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Appendix D: Case Studies of Application of Risk Assessment Model for Nutrients
Pages 37-66

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From page 37...
... Currently, the available data on the adverse effects of excess calcium intake In humans primarily concerns calcium intake from nutrient supplements and antacids. Of the many possible adverse effects of excessive calcium intake, the three most widely studied and biologically important are: kidney stone formation (nephrolithiasis)
From page 38...
... A number of dietary factors seem to play a role in determining the incidence of this disease. In addition to being associated with increased calcium intakes, nephrolithiasis appears to be associated with higher intakes of oxalate, protein, and vegetable fiber (Massey et al., 1993~.
From page 39...
... These reports described what appears to be the same syndrome at supplemental calcium intakes of 1.5 to 16.5 g (37.5 to 412.5 mmol) /day for 2 days to 30 years.
From page 40...
... . c Calcium intake from supplements and diet reported (for example, milk and yogurt consumption)
From page 41...
... A review of these reports revealed calcium intakes from supplements (and in some cases from dietary sources as well) in the range of 1.5 to 16.5 g (37.5 to 412.5 mmol)
From page 42...
... (1994) equation suggest that calcium intakes lower than the recommended intake levels derived for females (Appendix A)
From page 43...
... For individuals who are particularly susceptible to high calcium intakes, such as those with hypercalcemia and hyperabsorptive hypercalciuria, this level or below should be protective. UL for Adults Ages 19 through 70 years 2,500 mg (62.5 mmol)
From page 44...
... Although calcium supplementation in children may appear to pose minimal risk of MAS or hyperabsorptive hypercalciuria, risk of depletion of other minerals associated with high calcium intakes may be greater. With high calcium intake, small children may be especially susceptible to deficiency of iron and zinc (Golden and Golden, 1981; Schlesinger et al., 1992; Simmer et al., 1988~.
From page 45...
... Subpopulations known to be particularly susceptible to the toxic effects of calcium include individuals with renal failure, those using thiazide diuretics (Whiting and Wood, 1997) , and those with low intakes of minerals that interact with calcium (for example, iron, magnesium, and zinc)
From page 46...
... 1995. Milk-alkali syndrome associated with calcium carbonate consumption: Report of 7 patients with parathyroid hormone levels and an estimate of prevalence among patients hospitalized with hypercalcemia.
From page 47...
... 1997. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women.
From page 48...
... 1993. Effect of dietary oxalate and calcium on urinary oxalate and risk of formation of calcium oxalate kidney stones.
From page 49...
... 1996. Longterm effects of calcium supplementation on serum PTH, bone turnover, and bone loss in elderly women.
From page 50...
... Am J Clin Nutr 56: 10451048. Spencer H
From page 51...
... show that vitamin B,2-deficient animals receiving supplemental folate develop signs of neuropathology earlier than do controls. The monkey studies used dietary methods to induce vitamin BE deficiency, whereas the fruit bat studies used a well-described method involving nitrous oxide (Metz and van der Westhuyzen, 19879.
From page 52...
... a Refers to neurological relapses or progression of preexisting neurological manifestations while on folate therapy. b In two patients, the neurological progression was characterized as minimal or slight.
From page 53...
... Many studies have evaluated the periconceptional use of supplemental folate (in doses of approximately 0.4 to 5.0 ma) to prevent neural tube defects (see Table Dub.
From page 54...
... Intestinal Zinc Absorption. Although there has been some controversy regarding whether supplemental folate intake adversely affects intestinal zinc absorption (Butterworth and Tamura, 1989)
From page 55...
... , who found high serum folate concentrations to be associated with favorable pregnancy outcomes including (1) higher birth weight and Apgar scores of newborns, (2)
From page 56...
... The literature was reviewed to find cases in which vitamin B~2-def~cient patients who were receiving oral doses of folate experienced progression of necrologic disorders. Data were not available on which to set a no-observed-adverse-effect level (NOAEL)
From page 57...
... No data were found to suggest that other life stage groups have increased susceptibility to adverse effects of high supplemental folate intake. Therefore, the UL of 1,000 ~g/day is also set for adult pregnant and lactating women.
From page 58...
... , the highest reported total folate intake from food and supplements at the ninety-fifth percentile, 983 ~g/day, was found in females aged 30 through 50 years. This intake was obtained from food (which probably included fortified, ready-to-eat cereals, a few of which contain as much as 400 fig of folio acid/serving)
From page 59...
... Using either method of analysis and assuming regular use of an over-the-counter supplement that contains folic acid (ordinarily 400 fig per dose) , it is unlikely that intake of folate added to foods or as supplements would exceed 1,000 fig on a regular basis for any of the life stage or gender groups.
From page 60...
... 1949. Folic acid and the neurologic manifestations of pernicious anemia.
From page 61...
... 1949. Risk of neurological complications in pernicious anemia treated with folic acid.
From page 62...
... 1948. The development and progression of subacute combined degeneration of the spinal cord in patients with pernicious anemia treated with synthetic pteroylglutamic (folic)
From page 63...
... 1947. Liver extract, folic acid, and thymine in pernicious anemia and subacute combined degeneration.
From page 64...
... The only evidence of adverse effects associated with riboflavin comes from in vitro studies showing the formation of active oxygen species on intense exposure to visible or ultraviolet light (All et al., 1991; Floersheim, 1994; Spector et al., 19954. However, given the lack of any demonstrated functional or structural adverse effects in humans or animals following excess riboflavin intake, the relevance of this evidence to human health effects in vivo is highly questionable.
From page 65...
... Wright, National Center for Health Statistics, Centers for Disease Control and Prevention, 1997) showed that the highest mean intake of riboflavin from diet and supplements for any life stage and gender group reported was for males aged 31 through 50 years: 6.9 mg/day.
From page 66...
... Am J Clin Nutr 63:54-66.


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