Micronutrient deficiencies following bariatric surgery : a comparative analysis between sleeve gastrectomy and Roux-enY gastric bypass

1 Universidade Federal de Pernambuco, Departamento de Cirurgia, Recife, PE, Brasil. 2 Hospital das Clínicas, Universidade Federal de Pernambuco, Serviço de Cirurgia Geral, Recife, PE, Brasil. 3 Universidade Federal de Pernambuco, Curso de Medicina, Recife, PE, Brasil. Ferraz Micronutrient deficiencies following bariatric surgery: a comparative analysis between Sleeve Gastrectomy and Roux-en-Y Gastric Bypass. 2 Rev Col Bras Cir 45(6):e2016 The objective of the present study was to compare the prevalence of micronutrient deficiencies in patients submitted to SG and RYGB, in order to determine the need for nutritional support in the former group.


INTRODUCTION
I n recent years, several studies have compared the loss of excess weight, the incretinic response and the resolution of comorbidities between patients submitted to sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), showing statistical equivalence in the loss of excess weight and in the resolution rates of comorbidities in series with long-term follow-up 1,2 .
Micronutrient deficiency is an important complication associated with both obesity and bariatric surgery, especially in the first year of postoperative follow-up, with an incidence of up to 50% of vitamin deficiency in these patients 3 .Nutritional deficiencies are observed both in patients submitted to SG and in those submitted to RYGB and, when uncorrected, may represent a significant threat to the health of these patients 4 .
The mechanism by which a micronutrient deficiency ensues after bariatric surgery differs between SG and RYGB 5 .Nutritional changes related to SG are due to decreased food intake, increased gastric emptying velocity and duodenal-jejunal transit, and reduced secretion of hydrochloric acid and intrinsic factor 5,6 .In RYGB, nutritional deficiencies occur both by the restraining component, resulting in early satiety, and by the malabsorptive component, resulting from the exclusion of the duodenum and proximal jejunum 7,8 .

Original Article
Micronutrient deficiencies following bariatric surgery: a comparative analysis between sleeve gastrectomy and Roux-en-Y gastric bypass.
Ferraz Micronutrient deficiencies following bariatric surgery: a comparative analysis between Sleeve Gastrectomy and Roux-en-Y Gastric Bypass.

2
Rev Col Bras Cir 45 (6):e2016 The objective of the present study was to compare the prevalence of micronutrient deficiencies in patients submitted to SG and RYGB, in order to determine the need for nutritional support in the former group.We divided the study participants into two groups (SG and RYGB) and submitted them to laboratory measurements of hemoglobin, iron, ferritin, zinc and vitamin B12 in the preoperative periods and at three, six, 12 and 24 months after surgery for analysis of micronutrient deficiencies.The cut-off values for nutritional deficit were: <12mg/dl for hemoglobin; <50µg/dl for iron; <20ng/ml for ferritin; <70mg/dl for zinc; and <200pg/ml for vitamin B12.

METHODS
Due to the loss of follow-up, the number of patients in the postoperative evaluations was lower than in the preoperative period (SG=338 x RYGB=238); three months: SG=184 x RYGB=161; six months: SG=100 x RYGB=111; twelve months: SG=128 x RYGB=119; twenty-four months: SG=47 x RYGB=77.We analyzed the data in the SPSS software.
To describe the profile of the patients evaluated, we calculated the percentage frequencies and constructed the respective frequency distributions.For the quantitative variables, we calculated mean and standard deviation.We assessed normality of the quantitative variables with the Kolmogorov-Smirnov test.When the variable's normality was present, we used the Student's t-test to compare the measurements' means between the types of surgery to which the patients were submitted.In cases where normality was not present, we used the Mann-Whitney test.
The data in table 2 show that SG presented a significantly higher percentage of excess weight loss (%EWL) at three months (p<0.001) and six months (p=0.035) of postoperative follow-up.Two years after surgery, there was a reversal, with a trend of higher EWL% in the group submitted to RYGB, although without statistical significance (p=0.64).

Mean serum hemoglobin levels did not
show significant difference between the groups at any of the moments of analysis.Serum iron levels, in turn, showed a statistically significant difference between the groups (higher values for SG) at all moments of evaluation, except at six postoperative months (p=0.158).Regarding ferritin, serum levels were higher in the group submitted to RYGB, with statistical significance up to six months postoperatively.Zinc presented higher values in the SG group at six, 12 and 24 postoperative months, with statistical significance.Analysis of vitamin B12 levels did not show a statistically significant difference between the groups at any of the moments of analysis (Table 3).As for vitamin B12, its deficit was present in 11.5% (SG) and 6.2% (RYGB) at 12 months, and in 6.6% (SG) and 8.7% (RYGB) two years after surgery.There was no statistically significant difference in any of the evaluation moments.

DISCUSSION
Nutritional deficiencies are common after bariatric surgery.Even with the introduction of nutritional supplementation, a large proportion of patients have deficiencies, mainly of micronutrients, in the postoperative period 9 .The prevalence of anemia in patients who are candidates for bariatric surgery in some cases is higher than in the general population, reaching levels of 10% to 15%, while the prevalence of iron deficiency as an independent factor can reach 30% to 40% 10 .In our sample, we had an increase in the prevalence of patients with anemia at 24 months, although there was no significant difference when comparing their prevalence between SG and RYGB.This result contrasts with the study by Kheniser et al., who found a significantly higher prevalence of individuals with hemoglobin deficiency anemia in the group submitted to SG (42%) compared with RYGB (21%) after two years of follow-up 11 .
Probably, iron deficiency is the most common nutritional deficiency, and it is early developed by patients undergoing bariatric surgery, especially those undergoing techniques with disabortive components and duodenal deviations (RYGB and duodenal switch) 12 .In a study of micronutrient analysis after SG, Saif et al. reported no clinically relevant disturbance of iron and hemoglobin after five years of postoperative follow-up, despite findings of below-normal levels of these parameters in 28.6% and 25% of patients, respectively 13 .and chronic disease anemia in these patients 16 .
Ferritin measurement was used in order to correlate it with iron deficiency, since in a relevant number of obese patients, ferritin may display high values as a result of the associated chronic inflammatory activity 11 .The lower prevalence of serum ferritin deficiency in relation to iron in the preoperative period, as well as the increase in the number of ferritin deficient patients at the end of postoperative follow-up, can be explained by the number of patients presenting above-normal ferritin levels due to the inflammatory effect of obesity, which leads to hyperferritinemia, since it behaves as an acute phase protein 11 .Obese individuals generally have decreased serum zinc levels in relation to the general population 17 .After bariatric surgery, given the metabolic changes induced by this procedure, the prevalence of deficiency of this micronutrient tends to increase 17 .A study by Madan et al.   showed that the zinc deficit increased from 30% preoperatively to 36% one year after surgery 18 .
In addition, zinc deficiency also negatively affects pancreatic secretion and peripheral insulin action, as well as the action of growth hormone (GH), causing greater damage to the metabolism of obese individuals 14 .
A study conducted by Capoccia et al.
showed that, in obese patients undergoing bariatric surgery, serum zinc deficiency may increase from 4% to 9% preoperatively to 20% to 24% in an 18-month follow-up 15 .Another study, comparing different surgical techniques, revealed zinc deficiency after 12 months of surgery in 40.7% of the patients submitted to RYGB and in 18.8% of the patients undergoing SG 17 .
In the 24-month follow-up, the significant difference in the prevalence of zinc deficiency (SG=6.6%x RYGB=30.0%-p<0.05) may be related to the food transit deviation in patients submitted to RYGB, allied to the optimization of the time of gastric and proximal intestinal emptying in the patients submitted to the SG, allowing a greater contact of the nutrient with the brush border of the jejunum and proximal ileus enterocytes, as well as a possible difference of adhesion to vitamin supplementation between the groups.In our sample, patients submitted to RYGB had higher preoperative BMI, and this may be related to a psychological profile of greater resistance to dietary guidelines and vitamin supplementation.In the literature, the relationship between the development of B12 deficiency over time in patients submitted to RYGB and the need for supplementation of this vitamin in the postoperative period of this procedure is already well-defined 9 .In a follow-up series of 12 to 24 months, the incidence of this deficiency ranges from 3.6% to 11%, varying according to the route of supplementation (oral x intramuscular), local socioeconomic conditions, and technical details of the surgical procedure 19,20 .
Saif et al, in study that evaluated the nutritional behavior of 82 patients submitted to the SG one, three and five years postoperatively, found B12 deficit in 2.9% in the first year, without further identification of this alteration in three and five years 13 .In the same study, micronutrient replacement was used in 28.9% of the patients in the first year, 42.9% in the third year and 63.3% in the fifth year, highlighting the importance of supplementation in the prevention of B12 hypovitaminosis in such patients 13 .
In the present study, the analysis of the values in the pre-and postoperative periods did not show a significant decrease in the serum levels of this vitamin during follow-up, nor did it show a significant difference between the two techniques.This result should be evaluated considering that the participants of this study used intramuscular cyanocobalamin in the first postoperative month, which is related to a correction of the B12 deficit in 91% of the cases according to the literature 21 .
At the end a 24-month follow-up, we found that patients undergoing Sleeve Gastrectomy presented serum levels of iron and zinc superior to patients undergoing Roux-en-Y Gastric Bypass, and that the prevalence of the deficit of the latter micronutrient is significantly higher in the RYGB group.Thus, we can conclude that patients undergoing SG, though not needing the same nutritional support as those submitted to RYGB, do need some nutritional support.
We conducted this study in the General Surgery Service of the Hospital das Clínicas of the Federal University of Pernambuco (UFPE) during the period from 2012 to 2017, through which we evaluated 576 patients submitted to surgical treatment for obesity, 338 of whom to SG, and 238, RYGB.We included patients with indication for bariatric surgery according to the recommendations of the Brazilian Society of Bariatric and Metabolic Surgery, with ages between 18 and 65 years and absence of active use of alcohol and illicit drugs.We excluded from the research those carriers of prior digestive diseases able to compromise the nutritional status by intestinal malabsorption.
All individuals involved in the research had orientation on vitamin and mineral supplementation from the immediate postoperative period onwards, as follows: Centrum® (substances: multivitamins and minerals) -one crushed tablet orally daily, in continuous use; Citoneurin® 5000IU (substances: Vitamin B1 -thiamine hydrochloride= 100mg; Vitamin B6 -pyridoxine hydrochloride= 100mg; Vitamin B12 -cyanocobalamin= 5000mcg) -one flask in deep intramuscular injection at the end of the first postoperative month; Neutrofer® (substance: Ferrochelate glycinate) -one 500mg tablet (equivalent to 100mg Fe 3+ ) orally daily for 90 days postoperatively.The study was approved by the Ethics in Research Committee of the Health Sciences Center of the Federal University of Pernambuco (CEP/CCS/ UFPE), according to Resolution nº 196/96 of the National Health Council, on December 17, 2012, under CAAE number 11258913.3.0000.5208.

months 14 ,
while Capoccia et al. demonstrated, in an analysis of 138 patients submitted to SG, that in the first year the impact of bariatric surgery on serum iron levels was negligible with a daily oral supplementation of 5mg of this nutrient during the first six postoperative months 15 .Throughout the postoperative followup period, serum iron levels increased between each evaluation moment, and were significantly higher in the SG group than the levels presented by the RYGB group 12 and 24 months after surgery.The increased iron supplementation in the postoperative period, associated with maintenance of the duodenum and the proximal jejunum, may justify this increase in serum iron levels in patients submitted to SG in relation to preoperative levels and to the group submitted to RYGB at the end of the 24 months.The knowledge of obesity as a chronic systemic inflammatory state through the action of adipose tissue, responsible for the production of cytokines, such as tumor necrosis factor alpha (TNF-a) and Interleukin 6 (IL-6), and the discovery of hepcidin and its relationship with serum iron, have brought new insights into the relationship between obesity, iron deficiency, ferritin levels,

Table 1 .
Characteristics of study participants in the preoperative period.
1 SG: sleeve gastrectomy; ** RYGB: Roux en Y gastric bypass;1Chi-square of Pearson for proportion comparison (if the p-value <0.05, the proportions differ significantly); 2 Student's t-test for independent samples (if the p-value <0.05, the means differ significantly).

Table 2 .
Analysis of the percentage of excess weight loss (%EWL) in the postoperative period(3, 6, 12and 24 months after surgery) according to the type of surgery performed (SG x RYGB).

Table 4
subjects submitted to RYGB and in only 6.6% of those in the SG group (p=0.002).

Table 3 .
Analysis of serum micronutrient levels in the pre and postoperative periods(3, 6, 12and 24 months after surgery).

Table 4 .
Prevalence of micronutrient deficit in the pre and postoperative periods (12 and 24 months after surgery).