Slide ______1 ______A NEW LOOK AT B12 ______AND VITAM IN D ______Sandra M. Nettina, MSN, ANP, BC ______NP, Columbia Medical Practice ______President , NPAM Adjunct Clinical Faculty, JHU SON ______

Slide ______2 What do we know about vitamin B 12? ______

• Cobalamin is the largest and most complex of ______the B . ______• It is required for synsethis of DNA in RBCs, myelin, and other tissues. ______• Deficiency can result in hematologic, ______neurologic, and GI manifestations. • Deficiency occurs in 5-20% of the elderly, is ______often subclinical (Andres et al, 2004, CMAJ).

Slide ______Case St u d y 3 ______• Mary is a 54 yo WF wit h declining ment al and ______neurologic status over several months: dizzy, tremor, weak, anorexia, sore tongue, delirium ______• Hx of cocaine abuse/ narcotic dependence, ______chronic back pain, radiation treatment for rectal cancer, bipolar disorder ______• Medications included lithium 300mg bid, oxycodone LA 30mg tid, oxycodone/ acet. ______10/ 325 tid, Zoloft 50mg qd

Slide ______4 Case St u d y ______• Mrs. Smith is a 72 yo AA widowwho you see ______for the first time for /refill of lisinopril/ HCTZ 10/12.5mg ______• She also has arthritis but is otherwise healthy, ______takes caclium/ vit D and tylenol 650mg bid • She asks if you can give her vitamin B 12 shots ______like her previous physician (who retired) • She had been diagnosed with B12 deficiency ______due t o decreasing energy several years ago

Slide ______Co m p l e x Ab so r p t i o n 5 ______• Derived from animal products (meat, dairy) • B12/ animal protein bonds are severed in ______st omach by gast ri c secret i ons • B12 combines with R proteins from salivary and ______gast ric secret ions ______• Intrinsic factor is secreted by the fundus but binding is weak in the stomach ______• B12/ R protein complexes and intrinsic factor travel to duodenum ______• There are also B12/ R complexes secret ed in the bile

Slide ______6 Absorption (cont.) ______

• All B12/ R prot ein complexes are degraded by ______pancreatic enzymes ______• B12 is free to bind with intrinsic factor (IF) • B12/ IF travel t o dist al ileum ______• B12 attaches to mucosal cells and binds to ______transport proteins transcobalamin I, II, II ______

Slide ______7 Causes of Deficiency ______

• Decreased intake: ______– malnutrition ______– alcohol abuse – institutionalism ______– strict vegan diet • Lack of unbinding from animal sources (food ______malabsorption) due to problems with saliva, ______gast ric or biliary secret ions • in t he ileum

Slide ______Causes of Malabsorption 8 Pathophysiology Disorder ______Lack of int rinsic Pernicious anemia (autoimmune gastric ______factor atrophy) Total and partial gastrectomy ______Lack of R protein Atrophic gastritis of aging and ETOH abuse (food bound) Chronic H. pylori infection ______Long-term use of metformin Long-term use of H2 blockers and PPIs ______Pancr eat i c Chronic pancreatitis, pancreatectomy enzyme relat ed Long-term use of cholestyramine, cohchicine ______Damage to the Crohn’s disease, lymphoma, TB, celiac disease ileum Resection of last 80cm of small intestine Genet i c Transcobalamin (transport protein) deficiency def iciency

Slide ______9 Manifestations of B12 Deficiency ______

• Megaloblastic anemia: listlessness, fatigue, ______dyspnea, pallor (develop slowly) ______– MCV 110mm3 or great er • Neurologic: confusion, paresthesias of LE, ______dysequilibrium, loss of position and vibration ______• GI: smooth, sore, red tongue; mild diarrhea ______• May was and wane for years with partial remission when B12 is replaced

Slide ______10 Diagnosis ______

• CBC: decreased RBC, hct, hgb; elevated MCV ______Check B12, folic acid and RBC ______If normal, check methymalonic acid Incr eased MM A indicat es decreased t i ssue B12 ______Homocysteine may also be increased in B12 or ______folate or B6 deficiency ______

Slide ______11 Ot her Test s ______

• Instrinsic factor blocking antibody test ______– Only 50% sensitive ______• Antigastrin parietal cell antibody test – Only 50% specific ______• Schilling test usually not necessary ______– Combination of decreased , megablastic anemia, and instrinsic factor blocking ______ant ibodies is diagnost ic for pernicious anemia

Slide ______12 Back to Mary and Mrs. Smith ______

• Mary (neurologic decline and sore tongue) ______– B12, CBC, MMA, homocysteine normal, folic acid ______slightly decreased – Tx with MVI and folic acid, referred to neurologist ______and psychiatric inpatient – unresolved ______• Mrs. Smith (getting B12 shots for energy) ______– Normal B12, reviewed history for causes, try oral supplement, is maintaining serum B 12

Slide ______13 Su m m a r y ______

• Screening: about $100 for serum B12 level ______– Elderly ______– Malnourished – Institutionalized ______– Hx gastric or small intestinal surgery ______– Unexplained neuro manifestations – Long term use of metformin, PPIs ______

Slide ______Su m m ar y ( c o n t . ) 14 ______• Prevention: balanced diet containing animal products or food fortified with B12 ______– Need 2.4 mcg / day (cereal 4 x week) ______• Supplementation—consider with older adults – Parenteral administration is a myth ______– Even in pernicious anemia there is 1% passive ______diffusion so high dose 1000mcg suppl is effective – Nasal gel (Nascobal) is an option ______– Oral suppl of 1000mcg/ day x 1 month, then 125 to 500mg daily for most people

Slide ______15 Vit amin D ______• Vitamin D2 ergocalciferol—plants ______• Vitamin D3 —synthesized by humans in the skin when exposed t o UVB ______• Function—maintain levels of and ______phosphorous, other roles need more study – Regulates gene expression for numerous cell ______functions • Normal serum level 32ng/ml ______• Linus Pauling Institute at Oregon State U – http:/ / lpi.oregonstate.edu

Slide ______16 Def iciency ______

• Risk factors: elderly, obese, exclusively breast- ______fed infants, limited sun exposure, fat malabsorption, cystic fibrosis, inflammatory ______bowel disease ______• Manifestations ______– if deficient in childhood – Osteomalacia if deficient in adulthood ______• Muscle and bone weakness, bone pain

Slide ______17 Resear ch ______• Decreased risk of colon cancer (Terry et al, 2002, Nutr Cancer; Martinez et al, 1996, J Nat ______Can c er I n st ) ______• Slight decreased risk of breast cancer (John, et al, 1999, Cancer Epidemiology) ______• Decreased risk of falls by 50% (Bishoff et al, ______2003, J Bone Miner Res) • DM improvement, HTN prevention, ______depression, role in immunity

Slide ______18 Su p p l e m e n t ? ______• 100 IU per glass of milk, 200 IU can of tuna, ______400 IU salmon 4 oz • Hankinson and Willett (Nurses Health Study) ______recommend 1000 -1500 units a day, especially ______during winter, northern climate • Linus Pauling Institute recommends 2000 IU ______daily, aim for serum level of 32 ng/ ml • Hypervitaminosis D rare—50,000 IU/ day ______– Manifestations of excess calcium

Slide ______19 Popular Protocol ______• 50,000 per week x 3 month, recheck ______• Repeat or change to 1000-2000 per day as maintenance, then check yearly ______• Consider cost: about $100 per serum level ______

• Email me with any quest ions: ______– [email protected] ______Thank you!