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Original article
Anemia, iron and vitamin B12 deficiencies after sleeve gastrectomy compared to Roux-en-Y gastric bypass: a meta-analysis Yeongkeun Kwon, M.D.a, Hyun Jung Kim, M.P.H., Ph.D.b, Emanuele Lo Menzo, M.D., Ph.D., F.A.C.S., F.A.S.M.B.S.c, Sungsoo Park, M.D., Ph.D.a,*, Samuel Szomstein, M.D., F.A.C.S., F.A.S.M.B.S.c, Raul J. Rosenthal, M.D., F.A.C.S., F.A.S.M.B.S.c a
b
Division of Upper Gastrointestinal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea Institute for Evidence-based Medicine, The Korean Branch of Australasian Cochrane Center, Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea c Bariatric and Metabolic Institute, Section of Minimally Invasive Surgery, Cleveland Clinic Florida, Weston, Florida
Abstract
Background: The effective treatment of postoperative anemia and nutritional deficiencies is critical for the successful management of bariatric patients. However, the evidence for nutritional risk or support of bariatric patients remains scarce. The aims of this study were to assess current evidence of the association between 2 methods of bariatric surgery, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), and postoperative anemia and nutritional deficiencies. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for English-language studies using a list of keywords. Reference lists from relevant review articles were also searched. In the authors’ meta-analysis, they included studies with a duration of 412 months, those comparing SG with RYGB, and those with available outcome data for postoperative anemia and iron and vitamin B12 deficiencies. Of 36 potentially relevant studies, 9 met the inclusion criteria. Data were combined by means of a fixed-effects model or randomeffects model. Results: Compared with the SG group, the odds ratio for postoperative vitamin B12 deficiency in the RYGB group was 3.55 (95% confidence interval, 1.26–10.01; P o .001). In the subgroup analysis, studies in which prophylactic iron or vitamin B12 was administered lost significance in the odds ratio for postoperative vitamin B12 deficiency. Conclusion: The authors’ findings suggest that SG is more beneficial than RYGB with regard to postoperative vitamin B12 deficiency risk, whereas the 2 methods are comparable with regard to the risk of postoperative anemia and iron deficiency. Postoperative prophylactic iron and B12 supplementation, in addition to general multivitamin and mineral supplementation, is recommended based on the comparable deficiency risk of the 2 methods as indicated by subgroup analysis. (Surg Obes Relat Dis 2014;]:00–00.) r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.
Keywords:
Sleeve gastrectomy; Roux-en-Y gastric bypass; Anemia; Iron; Vitamin B12
Bariatric surgery is recognized as the most effective longterm treatment for morbid obesity; significant and durable * Correspondence: Sungsoo Park, M.D., Ph.D., Division of Upper Gastrointestinal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, Inchon-ro 73, Seongbukgu, Seoul 136-705, Korea. E-mail: [email protected]
weight loss, resolution or improvement of co-morbidities [1,2], and subsequent reduction in mortality are benefits that have been demonstrated by this procedure [3,4]. However, few studies have examined preoperative and postoperative nutritional status, and the reported prevalence of these deficiencies varies widely due to differences in the definitions of deficiency, patient populations, surgical techniques, supplement protocols, and length and completion of
1550-7289/14/$ – see front matter r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved. http://dx.doi.org/10.1016/j.soard.2013.12.005
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patient follow-up [5]. The effective treatment of postoperative anemia and nutritional deficiencies is critical for successfully managing bariatric patients in particular, considering their serious consequences [5]. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) have shown highly satisfactory results; therefore, they are among the most common types of bariatric surgery currently performed [6]. In recent years, SG has gained popularity as a stand-alone operation for the treatment of morbid obesity [7]. SG is simpler than laparoscopic RYGB and yields weight loss levels and co-morbidity resolution rates comparable to those achieved with RYGB [8,9]. The health benefits associated with the different bariatric surgery types have been well documented [10]; however, the nutritional risks associated with SG have not been described as frequently as those associated with RYGB [11–13]. The evidence for nutritional support of bariatric patients remains scarce, and data from individual studies may be insufficient to indicate the underlying pathophysiological changes or support the implementation of this therapy in clinical care. Moreover, prophylactic nutritional supplements are routinely prescribed after these types of surgery although there is no agreement on the dosage or form of nutrients required to avoid deficiency. Therefore, the authors performed a systematic review and meta-analysis of existing studies (1) to compare the anemia risk and the most common vitamin and mineral deficiencies (iron and vitamin B12) between patients undergoing SG and those undergoing RYGB and (2) to determine whether postoperative prophylactic micronutrient supplementation is related to anemia and nutritional deficiency risk after SG and RYGB.
Methods Search strategy We performed a systematic review of the published scientific literature. Relevant studies published between 1950 and July 1, 2013 were selected by searching MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The following combined text and Medical Subject Heading (MeSH) terms were used: sleeve gastrectomy (viz., gastric sleeve, sleeve gastrectomy, vertical gastrectomy, and longitudinal gastrectomy), gastric bypass (viz., gastric bypass, Roux-en-Y gastric bypass, gastroenterostomy, gastrojejunostomy, gastrojejunal anastomosis, gastrojejunal fixation, jejunogastric anastomosis, gastroileal bypass, gastric exclusion, malabsorptive bypass, long limb, short limb), anemia, and iron and vitamin B12 deficiencies (viz., anemia, anaemia, complete blood count, blood cell count, hematocrit, erythrocyte index, hemoglobin, micronutrient deficiencies, vitamin, mineral, iron, Fe, cobalamin, altered gastrointestinal function, nutrient absorption, malabsorption, nutrient supplementation, metabolic
complication, nutri*, micronutri*). All potentially eligible studies were considered for review regardless of primary outcome or language. A manual search using references of key articles published in English was also performed. Selection criteria Studies were considered for inclusion if they (1) compared SG and RYGB, (2) assessed the effects of SG and RYGB on postoperative anemia and nutritional status and reported means and standard deviations or proportion of deficiencies, and (3) had a study duration of 412 months. Most of the included studies had double-arm designs, and in 1 study [14] that had 42 interventional groups, the authors analyzed only the arms that received SG or RYGB. Exclusion criteria were as follows: (1) studies that included patients who underwent other types of bariatric surgery, (2) studies that did not provide postoperative anemia or nutritional status, and (3) further publications from included studies. Two independent investigators reviewed study titles and abstracts, and studies that satisfied the inclusion criteria were retrieved for full-text assessment. A third investigator resolved any disagreements. We extracted data on first author’s name, publication year, number, age, sex, and body-mass index (BMI) of participants, anemia or hemoglobin level, iron and vitamin B12 levels or proportion of deficiencies, follow-up duration, reference range for deficiency, surgical procedures, and postoperative nutrition protocol. The risk of bias was assessed according to the Cochrane Collaboration’s tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale for nonrandomized studies (NRSs) [15]. Study quality assessment addressed sequence generation, allocation concealment, and incomplete outcome data in RCTs and adequacy of selection, comparability, and outcome assessment in NRSs. This study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [16]. Statistical analysis Odds ratios (ORs) and 95% confidence intervals were calculated for all articles with sufficient data to compare SG with RYGB. Pooled ORs were calculated as the weighted average of the ORs for anemia and iron and vitamin B12 deficiencies at 1 year after surgery (except for 1 study [13]). Weighting was assigned according to the inverse of the variance. Heterogeneity was tested using the Cochrane Q test and quantified with the I2 statistic [17]. The value of the I2 statistic was used to select the appropriate pooling method; fixed-effects models were used for I2 o50% and random-effects models were used for I2 Z50%. The presence of bias was examined using a Begg's regression
Anemia after Bariatric Surgery / Surgery for Obesity and Related Diseases ] (2014) 00–00
test [18]. Statistical analyses were performed using Stata 12 (StataCorp, College Station, TX). The metan and metafunnel macros were used for meta-analytic procedures. P values of o0.05 were considered statistically significant. Results Studies included in the meta-analysis The authors identified 181 studies through electronic searches (Supplement 1). Of these, 147 were excluded based on the title and abstract, and thus, 36 studies were selected for further assessment. Nine studies fulfilled the authors’ inclusion criteria, and thus provided data for 1,104 participants [12–14,19–24]. Of these studies, 2 were from Greece and 1 each from Australia, Chile, India, Poland, Spain, Switzerland, and the United States. Table 1 lists the summary and study-specific characteristics. Studies were published as early as 2008 and 4 studies [13,14,19,21] had a randomized controlled design. Supplement 2 and Supplement 3 show the risk of bias in the included studies. All studies reported adequate effects of 2 bariatric surgeries on postoperative anemia and nutritional complications (implying that the study assessed the number or percentage of patients who developed complications or reported absolute values of hemoglobin, iron, or vitamin B12). Among 4 RCTs, 3 studies [13,14,19] showed a low risk of bias, and 1 study [21] did not provide methods of sequence generation and allocation concealment. Table 2 shows the postoperative nutritional strategies of the included studies. One study [19] did not report the nutritional protocol. General tablet multivitamin and mineral supplements were prescribed in 7 studies, and their specific proprietary names are summarized in Table 2. Postoperative prophylactic iron and vitamin B12 supplements were administered to both SG and RYGB patients in 2 studies [20,21], and 1 study [23] reported only vitamin B12 levels with prophylactic vitamin B12 supplementation. Postoperative anemia and iron and vitamin B12 deficiencies In the pooled analysis of 6 studies that assessed the number or percentage of patients who developed anemia or reported absolute values of hemoglobin (n ¼ 775) [13,14,19,20,22,24], the ORs of postoperative anemia were not higher after SG compared to RYGB in the RCT and NRS analyses (Fig. 1A) (Supplement 4). Only 1 study [19] reported a significant increase in postoperative anemia risk. Additionally, the heterogeneity was not significant in the individual estimates when the magnitude of the association was assessed. No evidence of publication bias was detected on Begg’s regression test (Supplement 5A). In the pooled analysis of 5 studies that assessed the number or percentage of patients who developed iron deficiency or reported absolute values of iron (n ¼ 682)[12,13,20,21,24], the ORs of postoperative iron deficiency were not higher after SG
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compared to RYGB in the RCT and NRS analyses (Fig. 1 B) (Supplement 4). All studies reported nonsignificant ORs. Moreover, heterogeneity was not significant between studies. No evidence of publication bias was detected on Begg’s regression test (Supplement 5B). In the pooled analysis of 6 studies that assessed the number or percentage of patients who developed vitamin B12 deficiency or reported absolute values of vitamin B12 (n ¼ 451) [12,13,20,21,23,24], RYGB was associated with higher ORs of postoperative vitamin B12 deficiency than SG in the RCT analysis (Fig. 1 C) (Supplement 4). Only 1 study [12] reported a significant increase in postoperative vitamin B12 deficiency risk. Additionally, the heterogeneity was not significant between studies. No evidence of publication bias was detected on Begg’s regression test (Supplement 5C). Subgroup analyses by postoperative prophylactic nutritional supplementation Table 3 shows the results of the meta-analysis comparing postoperative anemia and iron and vitamin B12 deficiencies in studies in which prophylactic iron or vitamin B12 supplements were administered. One study that provided no prophylactic iron or vitamin B12 supplementation showed that RYGB was associated with a higher postoperative vitamin B12 deficiency risk but not with iron deficiency, which was in agreement with whole-group analyses. However, studies that provided prophylactic iron or vitamin B12 supplementation did not show a significant OR in anemia and vitamin B12 deficiency risk. The pooled analysis of 2 studies that provided prophylactic iron and vitamin B12 supplementation in addition to general multivitamin and mineral supplementation did not show a significant OR for iron and vitamin B12 deficiency risk. Discussion Nutrient deficiencies are common after bariatric surgery. Despite routine vitamin and mineral supplementation after bariatric surgery, numerous patients show deficiencies in vitamins or trace elements. These deficiencies are related to the reduced food intake as well as the physiologic impact of surgically induced anatomic changes in the gastrointestinal tract. Any bariatric procedure with a malabsorptive effect, either RYGB or biliopancreatic diversion, can lead to an increased risk of postoperative nutrient deficiencies. However, thus far, the incidences of vitamin and mineral deficiencies after SG and their comparisons with those after RYGB have been seldom in being reported [11–13]. RYGB is currently the most commonly performed bariatric operation worldwide, superseding other restrictive and malabsorptive procedures because of the effective longterm weight loss and amelioration of co-morbidities associated with this procedure [1]. SG was initially introduced
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Table 1 Characteristics of the studies included in the analysis Year of publication
Randomized controlled trials Karamanakos 2008 et al. [19] (Greece) Kehagias et al. 2011 [13] (Greece)
Sample, size, Design no.
Baseline mean Baseline age, mean proportion of (SD), y women, %
Baseline BMI, Baseline Hb, Baseline iron Baseline mean (SD), mean (SD), level mean (SD), vitamin B12 kg/m2 level mean g/dL μmol/L (SD), рmol/L
Follow-up, months
Length of roux limb in RYGB, cm
Reference range for deficiency
16/16
RCT
37 (8.25)/ 30.6 (7.8)
75/93.8
46.6 (3.7)/ 45.1 (3.6)
13.4 (0.9)/ 13 (0.9)
NR
NR
12
150
NR
30/30
RCT
33.7 (9.9)/ 36 (8.4)
73.3/73.3
44.9 (3.4)/ 45.8 (3.7)
(13/13)a
(20/20)a
(3/3)a
36
150
43.9 (10.8)/ 44.9 (10.6) 48.3 (8.4)/ 47.9 (8.0)
63.9/72.2
48.6 (5.4)/ NR 46.1 (5.9) 37.0 (3.3)/36.2 NR (3.9)
(25/33.3)a
(30.6/13.8)a
12
100
Hb, men, o13.5 g/dL Hb, women, o12.5 g/dL Iron, o50 mg/dL Vit. B12, o200 рg/mL NR
NR
NR
12
150
Hb, men, o13.0 g/dL Hb, women, o11.5 g/dL
374 (166.7)/ 12 305 (110.5)
100
Hb, men, o30 g/L Hb, women, o119 g/L Iron, o9.0 μmol/L Vit. B12, o145 рmol/L
Paluszkiewicz 2012 [21] (Poland) Schauer et al. 2012 [14] (US)
36/36
RCT
50/50
RCT
Nonrandomized studies Toh et al. [24] 2009 (Australia)
121/64
Retrospective 48 (10)/ cohort 46 (12)
58/78
63.6/57.8
43.1 (5.2)/ 51.0 (11.2)
14.1 (5.3)/ Men, 14.6 13.4 (5.3) (1.3)/14.0 (1.4) Women, 13.2 (0.7)/ 13.6 (0.9)
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Study (Location)
86/50
Retrospective 43.5/41.9 cohort
71/74
44.2/46.5
NR
(3, overall)a
(3, overall)a
Todkar et al. [23] (India)
2011
50/71
Retrospective NR cohort
NR
NR
NR
NR
334.6 рg/mL, 12 overall
NR
Ruz et al. [22] (Chile) Moize et al. [20] (Spain)
2012
23/20
100/100
13.2 (1.1)/ 13.4 (1.2) (22/10)a
NR
6, 12
125, 150
294/61
42.0 (4.2)/ 37.3 (3.2) 47.4 (6.0)/ 51.6 (6.7)
NR
2013
Retrospective 35.9 (9.1) cohort Retrospective 45.2 (10.6)/ cohort 46.4 (11.6)
(26.5/30.8)a
(1.8/2.7)a
6, 12, 24, 48, 100 60
77/67.2
3, 6, 12, 24, 30, 36
150
Iron, o30 ng/mL Vit. B12, o150 рmol/L Vit. B12, o200 рg/mL Hb, women, o 12 g/dL Hb, men, o13.7 g/dL Hb, women, o12.2 g/dL Iron, 50–170 μg/dL Vit. B12, 250–1,050 рg/mL
BMI ¼ body mass index; Hb ¼ hemoglobin; NR ¼ not reported; RCT ¼ randomized controlled trial; RYGB ¼ Roux-en-Y gastric bypass; SD ¼ standard deviation; SG ¼ sleeve gastrectomy; Vit. ¼ vitamin. All data are presented by the order of RYGB and SG when needed. a Proportion of preoperative anemia or iron and vitamin B12 deficiency was presented (%).
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Gehrer et al. 2010 [12] (Switzerland)
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Table 2 Postoperative nutritional strategies of the studies included in the analysis Studies
Supplements Multivitamin and Mineral
Iron
SG
SG
Karamanakos et al. [19] NR 2008 Toh et al. [24] 2009 Daily, Oral
RYGB
Vitamin B12 RYGB
NR Daily, Oral
Gehrer et al. [12] 2010 One tableta daily, Oral Kehagias et al. [13] One tablet daily, Oral Daily 2011 First 6 months
SG RYGB NR
NR 1,000 μg every 3–6 months, Parenteral When deficient When deficient NR 80 mg daily, Oral Premenopausal 1,000–3,000 μg, Parenteral women When below 200 рg/mL after 6 months NR 500 mg daily, Oral 0.1 g daily, Sublingual 1,000 μg monthly, Sublingual When deficient
Todkar et al. [23] 2011 NR Paluszkiewicz et al. [21] One tablet daily, Oral 2012 Ruz et al. [22] 2012 One tabletb daily, Oral One tabletcd daily, 22 mg daily, 60 mg daily Oral Oral Schauer et al. [14] 2012 Yes NR Yes Moize et al. [20] 2013 One tablete daily, Oral 160 mg dailyf, Oral
NR Yes 1,000 μg monthly, Parenteralgh
NR ¼ not reported; RYGB ¼ Roux-en-Y gastric bypass; SG ¼ sleeve gastrectomy. a Beroccas. b Centrum, Wyeth Laboratories. c Maltofer vit, Andromaco Laboratories. d Elcal-D PLUS, Andromaco Laboratories. e Supradyn Activo, Bayer. f Tardyferon, Pierre Fabre Iberica. g Optovite B12, Normon. h Ideos Unidia, Procter & Gamble Pharmaceuticals.
as a first-step procedure to minimize the surgical risk of patients with a BMI of 455 followed by RYGB [25]. Nevertheless, this procedure has been increasingly used alone in patients with a BMI o50 because of its satisfactory results in ameliorating co-morbidities [6,13]. However, this procedure is not exempt from complications such as micronutrient deficiencies [11]. Moreover, Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery Patient-2013 Update by the American Association of Clinical Endocrinologists, The Obesity Society, and the American Society for Metabolic & Bariatric Surgery has given broad recommendations concerning micronutrient under-nutrition and management; however, evidence from level 1 studies are lacking for all relevant vitamins and minerals [26]. Anemia and iron and vitamin B12 deficiencies have been frequently observed and described after RYGB surgery with widely varying prevalences [27]. These deficiencies may arise from the substantial reduction in food intake and food intolerances. In a retrospective study of self-reported intake among 69 patients at 18 months to 4 years after RYGB [28], iron and vitamin B12 intake from food exceeded 100% of the recommended dietary allowance recommendations. In another study of 113 RYGB patients, foods that were ‘‘not well tolerated’’ included milk (25%), steak (16%), minced beef (12%), and bread (8%) [29], which contributed to reduced intake of dietary sources of iron and calcium. Data
show that SG and RYGB are associated with similar longterm weight loss with no differences in terms of dietary intake [20]. Iron deficiency in RYGB patients may also result from malabsorption (because the main sites of iron absorption have been bypassed) and from reduced bioavailability of dietary iron because of the lack of hydrochloric acid production in the small gastric pouch. One study indicated that patients who ate red meat less than once weekly had a significantly higher incidence of iron and vitamin B12 deficiencies than patients who ate red meat more than once weekly at 7 years after RYGB [30]. Blood loss through menstruation may also predispose premenopausal women to iron deficiency and anemia, leading to the prescription of prophylactic iron to these patients in many centers [31]. Prophylactic iron supplements are routinely prescribed after these types of surgery, although there is no agreement on the amount and form of iron that could efficiently prevent iron deficiency. Because a major component of RYGB, in addition to stomach reduction, is the exclusion of the duodenum and a portion of the jejunum, the authors expected that iron absorption after SG would be less affected than that after RYGB. The results, however, did not show differences in the iron deficiency risk between SG and RYGB. To explain this result, the authors must consider the relative capacity of distinct intestinal segments to absorb iron and their ability to adapt to increased iron transfer demands. One study
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Fig. 1. Meta-analysis of the effects of 2 bariatric surgeries (sleeve gastrectomy versus Roux-en-Y gastric bypass) on postoperative (A) anemia, (B) iron deficiency, and (C) vitamin B12 deficiency. ES ¼ effect size; I-V Subtotal ¼ fixed-effects analysis; DþL Subtotal ¼ random-effects analysis; SG ¼ sleeve gastrectomy; GB ¼ Roux-en-Y gastric bypass.
Table 3 Risk of anemia and nutritional deficiencies with or without postoperative prophylactic iron or vitamin B12 supplementation No. of Studies No prophylactic iron or vitamin B12 supplementation Iron deficiency 1 Vitamin B12 deficiency 1 Prophylactic iron supplementation (both SG and RYGB) Anemia 1 Prophylactic vitamin B12 supplementation (both SG and RYGB) Anemia 1 Vitamin B12 deficiency 1 Prophylactic iron and vitamin B12 supplementation Anemia 1 Iron deficiency 2 Vitamin B12 deficiency 2
Odds Ratio (95% CI)
PEff
I square
PHet
.689 .066
47.8 0.0
.167 .719
1.76 (0.74–4.17) 6.33 (2.73–14.64) 3.64 (0.82–16.10) 1.00 (0.30–3.34) 1.20 (0.55–2.64) 1.91 (0.83–4.42) 1.15 (0.58–2.26) 2.38 (0.95–6.01)
CI ¼ confidence interval; PEff ¼ P value of pooled effect; PHet ¼ P value of heterogeneity test.
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showed adaptations after ileojejunal transposition; they reported that transposed enterocytes took up some jejunal characteristics in terms of transferred iron, although jejunal values were not reached [32]. One study indicated the expression of genes involved in iron metabolism and found a gradient of mucosal nonheme iron (duodenum 4 jejunum 4 ileum) and regional differences in ferritin and transferrin receptor mRNA levels [33]. Therefore, after RYGB, patients may have some degree of adaptation to the exclusion of the duodenum and part of the jejunum, which may be potentiated by an increased iron-absorption stimulus as a result of the greater reduction in iron stores compared to that in patients undergoing SG. Vitamin B12 absorption involves a complex series of metabolic steps within the gastrointestinal tract. Vitamin B12 malabsorption and deficiency may occur in RYGB patients because of (1) decreased acid and pepsin digestion of protein-bound cobalamins from food, (2) incomplete release of vitamin B12 from R proteins by limited mixing of nutrients with pancreatic secretions in a shortened common channel, and (3) decreased availability of the intrinsic factor, which is secreted by the parietal cells of the stomach after being stimulated by food [34]. The small pouch constructed from the gastric cardia in the RYGB procedure is virtually absent of acid secretion, and food-bound vitamin B12 is maldigested and subsequently malabsorbed [35]. The authors’ results showed that SG had better outcomes with respect to postoperative vitamin B12 deficiency than RYGB, and the results were well in agreement with the subgroup analysis in which prophylactic vitamin B12 supplementation was not provided postoperatively. However, when prophylactic vitamin B12 supplementation was provided, the risk of deficiency in RYGB was comparable to that of SG. According to the literature, oral vitamin B12 supplementation successfully corrected deficiencies in 81% of cases [31,36]. Multivitamin supplementation alone, although containing 10 μg cyanocobalamin, did not prevent vitamin B12 deficiency in bariatric patients, but intramuscular cyanocobalamin supplementation corrected the deficiency in 91% of patients [12]. With vitamin B12 administered at 1,000 to 3,000 o mu 4 g intramuscularly, depending on serum levels, the prevalence of vitamin B12 deficiency at 1 year to 2 years after RYGB has been reported at 24% to 36% [36,37]. However, in a prospective study of 493 RYGB patients, vitamin B12 deficiency at 1 year after surgery was only 3.6% on a regime of 1,000 o mu 4 g vitamin B12 administered intramuscularly every 3 months [38]. Normal plasma vitamin B12 levels may be maintained with oral crystalline vitamin B12, but at very high doses, 4500 mg/d was sufficient to correct the majority (81%) of deficiencies [36]. A limitation of the authors’ meta-analysis was that an analysis of only RCTs could not be performed because of the paucity of such studies. The authors’ results should thus be interpreted with caution, as the risk of selection bias may
exist in NRSs. A second limitation is that the authors could not conduct sufficient pooled analyses when performing subgroup analyses due to the small number of studies. However, to elucidate the heterogeneity described in Fig. 1, subgroup analyses according to postoperative nutrition strategies were essential, and the authors believe that the results should be evaluated in future studies. A third limitation is that the long-term (412 months of followup) risk of anemia and iron and vitamin B12 deficiencies could not be assessed because only 3 studies provided relevant data. As bariatric patients require long-term postoperative nutritional care, this issue should be assessed in additional studies. Finally, the analysis may have been limited by the quality of the individual studies, despite the authors’ best efforts to perform a comprehensive search, and the scarcity of statistical evidence of bias. Nevertheless, in view of the novelty of the notion that comparing SG and RYGB may provide important clues for postoperative nutritional support strategies, the authors believe that this meta-analysis is important and has implications on the design of future RCTs. In summary, the authors’ findings suggest that SG is more beneficial than RYGB with regard to postoperative vitamin B12 deficiency risk in the analysis of RCTs, although the 2 methods are comparable in postoperative anemia and iron deficiency risk. Postoperative prophylactic iron and B12 supplementation, in addition to general multivitamin and mineral supplementation, is recommended based on subgroup analysis results, which showed comparable risks of nutritional deficiency associated with the 2 surgical methods. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. Appendix Supplementary data Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j. soard.2013.12.005. References [1] Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292:1724–37. [2] Maggard MA, Shugarman LR, Suttorp M, et al. Meta-analysis: surgical treatment of obesity. Ann Intern Med 2005;142:547–59. [3] Christou NV, Sampalis JS, Liberman M, et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg 2004;240:416–23. [4] Sjostrom L, Narbro K, Sjostrom D, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357: 741–52.
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[22] Ruz M, Carrasco F, Rojas P, et al. Heme- and nonheme-iron absorption and iron status 12 mo after sleeve gastrectomy and Roux-en-Y gastric bypass in morbidly obese women. Am J Clin Nutr 2012;96:810–7. [23] Todkar JS. SSS, Shah PS, Buffingtion C. Evaluation of S. Vit B 12 status after bariatric surgery in indian patients: need of effective mode of supplementation. Obes Surg 2011;21:1049–50. [24] Toh SY, Zarshenas N, Jorgensen J. Prevalence of nutrient deficiencies in bariatric patients. Nutrition 2009;25:1150–6. [25] Regan JP, Inabnet WB, Gagner M, Pomp A. Early experience with two-stage laparoscopic Roux-en-Y gastric bypass as an alternative in the super-super obese patient. Obes Surg 2003;13:861–4. [26] Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient—2013 update: cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Surg Obes Relat Dis 2013;9:159–91. [27] Shah M, Simha V, Garg A. Review: long-term impact of bariatric surgery on body weight, comorbidities, and nutritional status. J Clin Endocrinol Metab 2006;91:4223–31. [28] Warde-Kamar J, Rogers M, Flancbaum L, Laferrere B. Calorie intake and meal patterns up to 4 years after Roux-en-Y gastric bypass surgery. Obes Surg 2004;14:1070–9. [29] Balsiger BM, Kennedy FP, Abu-Lebdeh HS, et al. Prospective evaluation of Roux-en-Y gastric bypass as primary operation for medically complicated obesity. Mayo Clinic Proceedings 2000;75: 673–80. [30] Avinoah E, Ovnat A, Charuzi I. Nutritional status seven years after Roux-en-Y gastric bypass surgery. Surgery 1992;111:137–42. [31] Brolin RE, Leung M. Survey of vitamin and mineral supplementation after gastric bypass and biliopancreatic diversion for morbid obesity. Obes Surg 1999;9:150–4. [32] Schumann K, Elsenhans B, Forth W, Schroeder P. Intestinal iron transfer after ileojejunal transposition. Digestion 1991;50:182–93. [33] McKie AT, Raja KB, Peters TJ, Farzaneh F, Simpson RJ. Expression of genes involved in iron metabolism in mouse intestine. Am J PhysiolGastrointest Liv Physiol 1996;271:G772–9. [34] Fujioka K. Follow-up of nutritional and metabolic problems after bariatric surgery. Diabetes Care 2005;28:481–4. [35] Smith CD, Herkes SB, Behrns KE, Fairbanks VF, Kelly KA, Sarr MG. Gastric acid secretion and vitamin B12 absorption after vertical Roux-en-Y gastric bypass for morbid obesity. Ann Surg 1993;218: 91–6. [36] Brolin RE, Gorman JH, Gorman RC, et al. Are vitamin B12 and folate deficiency clinically important after roux-en-Y gastric bypass? J Gastrointest Surg 1998;2:436–42 [37] Skroubis G, Anesidis S, Kehagias I, Mead N, Vagenas K, Kalfarentzos F. Roux-en-Y gastric bypass versus a variant of biliopancreatic diversion in a non-superobese population: prospective comparison of the efficacy and the incidence of metabolic deficiencies. Obes Surg 2006;16:488–95. [38] Clements RH, Katasani VG, Palepu R, et al. Incidence of vitamin deficiency after laparoscopic Roux-en-Y gastric bypass in a university hospital setting. Am Surg 2006;72:1196–202.
Original article
Anemia, iron and vitamin B12 deficiencies after sleeve gastrectomy compared to Roux-en-Y gastric bypass: a meta-analysis Yeongkeun Kwon, M.D.a, Hyun Jung Kim, M.P.H., Ph.D.b, Emanuele Lo Menzo, M.D., Ph.D., F.A.C.S., F.A.S.M.B.S.c, Sungsoo Park, M.D., Ph.D.a,*, Samuel Szomstein, M.D., F.A.C.S., F.A.S.M.B.S.c, Raul J. Rosenthal, M.D., F.A.C.S., F.A.S.M.B.S.c a
b
Division of Upper Gastrointestinal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea Institute for Evidence-based Medicine, The Korean Branch of Australasian Cochrane Center, Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea c Bariatric and Metabolic Institute, Section of Minimally Invasive Surgery, Cleveland Clinic Florida, Weston, Florida
Abstract
Background: The effective treatment of postoperative anemia and nutritional deficiencies is critical for the successful management of bariatric patients. However, the evidence for nutritional risk or support of bariatric patients remains scarce. The aims of this study were to assess current evidence of the association between 2 methods of bariatric surgery, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), and postoperative anemia and nutritional deficiencies. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for English-language studies using a list of keywords. Reference lists from relevant review articles were also searched. In the authors’ meta-analysis, they included studies with a duration of 412 months, those comparing SG with RYGB, and those with available outcome data for postoperative anemia and iron and vitamin B12 deficiencies. Of 36 potentially relevant studies, 9 met the inclusion criteria. Data were combined by means of a fixed-effects model or randomeffects model. Results: Compared with the SG group, the odds ratio for postoperative vitamin B12 deficiency in the RYGB group was 3.55 (95% confidence interval, 1.26–10.01; P o .001). In the subgroup analysis, studies in which prophylactic iron or vitamin B12 was administered lost significance in the odds ratio for postoperative vitamin B12 deficiency. Conclusion: The authors’ findings suggest that SG is more beneficial than RYGB with regard to postoperative vitamin B12 deficiency risk, whereas the 2 methods are comparable with regard to the risk of postoperative anemia and iron deficiency. Postoperative prophylactic iron and B12 supplementation, in addition to general multivitamin and mineral supplementation, is recommended based on the comparable deficiency risk of the 2 methods as indicated by subgroup analysis. (Surg Obes Relat Dis 2014;]:00–00.) r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.
Keywords:
Sleeve gastrectomy; Roux-en-Y gastric bypass; Anemia; Iron; Vitamin B12
Bariatric surgery is recognized as the most effective longterm treatment for morbid obesity; significant and durable * Correspondence: Sungsoo Park, M.D., Ph.D., Division of Upper Gastrointestinal Surgery, Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, Inchon-ro 73, Seongbukgu, Seoul 136-705, Korea. E-mail: [email protected]
weight loss, resolution or improvement of co-morbidities [1,2], and subsequent reduction in mortality are benefits that have been demonstrated by this procedure [3,4]. However, few studies have examined preoperative and postoperative nutritional status, and the reported prevalence of these deficiencies varies widely due to differences in the definitions of deficiency, patient populations, surgical techniques, supplement protocols, and length and completion of
1550-7289/14/$ – see front matter r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved. http://dx.doi.org/10.1016/j.soard.2013.12.005
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patient follow-up [5]. The effective treatment of postoperative anemia and nutritional deficiencies is critical for successfully managing bariatric patients in particular, considering their serious consequences [5]. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) have shown highly satisfactory results; therefore, they are among the most common types of bariatric surgery currently performed [6]. In recent years, SG has gained popularity as a stand-alone operation for the treatment of morbid obesity [7]. SG is simpler than laparoscopic RYGB and yields weight loss levels and co-morbidity resolution rates comparable to those achieved with RYGB [8,9]. The health benefits associated with the different bariatric surgery types have been well documented [10]; however, the nutritional risks associated with SG have not been described as frequently as those associated with RYGB [11–13]. The evidence for nutritional support of bariatric patients remains scarce, and data from individual studies may be insufficient to indicate the underlying pathophysiological changes or support the implementation of this therapy in clinical care. Moreover, prophylactic nutritional supplements are routinely prescribed after these types of surgery although there is no agreement on the dosage or form of nutrients required to avoid deficiency. Therefore, the authors performed a systematic review and meta-analysis of existing studies (1) to compare the anemia risk and the most common vitamin and mineral deficiencies (iron and vitamin B12) between patients undergoing SG and those undergoing RYGB and (2) to determine whether postoperative prophylactic micronutrient supplementation is related to anemia and nutritional deficiency risk after SG and RYGB.
Methods Search strategy We performed a systematic review of the published scientific literature. Relevant studies published between 1950 and July 1, 2013 were selected by searching MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The following combined text and Medical Subject Heading (MeSH) terms were used: sleeve gastrectomy (viz., gastric sleeve, sleeve gastrectomy, vertical gastrectomy, and longitudinal gastrectomy), gastric bypass (viz., gastric bypass, Roux-en-Y gastric bypass, gastroenterostomy, gastrojejunostomy, gastrojejunal anastomosis, gastrojejunal fixation, jejunogastric anastomosis, gastroileal bypass, gastric exclusion, malabsorptive bypass, long limb, short limb), anemia, and iron and vitamin B12 deficiencies (viz., anemia, anaemia, complete blood count, blood cell count, hematocrit, erythrocyte index, hemoglobin, micronutrient deficiencies, vitamin, mineral, iron, Fe, cobalamin, altered gastrointestinal function, nutrient absorption, malabsorption, nutrient supplementation, metabolic
complication, nutri*, micronutri*). All potentially eligible studies were considered for review regardless of primary outcome or language. A manual search using references of key articles published in English was also performed. Selection criteria Studies were considered for inclusion if they (1) compared SG and RYGB, (2) assessed the effects of SG and RYGB on postoperative anemia and nutritional status and reported means and standard deviations or proportion of deficiencies, and (3) had a study duration of 412 months. Most of the included studies had double-arm designs, and in 1 study [14] that had 42 interventional groups, the authors analyzed only the arms that received SG or RYGB. Exclusion criteria were as follows: (1) studies that included patients who underwent other types of bariatric surgery, (2) studies that did not provide postoperative anemia or nutritional status, and (3) further publications from included studies. Two independent investigators reviewed study titles and abstracts, and studies that satisfied the inclusion criteria were retrieved for full-text assessment. A third investigator resolved any disagreements. We extracted data on first author’s name, publication year, number, age, sex, and body-mass index (BMI) of participants, anemia or hemoglobin level, iron and vitamin B12 levels or proportion of deficiencies, follow-up duration, reference range for deficiency, surgical procedures, and postoperative nutrition protocol. The risk of bias was assessed according to the Cochrane Collaboration’s tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale for nonrandomized studies (NRSs) [15]. Study quality assessment addressed sequence generation, allocation concealment, and incomplete outcome data in RCTs and adequacy of selection, comparability, and outcome assessment in NRSs. This study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [16]. Statistical analysis Odds ratios (ORs) and 95% confidence intervals were calculated for all articles with sufficient data to compare SG with RYGB. Pooled ORs were calculated as the weighted average of the ORs for anemia and iron and vitamin B12 deficiencies at 1 year after surgery (except for 1 study [13]). Weighting was assigned according to the inverse of the variance. Heterogeneity was tested using the Cochrane Q test and quantified with the I2 statistic [17]. The value of the I2 statistic was used to select the appropriate pooling method; fixed-effects models were used for I2 o50% and random-effects models were used for I2 Z50%. The presence of bias was examined using a Begg's regression
Anemia after Bariatric Surgery / Surgery for Obesity and Related Diseases ] (2014) 00–00
test [18]. Statistical analyses were performed using Stata 12 (StataCorp, College Station, TX). The metan and metafunnel macros were used for meta-analytic procedures. P values of o0.05 were considered statistically significant. Results Studies included in the meta-analysis The authors identified 181 studies through electronic searches (Supplement 1). Of these, 147 were excluded based on the title and abstract, and thus, 36 studies were selected for further assessment. Nine studies fulfilled the authors’ inclusion criteria, and thus provided data for 1,104 participants [12–14,19–24]. Of these studies, 2 were from Greece and 1 each from Australia, Chile, India, Poland, Spain, Switzerland, and the United States. Table 1 lists the summary and study-specific characteristics. Studies were published as early as 2008 and 4 studies [13,14,19,21] had a randomized controlled design. Supplement 2 and Supplement 3 show the risk of bias in the included studies. All studies reported adequate effects of 2 bariatric surgeries on postoperative anemia and nutritional complications (implying that the study assessed the number or percentage of patients who developed complications or reported absolute values of hemoglobin, iron, or vitamin B12). Among 4 RCTs, 3 studies [13,14,19] showed a low risk of bias, and 1 study [21] did not provide methods of sequence generation and allocation concealment. Table 2 shows the postoperative nutritional strategies of the included studies. One study [19] did not report the nutritional protocol. General tablet multivitamin and mineral supplements were prescribed in 7 studies, and their specific proprietary names are summarized in Table 2. Postoperative prophylactic iron and vitamin B12 supplements were administered to both SG and RYGB patients in 2 studies [20,21], and 1 study [23] reported only vitamin B12 levels with prophylactic vitamin B12 supplementation. Postoperative anemia and iron and vitamin B12 deficiencies In the pooled analysis of 6 studies that assessed the number or percentage of patients who developed anemia or reported absolute values of hemoglobin (n ¼ 775) [13,14,19,20,22,24], the ORs of postoperative anemia were not higher after SG compared to RYGB in the RCT and NRS analyses (Fig. 1A) (Supplement 4). Only 1 study [19] reported a significant increase in postoperative anemia risk. Additionally, the heterogeneity was not significant in the individual estimates when the magnitude of the association was assessed. No evidence of publication bias was detected on Begg’s regression test (Supplement 5A). In the pooled analysis of 5 studies that assessed the number or percentage of patients who developed iron deficiency or reported absolute values of iron (n ¼ 682)[12,13,20,21,24], the ORs of postoperative iron deficiency were not higher after SG
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compared to RYGB in the RCT and NRS analyses (Fig. 1 B) (Supplement 4). All studies reported nonsignificant ORs. Moreover, heterogeneity was not significant between studies. No evidence of publication bias was detected on Begg’s regression test (Supplement 5B). In the pooled analysis of 6 studies that assessed the number or percentage of patients who developed vitamin B12 deficiency or reported absolute values of vitamin B12 (n ¼ 451) [12,13,20,21,23,24], RYGB was associated with higher ORs of postoperative vitamin B12 deficiency than SG in the RCT analysis (Fig. 1 C) (Supplement 4). Only 1 study [12] reported a significant increase in postoperative vitamin B12 deficiency risk. Additionally, the heterogeneity was not significant between studies. No evidence of publication bias was detected on Begg’s regression test (Supplement 5C). Subgroup analyses by postoperative prophylactic nutritional supplementation Table 3 shows the results of the meta-analysis comparing postoperative anemia and iron and vitamin B12 deficiencies in studies in which prophylactic iron or vitamin B12 supplements were administered. One study that provided no prophylactic iron or vitamin B12 supplementation showed that RYGB was associated with a higher postoperative vitamin B12 deficiency risk but not with iron deficiency, which was in agreement with whole-group analyses. However, studies that provided prophylactic iron or vitamin B12 supplementation did not show a significant OR in anemia and vitamin B12 deficiency risk. The pooled analysis of 2 studies that provided prophylactic iron and vitamin B12 supplementation in addition to general multivitamin and mineral supplementation did not show a significant OR for iron and vitamin B12 deficiency risk. Discussion Nutrient deficiencies are common after bariatric surgery. Despite routine vitamin and mineral supplementation after bariatric surgery, numerous patients show deficiencies in vitamins or trace elements. These deficiencies are related to the reduced food intake as well as the physiologic impact of surgically induced anatomic changes in the gastrointestinal tract. Any bariatric procedure with a malabsorptive effect, either RYGB or biliopancreatic diversion, can lead to an increased risk of postoperative nutrient deficiencies. However, thus far, the incidences of vitamin and mineral deficiencies after SG and their comparisons with those after RYGB have been seldom in being reported [11–13]. RYGB is currently the most commonly performed bariatric operation worldwide, superseding other restrictive and malabsorptive procedures because of the effective longterm weight loss and amelioration of co-morbidities associated with this procedure [1]. SG was initially introduced
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Table 1 Characteristics of the studies included in the analysis Year of publication
Randomized controlled trials Karamanakos 2008 et al. [19] (Greece) Kehagias et al. 2011 [13] (Greece)
Sample, size, Design no.
Baseline mean Baseline age, mean proportion of (SD), y women, %
Baseline BMI, Baseline Hb, Baseline iron Baseline mean (SD), mean (SD), level mean (SD), vitamin B12 kg/m2 level mean g/dL μmol/L (SD), рmol/L
Follow-up, months
Length of roux limb in RYGB, cm
Reference range for deficiency
16/16
RCT
37 (8.25)/ 30.6 (7.8)
75/93.8
46.6 (3.7)/ 45.1 (3.6)
13.4 (0.9)/ 13 (0.9)
NR
NR
12
150
NR
30/30
RCT
33.7 (9.9)/ 36 (8.4)
73.3/73.3
44.9 (3.4)/ 45.8 (3.7)
(13/13)a
(20/20)a
(3/3)a
36
150
43.9 (10.8)/ 44.9 (10.6) 48.3 (8.4)/ 47.9 (8.0)
63.9/72.2
48.6 (5.4)/ NR 46.1 (5.9) 37.0 (3.3)/36.2 NR (3.9)
(25/33.3)a
(30.6/13.8)a
12
100
Hb, men, o13.5 g/dL Hb, women, o12.5 g/dL Iron, o50 mg/dL Vit. B12, o200 рg/mL NR
NR
NR
12
150
Hb, men, o13.0 g/dL Hb, women, o11.5 g/dL
374 (166.7)/ 12 305 (110.5)
100
Hb, men, o30 g/L Hb, women, o119 g/L Iron, o9.0 μmol/L Vit. B12, o145 рmol/L
Paluszkiewicz 2012 [21] (Poland) Schauer et al. 2012 [14] (US)
36/36
RCT
50/50
RCT
Nonrandomized studies Toh et al. [24] 2009 (Australia)
121/64
Retrospective 48 (10)/ cohort 46 (12)
58/78
63.6/57.8
43.1 (5.2)/ 51.0 (11.2)
14.1 (5.3)/ Men, 14.6 13.4 (5.3) (1.3)/14.0 (1.4) Women, 13.2 (0.7)/ 13.6 (0.9)
Y. Kwon et al. / Surgery for Obesity and Related Diseases ] (2014) 00–00
Study (Location)
86/50
Retrospective 43.5/41.9 cohort
71/74
44.2/46.5
NR
(3, overall)a
(3, overall)a
Todkar et al. [23] (India)
2011
50/71
Retrospective NR cohort
NR
NR
NR
NR
334.6 рg/mL, 12 overall
NR
Ruz et al. [22] (Chile) Moize et al. [20] (Spain)
2012
23/20
100/100
13.2 (1.1)/ 13.4 (1.2) (22/10)a
NR
6, 12
125, 150
294/61
42.0 (4.2)/ 37.3 (3.2) 47.4 (6.0)/ 51.6 (6.7)
NR
2013
Retrospective 35.9 (9.1) cohort Retrospective 45.2 (10.6)/ cohort 46.4 (11.6)
(26.5/30.8)a
(1.8/2.7)a
6, 12, 24, 48, 100 60
77/67.2
3, 6, 12, 24, 30, 36
150
Iron, o30 ng/mL Vit. B12, o150 рmol/L Vit. B12, o200 рg/mL Hb, women, o 12 g/dL Hb, men, o13.7 g/dL Hb, women, o12.2 g/dL Iron, 50–170 μg/dL Vit. B12, 250–1,050 рg/mL
BMI ¼ body mass index; Hb ¼ hemoglobin; NR ¼ not reported; RCT ¼ randomized controlled trial; RYGB ¼ Roux-en-Y gastric bypass; SD ¼ standard deviation; SG ¼ sleeve gastrectomy; Vit. ¼ vitamin. All data are presented by the order of RYGB and SG when needed. a Proportion of preoperative anemia or iron and vitamin B12 deficiency was presented (%).
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Gehrer et al. 2010 [12] (Switzerland)
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Table 2 Postoperative nutritional strategies of the studies included in the analysis Studies
Supplements Multivitamin and Mineral
Iron
SG
SG
Karamanakos et al. [19] NR 2008 Toh et al. [24] 2009 Daily, Oral
RYGB
Vitamin B12 RYGB
NR Daily, Oral
Gehrer et al. [12] 2010 One tableta daily, Oral Kehagias et al. [13] One tablet daily, Oral Daily 2011 First 6 months
SG RYGB NR
NR 1,000 μg every 3–6 months, Parenteral When deficient When deficient NR 80 mg daily, Oral Premenopausal 1,000–3,000 μg, Parenteral women When below 200 рg/mL after 6 months NR 500 mg daily, Oral 0.1 g daily, Sublingual 1,000 μg monthly, Sublingual When deficient
Todkar et al. [23] 2011 NR Paluszkiewicz et al. [21] One tablet daily, Oral 2012 Ruz et al. [22] 2012 One tabletb daily, Oral One tabletcd daily, 22 mg daily, 60 mg daily Oral Oral Schauer et al. [14] 2012 Yes NR Yes Moize et al. [20] 2013 One tablete daily, Oral 160 mg dailyf, Oral
NR Yes 1,000 μg monthly, Parenteralgh
NR ¼ not reported; RYGB ¼ Roux-en-Y gastric bypass; SG ¼ sleeve gastrectomy. a Beroccas. b Centrum, Wyeth Laboratories. c Maltofer vit, Andromaco Laboratories. d Elcal-D PLUS, Andromaco Laboratories. e Supradyn Activo, Bayer. f Tardyferon, Pierre Fabre Iberica. g Optovite B12, Normon. h Ideos Unidia, Procter & Gamble Pharmaceuticals.
as a first-step procedure to minimize the surgical risk of patients with a BMI of 455 followed by RYGB [25]. Nevertheless, this procedure has been increasingly used alone in patients with a BMI o50 because of its satisfactory results in ameliorating co-morbidities [6,13]. However, this procedure is not exempt from complications such as micronutrient deficiencies [11]. Moreover, Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery Patient-2013 Update by the American Association of Clinical Endocrinologists, The Obesity Society, and the American Society for Metabolic & Bariatric Surgery has given broad recommendations concerning micronutrient under-nutrition and management; however, evidence from level 1 studies are lacking for all relevant vitamins and minerals [26]. Anemia and iron and vitamin B12 deficiencies have been frequently observed and described after RYGB surgery with widely varying prevalences [27]. These deficiencies may arise from the substantial reduction in food intake and food intolerances. In a retrospective study of self-reported intake among 69 patients at 18 months to 4 years after RYGB [28], iron and vitamin B12 intake from food exceeded 100% of the recommended dietary allowance recommendations. In another study of 113 RYGB patients, foods that were ‘‘not well tolerated’’ included milk (25%), steak (16%), minced beef (12%), and bread (8%) [29], which contributed to reduced intake of dietary sources of iron and calcium. Data
show that SG and RYGB are associated with similar longterm weight loss with no differences in terms of dietary intake [20]. Iron deficiency in RYGB patients may also result from malabsorption (because the main sites of iron absorption have been bypassed) and from reduced bioavailability of dietary iron because of the lack of hydrochloric acid production in the small gastric pouch. One study indicated that patients who ate red meat less than once weekly had a significantly higher incidence of iron and vitamin B12 deficiencies than patients who ate red meat more than once weekly at 7 years after RYGB [30]. Blood loss through menstruation may also predispose premenopausal women to iron deficiency and anemia, leading to the prescription of prophylactic iron to these patients in many centers [31]. Prophylactic iron supplements are routinely prescribed after these types of surgery, although there is no agreement on the amount and form of iron that could efficiently prevent iron deficiency. Because a major component of RYGB, in addition to stomach reduction, is the exclusion of the duodenum and a portion of the jejunum, the authors expected that iron absorption after SG would be less affected than that after RYGB. The results, however, did not show differences in the iron deficiency risk between SG and RYGB. To explain this result, the authors must consider the relative capacity of distinct intestinal segments to absorb iron and their ability to adapt to increased iron transfer demands. One study
Anemia after Bariatric Surgery / Surgery for Obesity and Related Diseases ] (2014) 00–00
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Fig. 1. Meta-analysis of the effects of 2 bariatric surgeries (sleeve gastrectomy versus Roux-en-Y gastric bypass) on postoperative (A) anemia, (B) iron deficiency, and (C) vitamin B12 deficiency. ES ¼ effect size; I-V Subtotal ¼ fixed-effects analysis; DþL Subtotal ¼ random-effects analysis; SG ¼ sleeve gastrectomy; GB ¼ Roux-en-Y gastric bypass.
Table 3 Risk of anemia and nutritional deficiencies with or without postoperative prophylactic iron or vitamin B12 supplementation No. of Studies No prophylactic iron or vitamin B12 supplementation Iron deficiency 1 Vitamin B12 deficiency 1 Prophylactic iron supplementation (both SG and RYGB) Anemia 1 Prophylactic vitamin B12 supplementation (both SG and RYGB) Anemia 1 Vitamin B12 deficiency 1 Prophylactic iron and vitamin B12 supplementation Anemia 1 Iron deficiency 2 Vitamin B12 deficiency 2
Odds Ratio (95% CI)
PEff
I square
PHet
.689 .066
47.8 0.0
.167 .719
1.76 (0.74–4.17) 6.33 (2.73–14.64) 3.64 (0.82–16.10) 1.00 (0.30–3.34) 1.20 (0.55–2.64) 1.91 (0.83–4.42) 1.15 (0.58–2.26) 2.38 (0.95–6.01)
CI ¼ confidence interval; PEff ¼ P value of pooled effect; PHet ¼ P value of heterogeneity test.
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showed adaptations after ileojejunal transposition; they reported that transposed enterocytes took up some jejunal characteristics in terms of transferred iron, although jejunal values were not reached [32]. One study indicated the expression of genes involved in iron metabolism and found a gradient of mucosal nonheme iron (duodenum 4 jejunum 4 ileum) and regional differences in ferritin and transferrin receptor mRNA levels [33]. Therefore, after RYGB, patients may have some degree of adaptation to the exclusion of the duodenum and part of the jejunum, which may be potentiated by an increased iron-absorption stimulus as a result of the greater reduction in iron stores compared to that in patients undergoing SG. Vitamin B12 absorption involves a complex series of metabolic steps within the gastrointestinal tract. Vitamin B12 malabsorption and deficiency may occur in RYGB patients because of (1) decreased acid and pepsin digestion of protein-bound cobalamins from food, (2) incomplete release of vitamin B12 from R proteins by limited mixing of nutrients with pancreatic secretions in a shortened common channel, and (3) decreased availability of the intrinsic factor, which is secreted by the parietal cells of the stomach after being stimulated by food [34]. The small pouch constructed from the gastric cardia in the RYGB procedure is virtually absent of acid secretion, and food-bound vitamin B12 is maldigested and subsequently malabsorbed [35]. The authors’ results showed that SG had better outcomes with respect to postoperative vitamin B12 deficiency than RYGB, and the results were well in agreement with the subgroup analysis in which prophylactic vitamin B12 supplementation was not provided postoperatively. However, when prophylactic vitamin B12 supplementation was provided, the risk of deficiency in RYGB was comparable to that of SG. According to the literature, oral vitamin B12 supplementation successfully corrected deficiencies in 81% of cases [31,36]. Multivitamin supplementation alone, although containing 10 μg cyanocobalamin, did not prevent vitamin B12 deficiency in bariatric patients, but intramuscular cyanocobalamin supplementation corrected the deficiency in 91% of patients [12]. With vitamin B12 administered at 1,000 to 3,000 o mu 4 g intramuscularly, depending on serum levels, the prevalence of vitamin B12 deficiency at 1 year to 2 years after RYGB has been reported at 24% to 36% [36,37]. However, in a prospective study of 493 RYGB patients, vitamin B12 deficiency at 1 year after surgery was only 3.6% on a regime of 1,000 o mu 4 g vitamin B12 administered intramuscularly every 3 months [38]. Normal plasma vitamin B12 levels may be maintained with oral crystalline vitamin B12, but at very high doses, 4500 mg/d was sufficient to correct the majority (81%) of deficiencies [36]. A limitation of the authors’ meta-analysis was that an analysis of only RCTs could not be performed because of the paucity of such studies. The authors’ results should thus be interpreted with caution, as the risk of selection bias may
exist in NRSs. A second limitation is that the authors could not conduct sufficient pooled analyses when performing subgroup analyses due to the small number of studies. However, to elucidate the heterogeneity described in Fig. 1, subgroup analyses according to postoperative nutrition strategies were essential, and the authors believe that the results should be evaluated in future studies. A third limitation is that the long-term (412 months of followup) risk of anemia and iron and vitamin B12 deficiencies could not be assessed because only 3 studies provided relevant data. As bariatric patients require long-term postoperative nutritional care, this issue should be assessed in additional studies. Finally, the analysis may have been limited by the quality of the individual studies, despite the authors’ best efforts to perform a comprehensive search, and the scarcity of statistical evidence of bias. Nevertheless, in view of the novelty of the notion that comparing SG and RYGB may provide important clues for postoperative nutritional support strategies, the authors believe that this meta-analysis is important and has implications on the design of future RCTs. In summary, the authors’ findings suggest that SG is more beneficial than RYGB with regard to postoperative vitamin B12 deficiency risk in the analysis of RCTs, although the 2 methods are comparable in postoperative anemia and iron deficiency risk. Postoperative prophylactic iron and B12 supplementation, in addition to general multivitamin and mineral supplementation, is recommended based on subgroup analysis results, which showed comparable risks of nutritional deficiency associated with the 2 surgical methods. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. Appendix Supplementary data Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j. soard.2013.12.005. References [1] Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292:1724–37. [2] Maggard MA, Shugarman LR, Suttorp M, et al. Meta-analysis: surgical treatment of obesity. Ann Intern Med 2005;142:547–59. [3] Christou NV, Sampalis JS, Liberman M, et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg 2004;240:416–23. [4] Sjostrom L, Narbro K, Sjostrom D, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357: 741–52.
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