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2 Advanced Nutrition Mineral Nutrition Calcium in Health and Disease Prevention MargiAnne Isaia, MD MPH Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health No clear disorder of intra-cellular Calcium regulation Cell injury, damage, serious dysfunction – always associated with a rise in cytosolic Ca concentration – cell death Low Ca intake, high Ca losses from the body – osteoporosis During growth: - high demands of skeletal mineralization - extremely low-Ca diets lead to hypocalcemia - this is followed by hyper secretion of PTH with low serum P (undermineralization of the newly deposited bone matrix and osteoblast dysfunction = rickets) Nutritional hypo Ca – in Mg deficiency: severe alcoholism, intestinal fistula, malabsorption Both, PTH release from PT glands and bony response to PTH are dependent on Mg; both are defective in Mg deficiency Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Osteoporosis = the most common disorder of Ca metabolism involves regulation of ECF [Ca 2+] Characteristics: loss of bone mass (decreased bone mass/unit volume) micro architectural deterioration of bone tissue increased risk of fracture Causes for osteoporosis: - reduced Estrogen levels after menopause - dietary Ca deficiency - physical inactivity - excessive alcohol use - underweight - hereditary factors ( white women > risk than black women) - secondary to pathologic conditions: hyperthyroidism, hyperPTH, premature menopause (before age 42), hypogonadism in men (testosterone deficiency), chronic lung disease, Cushing’s disease, long term use of CS drugs or Heparine Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Osteoporosis Diagnostic Standards WHO Consensus Conference Bone Mineral Density BMD Normal < 1 SD below reference Osteopenia 1 – 2.5 SD below reference Osteoporosis > 2.5 SD below reference Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Bone architecture Revision of bony material Bone mass in adults is maintained locally by the balance between osteoclastic bone formation and osteoblastic bone formation Bone resorption and formation are “coupled” locally: when one goes up or down the other usually follows Resorption is much faster than formation: it takes at least 3 months to rebuild bone resorbed in 2-3 weeks Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Hormones and Bone Health Calcium regulating hormones: Parathyroid hormone PTH Calcitriol ( 1,25 dihydroxy Vitamin D3) Calcitonin- blocks bone resorption Sex hormones: Estrogen- acts on osteoclasts to inhibit bone resoption -acts on osteoblasts to stimulate bone formation Testosterone – stimulates bone formation and muscle growth Other systemic hormones Growth Hormone – regulator of skeletal growth stimulates production of IGF-1 Thyroid hormone – increases energy production of all cell Cortisol – large amount blocks bone growth (CS therapy) Insulin & Leptin – anabolic effect Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Humoral factors acting on bone cells Osteoblasts: Osteoclasts: PTH 1,25 dihydroxy Vitamin D Glucocorticoids Insulin-like Growth Factor (IGFs) Transforming Growth Factor b (TGF-b) Parathyroid hormone-related peptide (PTHrP) Osteoprotegerin (OPG) or Osteoclastogenesis inhibitory factor (OCIF) Calcitonin Bisphosphonate drugs Interleukin -1 Colony-stimulating factor-1 (CSF-1) Transforming Growth Factor a (TGF-a) Transforming Growth Factor b (TGF-b) Gallium nitrate Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Effect of age on hormonal influences PTH levels hwith age Growth Hormone and IGFs iwith age Vitamin D ioutdoor activity isynthesis by skin icalcitriol synthesis (kidney) iintestinal response Sex hormones iwith age Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Forms of Osteoporosis Type I - post-menopausal, loss of trabecular bone, women Type II – senile, loss of trabecular and compact bone, men and women Postulated mechanisms: Type I iEstrogen iBone formation & hbone resorption ibone volume hserum Calcium iPTH (2nd hypoPTH) & hurinary Ca i1, 25 dihydroxy Vitamin D iCa absorption Type II i1,25 dihydroxy Vitamin D iCa absorption & ibone formation (local gut conditions) iserum Calcium hPTH (2nd hyper PTH) hbone resorption ibone volume Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Osteoporosis – Diagnostic Patient history and physical examination Bone density scan (DEXA) Blood or urine tests Routine X-rays do not detect osteoporosis until 25% or more bone mass has been lost Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Physical Examination Tests for detection of Occult Vertebral Fractures: A. Wall-Occiput Test for Occult Thoracic Vertebral Fractures (+): being unable to touch the wall with the occiput when standing with the back and heels against the wall and the head positioned such as an imaginary line from the lateral corner of the eye to the superior junction of the auricle is parallel to the floor B. Rib-Pelvis Distance Test for Occult Lumbar Vertebral Fractures (+): the distance of less or equal to two finger breadths between the inferior margins of the ribs and the superior surface of the pelvis in the mid-axillary line Mineral Nutrition Calcium in Health and Disease Prevention NUTRITION HORMONES EXERCISE BONE MASS BONE ARCHITECTURE LIFESTYLE FACTORS FLEXIBILITY BONE STRENGTH Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Nutritional Determinants of Bone The bone mineral: hydroxyapatite Ca 10 (PO4)6 (OH)2 Ca, Phosphate, Magnesium, other minerals Boron intake - decreases urinary excretion of Ca, P, Mg - increases serum Estradiol It is postulated that Boron is necessary for formation of certain steroid hormones or hydroxylation of 25(OH) D Strontium - proposed as an agent for improving BMD (studies in Europe in postmenopausal women) Manganese, Zinc and Cooper – cofactors for enzymes essential to bone tissues Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health * * Nutritional Determinants of Bone Protein – sufficient in the diet to form adequate bone collagen matrix Increased protein in the diet – increased absorption of Ca - increased urinary Ca loss The overall acid-base balance of the diet will influence the impact of dietary protein on bone: a high intake of alkaline foods (fruits & vegetables) -may mitigate the calciuric effect of protein -may promote a net positive impact of Phosphorus on the skeleton Vitamin D Vitamin K serves as co-enzyme in the g-carboxylation of glutamic acids residues on protein 3 vitamin K dependent proteins in the bone: Osteocalcin - synthesized by osteocytes and binds to free Ca and to hydroxyapatite (70% of Osteocalcin is incorporated in bone matrix; 30% is found in the blood- its level is indicator for new bone formation Matrix gla protein Protein S CALCIUM CONTENT OF SELECTED VEGAN FOODS Food Amount Calcium (mg) Blackstrap molasses Collard greens, cooked Tofu, processed with calcium sulfate Calcium-fortified orange juice Soy or rice-milk, commercial, calcium-fortified, plain Commercial soy yogurt, plain Turnip greens, cooked Tofu, processed with nigari Tempeh Kale, cooked Soybeans, cooked Okra, cooked Bok choy, cooked Mustard greens, cooked Tahini Broccoli, cooked Almonds Almond butter Soy milk, commercial, plain 2 Tbsp 1 cup 4 ounces 8 ounces 400 357 200-330 300 8 ounces 6 ounces 1 cup 4 ounces 1 cup 1 cup 1 cup 1 cup 1 cup 1 cup 2 Tbsp 1 cup 1/4 cup 2 Tbsp 8 ounces 200-300 80-250 249 80-230 215 179 175 172 158 152 128 94 89 86 80 Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Prevention of Osteoporosis Healthy diet: Adequate intake of bone supporting nutrients: Ca, vitamin D, protein and vitamin K DRI 50-70 y 1200 mg Ca and 10 mcg (400 IU) > 70 y 1200 mg Ca and 15 mcg (600 IU) Vitamin D 1 mcg = 40 IU Avoid excess intake of P, vitamin D, protein, Sodium Avoid caffeine and alcohol Lifestyle Avoid smoking Reduce risk of falling Increase weight-bearing activity – 20 minutes 7x/week (stabilization of bone mass) for post menopausal women Increase muscle-strengthening exercises – 30-40 minutes 7x/week (help stabilize bone density) for post menopausal women Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Prevention of Osteoporosis Particularly important to consume adequate Ca and Vitamin D throughout infancy, childhood, adolescence Kid’s bones: A study of girls showed that average Calcium intake 500-1500 mg/d from 12-18 years of age was not associated with hip bone density at age 20, or with total bone mineral gain during the teen years. However, achievable levels of exercise and fitness have a favorable effect on bone. In the adult life: Engage in weight-bearing exercise to maximize bone strength and bone density to help prevent osteoporosis later in life Weight-bearing exercises – bones and muscles work against gravity while they bear your weight : walking, running, aerobics, skating Non-weight bearing exercises: swimming, bicycling, water aerobics Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health Prevention of Osteoporosis WHO Recommendation: Ca 500-600 mg/d “ The accumulated data indicate the possibility that the adverse effect of protein, in particular animal protein, might outweigh the positive effect of Calcium intake on Calcium balance. Instead, increase physical activity, reduce Na intake and animal protein intake and increase the consumption of fruit and vegetables”. Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Bone Health - - Osteoporosis-medications Estrogen – directly influence bone turnover enhances Ca absorption through its trophic effect on 1,25,(OH)2D When administered to post menopausal women, E lowers the bone remodeling rate and retards bone loss Risk: MI, stroke, Breast Cancer, Pulmonary Emboli, DVT FDA: hormone therapy to be used in the lowest possible dose, for the shortest duration - given with Progestin, if no hysterectomy If for the treatment of Osteoporosis alone, non-Estrogen treatment considered first Bisphosphonates ( Alendronate, Risendronate) structural analogues of pyrophosphate Inhibition of hydroxyapatite formation & bone resorption inhibition Special requirements for administration Side effects: upper GI symptoms Calcitonin- primary function to inhibit bone resorption Women with osteoporosis have an attenuated Calcium response to a Ca challenge Raloxifene – Selective Estrogen Receptor Modulator FDA approved for prevention and treatment of osteoporosis side effects: risk of DVT, accentuated hot flashes Parathyroid hormone (1-34) or Teriparatide not approved for use > 2 y Mineral Nutrition Calcium in Health and Disease Prevention Calcium and Prostate Cancer High Calcium intake appears to be down-regulating the production of active forms of Vitamin D Vitamin D is protective of the prostate High Calcium 2000 mg/day and/or dairy intake > 2.5 servings may be associated with the development of Prostate Cancer Calcium from cow’s milk and Prostate Cancer Insulin-like Growth Factor 1 (IGF-1) may potentiate cancer growth IGF-1 in milk help the baby grow; after growing process is ready, IGF-1 negative effect Milk drinking increases the human IGF-1 secretion IGF-1 and Prostate Cancer study: Cancer patients IGF-1 – 269.4 ng/ml , healthy controls – 248.9 ng/ml Relationship between Ca intake –dairy intake and PC risk remains unclear. Recommendation for men >19y Ca 1000- 1200 mg/d - intake below the upper tolerable limit (2500 mg/d) Mineral Nutrition Calcium in Health and Disease Prevention Cow’s milk intake and Type I Diabetes 1 or more dairy proteins from cow’s milk spark an auto-immune reaction with damage on pancreatic b-cells reason why American Academy of Pediatrics warns against early introduction of cow’s milk Auto-immune diseases: T1DM, Multiple Sclerosis, Rheumatoid Arthritis, and Celiac Disease correlated with intake of cow’s milk proteins Casein-milk protein – addictive (Food addiction) Cow’s Milk Allergy (CMA) 1.2%-17% Recurrent Otitis Media – more common and more severe in children with CMA Asthma, allergic rhinitis, dermatitis 3-4 x greater incidence in the children who had CMA in infancy compared with control group Cow’s milk intake and Childhood Obesity Dairy consumption and weight gain in children???? Cow’s milk and Ovarian Cancer Galactose can affect ovaries, increased IGF-1 (cancer assessed over 10 y) Mineral Nutrition Calcium in Health and Disease Prevention Calcium and High Blood Pressure Observational and experimental studies indicate that individuals who eat a vegetarian diet high in minerals (including Ca, Mg, K) and fiber, low in fat, tend to have reduced blood pressure. Clinical trials showed that increased Ca intake lowers BP and the risk of hypertension DASH – a study which tested the combined effect of nutrients, including Calcium from food on blood pressure DASH = Dietary Approaches to Stop Hypertension a multicenter research trial effect of three different diets on BP: - control, “typical American” diet - high fruits and vegetables diet - DASH diet: high fruits and vegetables, low fat (dairy) Of the three diets tested, the greatest decrease in BP with DASH diet DASH-Sodium study : DASH diet without Sodium restriction same effect on BP as severe Na restriction on the control diet ( Na: 1500 mg /day) Mineral Nutrition Calcium in Health and Disease Prevention Calcium deficiency if: - inadequate Calcium intake - decreased Calcium absorption - increased urinary Calcium loss Calcium supplementation: - post-menopausal women - amenorrheic women and Female Athlete Triad - Lactose intolerant individuals - poorly planned Vegan diet Mineral Nutrition Calcium in Health and Disease Prevention Calcium Supplementation If Calcium supplements required, bioavailability of Ca citrate > Ca carbonate Ca bioavailability determined using: serum Ca, urinary Ca, serum PTH Ca citrate – role in protecting against bone loss because of a greater PTH suppression (PTH suppression is critical in maintaining bone) PTH responsible for age-related bone loss hPTH g hleaching Ca from bones References: 5 ICVN, Loma Linda USA, 2008 Modern Nutrition in Health and Disease, Shils, 10th edition www.pcrm.org www. 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