Vitamin concentrations 5 years after gastric bypass

European Journal of Clinical Nutrition (2015), 1–7 © 2015 Macmillan Publishers Limited All rights reserved 0954-3007/15 www.nature.com/ejcn

ORIGINAL ARTICLE

Vitamin concentrations 5 years after gastric bypass E Aaseth1, MW Fagerland2, A-M Aas3, S Hewitt1, H Risstad1, J Kristinsson1, T Bøhmer4, T Mala1 and ET Aasheim1 BACKGROUND/OBJECTIVES: Few studies have investigated the effects of bariatric surgery on vitamin status in the long term. We examined changes in vitamin status up to 5 years after Roux-en-Y gastric bypass surgery. SUBJECTS/METHODS: Using a retrospectively maintained database of patients undergoing weight loss surgery, we identified all patients operated with Roux-en-Y gastric bypass at our tertiary care hospital during July 2004–May 2008. Data on vitamin concentrations and patient-reported intake of dietary supplements were collected up to July 2012. Linear mixed models were used to estimate changes in vitamin concentrations during follow-up, adjusting for age and sex. All patients were recommended daily oral multivitamin, calcium/vitamin D and iron supplements and 3-monthly intramuscular B-12 after surgery. RESULTS: Out of the 443 patients operated with gastric bypass, we included 441 (99.5%) patients with one or more measurements of vitamin concentrations (75.1% women; mean age 41.5 years, mean body mass index 46.1 kg/m2 at baseline). At 5 years after surgery, the patients' estimated mean vitamin concentrations were either significantly higher (vitamin B-6, folic acid, vitamin B-12, vitamin C and vitamin A) or not significantly different (thiamine, 25-hydroxyvitamin D and lipid-adjusted vitamin E) compared with before surgery. Use of multivitamin, calcium/vitamin D and vitamin B-12 supplements was reported by 1–9% of patients before surgery, 79–84% of patients at 1 year and 52–83% of patients 5 years after surgery. CONCLUSIONS: In patients who underwent gastric bypass surgery, estimated vitamin concentrations were either significantly increased or unchanged up to 5 years after surgery. European Journal of Clinical Nutrition advance online publication, 17 June 2015; doi:10.1038/ejcn.2015.82

INTRODUCTION Bariatric surgery is increasingly applied in the management of morbid obesity. One commonly used bariatric procedure is the Roux-en-Y gastric bypass,1,2 which in most patients leads to a substantial, long-term weight loss. This weight loss seems to result mainly from a reduction in energy intake, as gastric bypass causes limited malabsorption of energy-containing macronutrients.3,4 However, the anatomical and physiological changes introduced by the procedure confer a risk for the development of deficiencies in vitamins and other micronutrients. Reported clinical complications due to micronutrient deficiency after gastric bypass include anaemia, osteomalacia, pellagra, Wernicke encephalopathy and scurvy, as well as clinical deficiency states in breastfed infants after maternal surgery.5–12 Because of the risk for clinical deficiency, it is necessary to decide which vitamins should be monitored and at which intervals in patients who have undergone gastric bypass surgery. Monitoring of vitamin biomarkers may facilitate detection of suboptimal vitamin concentrations before clinical deficiency develops and can enable early intervention. However, vitamin assays can be costly, and it can be challenging to interpret the results of these assays, suggesting that resource use needs to be balanced. Several guidelines for post-operative monitoring after gastric bypass exist,13–16 but recommendations for supplementation and vitamin biomarker monitoring vary, reflecting a lack of robust evidence in this field. Few studies have addressed vitamin status in the long term after gastric bypass, and even fewer studies have evaluated a standard supplementation regime in this context.17 The aim of this study was to estimate changes in vitamin concentrations during long-term follow-up in patients undergoing 1

gastric bypass surgery. Our main focus was on changes from before surgery to 5 years after surgery. SUBJECTS AND METHODS Study design, surgical intervention and clinical characteristics Patients were identified from a retrospectively maintained database of all individuals who have undergone bariatric surgery at Oslo University Hospital since the inception of the multidisciplinary treatment programme in July 2004. Because we wished to focus on long-term follow-up, we considered as eligible for the study all patients who were operated July 2004–May 2008. Clinical and biochemical data were collected from electronic medical records, and the last follow-up visit was made in July 2012. Patients were eligible for surgery if they had a body mass index ⩾ 40 kg/m2 or ⩾ 35 kg/m2 with weight-related co-morbidities and had failed to achieve sustained weight loss through non-surgical intervention. Before surgery, each patient participated in educational group sessions, individual dietitian appointments and underwent a medical assessment that included blood tests and other investigations as clinically indicated. Patients underwent a standardised laparoscopic Roux-en-Y gastric bypass as described previously.18 The gastric pouch was 25 ml, the alimentary limb length 150 cm and the biliopancreatic limb 50 cm. After surgery, patients attended outpatient follow-ups with a dietitian, physician or a surgeon at 6 weeks, 6 months, 1 year, 2 years and 5 years after surgery. Additional follow-up visits were made if indicated by clinical need.

Supplements Post surgery, patients were prescribed daily supplementation with multivitamins (one tablet), 100 mg iron sulphate (one tablet or two tablets in women of fertile age), 500 mg calcium carbonate, 400 U vitamin D3 (one tablet twice daily) and 1 mg vitamin B-12 given intramuscularly every

Department of Morbid Obesity and Bariatric Surgery, Oslo University Hospital, Oslo, Norway; 2Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway; 3Department of Nutrition and Dietetics, Oslo University Hospital, Oslo, Norway and 4Department of Endocrinology, Oslo University Hospital, Oslo, Norway. Correspondence: Dr E Aaseth, Department of Morbid Obesity and Bariatric Surgery, Oslo University Hospital, Kirkevegen 89 B, 2407 Oslo, Norway. E-mail: [email protected] Received 13 October 2014; revised 22 April 2015; accepted 23 April 2015

Vitamin concentrations after gastric bypass E Aaseth et al

2 3 months. The multivitamin contained the recommended daily intake of vitamins and minerals in Norway (including 500 μg vitamin A, 1.4 mg thiamine, 2 mg vitamin B-6, 1 μg vitamin B-12, 200 μg folic acid, 60 mg vitamin C, 5 μg vitamin D3 and 10 mg vitamin E).19 Supplement regimens were individually adjusted after follow-up visits if considered clinically indicated based on blood test results. The patients' use of supplements was recorded at each visit. For this study, we considered supplements in the following five categories: multivitamin/mineral supplements; vitamin D supplements (with or without calcium) containing at least 400 U vitamin D3; iron supplements containing at least 65 mg iron sulphate (or similar form and dosage); vitamin B-12 given as intramuscular injections; and additional oral vitamin and mineral supplements prescribed during follow-up. For oral supplements, patients were considered to be adherent at a given followup time point if they reported taking a given supplement at least 5 days per week. For vitamin B-12, patients were considered adherent if using the supplement at least twice per year.

Blood samples and vitamin assays Blood was collected on the same day as the clinical visit, after an overnight fast. Serum aliquots were stored at –20 °C (–80 °C for vitamin C) until analysis within 2 weeks. Laboratory analyses were performed at the Nutrition Laboratory, Hormone Laboratory and Central Laboratory at Oslo University Hospital, Aker. For thiamine pyrophosphate, the method of analysis changed after 29 October 2008 (which altered the reference range), and we therefore excluded assays performed after this date. Supplementary Table 1 describes the methods used, tissue analysed and reference intervals for the different vitamins. We also measured haemoglobin, total cholesterol, high-density cholesterol, triacylglycerols and C-reactive protein (CRP). The detection limit for CRP was o1 mg/l. Reference intervals for concentrations of vitamins B-1, B-2, B-6, C, A and E were estimated separately for men and women based on mean ± 2 s.d. of vitamin concentrations in healthy controls.20 Reference intervals for vitamins with a log normal distribution were obtained by calculating mean ± 2 s.d. of log-transformed values and back transforming the result. For 25-hydroxyvitamin D and parathyroid hormone (PTH), we used reference intervals obtained in a previously described healthy population.21 For folic acid, vitamin B-12, haemoglobin, cholesterol, triacylglycerol and CRP, we used the reference intervals from the Departments of Clinical Chemistry at Oslo University Hospital, Aker. The analyte for vitamin E (α-tocopherol) is carried nonspecifically in plasma lipoproteins, and we therefore adjusted vitamin E concentrations for lipids (cholesterol and triacylglycerol) in order to reduce preanalytical variation.22

Patients with low vitamin concentrations As an exploratory analysis, we reviewed the 10 patients with the lowest vitamin concentrations in two ways. First, we reviewed electronic medical records to check whether patients' clinicians had noted any clinical signs and/or symptoms of vitamin deficiency. Second, we reviewed whether vitamin concentrations at the subsequent clinical visit were within the normal range. Possible biochemical signs of deficiency were not considered. Only patients with vitamin concentrations below the lower reference range were considered, and therefore at some time points fewer than 10 patients were reviewed.

Statistical analysis and ethics Locally weighted regression (lowess) scatter plot smoothing with a bandwidth of 0.25 was used to illustrate the time developments of the vitamin concentrations. Linear mixed models were fitted to repeated measures data on vitamin concentrations and clinical characteristics. The effect of time was modelled as piecewise linear with three periods: (i) 6 months before surgery to 1 year after surgery, (ii) 1 year to 2 years after surgery and (iii) 2 years to 5 years after surgery. The hypothesis of no overall time development was defined as no change in all three time periods. Each model contained three fixed effects for time, a random intercept and one random effect for time. To achieve numerical stability, vitamin E and haemoglobin were modelled without a random effect for time. An unstructured covariance matrix was used in all models. For each outcome, we fitted one model adjusting for age and sex. After model fit, mean values with 95% confidence intervals at four time points (before surgery, 1, 2 and 5 years after surgery) were estimated. The estimated change from before surgery to 5 years after surgery was estimated, and a Wald test for the hypothesis of no overall time development was European Journal of Clinical Nutrition (2015) 1 – 7

conducted. The statistical analyses were performed in Stata 13 (StataCorp LP, College Station, TX, USA). The main database is licensed by The Norwegian Data Protection Authority, and the patients gave written consent for the use of personal data for research and publishing purposes.

RESULTS Out of the 443 patients who underwent gastric bypass surgery during the study period, we included 441 patients (75.1% women, mean age at baseline 41.5 years) who had data available on vitamin concentrations for at least one time point. These time points and the numbers of patients with available vitamin concentrations were as follows: before surgery (n = 184 patients), and 6 months (n = 385), 1 year (n = 396), 2 years (n = 321) and 5 years (n = 264) after surgery. Supplementary Table 2 shows the number of observations for each vitamin during follow-up. At the 5-year follow-up, 264 out of the possible 330 patients (80%) attended—7 were dead and 59 did not attend for unknown reasons. Body mass index, concentrations of CRP, total cholesterol and triacylglyserol significantly (P o0.05) decreased from baseline to 5 years after surgery (Table 1). Concentrations of haemoglobin did not change significantly after surgery. Water-soluble vitamins Figure 1 shows individually observed vitamin concentrations during follow-up with lowess curves, and Table 2 shows age- and sex-adjusted estimated mean vitamin concentrations from baseline to 5 years after surgery with P-values for changes over time. At 5 years after surgery, the patients' estimated mean vitamin concentrations were significantly higher for vitamin B-6, folic acid, vitamin B-12 and vitamin C compared with before surgery. There was no significant change in thiamine concentrations from baseline to 5 years after surgery (P = 0.55). Fat-soluble vitamins and PTH Different patterns were observed for changes in vitamin A, 25-hydroxyvitamin D and vitamin E concentrations after surgery (Table 2). Concentrations of vitamin A increased significantly from baseline to 5 years (P = 0.02). 25-hydroxyvitamin D concentrations increased in the first year after surgery and then decreased to concentrations not significantly different from baseline at 5 years. PTH concentrations increased (P = 0.007) from baseline to 5 years (Table 2). Vitamin E and lipid-adjusted vitamin E concentrations did not change significantly from baseline to 5 years after surgery. Estimated mean concentations of vitamin E were lower, whereas lipid-adjusted vitamin E concentrations were higher at 1 and 2 years after surgery compared with baseline. Supplement use Patient-reported use of vitamin and mineral supplements is shown in Table 3. Few patients reported the use of supplements at baseline. Use of multivitamin, calcium/vitamin D and vitamin B-12 supplements was reported by 1–9% of patients before surgery, 79–84% of patients at 1 year and 52–83% of patients 5 years after surgery. Table 4 shows vitamin concentrations according to supplement use at 1 year and 5 years after surgery. Vitamin concentrations were generally significantly higher in patients who reported taking supplements. Patients with low vitamin concentrations In total, there were 163 patient visits where a patient had a vitamin concentration below the lower reference range. A review of medical notes revealed no severe symptoms or signs of clinical vitamin deficiency in these patients; however, negative findings of © 2015 Macmillan Publishers Limited


© 2015 Macmillan Publishers Limited

Abbreviations: BMI, body mass index; CI, confidence interval; PTH, parathyroid hormone. Characteristics were estimated in linear mixed models and are adjusted for age and sex.

(33.7, 35.1) (13.2, 14.0) (4.61, 4.80) (1.07, 1.19) (1.7, 2.9) (6.6, 7.5) 34.4 13.6 4.71 1.13 2.3 7.0 (30.7, 31.9) (13.0, 13.9) (4.29, 4.46) (0.99, 1.11) (1.5, 3.5) (6.3, 7.3) 31.3 13.4 4.37 1.05 2.5 6.8 (30.9, 32.1) (13.1, 13.9) (3.91, 4.07) (1.05, 1.17) (2.0, 4.1) (5.1, 6.1) 31.5 13.5 3.99 1.11 3.1 5.6 (44.2, 45.6) (13.7, 14.7) (4.80, 4.99) (1.67, 1.82) (9.1, 12.0) (5.6, 6.7)

Before surgery

44.9 14.2 4.89 1.75 10.6 6.2 374 428 428 428 422 363 BMI (kg/m ) Haemoglobin (g/dl) Total cholesterol (mmol/l) Triacylglycerols (mmol/l) C − reactive protein (mg/l) PTH (pmol/l)

2

1 year post operation 2 years post operation 5 years post operation

− 10.5 − 0.6 − 0.19 − 0.62 − 8.3 0.87

(−11.2, − 9.6) (−1.2, 0.03) (−0.30, − 0.08) (−0.71, − 0.53) (−9.7, − 6.8) (0.24, 1.51)

o0.001 0.06 o0.001 o0.001 o0.001 0.007

o0.001 0.10 o0.001 o0.001 o0.001 o0.001

Change from before surgery P-value change before P-value overall to 5 years post operation to 5 years post operation change over time Characteristics, mean (95% CI) n Characteristics

Table 1.

Clinical and biochemical characteristics in 441 patients before and after Roux-en-Y gastric bypass surgery, Oslo University Hospital, 2004–2012

3 clinical examinations were mostly not recorded. At the next follow-up visit (after patients had been recommended to change their supplementation regimen), vitamin concentrations were within the normal reference range in 140 of 163 cases (85.9%). DISCUSSION In this study of morbidly obese patients who underwent gastric bypass surgery and were recommended a standardised set of dietary supplements, we found that patients had either increased or unchanged estimated mean concentrations of vitamin A, thiamine, vitamin B-6, folic acid, vitamin B-12, vitamin C, 25hydroxyvitamin vitamin D and lipid-adjusted vitamin E at 5 years after surgery compared with before surgery. 25-Hydroxyvitamin vitamin D concentrations increased the first year after surgery and subsequently decreased, so that concentrations were no longer different from baseline levels. Fewer patients reported using the recommended vitamin D supplements at 5 years than at 1 year after surgery, whereas the use of intramuscular B-12 injections was more stable. Patients who reported taking vitamin supplements tended to have higher vitamin concentrations. Few studies have evaluated concentrations of vitamin B-6 and lipid-adjusted vitamin E in the long term after gastric bypass. Our findings are consistent with previous findings 1 year after surgery.19,23,24 Vitamin B-6 concentrations increased the first year after surgery and were thereafter stable. Possibly, the initial increase in vitamin B-6 concentrations is related to multivitamin supplementation. Folic acid concentrations increased gradually during the total 5-year follow-up, despite a decline in the proportion of patients taking multivitamin supplements. Increased folic acid concentration is sometimes seen in patients with intestinal bacterial overgrowth,25 but little is known about the prevalence and clinical relevance of this condition after gastric bypass surgery. Previous studies have found that obese patients tend to have lower serum concentrations of several vitamins including vitamin B-6, folic acid, vitamin C, vitamin E and 25hydroxyvitamin D.20,26,27 This may partially be explained by a low micronutrient intake,28 increased oxidative stress,20,29 increased extracellular matrix giving a dilution effect30 and altered enzyme activity. It can be hypothesised that, with surgery-induced weight loss, some of these factors or potentially other physiological alterations associated with severe obesity may be reversed and that concentrations of some vitamins therefore tend to normalise after surgery. In our study, vitamin C concentrations increased gradually during the first year after surgery in tandem with a decrease in CRP concentrations. Vitamin C concentrations increase with the intake of multivitamins, but a steeper increase in vitamin C concentrations than the gradual increase seen in Figure 1 would perhaps be expected if multivitamin supplementation was the sole explanation for the increase. Possibly, a gradual decrease in obesity-related inflammation could help explain the observed gradual increase in vitamin C concentrations. The roux-en-Y gastric bypass procedure alters the anatomy and physiology of the gastrointestinal tract. This may lead to reduced absorption of several micronutrients after gastric bypass,31,32 which further can contribute to changes in vitamin concentrations. Patients occasionally present with persistent vomiting in the first months after bariatric surgical procedures; this should always lead to prompt action to identify underlying pathology and prevent thiamine deficiency, which may lead to Wernicke encephalopathy in about 1/500 patients after bariatric surgery.10 The increased vitamin B-12 concentrations among our patients are in contrast to findings made in patients taking oral vitamin B-12 supplementation, where high deficiency rates have been reported.33–35 A lack of luminal intrinsic factor after surgery is a potential explanation for this finding.36 Other studies in patients using intramuscular injections have also shown adequate serum concentrations.23,24 European Journal of Clinical Nutrition (2015) 1 – 7


4

Figure 1. Vitamin concentrations before and after gastric bypass surgery. Symbols denote individual measurements in men (♦) and women (○), solid lines denote lowess curves and shaded areas denote reference intervals in women (given in Supplementary Table 1). Reference interval in men: vitamin A, 1.3–3.6 μmol/l; vitamin B-1, 72–141 nmol/l; vitamin B-6, 16–158 nmol/l; folic acid (vitamin B-9), 48 nmol/l; vitamin B-12, 150– 650 pmol/l; vitamin C, 33–100 mmol/l; 25-hydroxyvitamin D; 25-118 nmol/l, vitamin E, 16.9–47.5 μmol/l; lipid-adjusted vitamin E − / − (total cholesterol+triacylglycerols), 3.4–6.6 μmol/mmol. The upper limit of the assay was 45.4 nmol/l for folic acid and 1476 pmol/l for vitamin B-12.

In Sweden, a retrospective review of 293 gastric bypass patients who were recommended similar supplementation as in our study found median 25-hydroxyvitamin D of 42 mmol/l and PTH concentrations of 9.4 pmol/l at 11 years after gastric bypass.37 The lower 25-hydroxyvitamin D concentrations than in our study European Journal of Clinical Nutrition (2015) 1 – 7

could potentially be explained by a lower intake of vitamin D, with only 5% of patients reporting intake of vitamin D supplements.37 A high deficiency rate of 25-hydroxyvitamin D in the long term after gastric bypass has been reported previously.38,39 Despite vitamin D and calcium supplementation, we observed increased PTH © 2015 Macmillan Publishers Limited



Abbreviation: CI, confidence interval. Concentrations were estimated in linear mixed models and are adjusted for age and sex. Thiamine, blood thiamine pyrophosphate; vitamin B-6, serum pyridoxal-5phosphate; vitamin B-12, serum cobalamin; vitamin C, plasma ascorbic acid; vitamin A, serum retinol; vitamin D, serum 25-hydroxyvitamin D; vitamin E, serum α-tocopherol; lipids, cholesterol+triacylglycerol (mmol/l).

0.55 0.02 o0.001 o0.001 0.005 0.02 0.55 0.17 0.62 (92, 125) (39.0, 47.7) (22.1, 24.2) (512, 581) (50.9, 68.5) (1.75, 1.86) (56.7, 61.5) (22.7, 27.3) (3.54, 5.23) 109 43.3 23.1 547 59.7 1.80 59.1 25.0 4.39 (101, 109) (41.9, 50.1) (20.6, 22.4) (506, 566) (59.0, 65.3) (1.58, 1.69) (58.7, 64.4) (23.5, 25.1) (4.47, 4.78) 105 46.0 21.5 536 62.1 1.64 61.6 24.3 4.62 (100, 107) (46.2, 54.2) (19.0, 20.7) (453, 507) (60.0, 64.2) (1.63, 1.74) (65.3, 71.0) (22.4, 23.6) (4.47, 4.68) 103 50.2 19.9 480 62.0 1.68 68.1 23.0 4.57 (107, 120) (25.3, 40.9) (14.9, 17.0) (333, 395) (42.0, 50.1) (1.58,1.78) (56.5, 64.2) (25.6, 27.8) (3.96, 4.37) 114 33.1 15.9 364 46.0 1.68 60.3 26.7 4.17 379 436 421 425 339 425 369 387 353 Thiamine (nmol/l) Vitamin B-6 (nmol/l) Folic acid (nmol/l) Vitamin B-12 (pmol/l) Vitamin C (mmol/l) Vitamin A (μmol/l) Vitamin D (nmol/l) Vitamin E (μmol/l) Vitamin E adjusted for lipids (μmol/mmol)

Before surgery

1 year post operation

2 years post operation

5 years post operation

− 5.1 10.3 7.2 183 13.7 0.12 − 1.2 − 1.7 0.22

(-22, 12) (1.9, 18.6) (5.8, 8.6) (141, 224) (4.1, 23.2) (0.02, 0.22) (−5.3, 2.9) (−4.2, 0.7) (−0.65, 1.09)

Change from before surgery to 5 years post operation Concentrations, mean (95% CI) n Vitamins

Table 2.

Vitamin concentrations in 441 patients before and after Roux-en-Y gastric bypass surgery, Oslo University Hospital, 2004–2012

P-value change before to 5 years post operation

0.05 o0.001 o0.001 o0.001 o0.001 o0.001 o0.001 o0.001 0.004

P-value overall change over time

5 Table 3.

Patient-reported use of vitamin and mineral supplements

Multivitamin, n (%) Calcium/vitamin D, n (%) B-12 injections, n (%) Iron, n (%) Other supplementsb, n (%)

a

Before surgery

1 year post surgery

5 years post surgery

n = 349

n = 224

n = 253

40 5 3 6 20

(9.0) (1.1) (0.7) (1.4) (4.5)

189 177 181 105 23

(84.4) (79.0) (80.8) (46.9) (10.3)

177 132 211 60 30

(70.0) (52.0) (83.1) (23.7) (12.0)

a

For oral supplements, patients were considered to take the specified supplement if they reported taking that supplement at least 5 days per week. bAdditional supplements prescribed including vitamins or minerals.

concentrations after surgery, in accordance with previous studies.37,40 Perhaps the standard dose of 400 U vitamin D3 is too low to prevent an increase in PTH concentrations in some patients. A paper reported that these patients may need up to 5000 U vitamin D3 per day to maintain stable PTH concentrations.41 Key strengths of this study include the long-term follow-up after surgery and the evaluation of patient adherence to dietary supplementation regimens. We adjusted vitamin concentrations for age and sex and included a large number of patients, which enabled us to track mean concentrations with precision (that is, with relatively narrow 95% confidence intervals). We did not account for determinants of vitamin concentrations such as diet,42,43 medical co-morbidities,44 seasonal variation, smoking43,45 and alcohol consumption.43 The thiamine concentrations reported should be interpreted with caution, as our method showed some analytic variation in the period under study.19 The generalisability of our findings may not extend to other protocols for dietary supplementation and clinical follow-up after gastric bypass. Our findings might suggest that the proportion of patients taking recommended post-operative nutrient supplementation might fall over time, which underscores a need for long-term care. Figure 1 demonstrates the large interobservational variability showing that a few patients have vitamin concentrations below the reference range at each time point for each vitamin. We focused on vitamin concentrations during long-term followup and did not describe in detail the early changes in vitamin concentrations after surgery, which is important in the case of thiamine, where deficiency is typically reported in the first 6 months after surgery.10 Scurvy has also been reported 3 months after surgery.46 Undertaking a review of medical records in order to identify clinical signs and symptoms of vitamin deficiency may underestimate the true occurrence of such signs and symptoms, as this depends on the extent to which medical practitioners examine patients for signs and symptoms of vitamin deficiency. This study adds knowledge relevant to the long-term management of patients who undergo gastric bypass. As the number of patients who have undergone gastric bypass increases, it is likely that general practitioners will become more involved in the routine follow-up of these patients, particularly in the long term. Our findings of mostly stable or increased vitamin concentrations suggest that, with accumulating knowledge, it might be feasible to develop guidelines that can be implemented in the primary care setting. Such guidelines should outline a proposed schedule for follow-up visits, which biomarkers to monitor, which supplements to prescribe and when to consider referrals to specialist care. Practically feasible and cost-effective follow-up regimens of bariatric surgery patients in the primary care setting are an important area for future research. Our study also did not evaluate European Journal of Clinical Nutrition (2015) 1 – 7


6 Table 4.

Vitamin concentrations according to supplement use, 1 and 5 years after gastric bypass surgery P-value

1 year Supplement use

No supplement

Multivitamin use Vitamin Aa (μmol/l) Vitamin B-1b (nmol/l) Vitamin B-6b (nmol/l) Folic acidb (nmol/l) Vitamin Ca (mmol/l) Vitamin Ea (mmol/l) Vit E adjusted for lipidsa (μmol/mmol)

1.73 ± 0.45 111 ± 49.5 40.3 ± 29.7 18.8 ± 11.9 63.0 ± 17.9 23.5 ± 5.1 4.6 ± 0.9

1.74 ± 0.54 104 ± 30.5 33.6 ± 31.5 14.2 ± 11.5 53.8 ± 15.4 24.4 ± 5.6 4.1 ± 1.0

Vitamin D supplements 25-OH vit Da (nmol/l)

69.1 ± 25.6

Vitamin B-12 injections Vitamin B-12b (pmol/l)

468 ± 291

P-value

5 years Supplement use

No supplement

0.901 o 0.001 o 0.001 o 0.001 0.020 0.45 0.017

1.94 ± 0.55 180 ± 43.8 39.0 ± 39.8 23.6 ± 15.5 73.0 ± 23.9 24.0 ± 4.4 4.4 ± 0.14

1.78 ± 0.51 163 ± 38.7 21.5 ± 19.8 16.6 ± 7.7 37.3 ± 20.5 24.9 ± 1.3 4.0 ± 0.36

0.044 o0.001 o0.001 o0.001 0.026 0.67 0.28

54.7 ± 25.1

o 0.001

66.3 ± 20.6

53.1 ± 24.0

o0.001

305 ± 436

o 0.001

532 ± 452

279 ± 142

o0.001

Data were compared with an independent sample t-test, and mean ± s.d. serum values are presented. Data were compared using the Mann–Whitey U-test, and median ± interquartile range serum values are presented. Number of patients with biomarker level and supplement status 1 year after gastric bypass (supplement use/no supplement): vitamin A, 170/31; B-1,168/28; B-6,170/30; folic acid, 189/35; C, 116/24; E, 143/26; lipid-adjusted vitamin E, 127/24; 25-OH D, 175/49; B-12,249/41. Number of patients 5 years after gastric bypass (supplement use/no supplement): vitamin A, 171/70; B-1, 176/75; B-6, 176/76; folic acid, 175/75; C, 5/6; E: 5/6, lipid-adjusted vitamin E; 2/2, 25-OH D; 127/120, B-12; 211/41.

a

patient satisfaction, costs or the effectiveness of supplements towards preventing nutritional deficiencies, which are other areas relevant for future studies. CONFLICT OF INTEREST The authors declare no conflict of interest.

ACKNOWLEDGEMENTS EA (guarantor) and ETA collected the data; EA, A-MA, TM and ETA contributed to the study design and planned the study; EA cross-checked the data; EA and MWF carried out the statistical analysis; EA and ETA wrote the manuscript; TM, A-MA and ETA supervised the study. All authors contributed to the interpretation of results, critically revised the manuscript and approved the final version of the manuscript.

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b

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European Journal of Clinical Nutrition (2015) 1 – 7