1. Nutrients of Concern following Bariatric Surgery: Vitamin D and B Complex Vitamins Carolyn Moore, PhD, RD Associate Professor Department of Nutrition and Food Sciences Houston, Texas

2. Overview Obesity and bariatric surgery Sleeve gastrectomy vs. Roux-en Y gastric bypass procedures Supplementation prospective studies Vitamin D B vitamins Current recommendations Future directions

3. Obesity and Bariatric Surgery Over 30% of Americans are obese American Society for Metabolic and Bariatric Surgery (ASMBS) estimate 220,000 adults have surgery annually Bariatric surgery offers long-term weight loss 29% and 87% of excess body weight loss 1 to 2 years post surgery BMI >30 have a 50% - 100% ↑ risk premature death compared to healthy weight individuals ↑ risk for 40 obesity-related diseases - Type 2 diabetes, heart disease and cancer American Society for Metabolic & Bariatric Surgery (ASMBS); Beckman L, Earthman C. 2013. JAND 113: 398-399.

4. Candidates for Surgery BMI > 40 (Weight in kg/Height in m 2 ) BMI 35-40 with comorbidities Well-informed, motivated patient Previous attempts at medical weight loss programs

5. Diabetes Hypertension Hyperlipidemia Coronary artery disease Stroke Cholelithiasis Infertility Degenerative arthritis Sleep apnea/Asthma Venous insufficiency Gastroesophageal reflux Chronic daily headaches Depression/Social ramifications Associated Co-morbidities All of these conditions improve after surgery

6. Types of Bariatric Surgery Restrictive Procedures that reduce the volume of the gastric reservoir and limit the transit of food Sleeve gastrectomy Malabsorptive Procedures that prevent or reduce the absorption of nutrients Combination Roux-en-Y gastric bypass is considered restrictive and malabsorptive

7. Surgical Approach

8. Roux-en-Y Gastric Bypass (RYGB) Most effective long-term weight loss ≈ 70-80% Excess Weight Loss Improvement/ possible resolution of diabetes Increased satiety and glucose regulation Elevated glucagon-like peptide 1 (GLP-1) & peptide YY (PYY); inhibited ghrelin (appetite inducing) Isom KA et al. Nutr Clin Pract 2014: 29: 718-739

9. RYGB Rate of Weight Loss Excess Weight Loss (EWL) 53% to 77% EWL = Wt > BMI 25

10. RYGB Advantages/Disadvantages Advantages Rapid initial weight loss Minimally invasive approach is possible Durable long-term weight loss Minimal diet restrictions Better excess weight loss Low complication rate Disadvantages Cutting and stapling of stomach and bowel Portion of digestive track is bypassed, reducing absorption of essential nutrients Extremely difficult to reverse Complex surgery

11. Sleeve Gastrectomy (SG) RYGB SG

12. Sleeve Gastrectomy Changes Resection ≈ 2/3 of stomach may restrict nutrient intake 20-100 mL prevents consuming large quantities of food 70%-80% removal of stomach fundus where intrinsic factor and hydrochloric acid are released may inhibit micronutrient absorption Reduction of ghrelin Increased GLP-1 and PYY  improved glucose metabolism Isom KA et al. Nutr Clin Pract 2014; 29: 718-739

13. Sleeve Gastrectomy Rate of Weight Loss Average Excess Weight Loss (EWL) of ≈ 66% at 2 years

14. SG Advantages/Disadvantages Advantages Rapid initial weight loss Minimally invasive approach is possible Minimal diet restrictions Excellent excess weight loss Low complication rate Disadvantages Cutting and stapling of stomach Irreversible ? long-term weight loss

15. Bariatric Complications Associated with Vitamin D Deficiency ComplicationNutrient Deficiency HyperparathyroidismVitamin D, Calcium OsteoporosisVitamin D, Calcium OsteomalaciaVitamin D Musculoskeletal PainVitamin D Proximal MyelopathyVitamin D Immune Function (MS, type 1 diabetes, inflammatory bowel, asthma) Vitamin D Kushner RF & Still CD. Nutrition and Bariatric Surgery. 2015.

16. Vitamin D Supplementation Efficacy: Sleeve Gastrectomy Versus Gastric Bypass Surgery Adiposity and serum 25-hydroxyvitamin D [25(OH)D] Inverse relationship between fat mass Low 25(OH)D and high BMI Both children and adults Few prospective bariatric studies evaluating doses to prevent & treat Defined vitamin D status: < 20 ng/mL deficient 20 – 29 ng/mL insufficient ≥ 30 ng/mL sufficient Moore CE, Sherman V. Obes Surg. 2014; 12: 2055-60.

17. Vitamin D Study Design: SG vs RYGB Female SG or RYGB patients Houston Methodist Hospital BMI ≥ 40 or BMI ≥ 35 with high-risk comorbid conditions 2,000 IU of vitamin D3 and 1,500 mg calcium citrate chewable supplements daily for 3 months (Celebrate®) Height, weight, BMI, serum 25(OH)D and parathyroid hormone (PTH) measured preoperatively and at 3 months 24-hour dietary recalls Moore CE, Sherman V. Obes Surg. 2014; 12: 2055-60.

18. Figure 1. Subject Flow 337 Recruited 10 did not tolerate chewable tablet 327 Consumed Supplements 312 Gastric Bypass & 11 Sleeve Gastrectomy Completed 3 Months -4 did not return for 3 month visit

19. Vitamin D Study: Demographics 1 VariablesAll (n=23)SG(n=11)RYGB(n=12) ________________________________________________________________________________ Age (years) 41 ± 1138 ± 1043 ± 13 Ethnicity (%) White11 (48)4 (36)7 (58) Black 9 (39)4 (45)4 (33) Hispanic3 (13)2 (18)1 (8) Body Weight (lbs) 278 ± 52266 ± 47290 ± 55 Excess Body Weight 128 ± 47117 ± 47140 ± 47 BMI (kg/m2) 46.3 ± 8.144.8 ± 9.447.6 ± 6.8 1 Results are expresses as mean ± SD or (percentages). Moore CE, Sherman V. Obes Surg. 2014; 12: 2055-60.

20. Changes Serum 25(OH)D after 3 Months Variable nPre-Opn3 months P ____________________________________________________________ 25(OH)D [ng/mL] All2319.1 ± 9.0 2327.2 ± 8.4<0.001 SG 1118.5 ± 9.61126.3 ± 9.6 0.013 RYGB1219.6 ± 8.3 1228.1 ± 7.6 0.010 % Vitamin D deficient All2360.62326.10.005 SG1154.51127.30.083 RYGB1266.71225.00.005 Moore CE, Sherman V. Obes Surg. 2014; 12: 2055-60.

21. Dietary Intake of Vitamin D and Calcium Variable nPre-Opn3 monthsP _____________________________________________________________ Dietary Vitamin D (IU/d) RDA(600 IU/d) All23160 ± 11220236 ± 2000.151 SG11128 ± 889272± 2440.058 RYGB12188 ± 12411208± 1600.051 Dietary Calcium (mg/d) RDA (1,000-1200 mg/d) All23726 ±29920493 ± 2210.022 SG11702 ± 4019556 ± 1440.767 RYGB12747 ± 17811442 ± 2640.008 Moore CE, Sherman V. Obes Surg. 2014; 12: 2055-60.

22. Vitamin D Supplementation Conclusions Daily 2,000 IU vitamin D3 & 1,500 mg calcium for 3 mo. effective Vitamin D deficiency from 60.6% to 25.1% Increased 25(OH)D levels but did not reach ≥ 30 ng/mL in 63% Response very similar in RYGB and SG 3 months post surgery dietary vitamin D (236 ± 200 IU/d) intake was 1/3 of the RDA for women (600 IU/d) Dietary calcium (493 ± 221 mg/d) also ~ 1/2 RDA of 1,000 mg/d Chewable format not tolerated by all Moore CE, Sherman V. Obes Surg. 2014; 12: 2055-60.

23. Bariatric Neurologic Complications with Nutrient Deficiency Neurologic ComplicationNutrient Deficiency EncephalopathyThiamin, B12 MyelopathyB 12 Optic NeuropathyThiamin, B12 NeuropathyThiamin, B12 (rare B6, folate, niacin) Myopathy (rare)Vitamin D Kushner RF & Still CD. Nutrition and Bariatric Surgery. 2015.

24. Bariatric B Vitamin Deficiencies B complex vitamins water soluble, not stored to a large extent Proximal small intestine primary site of B vitamin absorption Greater risk following RYGB for B vitamin deficiencies Neurological complications of vitamin B12, thiamin, and folate deficiencies Estimated16% bariatric surgery cases Vitamin B12 deficiencies RYGB (42.1%) vs SG (5%) Wernicke’s encephalopathy report due to thiamin deficiency reported female 3 weeks following SG Differences in folate deficiency following RYGB (20%) or SG (18.4%)

25. Effectiveness of B Vitamin Supplementation following Bariatric Surgery Secondary analysis of Vitamin D study SG or RYGB females BMI ≥ 40 or BMI ≥ 35 with high-risk comorbid conditions Multi-vitamin supplements containing thiamin, B12, and folate as chewable tablets (Celebrate ®) Supplements contained 2 to 146 times the Recommended Dietary Allowances (RDA) for B vitamins. Moore CE, Sherman V. Obes Surg. 2015 25: 694-9.

26. B Vitamin Study Design Height, weight, BMI, serum measured preoperatively and at 3 months Serum folate Serum B12 Blood thiamin diphosphate (TDP) 24-hour dietary recalls Participants encouraged to increase protein intake Some consumed bariatric protein shakes containing 0.35 to 125 times the RDA for B vitamins Moore CE, Sherman V. Obes Surg. 2015 25: 694-9.

27. B Vitamin Composition of Supplements 1 Fortified Protein Shake 2 NutrientRDAVitamin %RDAProtein %RDA SupplementShake _______________________________________________________ Thiamin (mg)1.1121090 0.7535 Folic Acid (ug)40080020014068 Vitamin B 12 (ug)2.435014,58330012,500 1 Chewable supplements total intake (2 tablets/d) (Celebrate ®) 2 Bariatric Surgical Beverage (BariCare®)

28. Changes of B Vitamins after 3 Months Variable nPre-Operativen3 months P ___________________________________________________________________________________________ Thiamin (nmol/mL) All2388 ± 25 1993 ± 320.570 SG 994 ± 30 996 ± 38 0.944 RYGB1083 ± 201091 ± 28 0.593 Vitamin B12 All21498 ± 15020736 ± 3400.005 SG10483 ± 126 9632 ± 2290.036 RYGB11511 ± 17511821 ± 4000.033 Folate (nmol/L) All2113.1 ± 5.42016.4 ± 6.00.049 SG1010.8 ± 5.0 914.7 ± 7.00.208 RYGB1115.3 ± 5.11117.7 ± 4.90.131 Moore CE, Sherman V. Obes Surg. 2015 25: 694-9

29. Dietary Intake of B Vitamins Variable nPre-Operativen3 months P ____________________________________________________________________________________________ Dietary Thiamin RDA(1.1 mg/d) All221.6 ± 0.8200.9 ± 0.50.001 % of RDA145%82% Dietary B12 (ug/d) RDA (2.4 ug/d) All224.0 ± 2.1203.5 ± 1.90.642 % of RDA166%146% Dietary Folate RDA (400 ug/d) ALL22509 ± 28120330 ± 2600.044 % RDA125%82% Supplementation: Thiamin 12 mg, Vitamin B12 350 ug, Folate 800 ug per day Moore CE, Sherman V. Obes Surg. 2015; 25: 694-9.

30. Vitamin B Supplementation Conclusions 12 mg/d thiamin (1090 % RDA) maintained or slightly increased blood thiamin 800 ug folate/d (200% RDA) raised serum folate Serum B12 increased 48% in 3 months Similar RYGB and SG responses Despite a 63 % reduction of food intake there was a 75% reduction in number of folate or thiamin deficient participants Moore CE, Sherman V. Obes Surg. 2015; 25: 694-9.

31. Standard RYGB and SG Supplementation SupplementDosage Multivitamin1-2 daily; RDA for all; 2/d post op; >3 switch/d Calcium citrate divided dosages1,200 – 1,500 mg/d Vitamin D3,000 IU titrated to ≥ 30 ng/mL Folic acid400 ug/d in multivitamin Elemental iron18-27 mg/d Vitamin B12350 – 500 ug/d orally/sublingual, nasal, or 1,000 ug/month intramuscularly American Association Clinical Endocrinologist, Obesity Society, American Society for Metabolic & Bariatric Surgery; Kushner RF & Still CD. Nutrition and Bariatric Surgery. 2015.

32. Pre and Post Biochemical Surveillance Post SG and RYGB BiochemPresurgery2 Months Post Post 6 Months Post Yearly Serum folate√√√√ Thiamin (B1)√√√√ B12√√√√ Vitamin D, 25(OH)D √√√√ Kushner RF & Still CD. Nutrition and Bariatric Surgery. 2015.

33. Future Directions: Nutrition Need to better define micronutrient recommendations Explore how to ensure patient compliance with dietary and supplementation recommendations How effective are other potential routes of vitamin administration? Daily topical application of vitamin D? – used for psoriasis Injections of B12, sublinguinal? Beckman L, Earthman C. 2013; JAND 113: 398-399.

34. Future Directions Does repletion of vitamin D before bariatric surgery have any impact on clinical outcomes? RCT to assess improving vitamin D status before surgery on postoperative clinical outcomes What is the optimal dosing regimens of vitamin and minerals for repletion after each type of bariatric surgery? Staging supplement dosages post surgery? Cole AJ et al. Nutr Clin Pract 2014; 29: 751-758.

35. Resources CDR Weight Management Certificate Academy of Nutrition and Dietetics 2015 2 nd Edition Pocket Guide to Bariatric Surgery Weight Management Practice Group 2015

36. Thank You