Malnutrition in obesity before and after bariatric surgery

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Malnutrition in obesity before and after bariatric surgery Sonmoon Mohapatra, MD a, Keerthana Gangadharan, MBBS b, Capecomorin S. Pitchumoni, MD, MACG, MACP, MPH, FRCP (C), FRCP (Edin) c,∗ a

Department of Gastroenterology and Hepatology, Saint Peter’s University Hospital – Rutgers Robert Wood Johnson School of Medicine, New Brunswick, NJ, United States b Department of Internal Medicine, Saint Peter’s University Hospital – Rutgers Robert Wood, Johnson School of Medicine, New Brunswick, NJ, United States c Department of Gastroenterology, Hepatology and Clinical Nutrition, Saint Peter’s University Hospital – Rutgers Robert Wood Johnson School of Medicine, New Brunswick, NJ, United States

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Keywords: Obesity Bariatric surgery Roux-en-Y gastric bypass Sleeve gastrectomy Biliopancreatic bypass with duodenal switch Micronutrients

a b s t r a c t Bariatric surgeries are considered the only effective way of weight loss therapy in morbidly obese patients, i.e. body mass index ≥ 35. However, micronutrient deficiencies and malnutrition are common after most bariatric procedures and thus, pre- and postoperative nutritional assessment and corrections are advised. The present review is presented in an effort to describe in some detail about prevalence, and mechanisms of macro- and micronutrient deficiencies in obese and post-bariatric surgery individuals. We also aimed to summarize the data on screening and supplementation of macro- and micronutrients before and after bariatric surgeries. © 2019 Elsevier Inc. All rights reserved.

Introduction Over the last three decades, the prevalence of obesity worldwide has nearly tripled with an estimated 650 million or 13% of adults being obese in 2016.1 More than 1.9 billion adults were

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Corresponding author. E-mail address: [email protected] (C.S. Pitchumoni).

https://doi.org/10.1016/j.disamonth.2019.06.008 0011-5029/© 2019 Elsevier Inc. All rights reserved.

Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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estimated to be overweight during the same period with the prevalence of both overweight and obesity being slightly higher in women than men.1 Obesity is multifactorial in etiology, resulting from a complex interaction between genetic, environmental (including changes in gut microbiota), social and behavioral factors.2 Several socioeconomic changes occurring over the last few decades such as rapid economic growth, industrialization and use of mechanized transport have led to an increasingly sedentary lifestyle. These factors coupled with the nutritional transition to heavily processed, calorie-rich diets have created an “obesogenic” environment favoring a state of positive net energy balance resulting in excess body weight. In the affluent nations, the most dominant role among these factors is played by the increased availability and consumption of calorie dense, high carbohydrate diet that is otherwise nutritionally deficient.3 The alarming rise of obesity globally and in the United States (US) in particular could be attributed primarily to the increased availability and consumption of high calorie, nutrient deficient ‘fast foods’, ‘junk food’ or ‘ultra-processed food’ and calorie loaded soft-drinks which are available at low cost. Modern agricultural and food processing techniques are reported to cause a relative reduction in the micronutrient content of food products. Such a diet is associated with a decrease in intake of protein, fiber, vitamin A, C, D and E, zinc, potassium, magnesium and calcium.4,5 In affluent nations such as in the US, poverty is associated with overeating and undernourishment. Here, income (used as an indicator of socioeconomic status) is found to be inversely associated with obesity whereas in the developing countries obesity is more prevalent among the affluent.6,7 The association between educational attainment and obesity also depends on the country’s economy in that inverse associations are more common in the developed countries and positive associations in poorer countries. There are a number of excellent articles previously written on the malnutrition of obesity and after bariatric surgeries and this article is in an effort at combining and updating them.3 , 8–10

Types of obesity World Health Organization (WHO) defines overweight and obesity as abnormal or excessive fat accumulation that presents a risk to health.11 Body mass index (BMI) calculated by body weight in kilograms divided by height in meters squared is currently the most widely used criteria to identify and classify obesity. BMI of less than <18.5 kg/m2 is classified as wasting or underweight, 18.50 to 24.99 kg/m2 as the normal range for body weight, 25.00 to 29.99 kg/m2 as overweight, 30.00 to 39.99 kg/m2 as obese and ≥40.00 kg/m2 as morbidly obese.12 The definitions based on BMI however are not the same across different countries, as for example in India overweight and obesity are defined as BMI of 23.0–24.9 kg/m2 and ≥25 kg/m2 respectively.13 Although the classification based on BMI provides for an easy and practical tool, its clinical predictive value is highly debated.14 The anatomical location of fat accumulation has been observed to influence the functional status of the individual such as the metabolic profile and cardiovascular risk. In contrast to generalized accumulation of subcutaneous fat (generalized obesity) and accumulation of fat in the gluteo-femoral region, the accumulation of fat around the abdominal viscera (abdominal obesity or metabolic obesity) is strongly associated with complications such as type 2 diabetes and coronary artery disease.15–17 The visceral adipose tissue is an endocrine organ that is active metabolically, synthesizing hormones and cytokines (adiponectin, TNF-alpha, leptin etc.) that influence insulin resistance. The associated resident macrophages produce greater amounts of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and less of the insulinsensitizing and anti-atherosclerotic adiponectin.18 These changes favor the development of insulin resistance and promote endothelial dysfunction and atherosclerosis.19 The pathophysiology of type 2 DM is however a complex one and this may describe one aspect connecting body weight with type 2 DM. The cardiometabolic risk at different waist measurements also varies between populations according to the gender and ethnic background due to differences Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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Fig. 1. Sarcopenia and sarcopenic obesity.

in visceral fat accumulation which is found to be greater in Asians followed by non-Hispanic whites and least in African Americans.20–24 Such observations have given rise to the concepts of metabolically healthy, but obese (MHO) and metabolically obese, but normal weight (MONW) to describe subsets of individuals who have a normal metabolic profile despite having larger amounts of fat mass compared to at risk obese individuals and individuals who have significant risk for metabolic syndrome, diabetes and cardiovascular disease despite presenting with normal BMI respectively.25 Hence, the term “Metabolic obesity” in reference to visceral fat accumulation irrespective of body habitus may serve as a better identifier for those at risk for cardiovascular disease compared to currently used definitions of obesity such as those based on BMI.19 Metabolic obesity associated with metabolic syndrome (Type 2 DM, Hypertension, hyperlipidemia, coronary artery disease, syndrome X) is assessed by measurement of Waist-Hip ratio which is not as often performed in routine clinical practice compared to BMI assessment. Most of the studies in the literature on malnutrition in obese individuals are based on BMI and not on Waist-Hip ratio measurement to evaluate for metabolic obesity. Recently, a new concept of sarcopenic obesity has emerged, reflecting a combination of sarcopenia and obesity (Fig. 1).26 At this time, there is no consensus definition of sarcopenic obesity, and the definitions of sarcopenic obesity are based on the individual definitions of sarcopenia and obesity.26,27 The term “Sarcopenia” first coined by Rosenberg, is derived from the Greek word sarx (flesh) and penia (loss) which refers to the age-related loss of skeletal muscle mass.28 Apart from ageing, sarcopenia is caused by several other factors such as disuse (immobility or physical inactivity), disease (advanced organ failure, malignancy, neurodegenerative, or endocrine diseases), and inadequate nutrition. Sarcopenia is known to be associated with decreased mobility, lower muscle performance, and poorer metabolic health.29,30 Furthermore, evidence suggests that sarcopenia is associated with decreases in ease of locomotion, resting energy expenditure, nonstructured free living physical activity (physical activity not associated with exercise training), and increased fat mass which ultimately leads to obesity.30 On the other hand, obesity induces inflammation, adversely affects the function of satellite cells present in muscle, and thus, contributes to the development of sarcopenia.31 Moreover, recent evidence showed that visceral obesity is independently associated with future loss of skeletal muscle mass.32 Sarcopenia and Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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obesity share several pathophysiological mechanisms such as increased proinflammatory cytokines, oxidative stress, insulin resistance, hormonal changes and decreased physical activity. The increasing prevalence and serious consequences of sarcopenic obesity are now recognized as a major public health risk, especially in older individuals. Sarcopenic obesity has a significant impact on metabolic diseases and is associated with worse cardiovascular risk profiles, including hyperglycemia, hypertension, dyslipidemia, and insulin resistance.27 Furthermore, a recent meta-analysis has shown that sarcopenic obesity is associated with a 24% increase in the risk of all-cause mortality compared to patients without sarcopenic obesity, particularly in men.33 At this time, a consensus definition of sarcopenia is required to promote the standardized diagnosis and management of sarcopenic obesity. Furthermore, in addition to reducing body fat, increasing muscle mass and strength is needed to promote healthy ageing.

Types of bariatric surgery Laparoscopic or surgical procedures According to the annual estimates of the American Society for Bariatric surgery (ASMBS), in the United States alone, 228,0 0 0 bariatric procedures were performed in 2017.34 The National Institute of Health Consensus Conference on the Surgery for Obesity established the original indications and contraindications to bariatric surgery in 1991.35 These were updated by a follow up Consensus Conference in 2004 by the ASMBS.36 Bariatric surgery is considered for patients with clinically severe obesity having BMI ≥ 40 or ≥ 35 kg/m2 with comorbidities (such as diabetes, hypertension, arthritis that limits daily function, obstructive sleep apnea, Non-alcoholic fatty liver disease (NAFLD) and cardiopulmonary failure and documented failure at conventional, less invasive methods.37 As mentioned earlier, the definition of obesity is different in the Asian population and there is evidence supporting the expansion of the criteria to include patients with BMI between 30 and 34.9 kg/m2 and those with uncontrollable type 2 diabetes and metabolic syndrome.38 In addition to these, the patient needs to demonstrate compliance to long-term follow-up and understanding of the benefits and limits of the procedure. The risk of the procedure should also not exceed the risk of not providing treatment.39 In 2016, the 2nd Diabetes Surgery Summit (DSS) based on clinical evidence recommended the use of bariatric surgery to treat type 2 DM even in patients with only mild obesity when they are unable to achieve adequate glycemic control with oral or injectable medications.40 The number of bariatric procedures is predicted to increase with wider indications. What was once solely a cosmetic surgery has become a metabolic surgery. The nutritional deficiencies in post bariatric surgery patients depend on the type of procedure. By their function, bariatric surgical procedures can be categorized into 3 main types: Restrictive, malabsorptive and combined (restrictive and malabsorptive). Technically, it can be performed either surgically (mostly laparoscopic) or endoscopically and are described below in detail (Fig. 2). Presently, although nutritional deficiencies after bariatric surgical procedures have been well established, studies evaluating nutritional status after endoscopic bariatric therapies (EBTs) are lacking. 1. Adjustable gastric banding This is a purely restrictive procedure in which a soft silicone balloon is used to encircle the upper stomach below the gastroesophageal junction creating a small pouch similar to that in Roux-en-Y gastric bypass (RYGB). The silicone ring is connected to a subcutaneous abdominal infusion port to allow adjustment of the degree of restriction and pouch outflow. This once popular procedure is now rarely performed except in Australia.41 2. The Roux-en-Y gastric bypass The most commonly performed bariatric surgical procedure in the US a decade ago, the RYGB is performed by creating a proximal gastric pouch (by segmentation of the stomach) which is Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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Fig. 2. Types of bariatric procedures. A. Laparoscopic adjustable gastric banding. B. Vertical sleeve gastrectomy. C. Roux-en-Y gastric bypass. D. Biliopancreatic bypass with duodenal switch.

drained by creating a gastrojejunostomy by dividing the jejunum 30–100 cm distal to the ligament of Treitz and anastomosing the distal end of the separated limb (the alimentary limb called the roux limb) with the gastric pouch. The proximal segment of the small bowel (the biliopancreatic conduit) is joined to roux limb 75–100 cm from the site of gastrojejunostomy. The procedure has become unpopular because of less complex procedures such as sleeve gastrectomy. 3. Biliopancreatic bypass with duodenal switch (BPDS) In this procedure, the proximal duodenum is divided 2 cm below the pylorus and a sleeve gastrectomy is performed by excising most of the stomach and leaving behind only a “gastric sleeve”. The distal ileum is then divided following which its distal limb is anastomosed to the stomach and the proximal limb to the terminal ileum 50–100 cm from the ileocecal valve. BPDS is the most effective in terms of weight loss but results in more malabsorption related morbidities than the gastric bypass due to exclusion of significantly larger portion of small bowel.42 4. Vertical sleeve gastrectomy (VSG) The VSG was initially introduced as the first stage of BPDS as part of a two-stage approach to weight loss in super obese patients to reduce risk.43 The greater curvature of the stomach is mobilized from the vessels of the omentum by dividing the stomach using laparoscopic stapling starting a few centimeters from the pylorus and extending all the way toward the angle of his near the gastroesophageal junction. Apart from limiting intake by creating a narrow gastric tube by effectively removing the greater curvature of the stomach, this procedure also serves to Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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remove most of the ghrelin-producing cells of the gastric mucosa with the partial gastrectomy specimen. Currently, sleeve gastrectomy is the most popular procedure in the US and many other countries. Endoscopic bariatric procedures In recent years, many novel EBTs have emerged such as intragastric balloons, endoscopic sleeve gastroplasty (ESG), and primary obesity surgery endoluminal. With US Food and Drug Administration (FDA) approvals, these endoscopic techniques are becoming increasingly popular across the nation, despite the current lack of insurance coverage.44 Compared to surgical intervention, EBTs are anatomy preserving, reversible, achieve greater than 10% total body weight loss (TBWL) in majority of the patients with excellent safety and lower cost.45 EBTs are indicated for patients with 1) mild to moderate obesity (BMI 30–40 kg/m2 ) who do not qualify for bariatric surgeries or those who are unable to lose weight or maintain weight loss through non-surgical methods, such as moderate to intensive lifestyle interventions and/or pharmacologic interventions, and 2) those with severe obesity (BMI ≥ 40 kg/m2 ) who do not wish to pursue permanent surgical interventions. However, EBTs are contraindicated in patients with prior gastroesophageal (GE) surgery, large hiatal hernias (>3 cm), or gastric motility disorders. The primary component of the EBT is gastric volume reduction that reduces the stomach’s capacity via space-occupying devices, such as intragastric balloons (IGBs), remodel the stomach using endoscopic suturing devices, such as ESG, and divert excess calories away from the stomach, such as aspiration therapy (AT).45 1. Space occupying devices Space-occupying devices can be classified into balloon and nonballoon devices. A total of 3 endoscopically placed, space-occupying devices were approved for weight loss till date, which include the Orbera IGB (formerly known as BioEnterics; Apollo Endosurgery), the ReShape Duo integrated balloon (ReShape Medical, San Clemente, CA), and the Obalon balloon (Obalon Therapeutics, Carlsbad, CA).44 Non-balloon-based devices include the TransPyloric Shuttle and the Full Sense which are under clinical investigation. These endoscopic implantations are approved for a maximum duration of 6 months in patients with a BMI range of 30–40 kg/m2 . IGBs act as artificial space-occupying “bezoars,” which induces satiety via gastric distension and reduction in gastric emptying. However, since 2016, a total of 12 deaths have been reported to the FDA that occurred in patients with liquid-filled intragastric balloon systems worldwide. Thus, FDA recommends health care providers to instruct patients regarding symptoms of potentially life-threatening complications such as balloon deflation, gastrointestinal obstruction, ulceration, and gastric and esophageal perforation. In addition, patients with liquid-filled intragastric balloons need to be monitored closely during the entire term for other potential complications, including acute pancreatitis and spontaneous hyperinflation. 2. Aspiration assist device Aspire Assist device (Aspire Bariatrics, King of Prussia, PA) is recently approved by FDA, which comprises an endoscopically placed 30 Fr gastrostomy tube and an external device to facilitate the drainage of gastric contents 20 min after meal consumption. This device is approved in the US in patients with a BMI between 35 and 55 kg/m2 for up to 5 years, a higher BMI range than for IGBs. 3. Endoscopic sleeve gastroplasty ESG is an incisionless gastric volume reduction technique that has been successfully performed across many centers worldwide with reproducible results. The endoscopic sleeve is achieved by using Overstitch (Apollo Endosurgery), an FDA-approved endoscopic suturing device designed to place full-thickness stitches in a variety of interrupted or running patterns.44 The sutures are placed through the gastric wall along the greater curvature of the stomach from the prepyloric antrum to the GE junction, leaving a small pouch in the fundus. Compared to Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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laparoscopic sleeve gastrectomy (LSG),%TBWL (compared with baseline) was significantly lower in the ESG group compared with the LSG group (17.1% ± 6.5% vs 23.6% ± 7.6%, P < 0.01) at 6 months follow up.46 However, significant lower rates of adverse events were reported in ESG group compared with LSG patients (5.2% vs 16.9%, P < 0.05). 4. Primary obesity surgery endoluminal Primary obesity surgery endoluminal (POSE) uses a next-generation endoscopic suturing device, incisionless Operating Platform (USGI Medical, San Clemente, CA), to place transmural tissue anchor plications that reduce accommodation of the gastric fundus. Three additional plications are placed in the distal gastric body to limit gastric fundal accommodation and delay gastric emptying, respectively. Currently, there is conflicting evidence available regarding its efficacy. A largest case series involving 147 patients demonstrated 15.1% TBL and 44.9% EWL at 1 year.47 However, a recently concluded large US multicenter randomized controlled trial showed disappointing results of 4.9% TBL compared to 1.38% in the control group.48

Mechanism of nutritional deficiencies in the obese Obesity, usually a consequence of overeating can paradoxically be associated with nutritional deficiencies. Although these occur frequently even among those with normal weight, studies are consistent in establishing that the prevalence of nutritional deficiencies among obese individuals is higher than controls of same age and sex with normal weight.8,49 In a significant number of the obese patients this is observed to be an effect of the “obesogenic diet” that is dense in energy but devoid of several nutrients. The obesogenic diet is unbalanced, exemplified by highly processed fast foods, rich in carbohydrate with added sugar, saturated fat and sodium and often deficient in retinol, ß-carotene, vitamin D, vitamin E, vitamin C, folate, iron, and calcium as demonstrated by Damms-Machado et al50 The use of trans fats, although currently much decreased is also associated with health problems. A second postulated factor that is not as well studied is that obesity may itself result in malabsorption of certain nutrients by different mechanisms as described later.8 Another cause may be related to the frequent attempts to lose weight by adopting various crash diet programs with no regard for nutritional adequacy. Nutritional studies based on oral recall methods are associated with misreporting of dietary intake as obese individuals are likely to underreport intake of high carbohydrate/sugar rich foods which are low in micronutrient content.51 This article mostly reflects the nutritional status of the population with generalized obesity nearly excluding those with pure abdominal obesity.

Mechanisms of nutritional deficiencies post bariatric surgery Bariatric surgery has unfortunately become the answer to the epidemic of obesity worldwide. The most common nutritional deficiencies in post-bariatric surgery patients include iron, vitamin B12, calcium, vitamin D, folate, copper and zinc. The mechanism of malabsorption largely depends on the type of bariatric surgery performed. 1. Purely restrictive procedures such as LAGB can result in micronutrient deficiencies because of low nutrient intake and avoidance of nutrient rich food in the early months post operatively. This may occur in the later stages as well due to excessive band restriction. Food items such as meat, fibrous fresh fruits, and vegetables are poorly tolerated in most of these patients. 2. VSG is also a purely restrictive procedure and involves removal of the greater curvature of the stomach. Gastric resection of the body of stomach reduces mechanical digestion and acid secretion, thus, impairing digestion and absorption of iron, vitamin B12, and other protein bound nutrients. Additionally, intrinsic factor secretion is diminished resulting in further impairment of the absorption of the vitamin B12. There is a neurohumoral change because of Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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Fig. 3. Sites of micronutrients absorption and its effect after Roux-en-Y gastric bypass.

decreased secretion of Ghrelin (appetite stimulating hormone produced by gastric fundus) as a consequence of removing the gastric fundus which ultimately results in appetite suppression and low nutrition intake. 3. Malabsorptive procedures such as BPDS cause weight loss primarily through macronutrient malabsorption (as much as 25% of protein and 72% of fat), with concomitant micronutrient malabsorption. Another possible mechanism is decrease in gastrointestinal transit time resulting in secondary malabsorption of micronutrients. This is possibly related to bypassing the duodenum and jejunum or because of limited contact with the brush border secondary to a short common limb. Fat soluble vitamins such as vitamin D, A, E, K, and zinc absorption is highly impaired in addition to the other micronutrients’ deficiency such as iron, calcium, vitamin B12, and folate. 4. Nutrient deficiencies after RYGB can occur either because of primary or secondary malabsorption or from inadequate dietary intake. Increasing the length of the roux limb increases malabsorption after the procedure. It is however not clear how much of this is calorie malabsorption versus micronutrient malabsorption.52 The mechanisms of individual micronutrient deficiencies are discussed in detail in the following sections. The sites of micronutrient absorption and the metabolic effects of RYGB are demonstrated in Fig. 3.

List of nutritional deficiencies before and after bariatric surgery Nutritional deficiencies are greatly variable and are influenced by dietary as well as host-related (achlorhydria, malabsorption, systemic diseases such as Type 2 DM and use of Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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medications, e.g. PPI and metformin use causes vitamin B12 malabsorption) factors. Some of the common ones are described in the following sections. I. Macronutrients: Protein An essential macronutrient, Protein plays a key role in the growth and maintenance of the human body. It serves as a major structural component of several tissues and is used to produce enzymes, hormones and macromolecules such as hemoglobin. Important dietary sources include grains, nuts, legumes and animal protein such as meat, fish, poultry, eggs and dairy products. Deficiency of protein manifests as decreased muscle mass, weakness, brittle hair and as the severity increases there is onset of generalized edema. Impairment of growth and repair, immune response and production of enzymes and hormones may result in a myriad of symptoms. Evaluation of the protein status may include the determination of serum albumin or prealbumin levels, measurement of body composition by dual X-ray absorptiometry (DXA) or body impedance assessment (BIA). However, being a negative acute phase reactant, serum albumin should be assessed in the context of inflammatory status and hence has limited diagnostic value.53 Protein status in the obese Considering the nutritional inadequacy of the obesogenic diet, protein deficiency may occur in the obese but is not currently recognized as a major problem. The body habitus due to adipose tissue and edema may also make it difficult to discern clinical signs of protein deficiency among these individuals. Protein status post bariatric surgery The most severe macronutrient complication associated with bariatric surgical procedures is protein malnutrition. It has been reported most frequently after BPDS where it occurs in an estimated 3–21% of patients.54,55 Following RYGB an incidence of up to 13% has been estimated depending on the length of the Roux-limb.54,56 Complications resulting from protein malnutrition account for an annual hospitalization rate of 1% per year after malabsorptive procedures and are associated with poor outcomes.57,58 Many patients develop an intolerance to proteinrich food following bariatric surgery owing to factors such as smaller stomach size, altered gut anatomy and change in bilio-pancreatic function which lead to poor protein digestion and absorption. During the early post-operative phase, most patients are placed on a strict liquid diet and are unable to consume large quantities of food which in some cases may be complicated by protracted vomiting. These factors result in insufficient protein intake and absorption placing post-bariatric patients at a high risk of developing protein malnutrition. II. Micronutrients: Vitamins 1. Vitamin D A steroid hormone precursor, vitamin D plays a key role in calcium and phosphorous metabolism. Recent evidence suggests its preventive and therapeutic role in a wide range of conditions such as autoimmune diseases, certain types of cancers (esophagus, liver, breast, colon), cardiovascular disease, infectious diseases and type 2 diabetes mellitus.59,60 Deficiency manifests primarily as rickets in children and osteomalacia in adults.61-64 When less severe, the mineralization defect is not as pronounced and the high rates of bone turnover and loss due to secondary hyperparathyroidism results in osteoporosis and an increased risk of fractures.65 Endogenous synthesis on exposure of skin to Ultraviolet B radiation constitutes the major source of vitamin D in humans. Important dietary sources include fortified dairy products, egg yolk, oily fish (such as salmon, mackerel, and herring), fish liver oil and beef liver.66 Cholecalciferol is often used as a dietary supplement, usually in conjunction with calcium. At present, there is no consensus on the optimum serum levels of vitamin D. According to the most widely accepted standards, levels of 25 (OH)D less than 20 ng/mL (50 nmol/L) is defined as vitamin D deficiency, 21 to 29 ng/mL (52 to 72 nmol/L as insufficiency and more than 30 ng/mL is considered as sufficient vitamin D.59 , 67–70 Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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Table 1 Causes of low vitamin D levels in the obese. 1. Volumetric dilution in adipose tissue 2. Decreased exposure to sunlight due to lesser outdoor activities 3. Decreased synthesis of 25(OH)D secondary to a. NAFLD b. Inhibitory effect of leptin and IL-6 4. Inadequate dietary intake

Vitamin D status in the obese Vitamin D deficiency is the most common micronutrient abnormality among the obese, with an estimated prevalence of 25–90%.3,71 Studies have demonstrated an inverse relationship between the total body fat content and the circulating levels of 25(OH)D regardless of obesity status.72 A bidirectional genetic study estimated a 1.15% decrease in circulating levels of 25(OH) D with each unit increase in BMI.73 The adipose tissue functions as a storage site for vitamin D in the body. Volumetric dilution of the endogenously produced and ingested vitamin D in the expanded adipose tissue mass is a major cause of deficiency in the obese.74 Decreased exposure to sunlight due to higher rates of physical inactivity and the greater tendency among the obese to cover-up exposed skin is also considered.75 A cross-sectional study done to evaluate the effect of exercise on vitamin D levels in the obese found that the subjects reporting outdoor exercise were 47% less likely to have associated vitamin D insufficiency.76 The contribution of inadequate dietary intake however is unclear. The 5th Tromso study conducted in Norway reported a decreased intake of vitamin D among obese men compared to their non-obese counterparts. However, they did not find any such difference among obese women.77 Several other mechanisms have also been proposed to explain the low levels of vitamin D in obesity including decreased synthesis of 25(OH) D by the liver due to hepatic steatosis and the potential inhibitory effect of higher circulating levels of leptin and interleukin-6 on 25 (OH) D synthesis.78,79 Obesity is known to promote insulin resistance making it an important risk factor for Type 2 diabetes mellitus. Vitamin D improves glycemic control by increasing hepatic and peripheral uptake of glucose. It also stimulates the release of insulin from the pancreas through the VDR and by promoting calcium influx into the islet cells.80–82 A potential causal role of vitamin D deficiency in promoting obesity is also currently being explored. In a prospective cohort study, serum level of 25(OH) D below 50 nmol/L was found to be significantly associated with new-onset obesity.83 Such findings have led researchers to evaluate the effects of insulin supplementation on obese patients. However, most studies have been inconclusive and vitamin D supplementation has shown little to no effect on weight or inflammatory markers in the obese.84–86 The mechanisms of vitamin D deficiency in the obese patients are summarized in Table 1. Vitamin D status in post bariatric surgery patients The prevalence of vitamin D deficiency in post-bariatric surgery candidates can be as high as 100%.10 Following malabsorptive bariatric procedures, an estimated 10–25% and 25–48% patients have been shown to develop calcium deficiency by the end of 2 and 4 years respectively whereas 17–52% and 50–63% develop vitamin D deficiency during the same time period.87-90 In bypass procedures, food and supplements mix with bile and pancreatic enzymes only after the intestines join in the downstream common channel. This altered anatomy decreases absorption of fat-soluble vitamins such as vitamin D which rely on bile acids and other digestive enzymes for uptake.91,92 The shortened contact time with intestinal mucosa which occurs after VSG may also hamper nutrient absorption. There is however a significant incidence of secondary hyperparathyroidism in even those postoperative patients with vitamin D levels ≥30 ng/mL which suggests a selective calcium malabsorption.93 The duodenum can absorb as much as 80–100% of dietary calcium through a transcellular vitamin-D dependent active transport in settings of low intake. The absorption by the Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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remaining portion of the small intestine in the absence of duodenum and jejunum is less efficient resulting in absorption of only about 20% of dietary calcium. Procedures such as RYGB and BPDS bypass the preferential sites for calcium absorption, the duodenum and jejunum creating an increased risk for hypocalcemia.87,94 If left neglected, calcium and vitamin D deficiency and the resultant secondary hyperparathyroidism causes increased calcium resorption from the bone and over time may result in osteopenia, osteoporosis and osteomalacia. Bone mineralization defects are more likely to occur with RYGB than other procedures. Long-term screening and careful supplementation are necessary to prevent the sequelae of secondary hyperparathyroidism. Maintenance of 25-hydroxyvitamin D levels greater than 30 ng/mL is considered appropriate.93 However, since the paracellular absorption of calcium in the distal jejunum and ileum is less dependent on vitamin D, the effectiveness of vitamin D supplementation is questionable. 2. Vitamin B1 (Thiamine) Thiamine is an important cofactor for several biochemical processes involved in carbohydrate metabolism. Notably, Krebs cycle for ATP production and the pentose phosphate pathway required for the production of nucleotides and reduced NADP for various synthetic pathways. The human body cannot produce thiamine endogenously and it must be obtained from the diet. Important sources include wheat germ and whole grains, legumes, nuts, eggs, lean pork, fish, beef and organ meats. Vitamin B1 status in the obese There is inadequate data on the thiamine status in the general obese population. However, in patients undergoing bariatric surgery, the prevalence of thiamine deficiency is estimated to be between 15.5% and 29% in the preoperative group with a significantly higher prevalence among Hispanics and African-Americans as compared to Caucasians.95,96 The human body cannot produce thiamine endogenously and it must be obtained from the diet. Important sources include wheat germ and whole grains, legumes, nuts, eggs, lean pork, fish, beef and organ meats. Being water soluble, the limited reserves of thiamine in the body can get depleted within a matter of 2–3 weeks in the setting of insufficient intake or malabsorption.97 Moreover, metabolism of the high load of simple carbohydrates consumed by obese people requires greater expenditure of the body’s thiamine reserve which further accelerates its depletion. A graded increase in the dietary intake of carbohydrate among a group of healthy volunteers was noted to result in decreased amounts of plasma and urine thiamine.98 Vitamin B1 status in post bariatric surgery patients Multiple cases of non-alcoholic patients developing Wernicke’s encephalopathy post bariatric surgery have been reported.99–103 Beriberi has been observed following both restrictive and malabsorptive procedures. Wernicke Korsakoff syndrome (WKS) and peripheral neuropathy have been reported following vertical banded gastroplasty and incidences of WKS after AGB, RYGB and BPDS have been documented.104–107 Depending on the type of procedure and time frame considered, the prevalence of thiamine deficiency among post-bariatric patients is reported to range from <1 to 49%.10 These could be precipitated by a combination of factors including malabsorption resulting from duodenal bypass in procedures such as the Roux-en-Y gastric bypass (thiamine is primarily absorbed in the duodenum through active transport), greater thiamine demand due to the surgical stress and decreased oral intake as a consequence of the restricted stomach size or associated nausea and vomiting. Altered gut ecology resulting from small intestinal bacterial overgrowth is another proposed mechanism which causes malabsorption of thiamine due to bacterial production of thiaminases.108 Patients in critical care units, patients who are dehydrated from vomiting and those with postoperative complications which interfere with oral feeding are often given dextrose containing infusion which lacks thiamine and other vitamins. Periods of high carbohydrate intake such as with nasogastric feeding and total parenteral nutrition can also precipitate thiamine Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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deficiency. Therefore, screening for thiamine deficiency prior to surgery and thiamine supplementation after the procedure is recommended for all bariatric surgery patients.37 3. Vitamin B12 and folate Vitamin B12 is a vital water-soluble nutrient synthesized by microorganisms and acquired from animal-derived dietary sources such as dairy products, meats, poultry, fish and eggs. Although more common among the elderly and patients suffering from pernicious anemia, true vegans are also at high risk for deficiency unless their diet is supplemented with fortified foods such as cereals, soy-based products or vitamin supplements. Vitamin B12 serves a cofactor for enzymes methionine synthase and L-methyl-malonyl-coenzyme-A mutase and is involved in DNA synthesis, conversion of homocysteine to methionine, development and initial myelination of the central nervous system and maintenance of its normal function.109 Folate (vitamin B9) is essential for DNA methylation, nucleic acid synthesis and cell growth and division. Optimal folate levels have been shown to benefit neurodevelopmental, reproductive and cardiovascular health and have particular significance in preventing neural tube defects in the developing fetus.110–112 A potential benefit of folate has also been indicated in preventing insulin resistance although further studies are necessary to establish a causal link.113 Mandatory fortification of enriched cereal grain products with folic acid was started in the US in 1998 by the Food and Drug Administration.114 This resulted in a substantial decline in the percentage of population with low serum levels of folate in period immediately following the implementation. Similar regulations are currently in place in 53 countries although several of these have not yet been implemented.115 Vitamin B12 status in the obese The association between vitamin B12 levels and obesity is currently not clear. The prevalence of B12 deficiency among the obese is reported to be 2–18%.10 Several studies have reported lower B12 levels in overweight and obese individuals compared to their normal weight counterparts and have shown a significant negative correlation between observed vitamin B12 levels and BMI.116–118 However, few others have found either no correlation or even a positive correlation between BMI and B12 levels.119,120 Obese individuals are likely to have more carbohydrates and fat and less vitamin B12 containing animal protein in their routine diet. Several medications that are common in this population have also been noted to affect B12 absorption and stores. Notably, metformin therapy has been shown to be associated with biochemical vitamin B12 deficiency and anemia.121 Use of proton pump inhibitors for gastroesophageal reflux disease which is highly prevalent among the obese may also potentially increase risk for vitamin B 12 deficiency.122 Serum levels of 5-methyltetrahydrofolate and unmetabolized folic acid have been shown to be negatively associated with body mass index.123,124 According to Bradbury et al every 1 unit increase in BMI is associated with a 1% decrease in serum folate concentration.125 In contrast, a positive relation has been demonstrated between RBC folate levels and BMI, waist circumference, serum triglycerides and fasting plasma glucose.126 MeFox (5-methyltetrahydrofolate oxidation product) levels are also found to be significantly higher among the obese compared to the normal population.124 Obesity in pregnant women has been linked with low serum folate levels regardless of diet.127,128 In children born to obese mothers, adequate maternal serum folate levels during pregnancy are suggested to reduce the risk of child overweight and obesity by almost 43% when compared to obese mothers with low serum folate concentrations.129 Vitamin B12 status in post bariatric surgery patients Over one third of patients undergoing mixed procedures such as RYGB who do not receive specific supplementation develop post-operative vitamin B12 deficiency.130–132 The main mechanism is associated with the reduced secretion of intrinsic factor due to loss of parietal cell containing mucosa with the gastrectomy resulting in impaired vitamin B12 absorption.133,134 Other Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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factors include achlorhydria which impairs the conversion of pepsinogen to pepsin which is necessary for the release of vitamin B12 from its protein-bound dietary form and decreased dietary intake of B12 due to intolerance to food such as milk and meat.135 Purely restrictive operations such as gastric banding, on the other hand do not cause significant deficiency of either vitamin B12 or folate.136 Although possible, folate deficiency is not reported widely in recent studies among postoperative bariatric surgery patients. Multivitamin supplementation is usually adequate to meet the requirements and deficiencies are thought to occur in the setting of noncompliance to multivitamin supplements and decreased dietary intake. Low levels of serum folate have been reported from 6% to 65% among RYGB patients.137,138 4. Biotin Limited studies have shown the need of biotin, a water-soluble vitamin in many metabolic pathways. It serves as a covalently bound coenzyme for carboxylases and also plays roles in gene expression and cell signaling.139 Biotin supplementation improves fasting blood glucose and insulin levels. The therapeutic benefit of biotin supplementation is not well established. 5. Vitamins A, C, E & K An inverse relation between the BMI and concentrations of circulating antioxidants such as beta-carotene, alpha-tocopherol and vitamin C has been suggested, however the results across multiple studies have been inconsistent.140-143 Obesity is associated with a chronic low-grade systemic inflammation which is promoted by innate immune system activation in the adipose tissue triggering a systemic acute phase response. The resultant oxidative stress and generation of free radicals may induce endothelial dysfunction and predispose the patient to atherosclerosis.144 Antioxidants play an important protective role by scavenging the free radicals and limiting lipid peroxidation.144–146 Increased body fat is associated with greater storage of fat-soluble nutrients such as vitamins A, E and K in the adipose tissue. When assessing the serum concentrations of retinol, alphatocopherol and carotenoids, Neuhouser et al estimated that the obese participants had 2–10% lower nutrient concentrations compared to those with normal weight.147 Low serum concentrations of retinol in overweight and obese individuals have been found in multiple studies across different age groups and a negative correlation has been reported between serum retinol concentrations and BMI.148–150 A study done by Trasino et al on obese mice generated from high fat diet and genetic mutations demonstrated reduced vitamin A levels and signaling in multiple organs even with adequate dietary vitamin A intake. These were however not reflected in the serum retinol levels which were found to be within normal range.151 Vitamin A is essential for a wide range of physiological functions such as embryonic development, vision, immune function, maintenance of epithelial cell membranes etc.152–154 In addition, vitamin A has also been identified as a key regulator of adipose tissue function. Retinol and retinyl esters present in the adipose tissue account for almost 15–20% of the total retinoid content of the body.155 Adipose tissue expresses several retinoid receptor subfamilies such as RA receptor and retinoid X receptor and is considered to be a potential site for the action of retinoic acid 1.156,157 In rodents, dietary VA insufficiency or genetic manipulation of VA signaling pathways has been shown to promote adiposity.158,159 RA is reported to inhibit adipocyte differentiation in vitro and affect thermogenic capacity of rodents in vivo by promoting brown adipose tissue (BAT)-uncoupling protein 1 gene expression. Moreover, Vitamin A enriched diet in obese rats has been shown to decrease obesity and its associated complications by regulating various gene pathways in liver, adipose tissue, skeletal muscle and retina.160–162 III. Micronutrients: Minerals 1. Iron Iron deficiency (ID), a decrease in the total body content of elemental iron is the most common nutritional disorder and also the most frequent cause of anemia globally.163 According to the WHO report on worldwide prevalence of anemia (1993–2005), Iron deficiency anemia (IDA) Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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was estimated to affect ∼25% of the world’s population. Chronic IDA however goes largely unrecognized due to excellent compensatory mechanisms. In the obese, the prevalence of IDA is much higher at around 35%.164 A significant negative correlation is reported between low iron levels and BMI and being obese is found to more than double the likelihood of developing ID.165,166 These numbers are not applicable to the obese in the developing nations where the rates could be much higher. Absorption of iron takes place predominantly in the duodenum and in the upper parts of the jejunum.167 Dietary iron may be present in the heme (10%) or the ionic non-heme (90%) form. Non-heme iron is not as readily absorbed as heme and in the physiological pH exists in the oxidized, insoluble ferric (Fe+3 ) form. Gastric acid decreases the proximal duodenal pH enabling the reduction of Fe+3 to ferrous (Fe+2 ) by ferric reductases following which it is transported across the intestinal epithelium by divalent metal transporter-1 (DMT-1). Heme is supposedly transported into the enterocyte by the not yet completely identified heme carrier protein 1.168 It is acted upon by heme oxygenase to release ferrous iron which then enters into the circulation via transporter, ferroportin along a common pathway with dietary non-heme iron.169,170 Only a fraction of the ingested iron gets absorbed into the body. This may range from 5% to 35% depending upon the body’s iron status and the type of dietary iron. Hepcidin, a peptide hormone secreted by the liver negatively regulates the entry of iron from sources such as the small intestine, macrophages and liver into the plasma. It acts by binding to ferroportin and inducing its internalization and degradation. This results in decreased transferrin-bound iron leading to low plasma iron levels, macrophage iron loading and decreased erythropoiesis. Conversely, decreased hepcidin expression result in increased ferroportin which among other effects, increases dietary iron absorption. Iron deficiency could be either a) absolute, due to decrease in the total iron content of the body (e.g., after hemorrhages) or b) functional, due to an increased demand that temporarily outstrips supply (e.g., pregnancy) or due to sequestration of iron within cells of the reticuloendothelial system (e.g., in chronic inflammatory conditions). In developing nations, women of child bearing age and children are particularly at risk.171 Insufficient dietary intake and parasitic infections (in particular, hookworm infestation- Ancylostoma duodenale and Necator americanus) account for the majority of cases in these regions.172 In the industrialized nations, conditions causing decreased iron absorption and/or chronic blood loss are the more frequent causes. In its chronic state, ID is often asymptomatic and only detected on a screening-analysis. As such, ID and IDA often tend to get ignored, particularly in the obese who are presumed to be in a state of nutritional excess. When severe enough it may produce a constellation of symptoms including generalized fatigue, exertional dyspnea which may progress to shortness of breath at rest, headache, vertigo, syncope and may cause exacerbation of certain conditions such as angina and restless leg syndrome.173 Iron deficiency in the obese The prevalence of Iron deficiency among the obese is reported to be as high as 45%.10 Apart from poor dietary intake, increased iron requirement among obese individuals and impaired iron absorption in the duodenum are potential mechanisms contributing to iron deficiency among the obese.174,175 Hepcidin, a proinflammatory adipokine rises in serum concentration during chronic inflammatory states. This decreases the expression of the iron transporter ferroportin which reduces absorption of iron from the small intestinal lumen and also blocks the release of recycled iron from macrophages and prevents mobilization of stored iron from hepatocytes.176 Obesity is associated with a chronic low-grade inflammation which is mediated by the increase in release of pro-inflammatory cytokines from the expanded adipose tissue and altered gut microbiota. This is accompanied by a substantial rise in hepcidin concentrations which is proposed to be a major factor resulting in impaired iron absorption.177 Obese individuals tend to have higher mean hemoglobin and ferritin concentrations and lower transferrin saturation.178 The other end of the iron phenotype spectrum of obesity is represented by “dysmetabolic iron overload syndrome (DIOS)” which is characterized by high serum ferritin concentrations with normal or mildly elevated transferrin saturation. DIOS is Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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seen in approximately 15% of patients with metabolic syndrome and almost half the cases of nonalcoholic fatty liver disease (NAFLD).179 It is suggested that both iron deficiency and DIOS represent manifestations of the same underlying hepcidin mediated pathophysiological process. Furthermore, studies done on rodents have suggested a hepcidin-independent mechanism for the impaired iron absorption due to a fat-rich diet.180 Iron status in post bariatric surgery patients The prevalence of iron deficiency after bariatric surgery is estimated to range from 30%to 60%.181 However, the definitions used to define ID vary across these studies using either serum ferritin levels or transferrin saturations. Bariatric surgical procedures result in impaired absorption of dietary iron by causing hypochlorhydria and bypassing major sites of iron absorption such as duodenum and proximal jejunum. There is also decreased intake of oral iron due to the overall reduction in appetite and development of intolerance to food such as meat which constitutes a major source of iron in the western diet.182 Studies have shown almost a 50% net reduction of meat consumption per day, suggesting a decreased tolerance to red meats.183,184 Further, H. pylori infection and bacterial overgrowth which are reported with greater frequency in post bariatric surgery patients and chronic gastrointestinal blood loss may also play contributory roles.185,186 The role of H.pylori in the development of refractory iron deficiency is further supported by the improved responsiveness to iron therapy seen after H.pylori eradication.185 Patients who develop anemia postoperatively have been shown to have a twofold increase in risk of hospitalizations as well as duration of in-hospital stay.187 2. Zinc Zinc is a component of many metalloenzymes involved in key processes such as protein synthesis, immunological reactions, DNA synthesis, cell growth and repair and maintaining epithelial integrity. The standard dietary intake among the general population is reported to be frequently marginal or deficient.188,189 Important sources include breakfast cereals, beans, nuts, sea-food such as oysters, whole grains, dairy products, meat and poultry. Severe deficiency of zinc is usually seen in genetic conditions such as acrodermatitis enteropathica, in patients receiving total parenteral nutrition or penicillamine therapy for Wilson’s disease. Manifestations of severe deficiency include bullous pustular dermatitis, diarrhea, weight loss, alopecia, recurrent infections, hypogonadism in males, neurosensory disorders and problems with ulcer healing.190 Moderate deficiency, which is more common among the general population presents with milder manifestations of the same such as rough skin, poor appetite, loss of taste sensation (ageusia), mental lethargy and delayed wound healing.190 Zinc status in the obese Obese people have been found to have lower zinc concentrations in the plasma and erythrocytes and higher urinary excretion as compared to their lean counterparts.191,192 Zinc deficiency can be seen in up to 50% of patients undergoing bariatric surgery prior to the procedure.193 Zinc plays a significant role in the biosynthesis and action of insulin and its deficiency has been linked to metabolic syndrome. Zinc supplementation is shown to promote glucose uptake and free fatty acid release.194 In a study on obese mice, Zinc supplementation increased the circulating concentrations of leptin, the adipocyte-secreted protein/cytokine that serves as a feedback regulator of energy balance and also increases the macrophage infiltration into adipose tissue.195 Weight loss may be beneficial in improving zinc levels as supported by a study conducted on obese adult women which demonstrated a marked enhancement in the levels of zinc following a weight-loss program based on a balanced hypocaloric diet.196 Zinc status in post bariatric surgery patients Multiple studies have demonstrated a significant decline in serum zinc concentrations after bariatric procedures compared to preoperative values.197–199 The prevalence of zinc deficiency is much higher among patients who undergo BPDS (45–91%) when compared to other procedures Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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such as RYGB (15–21%) or LSG (11–14%).198 , 200–202 Deficiency occurs primarily due to decreased intestinal absorption as Zn is absorbed predominantly in the duodenum via DMT-1(Divalent Metal transporter-1) and to some extent in the proximal jejunum. Due to the lack of functional reserves, deficiency is likely to set in during the early stages after bariatric procedures.200,202 In pregnant women, zinc deficiency is associated with poor maternal health and gestational outcomes such as hypertension, prematurity and congenital disorders.203,204 Since bariatric surgery is more popular among women of child bearing ages than men, optimizing zinc status is important to mitigate adverse effects of deficiency in this group. A more aggressive supplementation is necessary in pregnancy because the requirements are higher. It is important to bear in mind that zinc, copper and iron may interfere with the absorption of each other and long term oral zinc supplementation may lead to decreased intestinal absorption and deficiencies of copper and iron.205,206 3. Copper A transition metal and essential trace element, copper serves as a cofactor of several redox enzymes and is involved in a variety of biological processes such as antioxidant defense, immune function and neuropeptide synthesis.207,208 Ceruloplasmin is the predominant Cu-dependent ferroxidase enzyme which plays an important role in iron mobilization. Important sources include seeds, nuts, grains, beans, liver and shellfish.209 Copper deficiency in adults can cause hematological abnormalities such anemia with neutropenia and neurological manifestations which mimic the myeloneuropathy observed with vitamin B12 deficiency.210,211 Copper status in post bariatric surgery patients Malabsorption resulting from bariatric surgery is the most common cause of acquired copper deficiency.212,213 In a study on Roux-en-Y patients who were followed up longitudinally for 24 months following surgery the incidence of copper deficiency post- operatively was found to be 18.8% and prevalence 9.6%.214 Absorption of copper occurs primarily in the duodenum which puts patients who undergo intestinal resection as part of malabsorptive procedures at risk.215 Moreover, gastric acid plays an important role in improving the bioavailability of dietary copper by freeing the copper bound to organic complexes and ligands.216 It may however take several years after surgery before the body’s copper stores get depleted and symptoms manifest. Copper deficiency also occurs in the setting of prolonged total parenteral nutrition without adequate copper supplementation.217 The estimated daily copper requirement in adult patients on TPN is approximately 0.3 mg.217 Since deficiency is fairly rare in the general US population, copper is sometimes not added to vitamin-mineral supplements and copper levels are rarely measured by physicians. Increasing awareness and early diagnosis is essential since although the hematological abnormalities improve following adequate supplementation, the neurological manifestations can be severe and often irreversible.218,219 Zinc supplements should be prescribed with caution since copper depletion is known to occur with higher doses of zinc supplementation. Excess zinc upregulates the production of a heavy metal binding protein, metallothionine which binds with greater affinity to copper leading to its excretion through the GI tract.219 4. Magnesium Magnesium, the second most common intracellular cation, is an important cofactor in over 300 enzymatic reactions. It plays a key role in carbohydrate metabolism by participating in phosphate transfer reactions and along with calcium it is essential for maintaining regular neuromuscular activity.220 An unprocessed food-based diet that is rich in whole grains, legumes, seeds, nuts, fish and dark green leafy vegetables (such as spinach) have high magnesium content. However, as much as 85% of this is lost during refining or processing.221 ‘Junk food’ or ‘obesogenic’ food lacks magnesium. Hypomagnesemia occurs in alcoholism, chronic renal failure, use of medications (such as PPIs, diuretics), malabsorption and chronic diarrhea. Multiple studies comparing the magnesium status in overweight and obese children have found serum magnesium levels to be significantly lower in the obese compared to their counterparts with normal BMI.222,223 Apart from the high intake of processed food among these children, one could also speculate Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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about the effect of calcium in diets containing large amounts of dairy products which have high calcium and low magnesium content. Calcium is known to compete with magnesium and reduce its intestinal absorption. Consumption of carbonated drinks (diet soda) could also impair Mg absorption due to higher phosphorus intakes while the caffeine content in these serves to increase renal Mg elimination.220,224 In adults, a consistent association has been found between low Mg status, and insulin resistance and metabolic syndrome and increasing Mg intake is suggested to have a protective effect.225,226 Experimental evidence suggests that consumption of fructose (honey, fruit-juice, corn syrup) with low magnesium diet induces insulin resistance and hypomagnesemia may be associated with macro- and micro-vascular complications such as cardiovascular disease, neuropathy and nephropathy.227 5. Selenium A component of the metallo-enzyme glutathione peroxidase, Selenium plays a role in scavenging free radicals, thyroid function and in preventing certain types of cancers and cardiovascular disease. Food rich in Se include nuts (such as brazil nuts), grains, bread, seafood and organ meat. Se deficiency is noted in nearly 58% of morbidly obese patients prior to bariatric surgery.116 The low levels of Se may be reflective of the increased oxidative stress among the obese or overweight patients. Severe deficiency may manifest as cardiomyopathy, myopathy, arrhythmias and muscle wasting. Se deficiency is associated with high homocysteine levels and cardiovascular disease.228,229 Postoperative decrease from baseline Se levels have been demonstrated in bariatric surgery patients.230 Dolan et al reported 14.5% patients who underwent BPDS as selenium deficient postoperatively.231 Following gastric bypass prevalence is reported between 14%and 22%. A study by Chia-Wen et al demonstrated a positive association between selenium levels and the prevalence of diabetes and metabolic syndrome, particularly in the highest quartile of the selenium group. These findings may along with a few similar studies support that central obesity and insulin resistance are either a cause or consequence between serum selenium gradients and diabetes.232

Recommendations on nutritional assessment before and after bariatric surgery Presently, prospective randomized controlled trials to assess the types and amounts of supplementation after bariatric surgery are lacking and the current recommendations are largely based on observational studies and expert opinions. Thus, available guidelines for supplementation are potential to change once new evidence is available. Current recommendations for nutritional supplementation before and after bariatric surgery are illustrated in Tables 2 and 3 and summarized below.10,37,233 Preoperative micronutrient screening recommendations 1. Selective micronutrients status should be monitored prior to the bariatric surgery and the deficiencies must be corrected to optimize the clinical status at the time of surgery. 2. Baseline mineral (calcium, iron), and vitamins (vitamins B1, B12, D, A, E, K, folate) screening is recommended for all patients who plan to undergo bariatric surgery. 3. Serum B12 solely may not be adequate for diagnosis of vitamin B12 deficiency, thus, serum methyl malonic acid (MMA) is the recommended assay for evaluation of vitamin B12 deficiency (for both symptomatic and asymptomatic patients). 4. Screening patients for iron status (but not for the purpose diagnose iron deficiency) may include the use of ferritin levels. A combination of tests (serum iron with serum transferrin saturation and total iron-binding capacity) is recommended for the evaluation of iron deficiency in pre-operative individuals. 5. Routine pre-operative screening of zinc and copper status is recommended for patients before RYGB or BPDS. Zinc assays should be interpreted keeping in mind that patients with Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

Symptoms of micronutrient deficiency

Normal lab range

Additional lab indices

Vitamin D

31–70 years: 15 mcg (600 IU) 71+ year: 20 mcg (800 IU)

Sunlight exposure, Fish liver oils, egg yolk, fortified dairy products and cereals

Rickets in toddlers Osteomalacia in adults, Arthralgia, myalgia, depression, fasciculation

25 (OH) D > 30 mg/mL (> 75 nmol/L)

Thiamine

M: 1.2 mg F: 1.1 mg

Enriched, fortified, or whole-grain products, cereals

Plasma thiamin: 4–15 nmol/L Thiamin, whole blood: 70–180 nmol/L Transketolase > 150 nmol/L Erythrocyte trasketolase activity (ETKA)/activity coefficient < 1.15

Vitamin B12

2.4 μg

Fortified cereals, meat, fish, poultry

Wet beriberi: Heart failure with high cardiac output, edema in the lower extremities Dry beriberi: Brisk tendon reflexes, peripheral neuropathy and/or polyneuritis, gait ataxia, convulsions Wernicke’s encephalopathy, if psychosis and hallucinations are present also known as Korsakoff psychosis Pernicious anemia, numbness and paresthesia, sore tongue, smooth and “beefy red” tongue, demyelination and axonal degeneration especially of peripheral nerves, spinal cords, and cerebrum Tinnitus, depression, dementia, ataxia Macrocytic anemia, neural tube defects, change in pigmentation or ulceration of skin, nails, or oral mucosa

↓ serum phosphorus ↓ Urinary calcium ↑ serum PTH ↑N-telopeptide ↑ Osteocalcin ↑ pyruvate or ↓ lactate ↓ Urinary thiamin

Seborrhoeic dermatitis like eruption, atrophic glossitis, angular cheilitis, conjunctivitis, intertrigo, neurological symptoms of somnolence, confusion, and neuropathy

Pyridoxal-5 -phosphate: 5–24 ng/mL

Folate

400 μg

Vitamin B6

1.5 mg

Grains, whole grain breads and bread products, fortified ready-to-eat cereals, dark leafy vegetables Fortified breakfast cereals, chickpeas, pork, turkey, and beef

Serum B12 (cobalamin) 20 0–10 0 0 pg/mL

↑ Serum methyl malonic acid (MMA)

↑ Serum homocysteine (tHcy)

Folate 340–1020 ng/mL for age ≥ 18 year

Normal MMA ↑ Serum tHcy

RBC glutamic pyruvate oxaloacetic transaminase Urinary 4-pyridoxic acid (continued on next page)

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Table 2 Symptoms of micronutrient deficiencies and their laboratory indices.

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Recommended Daily Intake

Sources

Symptoms of micronutrient deficiency

Normal lab range

Additional lab indices

Vitamin A

M: 900 mcg (3000 IU) W: 700 mcg (2333 IU)

Liver, dairy products, fish, darkly colored fruits, leafy vegetables

Plasma retinol 20–80 μg/dL

Retinol binding protein

Vitamin E

15 mg

Plasma alpha tocopherol

Plasma lipids

Vitamin K

M: 120 μg W: 90 μg

Vegetable oils, unprocessed cereal grains, nuts, fruits, vegetables, meats Green leafy vegetables, brussel sprouts, cabbage, plant oils and margarine

Night blindness, Bitot’s spot (foamy white spots on sclera of eye), endophthalmitis, loss of taste, hyper keratinization, corneal damage, xerosis, keratomalacia, perforation, and blindness Myelopathy, polyneuropathy (Late ≥ year after surgery), ophthalmoplegia, nystagmus, nyctalopia Easy bruising, bleeding gums, delayed blood clotting, heavy menstrual or nose bleeding, osteoporosis (advanced symptoms)

PT 10–13 s

↑Des-gamma

8 mg (Men and post-menopausal women) Menstruating females: 18 mg

Nonheme iron: Fruits, vegetables and fortified bread and grain products such as cereal Heme iron: Meat and poultry

Fatigue, impaired work performance and productivity, microcytic anemia, decreased immune function, enteropathy, spoon shaped nails (koilonychias), vertical ridges on nails, glossitis, dysphagia

Calcium

31–50 years: M: 10 0 0 mg, F: 10 0 0 mg 51–70 years: M: 10 0 0 mg, F: 1200 mg, 71+ years: M: 1200 mg, F: 1200 mg

Milk, cheese, yogurt, corn tortillas, calcium-set tofu, Chinese cabbage, kale, broccoli, Fortified foods and beverages

Low bone density, osteoporosis, neuromuscular hyperexcitability, muscle weakness, paresthesia

Serum iron: 60–170 μg/dL Transferrin 200–360 μg/dL Transferrin saturation: 20–50% Ferritin: 12–300 ng/mL (male) Ferritin: 12–150 ng/mL (females) Serum PTH (PTH > 65 pg/mL indicates ↓ calcium 25 (OH) D

Serum calcium (poor indicator of bone stores) Ionized calcium corrects for low albumin DXA scan (continued on next page)

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Iron

carboxyprothrombin (DCP) ↓ plasma phylloquinone ↑ TIBC Soluble transferrin receptor

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Table 2 (continued)

Symptoms of micronutrient deficiency

Normal lab range

Additional lab indices

Copper

900 μg

Organ meats, seafood, nuts, seeds, wheat bran cereals, whole grain products, cocoa products

Serum or plasma copper 11.8–22.8 mmol/L Ceruloplasmin 75–145 μg/dL

Decreased erythrocyte superoxide dismutase activity 24-hour urine copper

Zinc

M: 11 mg, F: 8 mg

Seafood such as shellfish, beans, nuts, whole-grain products and red meats

Anemia, leukopenia, hypopigmentation of hair, skin, and nails, optic neuropathy, myelopathy and unsteady gait (late complication), myopathy, polyneuropathy, Hypogeusia or ageusia (change in or absence of taste), skin lesions (acrodermatitis enteropathica, bullous pustular dermatitis), diarrhea, poor wound healing, hair loss, recurrent infections, infertility Muscle cramps, arrythmias, increased irritability of the nervous system with tremors, paresthesia, and palpitations Atrophy, degeneration, and necrosis of cartilage tissue, “Keshan disease” causing myocardial necrosis which leads to cardiomyopathy, Extreme fatigue, mental slowing, goiter, cretinism

Plasma zinc 60–130 μg/dL

↓ Serum zinc ↓ Erythrocyte zinc

Magnesium

M: 420 mg F: 320 mg

Whole wheat, spinach, almonds, cashews, peanuts, black Beans, avocado

Selenium

55 μg

Brazil nuts, yellowfin tuna, ham, pork, beef, turkey, chicken

(RBC zinc)

↓ Urinary zinc Plasma magnesium 1.7–2.2 mg/dL

↓Potassium ↓Calcium

Plasma selenium: 53.03–108.96 mg/L Whole blood selenium: 66.71–119.4 mg/L Plasma glutathione peroxidase: 196 to 477 U/L

–

LAGB: Laparoscopic adjustable gastric banding, RYGB: Roux-en-Y gastric bypass, VSG: Vertical sleeve gastrectomy, BPDS: Biliopancreatic bypass with duodenal switch, RDA: Recommended Dietary Allowance.

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Recommended Daily Intake

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Table 2 (continued)

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Prevalence of deficiency after bariatric surgery

Screening at baseline

Screening post bariatric surgery

Supplementation post bariatric surgery

Comments

Thiamine

15.5–29%

<1% to 49%

Yes

Recommended for high risk patients

Begin on day 1 of hospital discharge

Vitamin B12

2–18%

At 2–5 year of RYGB- (<20%) VSG- (4–20%)

Yes

Required for all patients Interval: Every 3 months for 1 year, and then yearly

Folate

Up to 54%

up to 65%

Yes

Routine screening for all patients

At least 12 mg daily and preferably a 50 mg dose of thiamine from the B-complex or multivitamin once or twice daily Supplement doses varies based on route of administration • Parenteral (IM or SQ): 10 0 0 μg monthly • Orally by liquid or disintegrating tablet, or sublingual: 350–500 μg daily 40 0–80 0 μg orally daily from the multivitamin 80 0–10 0 0 μg for women of childbearing age

Vitamin D and calcium

25–90%

20–100%

Yes

Routine screening for all patients

Fat soluble vitamins (A, E, K)

Vitamin A 14% Vitamin E 2.2% No data on vitamin K

Within 4 years of RYGB and BPDS up to 70%

Yes

Vitamin A: Within 1st post-operative year, particularly those with RYGB or BPDS or with associated protein-calorie malnutrition. Vitamin E and K: Only for symptomatic patients

Daily calcium: • LAGB, VSG, RYGB: 120 0–150 0 mg/day • BPDS: 180 0–240 0 mg/day Daily vitamin D3: 30 0 0 IU daily LAGB: Vitamin A 50 0 0 IU/d and vitamin K 90–120 μg/d RYGB and VSG: Vitamin A 50 0 0–10,0 0 0 IU/d and vitamin K 90–120 μg/d BPDS: Vitamin A 10,0 0 0 IU/d and vitamin K 300 μg/d Vitamin E 15 mg/d for all patients

Begin 0–3 months after surgery

• Begin on day 1 of hospital discharge • Greater than 10 0 0 mg of folic acid supplementation could mask vitamin B12 deficiency • May begin on day 1 of hospital discharge or 1 month post operatively • Calcium should be given in divided doses • May begin 2–4 weeks post operatively • Higher maintenance doses need to be considered in patients with prior history of vitamin A, E, or K deficiencies

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Micronutrients

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Table 3 Recommendations on screening and supplementation of micronutrients before and after bariatric surgeries.

Screening at baseline

Screening post bariatric surgery

Supplementation post bariatric surgery

Comments

Vitamin B6

Unknown

Rare

Only for symptomatic patients

Iron

Up to 45%

30–60% AGB (14%) SG (Up to 18%) RYGB (20–55%) BPD (13–62%) DS (8–50%)

No strong recommendation Yes

1.6 mg (as part of multivitamin supplement) Low risk (males or patient without history of prior iron deficiency anemia): 18 mg of iron from multivitamin High risk (menstruating females): 45–60 mg of daily elemental iron

Zinc

24–28% overall 74% of patients going for BPDS

BPD (45 to 91%) RYGB (15 to 21%) LSG (11 to 14%).

Patients plan for RYGB or BPDS

Annually for post RYGB or BPDS patients Patients with chronic diarrhea or iron deficiency anemia with a negative screening result for iron deficiency

Copper

Up to 70% in Pre-BPD women

BPDS- (Up to 90%) RYGB- (10–20%)

Patients plan for RYGB or BPDS

Annually for post RYGB or BPDS patients even if the patient asymptomatic

• Consider with unresolved anemia • Begin on day 1 of hospital discharge • Oral supplementation should be taken in divided doses separately from acid inducing medications, calcium supplements, foods high in polyphenols or phytates • Begin on day 1 of hospital discharge • It is suggested that the supplemental protocol contain a ratio of 8–15 mg of supplemental zinc per 1 mg of copper, to minimize the risk of copper deficiency • Begin on day 1 of hospital discharge

Magnesium

35%

32%

Screening helpful but no strong recommendation

Screening helpful but no strong recommendation except for BPDS patients

Required for all patients Interval: Every 3 months for 1 year, and then yearly

LABG/VSG: 8–11 mg/d (multivitamin with mineral containing 100% of the RDA) RYGB: 8–22 mg/d (multivitamin with mineral containing 10 0–20 0% of the RDA) BPDS: 16–22 mg (multivitamin with mineral containing 200% of the RDA) LAGB/VSG: 1 mg/d (multivitamin with mineral containing 100% of the RDA) RYGB or BPDS: 2 mg/d (multivitamin with mineral containing 200% of the RDA) Oral magnesium citrate, 300 mg/day may be helpful

–

25 (OH) D: 25-hydroxyvitamin D, PTH: parathyroid hormone, MMA: Serum methyl malonic acid, tHcy: Serum homocysteine, PT: Prothrombin time, TIBC: Total iron binding capacity, DXA: Dual-energy X-ray absorptiometry.

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Table 3 (continued)

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obesity have lower serum zinc levels and lower concentrations of zinc in plasma and erythrocytes than leaner individuals. Thus, repletion of zinc is indicated when signs and symptoms are evident and zinc assays are severely low. Serum copper and ceruloplasmin are recommended for screening indices, but are acute-phase reactants and thus, need to be interpreted carefully. Erythrocyte superoxide dismutase is a more precise biomarker and can be used for screening of copper deficiency when it is available and affordable. Post bariatric surgery micronutrient screening recommendations 1. Routine screening for iron, folate, vitamin B12, and vitamin D status is recommended for all patients. Post-surgical screening for vitamin B12 and iron are recommended within 3 months after surgery, then every 3–6 months until 12months, and annually or as clinically indicated for all patients. Serum B12 may not be adequate to identify B12 deficiency and this, it is recommended to include serum MMA with or without homocysteine to identify B12 deficiency in symptomatic and asymptomatic patients and in patients with history of B12 deficiency or preexisting neuropathy. Iron status in post-WLS patients should be monitored using a complete blood count, iron panel, total iron binding capacity, ferritin, and soluble transferrin receptor (if available), along with clinical signs and symptoms. 2. Patients should be screened for vitamin A deficiency within the first post-operative year particularly those who have undergone RYGB or BPDS or have associated protein calorie malnutrition, regardless of symptoms. Whereas, vitamin E and K deficiencies are uncommon after bariatric surgeries, and patients who are symptomatic should be screened. 3. Routine post-surgical screening for thiamine deficiency is recommended for high-risk groups especially in patients with risk factors for thiamine deficiency such as females, blacks, patients who not attending a nutritional clinic after surgery, patients with GI symptoms (intractable nausea and vomiting, jejunal dilation, mega-colon, or constipation, or rapid weight loss) or with concomitant medical conditions such as cardiac failure (especially those receiving furosemide) or on parenteral nutrition or with excessive alcohol use, and have neuropathy or encephalopathy. If signs and symptoms or risk factors are present in post-bariatric patients, thiamine status should be assessed at least during the first 6months, then every 3–6 months until symptoms resolve. 4. Post-RYGB and BPDS patients should be screened at least annually for zinc and copper deficiency. Zinc should be measured in all post bariatric patients who are symptomatic for iron deficiency anemia but screening results for iron deficiency anemia is negative or who have chronic diarrhea. 5. Routine screening of copper status in post bariatric patients is recommended at least annually after BPDS and RYGB even in the absence of clinical signs or symptoms of deficiency. In post-WLS patients, serum copper and ceruloplasmin are the recommended biomarkers for determining copper status because they are closely correlated with physical symptoms of copper deficiency. 6. Routine screening for selenium levels is not currently recommended and should be measured in patients with RYGB or BPDS who have unexplained anemia or fatigue, persistent diarrhea, cardiomyopathy, or metabolic bone disease. Nutritional supplementation after bariatric surgeries 1. In order to optimally preserve lean tissue mass during post-operative weight loss, current consensus guidelines based on clinical and experimental evidence suggest high protein supplementation along with regular resistance training and aerobic exercises. Depending upon the type of surgery, average daily protein intake of 60–120 g after RYGB, 60–80 g or 1.1 g/kg of ideal body weight after LSG and 90 g (an increase of 30%) following BPDS is recommended. Severe malnutrition after bariatric surgery should prompt hospital admission for initiation of nutritional support. 2. Minimal daily nutritional supplementation should include 2 adult multivitamins (all in chewable form for 3–6 months) for patients with RYGB and LSG, and 1 adult multivitamin for patients with LAGB. Mineral (each containing iron, folic acid, and thiamine) supplements, Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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3.

4.

5.

6.

7.

8.

9.

10.

11.

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120 0–150 0 mg of elemental calcium (in diet and as citrated supplement in divided doses), at least 30 0 0 international units of vitamin D (titrated to therapeutic 25- hydroxyvitamin D levels >30 ng/ml) should be given to all patients. Folic acid should be supplemented in all women of childbearing age to reduce the risk of fetal neural tube defects. There is a lack of consensus on the efficacy and appropriate doses for oral route of prophylaxis and therefore many guidelines recommend lifelong vitamin B12 injections for RYGB patients. In patients with symptomatic deficiency, intramuscular B12 remains the gold standard of therapy. High dose oral Vitamin B12 can however be considered for either prophylaxis or in patients with asymptomatic deficiency when there are concerns with compliance or adherence to intramuscular therapy. The dosage for supplementation varies based on route of administration: 350–500 mg per day orally by disintegrating tablet, liquid or sublingual; 10 0 0 mg monthly in Parenteral (IM or SQ); Nasal spray as recommended by manufacturer. In patients who have undergone bariatric surgery with severe vitamin D malabsorption, oral doses of vitamin D2 or D3 may need to be as high as 50,0 0 0 units 1–3 times weekly to daily, and more recalcitrant cases may require concurrent oral administration of calcitriol (1,25—dihydroxy vitamin D). Hypophosphatemia is usually due to vitamin D deficiency and oral phosphate supplementation should be provided for mild to moderate hypophosphatemia (1.5–2.5 mg/dL). Bone density measurements with use of axial (spine and hip) dual-energy x-ray absorptiometry (DXA) may be indicated to monitor for osteoporosis at baseline and at about 2 years in patients with RYGB or BPDS. Anemia without evidence of blood loss warrants evaluation of nutritional deficiencies as well as age appropriate causes during the late postoperative period. Deficiencies in vitamin B12, folate, protein, copper, selenium, and zinc and should be evaluated when routine screening for iron deficiency anemia is negative. Thiamine supplementation should be included as part of routine multivitamin with mineral preparation. Patients with severe thiamine deficiency (suspected or established) should be treated with intravenous thiamine, 500 mg/d, for 3–5 days, followed by 250 mg/d for 3–5 days or until resolution of symptoms, and then to consider treatment with 100 mg/d, orally, usually indefinitely or until risk factors have resolved. Mild deficiency can be treated with intravenous thiamine, 100 mg/d, for 7–14 days. In recalcitrant or recurrent cases of thiamine deficiency without any risks for thiamine deficiency, the addition of antibiotics for small intestine bacterial overgrowth should be considered. Post bariatric surgery patients should take vitamins A, E, and K, with dosage based on type of procedure: LAGB: Vitamin A 50 0 0 IU/d and vitamin K 90–120 ug/d. RYGB and SG: Vitamin A 50 0 0–10,0 0 0 IU/d and vitamin K 90–120 ug/d. LAGB, SG, RYGB, BPDS: Vitamin E 15 mg/d DS: Vitamin A (10,0 0 0 IU/d) and vitamin K (300 mg/d) Higher maintenance doses of fat-soluble vitamins may be required for post-WLS patients with a previous history of deficiency in vitamin A, E, or K. Water-miscible forms of fat soluble vitamins are also available to improve absorption. Special attention should be paid to post-WLS supplementation of vitamin A and K in pregnant women. Zinc should be routinely supplemented following malabsorptive procedures. Zinc deficiency should be considered in patients with hair loss, pica, significant dysgeusia, or in male patients with hypogonadism or erectile dysfunction. Copper supplementation (2 mg/d) should be included as part of routine multivitamin with mineral preparation. In severe deficiency, treatment can be initiated with IV copper (2– 4 mg/d) A˚ ∼ 6 days. Subsequent treatment or treatment of mild to moderate deficiency can usually be achieved with oral copper sulfate or gluconate 3–8 mg/d until levels normalize and symptoms resolve. Patients who are treated for zinc deficiency or using supplemental zinc for hair loss should receive 1 mg of copper for each 8–15 mg of zinc as zinc replacement can cause copper deficiency. There is insufficient evidence to support routine selenium screening or supplementation after bariatric surgery.

Please cite this article as: S. Mohapatra, K. Gangadharan and C.S. Pitchumoni, Malnutrition in obesity before and after bariatric surgery, Disease-a-Month, https://doi.org/10.1016/j.disamonth.2019.06.008

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Conclusion The nutritional assessment before and after bariatric procedures is mandatory and should be life-long. The short-term follow-ups should aim at avoiding life threatening complications from severe nutritional deficiencies whereas the goal of long term follow ups should be to prevent serious consequences such as malnutrition, and osteoporosis. A healthy dietary behavior and structured physical exercise should be encouraged to maintain muscle mass and bone health. Future research is warranted to better define the long-term outcome, quality of life, and healthcarerelated costs.

Conflict of interest The authors declare no conflict of interest

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