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9 Vitamin B12
Pages 306-356

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From page 306...
... Individuals with vitamin B12 deficiency caused by a lack of intrinsic factor require medical treatment. The median intake of vitamin B12 from food in the United States was estimated to be approximately 5 ~g/day for men and 3.5 ~g/day for women.
From page 307...
... An aclequate supply of BE is essential for normal blood formation and neurological function. Physiology of Absorption, Metabolism, Storage, and Excretion Small amounts of BE are absorbed via an active process that requires an intact stomach, intrinsic factor (a glycoprotein that the parietal cells of the stomach secrete after being stimulated by fooci)
From page 308...
... The liver takes up approximately 50 percent of the BE and the remainder is transported to other tissues. If there is a lack of intrinsic factor (as is the case in the condition called pernicious anemia)
From page 309...
... Because of the lack of ciata on dairy foocis and most forms of reci meat and fish, a conservative acljustment for the bioavailability of naturally occurring BE is used in this report. In particular, it is assumed that 50 percent of clietary BE is absorbed by healthy adults with normal gastric function.
From page 310...
... However, in the absence of intrinsic factor, essentially all the B12 from the bile is excreted in the stool rather than recirculated. Thus, B12 deficiency develops more rapidly in inclivicluals who have no intrinsic factor or who malabsorb B12 for other reasons than it floes in those who become complete vegetarians and thus ingest no B12.
From page 311...
... . This leacis first to an increase in the erythrocyte distribution width inclex and ultimately to an elevated mean cell volume.
From page 312...
... Some of these complaints may be related to the underlying gastric clisorcler in pernicious anemia. SELECTION OF INDICATORS FOR ESTIMATING THE REQUIREMENT FOR VITAMIN B12 Search of the literature revealed numerous indicators that could be consiclereci as the basis for deriving an Estimated Average Requirement (EAR)
From page 313...
... The reduction of elevated MMA values with BE therapy has also been reported in other studies Joosten et al., 1993; Naurath et al., 1995; Norman and Morrison, 1993~. Increased activity of anaerobic flora in the intestinal tract may increase serum MMA values; treatment with antibiotics decreases the serum MMA concentration in this situation (Lindenbaum et al., 1990~.
From page 314...
... Serum MMA values from older studies may not be comparable with those obtaineci recently because of improvements of methods over time (Beck, 1991; Green and Kinsella, 1995~. More importantly, no stuciies were found that examined directly the relationship of BE intake and MMA concentrations.
From page 315...
... Until 1978 raclioliganci binding assays frequently gave higher results; the binciing protein for BE used in these assays would also bind analogues of BE (Beck, 1991; Russell, 1992~. Since 1978 the use of purified intrinsic factor as the binder in commercial radioisotope dilution assay kits has resulted in serum concentrations of BE comparable with those obtained from microbiological assays.
From page 316...
... This was found in patients with pernicious anemia or previous gastrectomy who experienced early hematological relapse: serum methylmalonic acid (MMA) , total homocysteine, or both were elevated in 95 percent of the instances of relapse whereas the serum BE value was low (less than 150 omol/L r200 o~/mL]
From page 317...
... These estimates are consistent with the 2.9 percent prevalence of intrinsic factor antibody in inclivicluals older than 60 years (Krasinski et al., 1986~. Earlier studies reported a higher prevalence of antiintrinsic factor antibody in blacks with pernicious anemia than in whites with pernicious anemia (Carmel, 1992)
From page 318...
... The demonstration of circulating intrinsic factor autoantiboclies is almost diagnostic of type A gastritis and pernicious anemia (Tofu et al., 1997~. FACTORS AFFECTING THE VITAMIN B12 REQUIREMENT Aging Plasma vitamin BE tencis to decrease and serum methylmalonic acid (MMA)
From page 319...
... <200 (1 70-900 pg/ml) Intrinsic factor antibody l\ Homocysteine, methylmalonic acid _/ False-positive \ Cbl assay: repeat in 1 year l Pernicious anemia 1,000,ug IM B,2 x 5 days, then 500-1,000,ug IM every month; consider oral replacement at 500-1,000 ,ug/d Algorithm for cobalamin (Cbl)
From page 320...
... In the general elderly population, many cases of atrophic gastritis may remain uncliagnoseci. Food-Bound B~2Malabsorption Testing of inclivicluals who have low serum BE values but who do not have pernicious anemia reveals a substantial proportion with malabsorption of protein-bounci BE (Carmel et al., 1987, 1988; Jones et al.,1987~.
From page 321...
... Vitamin C with BY Low serum BE values reported in persons receiving megadoses of vitamin C are likely to be artifacts of the effect of ascorbate on the radioisotope assay for BE (Herbert et al., 1978) and thus not a true nutrient-nutrient interaction.
From page 322...
... is set for the recommencleci intake for infants. The AI reflects the observed average vitamin BE intake of infants feci principally with human milk.
From page 323...
... Using the average human milk volume of 0.78 L/ciay cluring the first 6 months and the higher average BE content of 0.42 GAL, the AI for BE for the infant 0 through 6 months of age fed human milk would be 0.33 Gay, rounded up to 0.4 fig. Maintenance of Normal Methylmalonic Acid Concentrations.
From page 324...
... The BE status of the infant is clearly abnormal by about 4 to 6 months of age. In case studies of infants born to strict vegetarians who were iclentifieci because of clinical signs of BE deficiency, human milk concentrations have been reported to be 0.02 (Hoey et al., 1982)
From page 325...
... In one study of three infants exclusively feci human milk who haci clinically observable BE deficiency caused by low maternal consumption of animal products, one infant was treated parenterally with BE whereas two infants were treated with small oral BE closes Jac~hav et al., 1962~. At 9 months of age, 0.1 ~g/ciay of oral BY normalized bone marrow within ~ clays in one of the two infants given oral closes and procluceci profound improvements in behavior by 18 days (after a total of 1.8 fig of BE had been given)
From page 326...
... The sensitivity of plasma MMA to distinguish the group of infants born to macrobiotic mothers from those born to omnivorous mothers was 85 percent (Schneecle et al., 1994~. The average intake of BE by these infants, who were exclusively feci human milk for a mean of 4.8 months and then at least partially feci human milk for 13.6 + 6.6 (stanciarci cleviation)
From page 327...
... A low serum BE value in persons with pernicious anemia was assumed to indicate incomplete response to treatment. Primary Criterion: Maintenance of Hematological Status and Serum B'2 Values.
From page 328...
... Assumptions that were integral to the application of this method are shown in Box 9-1. In brief, this method involves estimating the amount of BE requirecT ciaily to maintain hematological and serum BE status of inclivicluals with pernicious anemia in remission; subtracting the amount of enclogenous BE lost from the bile in excess of that lost by a healthy incliviclual; and, because the value is to be used for inclivicluals with normal ability to absorb BE from food, correcting for bioavailability.
From page 329...
... Cumulative Number Achieving Maximum Erythropoiesis (n= 7) 0.5 1 1 1.0 2 3 1.4 1 4 2.0 2 6 4.0 1 7 SOURCE: Darby et al.
From page 330...
... was clesigneci to determine the effective dosage of intrinsic factor concentrates, not to estimate the BE requirement, but it suggests that 1.4 fig of BE exceeds the requirement for absorbed BE in most of the subjects tested. The often-citeci study of Sullivan and Herbert (1965)
From page 331...
... give evidence that 1.5 ~g/ciay of clietary BE is not sufficient to maintain hematological status and serum BE in half of the subjects stuclieci. The meager ciata provicleci by the studies of vegetarians indicate that the BE average requirement should probably be at least 1.5 ~g/ciay, but a higher average requirement is not ruled out.
From page 332...
... 332 DIETARY REFERENCE INTAKES TABLE 9-6 Other Studies of Subjects with Pernicious Anemia Consiclereci in Setting the Estimated Average Requirement for Vitamin B12 for Adults Reference Number of Subjects Age Range (y) Treatme Suggested IMa requirement > 2.
From page 333...
... 1 mg of slow-re le ase B 1 2 IM every 2 or 3 mo for at least 8 y. The less-frequent dose was equivalent to 1.7 fig of B12/d.b 35 received 1 mg of B12 IM every 5-6 mo, 6 received it every 3-4 mo, 3 received it every 2 mot Smallest and most frequent dose was equivalent to 0.8-1.0 Fig of B12/d-d 2.0 fig oral dose of B12 Co60 given with intrinsic factor.
From page 334...
... ) not caused by disease or vegetarianism Suggested dietary B12 average requirement > 1.
From page 335...
... d NA = not available. Possible Ancillary Method: Maintenance of a Serum B~2 Concentration That Is Consistent with a Normal Circulating MMA Value Several investigators have urgeci the use of the serum MMA concentration as the most sensitive inclicator of B~2 status (Linclenbaum et al., 1990; Moelby et al., 1990; Savage et al., 1994b; Stabler et al., 1996~.
From page 336...
... Slightly more than 40 percent of the 70 elderly TABLE 9-8 Vitamin B12 Status: Occurrence of Low Serum Values for Two Age Groups Serum Values of Subjects Elderly Subjects Healthy Younger from Framingham Control Subjectsa Studyb (Number [ % ]
From page 337...
... A study of a macrobiotic population (Miller et al., 1991) revealed that more than half of the adults haci low serum BE concentrations and nearly onethirci were excreting high amounts of MMA, but clietary information from the study was not sufficient for drawing conclusions.
From page 338...
... A for Women 19-30 years 2.4 ~g/day of vitamin BE 31-50 years 2.4 1lg/day of vitamin BE Adults Ages 5 ~ Years and Older Evidence Considered in Estimating the Average Requirement Because 10 to 30 percent of people older than 50 years are estimated to have atrophic gastritis with low stomach acid secretion (Andrews et al., 1967; Hurwitz et al, 1997; Johnsen et al., 1991; Krasinski et al., 1986) , they may have decreased bioavailability of BE from food.
From page 339...
... An increase in the number of intrinsic factor-B~2 receptors was observed in pregnant mice and found to be regulated by placental lactogen (Robertson and Gallagher, 1983~. A greater absorption of oral BE was reported from the single study of pregnant women (Hellegers et al., 1957)
From page 340...
... The importance of acloquate maternal intake cluring pregnancy is supported by the appearance of BE cleficiency in infants at 4 to 6 months when their mothers have been strict vegetarians for only 3 years (Specker et al., 1990~. Fetal Accumulation.
From page 341...
... In several studies of infants with clinical signs of BE deficiency caused by low maternal intake or absorption of the vitamin, maternal plasma concentrations of the vitamin were found to be normal or low normal, suggesting that maternal BE stores are less important than current maternal intake (Hoey et al., 1982; Johnson and Roloff, 1982; Kuhne et al., 1991; Sklar, 1986~. This is also inclicateci by the observation that the length of time that mothers haci been strict vegetarians was not correlated with the urinary MMA concentrations of their infants (Specker et al., 1988~.
From page 342...
... Patients with atrophic gastritis, pancreatic insufficiency, or prolongeci omeprazole treatment (Bellou et al., 1996; Gueant et al., 1990; Suter et al., 1991; Termanini et al., 1998) will have clecreaseci bioavailability of fooci-bounci BE and will require normal amounts of crystalline BE (either in foocis fortified with BE or as a supplement)
From page 343...
... Dietary Intake Because a generous intake of animal foocis is common in the United States and Canada, meclian BE intake from food is well above the EAR. For example, in the United States the meclian ciaily intake from food by young adult men has been reported to be approximately 4 to ~ fig and by young adult women, 3 fig Appendixes G and H)
From page 344...
... It refers to the percentage contribution to the American diet for both men and women, based on 1995 CSFII data. c 1 fig represents 20% of the Recommended Daily Intake (6.0 fig)
From page 345...
... Adults 2 19 Years Food Group Men Women Ages 51-70 Years Men Women Ages 70+ Years Men Women Ready-to-eat cereals 4.7 8.2 7.8 10.3 10.9 11.9 Soy-based 0.7 0.5 0.9 0.5 1.2 0.3 supplements and meal replacements Milk-based 0.2 0.2 0.2 0.3 0.5 0.3 supplements and meal replacements Total 5.6 8.9 8.9 12.1 12.6 12.5 a CSFII = Continuing Survey of Food Intake by Individuals. b Refers to the percentage contribution to the American diet for both men and women, based on 2-day weighted 1995 CSFII data.
From page 346...
... . TOLERABLE UPPER INTAKE LEVELS Hazard Identification Adverse Effects No adverse effects have been associated with excess BE intake from food or supplements in healthy inclivicluals.
From page 347...
... Cyanocobalamin may increase the risk of irreversible neurological damage (from the optic atrophy)
From page 348...
... 1972. Interrelation of serum vitamin B12, total body vitamin B12, peripheral blood morphology and the nature of erythropoiesis.
From page 349...
... The expected findings of very low serum cobalamin levels, anemia, and macrocytosis are often lacking. Arch Intern Med 148:1712-1714.
From page 350...
... 1988. Food cobalamin malabsorption occurs frequently in patients with unexplained low serum cobalamin levels.
From page 351...
... 1978. Low serum vitamin B12 levels in patients receiving ascorbic acid in megadoses: Studies concerning the effect of ascorbate on radioisotope vitamin B12 assay.
From page 352...
... 1993. Cobalamin absorption and serum homocysteine and methylmalonic acid in elderly subjects with low serum cobalamin.
From page 353...
... 1990. The relationship between clinically confirmed cobalamin deficiency and serum methylmalonic acid.
From page 354...
... 1986. Cyanocobalamin absorption in the elderly: Results for healthy subjects and for subjects with low serum cobalamin concentration.
From page 355...
... 1990. Vitamin B-12: Low milk concentrations are related to low serum concentrations in vegetarian women and to methylmalonic aciduriain theirinfants.
From page 356...
... 1994. Cobalamin and cobalamin-binding capacity in human milk.


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