Abstract
Abstract
Background:
Duodenal bypass and intestinal malabsorption from Roux-en-Y gastric bypass (RYGB) can exacerbate known nutritional deficiencies of morbidly obese patients and worsen symptoms. Preventatively, most bariatric patients use postoperative nutritional supplementation. This study evaluated Nuvista® (Nutricia North America, Rockville, MD) and its potential as an adequate single nutritional supplement.
Subjects and Methods:
From October 2009 to June 2010, 25 patients enrolled in a prospective, consecutive pilot study. Each underwent laparoscopic RYGB. The study group consumed two packs of Nuvista daily. The control group received standard nutritional supplements. Both groups had the same postoperative diet. Laboratory and demographics were compared at baseline and 12 months. Statistical analysis included paired t test, and a value of P<.05 was significant.
Results:
The study and control groups (16 and 9 patients, respectively) had statistically similar demographic profiles. Both groups had preoperative elevations of hemoglobin A1c (HbA1c) (6.2% and 6.2%, respectively), low-density lipoprotein (LDL) (108.2 mg/dL and 199.2 mg/dL, respectively), and high-density lipoprotein (HDL) (55.1 mg/dL and 48.0 mg/dL, respectively) and deficiencies in vitamin D with respective mean values of 20.6 ng/mL and 22.7 ng/mL (normal range, 30–100 ng/mL). Postoperatively, the study group had significant increases in phosphorus (P=.02), iron (P=.03), vitamin D (P=.05), zinc (P=.01), and HDL (P≤.01) and significant decreases in body mass index (BMI) (P≤.01), creatinine (P=.02), HbA1c (P=.01), triglycerides (P≤.01), and LDL (P≤.01). The control group had a significant increase in HDL (P=.01) and significant decreases in BMI (P≤.01), hemoglobin (P=.01), creatinine (P≤.01), albumin (P=.05), HbA1c (P=.05), zinc (P≤.01), triglycerides (P=.03), and LDL (P=.01). No change in mean parathyroid hormone value was seen.
Conclusions:
Nuvista can provide adequate supplementation to bariatric patients 12 months after RYGB. Lifelong biochemical follow-up is necessary to personalize the diet and nutritional supplementation to compensate for the pathophysiologic changes of the gastric bypass.
Introduction
After failing diets and exercise programs, morbidly obese patients may opt to undergo bariatric surgery. In the United States, the majority of these individuals have a Roux-en-Y gastric bypass (RYGB). Following such a procedure, these preoperative vitamin and mineral deficiencies may be exacerbated by bypassing the duodenum and delaying absorption along the course of the small intestine. Vitamin D deficiency may be associated with secondary hyperparathyroidism, which results in bone loss, fractures, muscle weakness, and inadvertent falls.5,6 Other pathophysiologic consequences of vitamin D deficiency include exacerbation of type 2 diabetes, hypertension, and malignancies.7,8
In general, bariatric surgery is used on a cohort of patients who are nutritionally depleted preoperatively. Postoperatively, every patient requires dietary guidance and biochemical surveillance to avert a plethora of nutritional complications. Based on these various nutritional complications, a host of commercial products are available to prevent and treat these deficiencies. However, no single product addresses all of the nutritional deficits. Recently, a novel bariatric product, Nuvista® (Nutricia North America, Rockville, MD), was developed to address many of the postoperative deficits following a laparoscopic RYGB. Previously, Nuvista was used as part of a preoperative 1200-calorie regimen for 4 weeks immediately before the bariatric procedure. Based on this preoperative diet regimen, the volume of the lateral segment of the liver decreased by 43.4%. 9 This current report details the postoperative utilization of Nuvista for 12 months. Nuvista was used, as a single nutritional supplement, to address the potential postoperative deficits following an RYGB in morbidly obese patients.
Subjects and Methods
This prospective, consecutive pilot study was approved by the Western Institutional Review Board and identified as protocol number 20081274. From October 2009 to June 2010, all morbidly obese patients undergoing an RYGB were invited to participate in the nutritional trial. Every patient was offered Nuvista consecutively, and no randomization was used to determine each cohort. Overall, 16 patients agreed to participate. Each patient met the National Institutes of Health guidelines for bariatric surgery, including a body mass index (BMI) above 40 kg/m2 or a BMI greater than 35 kg/m2 associated with a co-morbidity such as hypertension, diabetes, or coronary artery disease. Exclusion criteria for the trial included morbidly obese patients with previous gastrointestinal surgery, renal insufficiency or failure, severe hepatic disease (cirrhosis), elevated liver-associated enzymes, familial hypercalcemia, pregnancy, age below 18 years or above 65 years, or preoperative corticosteroid use.
Baseline demographics were obtained at 4 weeks preoperatively, including weight, height, BMI, and race. As well, a standard laboratory analysis was obtained simultaneously. A control group of 9 RYGB patients was used for comparison. The control group underwent the same studies and analyses as the study group. From a surgical standpoint, each patient in the study or control group underwent a laparoscopic RYGB. The RYGB was completed with a gastric pouch that measured 30 mL and a 150-cm Roux limb. Postoperatively, each patient was started on a clear liquid diet on postoperative Day 1 and advanced gradually to a solid diet over the course of 8 weeks. Postoperatively, each study patient consumed two packets of Nuvista every day for 1 year, whereas the control group did not receive supplementation with Nuvista.
Supplemental recommendations for the control group included daily consumption of 2000 IU of vitamin D3, 1500–2000 mg of calcium citrate, 60–80 g of protein, 350 μg of vitamin B12, and a multivitamin twice a day (18–36 mg of elemental iron). Each patient from the control group received a list of prospective nutritional agents to help supplement their respective postoperative diets. Again, the study group received two packets of Nuvista daily postoperatively for 1 year. No further supplements were given to the study group postoperatively. Each packet of Nuvista contains 150 calories, 15 g of protein, 19 g of carbohydrates (5 g is prebiotic soluble fiber), and 2.5 g of fat. The other supplements within Nuvista include 1000 IU (25 mg) of vitamin D3, 750 mg of calcium, 25 mg of elemental iron, and 175 μg of vitamin B12. Nuvista is also lactose free. Laboratory data and demographics were compared for both groups at baseline and 12 months. A paired t test with a value of P<.05 was used to define significance.
Results
In total, 16 patients were enrolled in the study group: 14 were females, mean age was 47±2 years, and mean BMI was 44.8±4.4 kg/m2. The control group had 9 patients in total (8 females), with a mean age of 43±13 years and a mean BMI of 42±3.6 kg/m2. Each group was compared at 12 months with its own preoperative baseline values. Table 1 shows results of study patients at baseline versus 12 months, and Table 2 shows the results of control patients at baseline versus 12 months. Preoperative abnormalities were found in both study and control patient groups. The study and control groups were found to have elevations in hemoglobin A1c (HbA1c) (6.2% and 6.2%, respectively), low-density lipoprotein (LDL) (108.2 mg/dL and 199.2 mg/dL, respectively), and high-density lipoprotein (HDL) (55.1 mg/dL and 48.0 mg/dL, respectively). Both the study (n=14 patients) and control (n=8 patients) groups were also found to have preoperative deficiencies in vitamin D with respective mean values of 20.6 ng/mL and 22.7 ng/mL (normal range, 30–100 ng/mL).
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; BUN, blood urea nitrogen; HbA1c, hemoglobin A1c; LDL, low-density lipoprotein; NS, not significant; PTH, parathyroid hormone; TIBC, total iron-binding capacity.
Insufficient number of patients for comparison.
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; BUN, blood urea nitrogen; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NS, not significant; PTH, parathyroid hormone; TIBC, total iron-binding capacity.
Significant changes in values were noted in both groups at the 12-month follow-up. As shown in Table 1, the study group had a significant increase in phosphorus, iron, vitamin D, zinc, and HDL. There was a significant decrease in BMI, creatinine, HbA1c, triglycerides, and LDL. Table 2 shows a significant increase of HDL in the control group. A significant decrease was noted for the control group in BMI, hemoglobin, creatinine, albumin, HbA1c, zinc, triglycerides, and HDL. Of note is that neither group showed any changes in the mean parathyroid hormone (PTH) value at 12 months. Table 3 shows the absolute difference in mean values at 12 months for the control and study groups.
Insufficient number of patients for comparison of change at 12 months from baseline.
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; BUN, blood urea nitrogen; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NS, not significant; PTH, parathyroid hormone; TIBC, total iron-binding capacity.
Discussion
At this time, the general recommendations from the American Society of Metabolic and Bariatric Surgery following bariatric surgery include daily aliquots of 50–80 g of protein, 2000 IU of vitamin D, 1500–2000 g of calcium, and 18–36 mg of iron. 10 Obviously, these recommendations are purely guidelines, and each individual patient requires diligent follow-up on a yearly basis to ensure that potential nutritional deficiencies are diagnosed quickly and treated appropriately. Postoperative supplementation for the bariatric patient may depend on the amount and quality of food ingested, surgical complications, and physiologic adaptation of the gastrointestinal tract. Moreover, the ideal postoperative supplement for bariatric patients undergoing an RYGB should be ingested easily, affordable, palatable, and replete with an abundance of nutrients. Two packets of Nuvista were ingested daily in this pilot study for 12 months postoperatively by 16 patients undergoing RYGB. Overall, two packets of Nuvista contain the recommended allotments of vitamin D, B12, iron, calcium, and minerals. Nuvista is approximately 20–30 g deficient in terms of daily protein recommendations.
Numerous studies document vitamin D deficiency preoperatively in up to 20%–68% of bariatric patients.1,2,11,12 The risk factors include African-American race (increased melanin), decreased exposure to ultraviolet light, decreased bioavailability in adipose tissue, and decreased hepatic hydroxylation secondary to nonalcoholic steatohepatitis. 13 Postoperatively, vitamin D deficiency may be exacerbated because it is a fat-soluble vitamin that is absorbed in the terminal ileum. Based on our surgical technique, vitamin D would not encounter bile salts for at least 150 cm after traversing the Roux limb. Preoperatively, this study documented 14 patients (88%) with vitamin D deficiency in the study group and 8 patients (89%) in the control group, using 30 ng/mL as the lower limit of normal. Postoperatively at 1 year, 11 patients (69%) in the study group showed biochemical evidence of vitamin D deficiency, whereas 6 patients (67%) in the control had decreased vitamin D levels. It is interesting that the overall mean value of vitamin D in the study group was significantly increased. Regardless, the results from this trial are alarming given the fact that all of the patients participated in a standardized trial. Clearly, all of these patients require lifelong follow-up and aggressive supplementation with increased levels of vitamin D and calcium. At present, the study and control patients who are vitamin D deficient are receiving increased amounts of vitamin D weekly (50,000 IU) along with 2000 mg of calcium daily. Vitamin D levels for patients with deficient levels are now checked every 3 months to ensure normal levels.
These biochemical results are not unique as the literature documents that calcium levels may remain within normal limits as PTH levels increase over the first 18 months postoperatively. 14 As long as adequate calcium and vitamin D supplementation continues, PTH levels usually return to normal. Without adequate calcium and vitamin D supplementation, PTH may remain elevated with unopposed mobilization of calcium from bone. Long-term unopposed PTH elevations may alter bone mineral density within the lumbar, pelvic, and femoral neck regions.15,16 Based on the current number of gastric bypasses performed annually, the number of postmenopausal women and elderly men with osteoporosis undergoing bariatric surgery will only increase over the next decade. This scenario seems likely to produce more individuals with potential musculoskeletal abnormalities. Bone density scans were not used in this study, but all postmenopausal women and vitamin D-deficient patients were asked to consult their respective primary care physicians regarding a bone density scan.
Although the majority of calcium is absorbed in the duodenum and proximal jejunum, the body compensates to avoid hypocalcemia postoperatively in RYGB patients. Even with minute decreases in calcium, secondary hyperparathyroidism compensates by converting vitamin D into its active form in the kidney and liver to increase intestinal absorption of calcium. As noted previously, if all else fails, increases in PTH levels enhance bone resorption to stabilize calcium levels. If this occurs, osteoporosis may develop. Hypocalcemia was not evident in any control or study patient postoperatively. However, elevated PTH levels were found in 1 (6%) study patient and 1 (11%) control patient at the 1-year follow-up. The amount of calcium and vitamin D supplementation in Nuvista was appropriate based on the recommended guidelines. Obviously, increased supplementation is required for this select group of patients, and long-term follow-up is required to follow calcium and vitamin D levels. Furthermore, any sustained elevations of PTH may warrant further increases in calcium and vitamin D supplementation. Of note is that calcium was administered as calcium carbonate to enhance absorption in control and study patients.
In contrast to the vitamin D–calcium–PTH axis, the physiologic absorption of vitamin B12 begins in the stomach. Initially, gastric acid is required to cleave pepsinogen to pepsin. In turn, pepsin releases vitamin B12 from its protein compound. Subsequently, intrinsic factor secreted from parietal cells binds to vitamin B12 as it traverses the small intestine towards the terminal ileum. The intrinsic factor–vitamin B12 complex is then absorbed at the terminal ileum. Unfortunately, RYGB results in decreased gastric acid and bioavailability of intrinsic factor and predisposes these patients to vitamin B12 deficiency. Previous reports have illustrated vitamin B12 deficiency in 12%–35% of patients postoperatively after RYGB. 17 If these levels are not supplemented, vitamin B12 deficiency may cause megaloblastic anemia as well as polyneuropathies and paresthesias. Postoperatively, vitamin B12 deficiency was not apparent in any patient. Usually, the body has a large reservoir of vitamin B12, and deficient levels may not be evident for several years following an RYGB. Therefore, vitamin B12 levels should be assessed yearly in order to avert this specific deficiency.
The most efficient regions of iron absorption are the duodenum and proximal jejunum. Obviously, these regions are bypassed following an RYGB. Also, iron absorption is altered secondary to decreased gastric acid that inhibits ferric iron reduction to the absorbable ferrous form. Finally, postoperative RYGB patients appear less tolerant of red meats, which are a vital source of dietary iron. Ultimately, a decrease in total iron body stores may result in a decrease in erythropoiesis, which may induce a concurrent iron-deficient anemia. Moreover, premenopausal women are at an increased risk for iron deficiency following an RYGB. Preoperatively, iron deficiency was seen in 0% of the study group and 11% of the control group. Over the course of 12 months, no patients developed iron deficiency, and only 1 patient was anemic in the control group.
Various other vitamins and minerals were measured during this pilot study. No deficiencies were noted for these various elements. The importance of these various minerals remains a topic of research. It is interesting that normal zinc levels correlate with normal thresholds regarding foods that are characterized as bitter, sweet, sour, or salty. 18
Deficiencies in protein absorption are rare following an RYGB and range from 1.3% to 13% in only a few studies.19,20 Of note is that these studies used a distal RYGB with a short common channel. Normal absorption requires gastric proteases such as pepsin and pancreatic enzymes, including trypsin, chymotrypsin, and carboxypeptidases. Also, peptidases located in the small bowel brush border digest and absorb the smaller peptides as they traverse the small intestine. Recommended daily intake of protein should approximate 50 g 21 with an increase to 1–1.5 g/kg of ideal body weight during weight loss. 22 The overall physiologic process of protein absorption remains fairly intact following an RYGB. Therefore, protein insufficiency may be caused by cultural and economic factors, customary eating habits, decreased caloric volume, dysphagia, vomiting, dumping, and changes in taste. 15 Nuvista contains 15 g of protein per packet for a total of 30 g/day. More protein can be supplemented by mixing Nuvista with milk versus water. Regardless, the patient must ingest more protein to obtain at least 50–60 g of protein/day. No patients were identified with protein deficiency in either group when measuring albumin, pre-albumin, or transferrin levels. Despite the protein deficit in Nuvista, all of the bariatric patients were able to consume an extra 20–30 g of protein daily regardless of vegetarian, vegan, or pescatarian diet.
One limitation of this study may include a potential selection bias as the cohorts were not randomized, and patient participation in either group was completely voluntary.
The intent of Nuvista was to simplify postoperative supplementation for bariatric patients with a single agent while avoiding nutritional deficiencies at an affordable price. From a commercial standpoint, the retail cost of Nuvista has been priced to compete with similar commercial products. Obviously, the trial patients did not incur any costs while ingesting Nuvista. From a compliance standpoint, a previous publication documented that Nuvista was well tolerated, with patients preferring vanilla and strawberry versus chocolate. 9 As noted earlier, Nuvista is lactose free, and this may account for some of the compliance postoperatively. A larger study population with further follow-up would truly document efficacy for the product.
In general, each patient who undergoes an RYGB requires lifelong follow-up with some type of nutritional supplement. The exact type of supplement may be dependent on several factors that were listed previously, such as dietary and cultural habits, surgical complications and technique, and quality and quantity of food. This pilot study showed that Nuvista provided adequate supplementation to bariatric patients 12 months postoperatively after an RYGB. However, lifelong biochemical follow-up is still required to continue to modify each respective patient's diet and nutritional supplementation as the body ages and adapts to the pathophysiologic changes of the gastrointestinal tract.
Footnotes
Disclosure Statement
F.B. was a consultant for Nutricia North America and received an honorarium for his time. M.F., N.G.R., K.V., C.G., and C.L. declare no competing financial interests exist.
