Folate supplementation unnecessary?
Unnecessary folate supplementation for sickle cell disease can hamper recognition of pernicious anemia, according to a case report in the May 29th issue of The New England Journal of Medicine.
This goes against a raft of published studies to the contrary.
"This is absolutely NOT a case of Folate Supplementation May Mask Pernicious Anemia in Sickle Cell Disease. Pure and simple, this is a case of medical misadventure", says Ron Law from New Zealand.
See also this recent article by Chris Gupta, aptly titled "The FDA vs. Folic Acid".
Folate Supplementation May Mask Pernicious Anemia in Sickle Cell Disease
Reuters Health Information 2003.
By Will Boggs, MD
NEW YORK (Reuters Health) May 28 - Unnecessary folate supplementation for sickle cell disease can hamper recognition of pernicious anemia, according to a case report in the May 29th issue of The New England Journal of Medicine.
Patients with sickle cell disease often receive folate supplementation, the authors explain, though clinical folate deficiency is rare and there is no objective evidence of a benefit from routine folate supplementation in such patients.
Dr. Ralph Carmel from New York Methodist Hospital in New York and associates describe a 29-year-old black woman with sickle cell disease who presented with treatment-resistant anemia, unsteady gait, and mental changes.
After more than a year of frequent admissions for painful crisis (and an elevated mean corpuscular volume that was apparently overlooked), the women was admitted with sensory changes, confusion, impaired memory, and inappropriate behavior and found to have megaloblastic anemia.
Her serum cobalamin (vitamin B12) was well below the lower limits of normal, and cobalamin deficiency was confirmed by a serum methylmalonic acid level in excess of 10,000 nmol/L (normal ranges from 30 to 279), the report indicates. The diagnosis of pernicious anemia was established after measuring serum gastrin levels of 1062 ng/L (normal > 90) and identifying antibodies to intrinsic factor in her blood.
The patient had received folate supplementation since 1995, the researchers note, and her serum folate level exceeded 20 g/L.
The patient's anemia resolved and her mental status changed dramatically after discontinuation of folic acid supplements and institution of cobalamin injections, the investigators report. The patient has had no painful crises or need for transfusions after a year of monthly cobalamin injections.
"Clinicians need to think of B12 deficiency (which is very treatable) as a possible complication whenever blood count changes or neurological symptoms appear in patients with sickle cell anemia, rather than automatically assuming it is a part of the sickle cell process," Dr. Carmel told Reuters Health.
"Folate supplementation is not completely risk-free," Dr. Carmel said. "This message extends beyond the sickle cell world and may be especially relevant to the geriatric world, where B12 deficiency is especially common."
"Studies proving a need for folate supplementation are rare," Dr. Carmel added. "The only randomized controlled prospective study ever published has found no evidence of clinical benefit. Nevertheless, physicians taking care of patients continue giving folate, for theoretical reasons and subjective reasons, and are often resistant to suggestions that it is unnecessary. If there ever were reasons for using it, they have largely disappeared today with folate fortification of the American food supply."
N Engl J Med 2003;348:2204-2207.
Comment on this article from Ron Law in New Zealand:
This is absolutely NOT a case of Folate Supplementation May Mask Pernicious Anemia in Sickle Cell Disease. Pure and simple, this is a case of medical misadventure.
The facts (as reported)
The woman had clinical signs of pernicious anaemia.
The woman had laboratory evidence of pernicious anaemia
Neither were acted upon by the clinician. The evidence was there for all to see -- there was no masking of either haematological or neurological symptoms-- they just were not noticed by the practitioner(s).
Folate supplementation was ceased at the same time B12 therapy was instituted -- the B12 cured the problem -- not the removal of folate.
Why do medical practitioners still utilise the barbaric, though very lucrative, practice of injecting B12. It is a part of medical folklore going back some 50 or more years. Subligual B12 or even high dose oral B12 is perfectly efficacious. About 1-2% of B12 gets absorbed passively -- so oral doses above 100 ug/day provide sufficient B12 to treat pernicious anaemia.
Although the authors claim there is no proven benefit from using folate supplements in sickle cell disease, the following extract from the NIH website is worth noting...
"A report on this workshop will be available in the coming months along with recommendations of the workshop regarding initiatives. Highlights from the meeting included reports from several investigators that resting energy expenditure is elevated in persons with sickle cell disease. Establishment of eucaloric balance is often difficult and patients with the disease compensate by decreasing activity. A number of nutritional approaches were noted to have promise for the patient with sickle cell disease and to warrant further study including magnesium, zinc, antioxidant nutrients, n-3 fatty acids, L-glutamine, and folate. There was a high level of enthusiasm for continuing nutritional research in sickle cell disease."
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
MINUTES OF THE SEVENTY-SIXTH MEETING OF THE
SICKLE CELL DISEASE ADVISORY COMMITTEE
June 7, 1999
The Sickle Cell society promotes folic acid for women...
"Pregnancy in sickle cell disease is a dangerous time for both the mother and the baby. Affected pregnant women should be looked after by a unit experienced in the care of women with this condition.
Blood transfusion may be needed in some women with poor obstetric history or a severe form of sickle cell disease. Regular folic acid, prompt treatment of infections and crisis, and an increased fluid intake make it possible for most women to have successful pregnancies."
There are numerous papers on folate supplementation in sickle cell patients... eg J Pediatr Hematol Oncol 2001 Mar-Apr;23(3):165-9 Red blood cell folate and serum vitamin B12 status in children with sickle cell disease.
Kennedy TS, Fung EB, Kawchak DA, Zemel BS, Ohene-Frempong K, Stallings VA.
Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
PURPOSE: To determine red blood cell (RBC) folate and serum vitamin B12 levels in children with sickle cell disease, SS-type, and to evaluate the associations of these nutrient levels with growth and hematologic parameters. PATIENTS AND METHODS: Subjects enrolled in this prospective, cross-sectional study were recruited from one tertiary care setting. Complete blood counts, measurement of red blood cell (RBC) folate and serum vitamin B12, anthropometric measures (height, weight, skinfold measurements), pubertal status, and 24-hour dietary recalls were obtained from 70 patients ages 1 to 19 years. RESULTS: Low RBC folate levels were found in 15% of the children. Fifty-seven percent of the sample had inadequate dietary folate intake. Three percent of the children had low serum vitamin B12 levels. All children and adolescents sampled had adequate dietary intake of vitamin B12. Both RBC folate (P = 0.01) and serum vitamin B12 levels (P less than 0.01) decreased with increasing age. CONCLUSIONS: More than half of the subjects had inadequate intake of folate from food, and despite daily folate supplementation, 15% had low RBC folate levels. Low serum vitamin B12 levels were rare, and dietary vitamin B12 intake was adequate. Additional research is needed to explore the effects of improved folate status, the need for folate supplementation, and the relationship of folate, vitamin B12, and homocysteine levels and the risk for vascular damage and stroke in children with sickle cell disease.
PMID: 11305720 [PubMed - indexed for MEDLINE]
The Boston Globe - FDA muffed chance to reduce birth defects
Folic acid 'cuts blood pressure'
Folic acid may help keep blood pressure in check, US researchers believe.
High Folic Acid May Slow Mental Aging
A diet higher in folate has been linked to a variety of health benefits such as reducing birth defects and warding off heart disease and strokes. Moreover, according to a Dutch study, taking 800 micrograms of folic acid a day might also help ward off the cognitive decline of aging.
Folic acid 'cuts dementia risk'
Eating plenty of folic acid - found in oranges, lemons and green vegetables - can halve the risk of Alzheimer's disease, a study has suggested. US National Institute on Aging experts monitored diets over seven years. They found adults who ate the daily recommended allowance of folates (B vitamin nutrients) had a reduced risk of the disease.
Still not enough folate despite fortification
Folate intake in the US has not met the FDA's targets following the mandated fortification of enriched grain products with the B vitamin that began in 1998, according to a recent study. The study assessed that none of the subgroups met the FDA's goal of bringing 50 percent of women up to the daily-recommended intake levels. Despite significant improvements and widespread fortification, only 39 percent of white women, 26 percent of black women, and 28 percent of Mexican American women attained the 400 microgram per day target for folate consumption.
January 2007: Folate Levels Fall in Young U.S. Women
"This is a cause of substantial concern," said Dr. Nancy Green, medical director for the March of Dimes, which campaigns for birth defects prevention. Folate is a naturally occurring B vitamin. An artificial version, which is more easily metabolized by the body, is folic acid.
posted by Sepp Hasslberger on Saturday July 12 2003
updated on Friday January 5 2007
URL of this article:
The FDA versus Folic Acid
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December 21, 2004 - Sepp Hasslberger
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