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  1. MICRONUTRIENTS Past, Present, Future

  2. Disclosure Statement Zubin Austin, BScPhm, MBA, MISc, MEd, PhD received an honorarium from Pfizer Consumer Healthcare, a division of Pfizer Canada Inc., to help develop and present this Continuing Education program.

  3. Micronutrients: Past, Present, FutureObjectives • To illustrate the evolution from classic nutritional deficiency diseases to the concept of optimum nutrition • To review nutritional biochemistry in relation to optimum nutrition • To examine specific nutrients and their roles in optimum nutrition • To address the controversies and the conflicting data associated with micronutrient nutrition

  4. The Past

  5. Classic Deficiency Diseases

  6. Classic Deficiency Diseases Scurvy Goitre Rickets

  7. The Present

  8. Ames’ Triage Theory: Cellular Level Energy Production: Short Term Survival DNA Repair Mechanism: Long Term Health ®Prometheus 2004. Energy production is critical to survival. The diagram on the left shows the biochemical pathway for energy production (ATP). The human body will always favour short-term survival over long term health (shown in the diagram on the right). If micronutrients are in short supply, then long term health suffers because unrepaired DNA leads to diseases like cancer or premature cell death.

  9. Selected Nutrients and Their Roles • Calcium • Vitamin D • Folic Acid • Vitamin E • Vitamin B12 • Omega-3 Fatty Acids • Phytosterols

  10. Calcium

  11. Calcium and Its Functions • Only about 1% of the body’s calcium is found outside the bones and teeth • Calcium’s functions are critical to good health

  12. Calcium and Bone Health • Osteoporosis prevention and treatment • 30 to 40 mmol (1200 to 1600 mg) of calcium daily • Sufficient vitamin D to maintain serum 25-hydroxy vitamin D levels above 80 nmol/L, or about 25 μg (1000 IU) vitamin D daily Heaney, Weaver, 2003

  13. Potential Benefits of CalciumUnder Investigation

  14. Calcium: Recommended Dietary Allowance • Calcium requirements among Canadians increase during adolescence and decrease after the age of 19 • Mean calcium intake was below the RDA in all women, especially in women over the age of 50 • Calcium intake was slightly higher only in younger men (18-34 years); in men 35 to 49 years, intake was below the RDA Dolega-Cieszkowki JH, et al. Appl Physiol Nutr Metab 2006; 31:753-8

  15. Meeting Calcium Needs with Food This food provides just over 1,200 mg of calcium and almost 1,000 kcals 1 ½ cups spinach salad Two 8 oz. glasses of milk 1 cup broccoli 6 oz. yogurt 1 cup red kidney beans 1 oz. cheddar cheese 1/4 cup almonds

  16. Calcium, Magnesium and Vitamin DA Cooperative Relationship • Magnesium affects the metabolism of calcium and vitamin D. • Vitamin D improves the absorption of calcium. • Calcium promotes muscle contraction, and magnesium helps muscles relax. • Magnesium holds calcium in tooth enamel thereby promoting resistance to tooth decay. Sizer, Whitney, Piché. Nutrition: Concepts and Controversies. First Canadian Ed. Nelson Education Ltd: Toronto, 2009.

  17. Vitamin D

  18. Some Conditions Associated with Vitamin D Deficiency • Rickets • Osteomalacia • Accelerated osteoporosis

  19. Functions/Potential Benefits of Vitamin D at Recommended Levels Helps • prevent and cure rickets in children • the body use calcium and phosphorus properly • maintain healthy bones Necessary for • strong bones and normal growth in children • calcium absorption

  20. Cancer Colorectal Breast Prostate Cardiovascular disease Hypertension Atherosclerosis Autoimmune diseases Multiple Sclerosis Diabetes (Type 1 and 2) Other (IBS, Rheumatoid Arthritis, Lupus) Microbial Infections Tuberculosis Vitamin D Potential Benefits Beyond Bone Health Grant WB, Holick MF. Altern Med Rev 2005; 10:94-111.

  21. Vitamin D: Potential Benefits Beyond Bone Health Canadian Studies of Vitamin D Status • Vieth et al. Eur J Clin Nutr 2001; 55:1091-7. (young women, Toronto) • Rucker et al. CMAJ 2002; 166:1517-24. (adults, Calgary) • Ward. CMAJ 2005; 172:769-70. (Canadian children with rickets) • Roth et al. Can J Public Health 2005; 96:443-9. (children, Edmonton) • Weiler et al. Bone 2008; 42:498-504. (Canadian Aboriginal women) • Mark et al. Clin Chem 2008; 54:1283-9. (Quebec youth)

  22. Vitamin DChanging Recommendations • New Osteoporosis Canada Vitamin D Guidelines (2010) for adults without osteoporosis or conditions affecting Vitamin D absorption: • Adults under 50: 400-1000 IU per day • Adults 50 and over: 800-2000 IU per day • A daily supplement of 800 IU should be regarded as a minimum dose for all adults with osteoporosis, regardless of age, and doses up to 2000 IU are often recommended Hanley DA, Cranney A, Jones G, Whiting SJ, Leslie WD, for the Guidelines Committee of the Scientific Advisory Council of Osteoporosis Canada. Vitamin D in adult health and disease: a review and guideline statement from Osteoporosis Canada (summary). CMAJ 2010; 182(12):1315-1319.

  23. Food Sources of Vitamin D • One serving of salmon plus one serving of milk = 6.8 μg of vitamin D • Two servings of milk provides = 5 μg (200 IU) of vitamin D • Children and Adults DRI 9 to 70 years = 15 μg daily (600 IU) • Osteoporosis Canada recommends 20 – 50 μg or 800 – 2000 IU of vitamin D for adults 50 years and over • If the DRI recommended intakes are revised upward, it will be difficult to meet vitamin D requirements through diet alone • 1 μg = 40 IU Vitamin D

  24. Folic Acid

  25. Conditions Associated withFolic Acid Deficiencies • Impaired cell division and protein synthesis, which affects rapidly growing tissues • Anemia  • Gastrointestinal upset (heartburn, diarrhea, constipation)   • Depression, mental confusion, fatigue, irritability, headache

  26. Folic AcidFunctions/Potential Benefits at Recommended Levels • Necessary for • several enzymatic reactions • red blood cell formation and the maturation of red and white blood cells • normal growth and development • Required for amino acid metabolism and the formation of nucleic acids that form DNA • Helps maintain normal function of the intestinal tract (maintenance of epithelial cell integrity) • Adequate amounts of folic acid can help reduce the risk of birth defects of the brain and spine

  27. Potential Benefits Under Investigation • It has been theorized that folic acid may be important in reducing the risk of cancer development from pre-cancerous lesions in the colon, and possibly at other sites. • Along with vitamins B6 and B12, supplemental folic acid may help those with inadequate intake to prevent a rise in blood levels of homocysteine (believed to be a risk factor for heart disease). • Folic acid may counterbalance the effect of alcohol on breast cancer risk.

  28. DNA Synthesis The right side of the diagram shows the point at which folic acid is essential to DNA synthesis. Without adequate folic acid, DNA synthesis and repair is impaired. Unrepaired DNA leads to diseases like cancer as suggested by the Ames’ triage theory discussed earlier.

  29. Folic Acid and Neural Tube Defects • Addition of folic acid to white flour and pasta products (150 μg/100 g flour) adds about 100 μg of folic acid to the average woman’s diet of 200 μg. • The result was that births complicated by NTDs decreased by 20-50%. • Estimated 40% of women of childbearing age are not reaching the recommended 400 μg folic acid levels even with food fortification; therefore, supplementation is required. Can Epidemiol Bio Prev, 2007

  30. Folic Acid and Heart Disease • Low blood levels of folic acid • Linked with a higher risk of fatal CHD (coronary heart disease) and stroke • Folic acid fortification of food • Related to a decline in stroke and heart disease deaths • Higher blood levels of folic acid and other B vitamins • Related to lower concentrations of homocysteine • But… link between folic acid, homocysteine and CVD has been difficult to establish (HOPE and VISP trials) • Ensuring daily adequate intake of vitamins/minerals at the RDA levels is more beneficial than consuming high dose single supplements of B vitamins

  31. Folic Acid and Cancer • Folic acid may reduce • the risk of colorectal and breast cancers which may be related to alcohol consumption combined with low folate intake • Early epidemiological studies showed that long-term use of multivitamins containing folic acid (on average 0.4 mg) reduced the risk of colon cancer by 75%. • Recently, studies have shown that higher amounts of daily folic acid (1 mg) may be associated with increase in the risk of adenomas. Grau MV. J Natl Cancer Inst 2003; Giovannucci E. Ann Intern Med 1998; JAMA 2007; Can Epi Biomarkers Prev 2007.

  32. Cancer: The Folic Acid Controversy How folic acid may protect against colorectal cancer Decreased dietary folate intake (↓ SAM, ↓ folate-derived cofactors) DNA hypomethylation may activate cancer genes or cause chromosomal rearrangementand instability Faulty DNA synthesis may cause futile cycle of DNA breakage and repair Lamprecht, Lipkin. Chemoprevention of colon cancer by calcium, vitamin D, and folic acid: Molecular mechanisms.Nature Rev Cancer 2003; 3:601-14. Colorectal cancer

  33. Recommendations for Folic Acid

  34. Meeting Folic Acid Needs With Food The foods on this slide add up to 432 mcg of folic acid. ½ cup asparagus 1 ½ cups spinach 1 cup of corn 8 oz. orange juice ¾ cup enriched cereal

  35. Vitamin E

  36. Vitamin EFunctions/Potential Benefits at Recommended Levels Necessary for • the formation of normal red blood cells, muscle, and tissue • immune functions Helps protect • fat in tissues from oxidation • cells from free radical damage by protecting cell membrane phospholipids

  37. Reduces LDL oxidation in tissues, which may be important for cardiovascular health May prevent oxidative damage of free radicals May reduce risk of cataracts risk of prostate cancer Suggestion that with Vitamins A and C may decrease the proliferation of abnormal/malignant cells in patients with colorectal cancer May play a role in the treatment of neurological diseases such as Alzheimer’s disease and Parkinson’s disease Vitamin EPotential Benefits Under Investigation

  38. ControversyVitamin E and Heart Disease • Free radicals damage cells (oxidative stress) and contribute to the development of CVD; vitamin E may help prevent or delay CVD by limiting the oxidation of LDL-C. • If vitamin E can help to reduce the damaging effects of oxidation, then optimal intakes of vitamin E should reduce the risk of heart disease.

  39. ControversyVitamin E and Heart Disease • The controversy arises when vitamin E is used in secondary prevention trials, such as the HOPE and HOPE-TOO trials, where the participants: • have several risk factors for chronic disease, or • have already been diagnosed with a chronic disease. • These participants may have an altered biochemistry that is difficult to treat with supplements alone. • Under these conditions, vitamin E may act as a pro-oxidant.

  40. Vitamin EAn Optimal Dose • Using data from two large cohorts (Nurses’ Health Study and the Health Professionals Follow-up Study), vitamin E (> 100 IU/day) for at least 2 years could result in a 40% reduction in the incidence of CHD. • Continuing vitamin E research will help determine the optimal dose, likely > 100 IU and < 400 IU, and whether vitamin E plays a role in reducing the risk heart disease.

  41. Vitamin E and Heart DiseaseResolving the Controversy The best advice • healthy individuals consume multivitamin/mineral preparations that contain up to 100 IU of vitamin E per day • Supplementation and dietary intake of vitamin E is not likely to exceed 200 IU, well below the upper level of 1,500 IU • Individuals who have risk factors for heart disease or already have heart disease should not take high dose (> 400 IU) vitamin E supplements

  42. Recommendations for Vitamin E Principle sources Vegetable oils 1 tbsp = 2.4 mg Wheat germ, 2 tbsp = 6 mg Nuts and seeds 2 tbsp = 9.0 mg Recommended Dietary Allowance for Adults: 22 IU or 15 mg per day

  43. Vitamin B12

  44. Vitamin B12Complementary Role • Folate and vitamin B12 are closely related; In their roles as coenzymes needed for new cell synthesis, each depends upon the other for activation. • Significant sources of folate include • vegetables and fruit such as leafy green vegetables, legumes and seeds, and grains such as cereal and pasta. • Significant sources of vitamin B12 derived only • from animal products (meat, fish, poultry, milk, cheese, eggs).

  45. Problems Associated with B12 Deficiencies • Vitamin B12 deficiency is relatively common in North America (> 30% of women ages 19-30 and > 20% of women ages 31-51) • Anemia • Severe neurological disease • Fatigue • Tingling or numbness

  46. Vegetarianism and B12 Deficiency • Lacto-ovo vegetarians should be able to meet their requirements for vitamin B12 with adequate planning • BUT… vegans may have difficulty meeting their needs • Breast-fed infants of poorly nourished vegan mothers are at risk for a fatal syndrome of body tremors and facial twitches • Vitamin B12 • Is critical for pregnant and lactating women • deficiency in older children and adolescents may be associated with impaired reasoning and memory Am J Clin Nutr 2003; 78: 3-6, 131-6; Morbidity and Mortality Weekly Reports 2003; 52:61-4; Am Clin Nutr 2000; 72:762-9.

  47. Vitamin B12Functions/Potential Benefits at Recommended Levels • Like folate, vitamin B12 helps cells multiply, which is especially important to red blood cells and the cells that line the digestive tract Vitamin B12 helps maintain the sheaths that surround and protect nerve fibres

  48. Vitamin B12Potential Benefits Under Investigation • Along with vitamins B6 and folate, supplemental vitamin B12 may • help those with inadequate intakes prevent a rise in blood levels of homocysteine • aid in the treatment of dementia