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TABLE 8-12Dose and Duration of Oral Folate Administration and the Occurrence of Neurological Manifestations in Patients with Pernicious Anemia

StudyNumber of SubjectsDose (mg/d)DurationOccurrence of Neurological Manifestationsa
Crosby, 196010.352 y1 of 1
Ellison, 196010.33–13 mo1 of 1
Allen et al., 199030.4–13–18 mo3 of 3
Baldwin and Dalessio, 196110.516 mo1 of 1
Ross et al., 194841.259–23 mo1 of 4
Chodos and Ross, 195141.25b3.5–26 mo3 of 4
Victor and Lear, 195621.5–2.5510–39 mo2 of 2
Conley and Krevans, 195114.53 y1 of 1
Schwartz et al., 195048548 mo32 of 48
Ross et al., 19482520–23 mo1 of 2
Conley and Krevans, 195125–82–2.5 y2 of 2
Will et al., 1959365–101–10 y16 of 36
Bethell and Sturgis, 1948155–2012 mo4 of 15
Chodos and Ross, 1951115–303–25 mo7 of 11
Israels and Wilkinson, 1949205–4035 mo16 of 20
Wagley, 1948105–60012 mo8 of 10
Ellison, 196015.4–6.42 y1 of 1
Victor and Lear, 195616.682.5 y1 of 1
Berk et al., 19481210> 17 mo3 of 12
Best, 195911026 mo1 of 1
Spies and Stone, 194711022 d1 of 1
Ross et al., 1948610–15≤ 12 mo4 of 6
Hall and Watkins, 19471410–152–5 mo3 of 14
Heinle et al., 19471610–40≤ 12 mo2 of 16
Jacobson et al., 1948110–655 mo1 of 1
Heinle and Welch, 1947110–1004 mo1 of 1
Spies et al., 194838≥1024 mo28 of 38
Ross et al., 194871528–43 moc3 of 7
Chodos and Ross, 195111510.5 moc1 of 1
Fowler and Hendricks, 1949215–204–5 mo2 of 2
Vilter et al., 19472150–50010–40 d4 of 4

NOTE: All studies except Allen et al. (1990) were conducted before folate was added to any foods as a fortificant. In most of the case reports for which hematological status was reported, some degree of hematological improvement occurred. Studies are presented in increasing order by dose. When different doses were reported within a study, there is more than one entry for that study. Case reports that covered hematological rather than neurological effects were excluded, namely, Alperin (1966), Heinle and Welch (1947), Herbert (1963), Reisner and Weiner (1952), Ritz et al. (1951), Sheehy et al. (1961), and Thirkettle et al. (1964). The exception was the study by Allen et al. (1990) in which the subjects were vitamin B12 deficient but did not have pernicious anemia.

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. Neurological progression was also observed when the dose was increased to 15 mg/d in these patients.

c

The initial dosage of 1.25 mg/d was increased to 15 mg/d after variable durations of treatment. Neurological progression occurred only at 15 mg/d in these patients.

Refers to neurological relapses or progression of preexisting neurological manifestations while on folate therapy.

In two patients, the neurological progression was characterized as minimal or slight. Neurological progression was also observed when the dose was increased to 15 mg/d in these patients.

The initial dosage of 1.25 mg/d was increased to 15 mg/d after variable durations of treatment. Neurological progression occurred only at 15 mg/d in these patients.

From: 8, Folate

Cover of Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline
Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline.
Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline.
Washington (DC): National Academies Press (US); 1998.
Copyright © 1998, National Academy of Sciences.

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