CALCIUM&Vit D FRIEND OR FOE?

CALCIUM&Vit D FRIEND OR FOE? Raheela Khawaja, M.D. Clinical Associate Professor of Medicine Division Of Endocrinology Department of Internal Medicine Ohio State University, Columbus OH

Is Calcium & Vit D a friend? 1. Agree 2. Disagree 50% 50% 1 2

Outline Questions Why Calcium &Vit& D is important? How much is enough? How can we take it? How do we make sure it is enough? Can too much calcium be causing cardiovascular events?

Total Body Calcium Bone (99%) 60% inorganic Calcium hydroxyapatite Ca 2+ Intracellular Ca 2+ Blood (8.6-10.4 mg/dl) <1% of calcium needed for vascular contraction and vasodilation, muscle muscle function, nerve nerve transmission, intracellular signaling and hormonal secretion Ionized Ca 2+ (4.4-5.6 mg/dl) Bound Ca 2+ Alb

Effect of Ca+Vit D Benefit of calcium and vitamin D supplementation in patients with osteoporosis comes largely from prospective, randomized, placebo- controlled trials showing beneficial effect on Bone Density WHI 36,282 postmenopausal women (Ages 50 to 69 years ) Calcium (1000 mg/day) plus vitamin D (400 international units/day) or placebo 7 yr follow-up Hip bone mineral density was 1.06 percent higher in the calcium-vitamin D group when compared to the placebo group. Risk of kidney stones was increased in WHI (HR1.17,CI1.02-1.34) 1.34) Daly RM, Brown M, Bass S, et al. Calcium- and vitamin D3-fortified milk reduces bone loss at clinically relevant skeletal sites in older men: a 2-year randomized controlled trial. J Bone Miner Res 2006; 21:397. Meier C, Woitge HW, Witte K, et al. Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. J Bone Miner Res 2004; 19:1221. Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006; 354:669. Zhu K, Bruce D, Austin N, et al. Randomized controlled trial of the effects of calcium with or without vitamin D on bone structure and bone-related chemistr in elderly women with vitamin D insufficiency. J Bone Miner Res 2008; 23:1343.

Risk of hip fracture: Vitamin D plus calcium versus placebo

Calcium turnover

Recommended Dietary Allowances (RDAs) for Calcium Age Male Female Pregnant Lactating 0 6 months* 200 mg 200 mg 7 12 months* 260 mg 260 mg 1 3 years 700 mg 700 mg 4 8 years 1,000 mg 1,000 mg 9 13 years 1,300 mg 1,300 mg 14 18 years 1,300 mg 1,300 mg 1,300 mg 1,300 mg 19 50 years 1,000 mg 1,000 mg 1,000 mg 1,000 mg 51 70 years 1,000 mg 1,200 mg 71+ years 1,200 mg 1,200 mg 1. Committee to Review Dietary Reference Intakes for Vitamin D and Calcium, Food and Nutrition Board, Institute of Medicine. 2. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.

Which food has the most calcium? 1. 8 Oz glass of 2% milk 2. 8 Oz glass of skim milk 3. 8 Oz glass of soya milk 4. 8 oz cup of Yogurt 5. 1.5 Oz Cheddar cheese 23% 27% 17% 20% 13% 1 2 3 4 5

Food Selected Food Sources of Calcium Milligrams (mg) per serving Percent DV* Yogurt, plain, low fat, 8 ounces 415 42 Orange juice, calcium-fortified, 6 ounces 378 38 Mozzarella, part skim, 1.5 ounces 333 33 Sardines, canned in oil, with bones, 3 ounces 324 32 Cheddar cheese, 1.5 ounces 306 31 Yogurt, fruit, low fat, 8 ounces 313-384 31-38 Milk, nonfat, 8 ounces 296 30 Milk, reduced-fat (2% milk fat), 8 ounces 296 30 Milk, buttermilk, 8 ounces 280 28 Milk, whole (3.25% milk fat), 8 ounces 272 27

Selected Food Sources of Calcium Soy beverage, calcium-fortified, 8 ounces 80 500 8 50 Ice cream, vanilla, ½ cup 84 8 Chinese cabbage, raw, 1 cup 74 7 Tortilla, corn, ready-to-bake/fry, 1 medium 46 5 Tortilla, flour, ready-to-bake/fry, one 6" diameter 39 4 Sour cream, reduced fat, cultured, 2 tablespoons 32 3 Bread, white, 1 ounce 31 3 Broccoli, raw, ½ cup 21 2 Bread, whole-wheat, 1 slice 30 3 Cheese, cream, regular, 1 tablespoon 14 1

FORMULA (OSGD) Supplement Facts Sources of Calcium

Compare Elemental Calcium Data from: Lexi-Comp databased, Accessed 1/4/2010 Calcium Salt Calcium Acetate Calcium Bicarbonate Calcium Chloride Calcium Citrate Calcium Glubionate Calcium Gluconate Calcium Lactate Calcium Po4 Elemental Ca (mg /gm) 250 400 270 211 64 90 130 390

Tolerable Upper Intake Levels (ULs) for Calcium Age Male Female Pregnant Lactating 0 6 months 1,000 mg 1,000 mg 7 12 months 1,500 mg 1,500 mg 1 8 years 2,500 mg 2,500 mg 9 18 years 3,000 mg 3,000 mg 3,000 mg 3,000 mg 19 50 years 2,500 mg 2,500 mg 2,500 mg 2,500 mg 51+ years 2,000 mg 2,000 mg

Calcium homeostasis - PTH action PTH 25OH VIT D Increased 1-alpha hydroxylase Decreased Po4/Hco3 absorption Increased Ca reabsorption 1:25OH vit D Increased Ca Absorption Increased Ca Turnover with Net Resorption Plasma/ICF Ca++

Who has the most Vit D deficiency? 1. Hispanics 2. African American adolescent 3. Caucasians girls/females 4. Healthy students 5. Physicians 6. Pregnant girls 30% 20% 13% 13% 13% 10% 1 2 3 4 5 6

Vitamin D: The Sunshine Vitamin Body can make it if exposed to enough sunlight Made from cholesterol in the skin

Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health nmol/l = 0.4 ng/ml nmol/l ng/ml Health status <30 <12 Associated with vitamin D deficiency, leading to rickets in infants and children and osteomalacia in adults 30 50 50 12 20 20 20 Generally considered inadequate for bone and overall health in healthy individuals Generally considered adequate for bone and overall health in healthy individuals >125 >50 Emerging evidence links potential adverse effects to such high levels, particularly >150 nmol/l (>60 ng/ml) Vit D Deficiency <20ng/ml VitD insufficiency 21-29ng/ml

FOOD SOURCES OF VIT D Food IU per serving Percent DV Cod liver oil, 1 tablespoon 1,360 340 Salmon (sockeye), cooked, 3 ounces 447 112 Mackerel, cooked, 3 ounces 388 97 Tuna fish, canned in water, drained, 3 ounces 154 39 Orange juice fortified with vitamin D, 1 cup (check product labels, as amount of added vitamin D varies) 137 34 Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 1 cup 115 124 29 31 Yogurt, fortified with 20% of the DV for vitamin D, 6 ounces 88 22 Margarine, fortified, 1 tablespoon 60 15 Liver, beef, cooked, 3.5 ounces 49 12 Sardines, canned in oil, drained, 2 sardines 46 12 Egg, 1 large (vitamin D is found in yolk) 41 10 Ready-to-eat cereal, fortified with 10% of the DV for vitamin D, 0.75 1 cup 40 10 Cheese, Swiss, 1 ounce 6 2 U.S. Department of Agriculture, Agricultural Research Service. 2010. USDA National Nutrient Database for Standard Reference, Release 23.

Recommended Dietary Allowances (RDAs) for Vitamin D (IU) ge (yrs) ale Female Pregnancy Lactation m Endocrine Practice and IOM guidelines July 2011 96(7):1911-1930

Tolerable Upper Intake Levels (ULs) for Vitamin D Age Male Female Pregnancy Lactation 0 6 months 7 12 months 1 3 years 4 8 years 9 years 1,000 IU 1,000 IU 1,500 IU 1,500 IU 2,500 IU 2,500 IU 3,000 IU 3,000 IU 4,000 IU 4,000 IU 4,000 IU 4,000 IU 1. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.

FDA-Health Claim In 1993, the U.S. Food and Drug Administration authorized a health claim related to calcium and osteoporosis for foods and supplements. In January 2010, this health claim was expanded to include vitamin D. Model health claims include the following: "Adequate calcium throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis" and "Adequate calcium and vitamin D as part of a healthful diet, along with physical activity, may reduce the risk of osteoporosis in later life" U.S. Food and Drug Administration. Food labeling: health claims; calcium and osteoporosis, and calcium, vitamin D, and osteoporosis

Calcium and CVS In the Iowa Women's Health Study, higher calcium intake was associated with reduced ischemic heart disease mortality in postmenopausal women Results from other prospective studies have shown no significant associations between calcium intake and cardiac events or cardiovascular mortality Data for stroke are mixed, with some studies linking higher calcium cium intakes with lower risk of stroke, while others have found no associations or trends in the opposite direction 1. Relation of calcium, vitamin D, and dairy food intake to ischemic heart disease mortality among postmenopausal women. Am J Epidemiol. 1999 Jan 15;149(2):151-61. 2. Chung M, Balk EM, Systematic Review of Health Outcomes. Evidence ReportAssessment No. 183. (Prepared by Tufts Evidence-August 2009.

Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010 Jul 29;341:c3691 Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR. 11 studies involving 11,921women found that women taking calcium supplements (about 1,000 mg/day in most of the studies) had a 27% increased risk of myocardial infarction 5 trials involving 8151pt 31%(lab data was available) Calcium and heart attacks. Doesn't apply to most calcium prescriptions. BMJ. 2010 Sep 15;341:c5003. Calcium and heart attacks.making too much of a weak case. BMJ. 2010 Sep 15;341:c4997. Calcium and heart attacks. No evidence for increased risk. BMJ. 2010 Sep 15;341:c4995. Calcium and heart attacks. The heart of the matter. BMJ. 2010Sep 15;341:c4993

What about Ca+D? The Women's Health Initiative (WHI) study -- a seven-year trial of over 36,000 women - - found no cardiovascular effect of taking combined calcium and vitamin D supplements, but the majority of participants were already taking personal calcium supplements, which may have obscured any adverse effects

Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women s Health Initiative limited access dataset and meta-analysis BMJ 16,718 women who were not taking personal calcium supplements at the start of the trial and found that those allocated to combined calcium and vitamin D supplements were at an increased risk of cardiovascular events, especially heart attack. By contrast, in women who were taking personal calcium supplements at the start of the trial, combined calcium and vitamin D supplements did not alter their cardiovascular risk.

. Cumulative incidence of myocardial infarction, stroke, composite of myocardial infarction, stroke, or sudden death, and death by treatment allocation in five studies that contributed patient level data

Calcium & Vit D is a friend? 1. Agree 2. Disagree 60% 40% 1 2

Case 65 years old female moves to the area and establishes her care with you.she does have complain of generalized fatigue, excessive flatulence and not feeling well which is more pronounced for the last few months. She is postmenopausal since age 48. She has been on Fosamax,calcium 600 mg twice a day with Vit D 1000 iu once a day for the last 5 years. Her family history is significant for diabetes.hashimoto s s hypothyroidism and coronary artery disease.

O/E She is thin built.weight 110 lbs, Ht 5 feet 2 inch. Rest of the exam was normal. Routine labs showed Hg 8 (11.7-15.5 15.5 g/dl)microcytic microchromic anemia Glucose 80 mg/dl Calcium 8.4(8.5 (8.5-10mg/dl) with albumin 3.8 Vit D 15 (30-88 ng/ml) Intact PTH 95(14 (14-72 pg/ml) TSH 2.0 (.35-5.5 5.5 µiu/ml) 24 hr urine calcium 84 mg/24 hr

Diagnosis? 1. Hypothyroidism 2. Secondary hyperparathyroidism 3. Primary hyperparathyroidism 4. Osteoporosis 5. All of the above 17% 20% 23% 27% 13% 1 2 3 4 5

Treatment Vit D 3 (Cholecalciferol( Cholecalciferol) 400,800,1000,2000,5000,10,000,50,000 (For 100 units 0.7-1.0ng/ml) Vit D2(ergocalciferol)400,50,000 or liquid 8000/ml Calcidiol Calcitriol Dihydrotachysterol(DHT)

Summary The federal government's 2010 Dietary Guidelines for Americans notes that "nutrients should come primarily from foods. Foods in nutrient-dense, mostly intact forms contain not only the essential vitamins and minerals that are often contained in nutrient supplements, but also dietary fiber and other naturally occurring substances that may have positive health effects....dietary supplements...may be advantageous in specific situations to increase intake of a specific vitamin or mineral."

11/30/2010