Folic Acid in the Treatment of Pernicious Anemia

Abstract

1. Folic acid in daily doses of 15 to 50 mg., orally, or 20 mg. intramuscularly, usually produced a submaximal reticulocytosis in patients with pernicious anemia. 2. In 3 patients the hemoglobin and red cells rose to a level of about 12.0 Gm. and 4.3 million respectively without further rise after 3 months of therapy. 3. Folic acid in the above doses failed to prevent the development or progression of neurological symptoms indicative of subacute combined sclerosis. 4. In 5 patients folic acid in doses of 5 or 10 mg. orally daily combined with ½ unit of liver extract injected intramuscularly daily produced a reticulocytosis greater than that anticipated from adequate liver extract therapy alone. 5. With combined liver extract and folic acid therapy there was evidence of improvement in the symptoms and signs of subacute combined sclerosis in 3 patients. 6. Folic acid, combined with ½ unit of liver extract, was found to produce a complete hematological remission. 7. Folic acid, alone or in combination with small doses of liver extract, produced an improvement in appetite and general well-being in patients with pernicious anemia. 8. The possible enhancing effect of liver extract when combined with folic acid cannot be due to the folic acid content of the former since 1 unit of liver extract contains only 0.38 micrograms of folic acid.31 9. Folic acid administered to a patient with macrocytic anemia due to faulty postoperative intestinal digestion and absorption, produced a complete remission in the blood picture and a marked improvement in signs and symptoms.

Optic atrophy in experimental vitamin B12 deficiency in monkeys

“…9-11) developed optic atrophy and visual changes approximately 1 year sooner than the other B12 deficient monkeys. This rapid progression of visual deficit in the monkeys supports the observation in humans that folic acid therapy hastens the development of the neurologic manifestations of pernicious anemia (Heinle & Welch 1947, Meyer 1947, Ross et al 1948, Israels & Wilkinson 1949, Schwartz et al 1950, Stambolian & Behrens 1977.…”

Scientific opinion on the tolerable upper intake level for folate

“…Sixteen publications reported on prospective case series (Berk et al., 1948; Bethell & Sturgis, 1948; Chodos & Ross, 1951; Davidson & Girdwood, 1947; Hall & Watkins, 1947; Heinle et al., 1947; Israëls & Wilkinson, 1949; Meyer, 1947; Ross et al., 1948; Schwartz et al., 1950; Spies et al., 1948; Spies & Stone, 1947; Vilter et al., 1947; Wagley, 1947; Wilkinson, 1948; Will et al., 1959). The vast majority of cases were PA patients (Bethell & Sturgis, 1948; Chodos & Ross, 1951; Hall & Watkins, 1947; Heinle et al., 1947; Israëls & Wilkinson, 1949; Meyer, 1947; Ross et al., 1948; Spies et al., 1948; Wilkinson, 1948; Will et al., 1959), while a few cases were related to patients with gastric resection (Chodos & Ross, 1951; Heinle et al., 1947; Meyer, 1947; Ross et al., 1948; Wagley, 1947) or sprue (Chodos & Ross, 1951; Davidson & Girdwood, 1947; Spies et al., 1948; Wagley, 1947). Cases were patients treated with folic acid as an alternative to liver extract, which was the standard treatment for PA at that time (Berk et al., 1948; Bethell & Sturgis, 1948; Chodos & Ross, 1951; Davidson & Girdwood, 1947; Heinle et al., 1947; Ross et al., 1948; Will et al., 1959) or patients treated with folic acid as first therapy or after an interruption of the therapy with a liver extract (Berk et al., 1948; Bethell & Sturgis, 1948; Hall & Watkins, 1947; Heinle et al., 1947; Israëls & Wilkinson, 1949; Meyer, 1947; Spies & Stone, 1947; Wagley, 1947; Wilkinson, …”

“…Sixteen publications reported on prospective case series (Berk et al, 1948;Bethell & Sturgis, 1948;Chodos & Ross, 1951;Davidson & Girdwood, 1947;Hall & Watkins, 1947;Heinle et al, 1947;Israëls & Wilkinson, 1949;Meyer, 1947;Ross et al, 1948;Schwartz et al, 1950;Spies et al, 1948;Spies & Stone, 1947;Vilter et al, 1947;Wagley, 1947;Wilkinson, 1948;Will et al, 1959).…”

The history of folic acid

“…Soon after the synthesis of folic acid in 1945, it became apparent that it was effective in the treatment of megaloblastic anaemia of all types, but particularly those which had previously been found refractory to refined liver preparations, such as the megaloblastic anaemia of sprue (Hanes, 1942; Davidson et al , 1947), coeliac disease, pregnancy and malnutrition. It was also found to be temporarily effective in curing anaemia in Addisonian pernicious anaemia (Moore et al , 1945; Vilter et al , 1945), but it became apparent that the anaemia relapsed and neurological damage was not improved by folic acid (Amill & Wright, 1946) and was even made worse or precipitated by this therapy (Vilter et al , 1946; Hall, 1947; Heinle & Welch, 1947; Meyer, 1947).…”