Introduction

Zinc is one of the essential trace elements in the human body, playing a crucial role in numerous cellular metabolic processes [1, 2]. In addition to excessive accumulation of fat in the body, obesity is also associated with varying degrees of micronutrient and vitamin deficiencies [3]. Poor absorption of vitamins and micronutrients is also a common complication following bariatric surgery (BS) [4].

The absorption of zinc primarily relies on specific transporters expressed in the duodenum and proximal jejunum [5]. Different surgical procedures may affect zinc absorption due to altered gastrointestinal outcomes. Although both the British Obesity and Metabolic Surgery Society (BOMSS) [6] and the American Society for Metabolic & Bariatric Surgery (ASMBS) [7] recommend routine zinc supplementation after BS, there is currently no consensus on the optimal postoperative zinc supplementation dosage and monitoring protocol. In fact, there are even conflicting recommendations from some sources.

We have limited knowledge on zinc deficiency post BS, and research on the association between zinc deficiency and BS is also scarce. Therefore, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [8], this study aims to investigate all literature reports on zinc deficiency following BS through a systematic review and meta-analysis.

Methods

This study was conducted following the guidelines of the PRISMA and the Meta-analysis of Observational Studies in Epidemiology (MOOSE). The following tasks were independently performed by two researchers and cross-checked by a third researcher. Any disagreements were resolved through joint discussions involving all three researchers.

Search Strategy

We conducted a comprehensive systematic search using a combination of subject headings and free-text terms to retrieve relevant studies on the association between bariatric surgery and zinc deficiency. The search was conducted in PubMed, Cochrane, Web of Science, and Embase databases, with the search period ending in July 2022. The search terms used included “Bariatric surgery,” “Gastric bypass,” “LSG,” “Roux-en-Y gastric bypass,” “RYGB,” “biliopancreatic diversion with duodenal switch,” “BPD/DS,” “Zinc,” and “Zinc deficiency.” In addition, we manually searched the reference lists of identified studies to ensure a comprehensive review.

Literature Screening

We manually screened all retrieved records by reviewing the titles and abstracts of the articles, excluding those that clearly did not meet the inclusion criteria. Subsequently, we obtained and read the full texts of the remaining articles to determine whether they met the predefined inclusion and exclusion criteria. Inclusion criteria: The inclusion criteria include obese patients who have undergone bariatric surgery, without restrictions on region, ethnicity, gender, age, or preoperative zinc deficiency status. The studies should report data on the prevalence of zinc deficiency or serum zinc levels in patients preoperatively and postoperatively. The included studies should be clinical trials, cohort studies, or retrospective studies. The follow-up duration for postoperative serum zinc levels should be equal to or greater than 1 year. The studies should have a sample size of equal to or greater than 40 cases. Only studies published in full-text format with complete data will be included. Exclusion criteria: The exclusion criteria include duplicate publications, studies with incomplete data on the outcomes of interest and inability to obtain complete data by contacting the authors, animal experiments, literature reviews, meta-analyses, case reports, conference summaries, undergraduate and postgraduate theses, letters, and commentaries.

Data Extraction

A standardized data extraction table was designed to extract data from the included literature. The extracted data include the following: study characteristics (first author, study type, follow-up time), preoperative information (sample size, gender ratio, mean age, BMI, type of surgery, preoperative serum zinc level, prevalence of preoperative zinc deficiency), postoperative vitamin and micronutrient supplementation protocols, outcome measures (postoperative BMI, postoperative serum zinc level, postoperative zinc deficiency prevalence). To facilitate better analysis and interpretation of the results, the serum zinc levels reported in different studies were converted to the base unit of micrograms per deciliter.

Quality Assessment

Considering that all included studies are observational, the NOS (Newcastle–Ottawa Scale) [9] was applied to assess the quality of the studies. The NOS scale evaluates studies based on three main modules with a total of eight items. These modules include selection of study participants (four items, one point for each item), comparability (one item, two points for each item), and assessment of exposure/outcome (three items, one point for each item). The maximum score achievable is nine points.

Data Analysis

All statistical analyses were performed using Stata version 17 software. Mean and standard deviation were used to evaluate preoperative and postoperative serum zinc levels and BMI changes. Disease prevalence and 95% confidence intervals were used to assess the prevalence of preoperative and postoperative zinc deficiency. The heterogeneity of included studies was assessed using the I2 test. Generally, I2 values less than 25% indicate no heterogeneity, values between 25 and 50% indicate low heterogeneity, values between 50 and 75% indicate moderate heterogeneity, and values greater than 75% indicate high heterogeneity. If there is low or moderate heterogeneity, a fixed-effects model is applied for the meta-analysis. If there is high heterogeneity, a random-effects model is used. If fewer than three studies are included, the I2 test is not performed. Subgroup analysis was performed based on the surgical procedures. As the single-anastomosis gastric bypass (OAGB) is considered a simplified version of RRYGB with similar pathological and physiological changes in the gastrointestinal tract, OAGB and RYGB were grouped together for analysis. Publication bias was assessed by funnel plot and Egger’s test. Sensitivity analysis was performed by sequential exclusion of studies.

Results

Literature Retrieval Process and Results

After conducting systematic database and manual searches, a total of 1091 articles were retrieved. After excluding duplicate articles, there were 970 remaining. After reading the titles and abstracts to eliminate irrelevant articles, 37 articles were left for full-text screening. Finally, a total of 15 articles that met the criteria were included (Fig. 1).

Fig. 1
figure 1

Literature search process diagram

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Baseline Characteristics and Quality Assessment of Included Studies

A total of 15 articles [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24] were included in this study (Table 1). All cases were sourced from hospitals or clinics where they were receiving medical treatment. A total of 2993 patients were included in the study, originating from different countries, including China, Spain, Switzerland, the UK, France, the Netherlands, the USA, Brazil, Iran, and Qatar, among others. The surgical approaches involved in the study included laparoscopic sleeve gastrectomy (LSG), RYGB, BPD/DS, and OAGB, among others. The primary surgical types constituted LSG, RYGB, and BPD/DS. The average age of the study population was 43.1 SD12.2 years, with an average preoperative BMI of 48.2 SD10.8 kg/m2.

Table 1 Basic characteristics of included literature
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The quality of the included studies was evaluated using the NOS tool, with scores ranging from 5 to 8. Among the included studies, three received a score of 8, four received a score of 7, seven received a score of 6, and one received a score of 5. No low-quality studies were included in this research. For a detailed assessment of the quality of the included studies, please refer to Table 2.

Table 2 Quality assessment of included literature
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The Impact of BS on Serum Zinc Levels

Analysis of 15 studies revealed that 9 studies reported zinc deficiency after 6 months post-surgery. The results indicated a significant increase in the risk of zinc deficiency at 6 months post-surgery compared to preoperative levels (RR = 2.45, 95% CI 1.62, 3.69; I2 = 80.0%; Fig. 2A). Furthermore, 11 studies reported zinc deficiency after 1 year post-surgery, and the risk of patients developing zinc deficiency remained high at 1 year post-surgery (RR = 3.08, 95% CI 2.09, 4.48; I2 = 77.8%; Fig. 2B). Additionally, six studies reported zinc deficiency after 2 years post-surgery, and it was observed that the risk of developing zinc deficiency significantly increased after 2 years of BS (RR = 3.28, 95% CI 2.24, 4.79; I2 = 58.1%; Fig. 2C). These findings suggest an increased risk of zinc deficiency in patients after BS.

Fig. 2
figure 2

The risk ratio of zinc deficiency after weight loss surgery. A Risk ratio of zinc deficiency at 6 months post-BS. B Risk ratio of zinc deficiency at 1 year post-BS. C Risk ratio of zinc deficiency at 2 years post-weight loss surgery. BS, bariatric surgery

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A total of 10 studies reported the serum zinc levels of patients before BS, involving a total of 1792 individuals. The average serum zinc concentration was 87.8 SD23.4 μg/dL. Moreover, 7 studies reported the serum zinc levels of patients 6 months after BS, comprising a total of 1064 individuals. The average serum zinc concentration was 79.2 SD20.3 μg/dL. Additionally, 11 studies reported the serum zinc levels of patients 1 year after BS, involving a total of 1304 individuals. The average serum zinc concentration was 79.7 SD20.6 μg/dL.

Among the 15 included studies, 6 studies reported the serum zinc levels of patients before and 6 months after BS. It was found that the serum zinc levels of patients decreased by 6.29% (95% CI − 12.17%, − 0.41%) after 6 months of BS (Fig. 3A). Nine studies reported the serum zinc levels of patients before and 1 year after BS. Using a random-effects model analysis, it was found that the serum zinc levels of patients decreased by 8.97% (95% CI − 12.20%, − 5.74%) after 1 year of BS (Fig. 3B).

Fig. 3
figure 3

Changes in serum zinc levels after bariatric surgery. A Comparison of serum zinc changes at 6 months post-surgery compared to pre-surgery levels. B Comparison of serum zinc changes at 1 year post-surgery compared to pre-surgery levels. C Subgroup analysis of serum zinc changes at 6 months post-surgery compared to pre-surgery levels. D Subgroup analysis of serum zinc changes at 6 months post-surgery compared to pre-surgery levels

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Based on the type of surgery, the analysis was further divided into three groups: LSG, RYGB/OAGB, and BPD/DS. After 6 months of surgery, the serum zinc levels of patients in the LSG group decreased by 7.58% (95% CI − 16.03%, 0.86%; Fig. 3C), the RYGB/OAGB group decreased by 6.91% (95% CI − 12.39%, − 1.43%; Fig. 3C), and the BPD/DS group decreased by 16.20% (95% CI − 21.80%, − 10.60%; Fig. 3C).

One year post-surgery, the serum zinc levels of patients in the LSG group decreased by 9.40% (95% CI − 16.44%, − 2.36%; Fig. 3D), the RYGB/OAGB group decreased by 9.33% (95% CI − 10.73%, − 7.92%; Fig. 3D), and the BPD/DS group decreased by 22.30% (95% CI − 30.14%, − 14.46%; Fig. 3D).

A total of 13 literatures reported the incidence of zinc deficiency 1 year after surgery, and I2 = 95.214%. Using random effects model analysis, the aggregate prevalence of zinc deficiency 1 year after surgery was 26.1% (95% CI 17.3%, 34.9%; Supplementary Fig. 2).

Publication Bias and Sensitivity Analysis

In order to assess publication bias, funnel plots and Egger’s test were used. All funnel plots showed good symmetry (Supplementary Fig. 1AB), and the corresponding p-values from Egger’s test were 0.772 and 0.686, all of which were greater than 0.05, indicating no significant publication bias in the results. Sensitivity analysis was conducted using the one-study-removed approach, and the results did not show significant changes. This suggests good overall stability of the results of this meta-analysis (Supplementary Fig. 1CD).

Discussion

Our research has revealed that obese patients not only exhibit zinc deficiency preoperatively but also experience exacerbated occurrences postoperatively. Mahawar’s study revealed that over 50% of patients already had zinc deficiency before undergoing BS [5]. Serum zinc deficiency increases the risk of various metabolic diseases. Zinc deficiency is implicated in the pathogenesis of type 2 diabetes and may potentially increase the incidence of diabetes [25]. These studies highlight the importance of zinc in human physiological processes and emphasize the need for active monitoring and supplementation after surgery.

The specific mechanisms underlying the decrease in serum zinc levels after BS have not been fully clarified. However, possible reasons could include inadequate dietary intake, early damage to the intestinal mucosa, and bypassing of the main absorption pathways. Due to the limited absorption capacity in patients who undergo BS, zinc absorption capacity may become saturated [5]. Rose’s study found that in patients who underwent RYGB surgery, the serum zinc concentration significantly decreased within 4 h after a single oral dose of 15 mg zinc supplement at 3 months post-surgery. The area under the curve (AUC) of serum zinc decreased by an average of 89% [26]. In Ruz’s study, the zinc absorption rate decreased from 32.3% pre-surgery to 13.6% at 6 months post-surgery and then increased to 21% at 18 months post-surgery [21]. It is evident that RYGB surgery not only leads to a reduction in dietary zinc intake but also results in decreased zinc absorption.

It has become a consensus among bariatric surgeons and nutritionists to recommend routine supplementation of multivitamins for patients who have undergone BS. In this study, it was found that despite the routine supplementation of multivitamins and trace elements after surgery, significant serum zinc deficiency still occurred postoperatively. Salle’s study showed that despite receiving a supplementation of 15 mg/day of zinc, 42.5% of patients still presented with zinc deficiency at 1 year post-surgery. This result suggests that the postoperative zinc supplementation needs of patients may have been underestimated [22]. Hung’s study found that a supplementation dose of 7.5 mg/day of zinc may also be insufficient for obese individuals who undergo LSG [10]. This suggests that higher doses of zinc supplementation may be necessary to prevent zinc deficiency in these patients. Ruz suggests that a daily supplementation of 9.5 mg of zinc after RYGB surgery is insufficient to prevent zinc deficiency [21]. They recommend higher doses of 40–60 mg/day of zinc. However, it is important to consider the tolerable upper intake level of zinc, which is set at 40 mg/day. Excessive zinc supplementation can lead to zinc toxicity and interfere with the absorption of other essential elements like iron and copper. Therefore, the suggestion to supplement such high doses of zinc may not be appropriate and needs careful consideration. According to the BOMSS guidelines [6], it is recommended that all patients who undergo BS should take zinc supplements. For patients undergoing LSG and RYGB, the recommended initial dose is 15 mg/day. For patients with additional needs, such as those undergoing BPD/DS, the recommended initial dose is 30 mg/day. While supplementing with zinc, it is important to pay attention to the supplementation of copper.

Conclusion

In conclusion, patients undergoing bariatric surgery have a significantly increased risk of zinc deficiency postoperatively. This study suggests that it may be advisable to test serum zinc levels. Regular monitoring of serum zinc levels and timely adjustment of zinc supplement dosage are recommended.