Concomitant determination of thiamin and its phosphate esters in human blood and serum by high-performance liquid chromatography. J Chromatogr 1991;564:127–36.[Medline]
  23. Zannoni V, Lynch M, Goldstein S, Sato P. A rapid micromethod for the determination of ascorbic acid in plasma and tissues. Biochem Med 1974;11:41–8.[Medline]
  24. Svendsen M, Tonstad S. Accuracy of food intake reporting in obese subjects with metabolic risk factors. Br J Nutr 2006;95:640–9.[Medline]
  25. Rybak ME, Jain RB, Pfeiffer CM. Clinical vitamin B6 analysis: an interlaboratory comparison of pyridoxal 5'-phosphate measurements in serum. Clin Chem 2005;51:1223–31.[Abstract/Free Full Text]
  26. Moor de BA, Wartanowicz M, Ziemlanski S. Blood vitamin and lipid levels in overweight and obese women. Eur J Clin Nutr 1992;46:803–8.[Medline]
  27. Harnroongroj T, Jintaridhi P, Vudhivai N, et al. B vitamins, vitamin C and hematological measurements in overweight and obese Thais in Bangkok. J Med Assoc Thai 2002;85:17–25.[Medline]
  28. Boylan LM, Sugerman HJ, Driskell JA. Vitamin E, vitamin B-6, vitamin B-12, and folate status of gastric bypass surgery patients. J Am Diet Assoc 1988;88:579–85.[Medline]
  29. Kant AK. Interaction of body mass index and attempt to lose weight in a national sample of US adults: association with reported food and nutrient intake, and biomarkers. Eur J Clin Nutr 2003;57:249–59.[Medline]
  30. Galan P, Viteri FE, Bertrais S, et al. Serum concentrations of beta-carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population. Eur J Clin Nutr 2005;59:1181–90.[Medline]
  31. Gascon-Vila P, Garcia-Closas R, Serra-Majem L, et al. Determinants of the nutritional status of vitamin E in a non-smoking Mediterranean population. Analysis of the effect of vitamin E intake, alcohol consumption and body mass index on the serum alpha-tocopherol concentration. Eur J Clin Nutr 1997;51:723–8.[Medline]
  32. Wallstrom P, Wirfalt E, Lahmann PH, Gullberg B, Janzon L, Berglund G. Serum concentrations of beta-carotene and alpha-tocopherol are associated with diet, smoking, and general and central adiposity. Am J Clin Nutr 2001;73:777–85.[Abstract/Free Full Text]
  33. Canoy D, Wareham N, Welch A, et al. Plasma ascorbic acid concentrations and fat distribution in 19 068 British men and women in the European Prospective Investigation into Cancer and Nutrition Norfolk cohort study. Am J Clin Nutr 2005;82:1203–9.[Abstract/Free Full Text]
  34. Reitman A, Friedrich I, Ben-Amotz A, Levy Y. Low plasma antioxidants and normal plasma B vitamins and homocysteine in patients with severe obesity. Isr Med Assoc J 2002;4:590–3.[Medline]
  35. Carrodeguas L, Kaidar-Person O, Szomstein S, Antozzi P, Rosenthal R. Preoperative thiamine deficiency in obese population undergoing laparoscopic bariatric surgery. Surg Obes Relat Dis 2005;1:517–22.[Medline]
  36. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000;72:690–3.[Abstract/Free Full Text]
  37. Harris SS, Dawson-Hughes B. Reduced sun exposure does not explain the inverse association of 25-hydroxyvitamin D with percent body fat in older adults. J Clin Endocrin Metab 2007. Internet: http://jcem.endojournals.org/cgi/rapidpdf/jc.2007-0722v1 (accessed 13 June 2007).
  38. Waki M, Kral JG, Mazariegos M, Wang J, Pierson RN Jr, Heymsfield SB. Relative expansion of extracellular fluid in obese vs. nonobese women. Am J Physiol Endocrinol Metab 1991;261/2:E199–203.
  39. Schweigert FJ. Inflammation-induced changes in the nutritional biomarkers serum retinol and carotenoids. Curr Opin Clin Nutr Metab Care 2001;4:477–81.[Medline]
  40. Ali AT, Paiker JE, Crowther NJ. The relationship between anthropometry and serum concentrations of alkaline phosphatase isoenzymes, liver-enzymes, albumin, and bilirubin. Am J Clin Pathol 2006;126:1–6.
  41. Stephensen CB, Gildengorin G. Serum retinol, the acute phase response, and the apparent misclassification of vitamin A status in the third National Health and Nutrition Examination Survey. Am J Clin Nutr 2000;72:1170–8.[Abstract/Free Full Text]
  42. Gray A, McMillan DC, Wilson C, Williamson C, O'Reilly DS, Talwar D. The relationship between plasma and red cell concentrations of vitamins thiamine diphosphate, flavin adenine dinucleotide and pyridoxal 5-phosphate following elective knee arthroplasty. Clin Nutr 2004;23:1080–3.[Medline]
  43. Friso S, Jacques PF, Wilson PWF, Rosenberg IH, Selhub J. Low circulating vitamin B6 is associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels. Circulation 2001;103:2788–91.[Abstract/Free Full Text]
  44. Wannamethee SG, Lowe GD, Rumley A, Bruckdorfer KR, Whincup PH. Associations of vitamin C status, fruit and vegetable intakes, and markers of inflammation and hemostasis. Am J Clin Nutr 2006;83:567–74.[Abstract/Free Full Text]
  45. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest 2005;115:1111–9.[Medline]
  46. Ford ES. Body mass index, diabetes, and C-reactive protein among U.S. adults. Diabetes Care 1999;22:1971–7.[Abstract/Free Full Text]
  47. Taysi S. Oxidant/antioxidant status in liver tissue of vitamin B6 deficient rats. Clin Nutr 2005;24:385–9.[Medline]
  48. Zittermann A. Vitamin D and disease prevention with special reference to cardiovascular disease. Prog Biophys Mol Biol 2006;92:39–48.[Medline]
  49. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006;84:18–28.[Abstract/Free Full Text]
  50. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–81.[Free Full Text]
  51. The Heart Outcomes Prevention Evaluation (HOPE). Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567–77.[Abstract/Free Full Text]
Received for publication July 31, 2007. Accepted for publication September 6, 2007.




This article has been cited by other articles:


Home page
 Am. J. Clin. Nutr.Home page
E. T Aasheim, S. Bjorkman, T. T Sovik, M. Engstrom, S. E Hanvold, T. Mala, T. Olbers, and T. Bohmer
Vitamin status after bariatric surgery: a randomized study of gastric bypass and duodenal switch
Am. J. Clinical Nutrition, July 1, 2009; 90(1): 15 - 22.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
F. Formelli, E. Meneghini, E. Cavadini, T. Camerini, M. G. Di Mauro, G. De Palo, U. Veronesi, F. Berrino, and A. Micheli
Plasma Retinol and Prognosis of Postmenopausal Breast Cancer Patients
Cancer Epidemiol. Biomarkers Prev., January 1, 2009; 18(1): 42 - 48.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
S. Ledoux and E. Larger
Nutritional deficiencies after Roux-en-Y gastric bypass can be prevented by standard multivitamin supplementation
Am. J. Clinical Nutrition, October 1, 2008; 88(4): 1176 - 1176.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Supplemental data
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Aasheim, E. T
Right arrow Articles by Bøhmer, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aasheim, E. T
Right arrow Articles by Bøhmer, T.
Agricola
Right arrow Articles by Aasheim, E. T
Right arrow Articles by Bøhmer, T.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS