Health Supreme by Sepp Hasslberger

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July 12, 2003

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.

An aside...

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."

Bethesda, Maryland
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]

See also

BMJ - Is folic acid the ultimate functional food component for disease prevention?

BMJ - "Let food be thy medicine..."

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.

Four in 10 mothers 'need vitamin pills'

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:


Related Articles

The FDA versus Folic Acid
"Folate prevents colon cancer: Annals of Internal Medicine, 1998; 129:517-524 Folate prevents cardiovascular disease: JAMA, 1993, Dec 8: 2693-2698 & 2726-2727 Folate protects against dna damage: Proc of the Nat Academy of Sciences, 1997 94(7):3290-5 Folate protects against dna damage: Baillieres Clinical Hematology, 1995, 8(3):461-78 Folate protects against birth defects: Folates and the Fetus. Lancet, Feb 26, 1977, p 462 Folate metabolism in pregnancy: Am J Obstetrics and Gynecology, 1967... [read more]
July 14, 2003 - Chris Gupta

Most Pain Killers Deplete The Body Of The B Vitamin Folic Acid
With all negative news concerning Non Steroidal Anti Inflammatory Drugs (NSAID's) and the Cox 2 inhibitors Vioxx, Celebrex and Naproxin, it is notable that all the experts - doctors and pharmacists - have failed to mention one salient fact. All of these drugs, including the oldest pain killer Asprin, deplete the body of the B vitamin Folic acid. Folic acid is one of the most common vitamin deficiencies and... [read more]
December 25, 2004 - Chris Gupta

July 1, 2005: The Day CODEX Will Protect You From High-Dose Dietary Supplements?
Here is a good summary of how unscientific these so called scientific bodies can be when it comes to protect their cronies. Given such huge benefits from supplements, these shenanigans should be countered and the whole sham initiative turned against the preparators. Sadly the authorities know that such a counter initiative is difficult and costly, hence unlikely, and they will continue to blatantly abuse us. Hopefully we can prove their... [read more]
November 10, 2004 - Chris Gupta

Forget Cholesterol - it's really not relevant
For decades we have been told that we must avoid cholesterol at any cost if we want to stay healthy. Want to protect your heart and arteries? Then forget cholesterol, it is almost certainly one of the great myths of 20th century medicine. As a matter of fact, there seem to be certain benefits to high cholesterol that medical authority is very reluctant to tell us about. In his article... [read more]
June 03, 2003 - Sepp Hasslberger

Eliminating Painkillers - Naproxen To Follow Vioxx, Celebrex
Management of chronic pain is getting more difficult - at least the much touted chemical route seems to be turning into a rather rocky path, with several of the "blockkbuster" painkillers showing stunning rates of increase of heart trouble after Vioxx was recently withdrawn from the market. According to a recent Health News article, the FDA has just halted a clinical trial involving Naproxen, as signs emerged that the drug... [read more]
December 21, 2004 - Sepp Hasslberger

Supplements do cut risk of heart attack - say Swedish researchers
Under the title "Multivitamins may reduce heart attack risk, new study" the Journal of Nutrition reports that those Swedes who regularly consume a multivitamin supplement seem to be better protected against heart attacks than others who do not supplement their diet. "This inverse association was not modified by such healthy lifestyle habits as consumption of fruits and vegetables, intake of dietary fibre, smoking habits and level of physical activity, although... [read more]
August 02, 2003 - Sepp Hasslberger




Readers' Comments

This is an earlier article that may have prompted the very one-sided piece in the New England Journal of Medicine.

"The failure to require mandatory fortification of flour with folic acid is public health malpractice."

British Medical Journal 2003;326:1054 (17 May)

Inertia on folic acid has caused thousands of unnecessary deaths

BMJ Anna Ellis

As many as 350 000 deaths could have been prevented over the last decade if the UK government had acted on the compelling evidence for the benefits of folic acid, a conference was told last week. Had flour been fortified with folic acid when the evidence regarding neural tube defects was published, thousands of people would not have died from coronary heart disease.

Godfrey Oakley, visiting professor at the department of epidemiology at the Rollin School of Public Health of Emory University, Atlanta, said: "The failure to require mandatory fortification of flour with folic acid is public health malpractice." He was speaking at a conference in London organised by Dr Jean-Pierre Lin, consultant paediatric neurologist responsible for the spina bifida services at Guy's and St Thomas's hospitals on behalf of the charity the Little Foundation and MacKeith meetings (a product of publishers MacKeith Press).

Recent evidence shows not only the benefits of folic acid in preventing neural tube defects but that it is protective against heart disease, strokes, deep vein thrombosis, and pulmonary embolism. Folic acid lowers concentrations of homocysteine, an amino acid that for about 15 years has been believed to be associated with heart attacks and strokes.

Dr David Wald, a cardiologist at Southampton General Hospital, said: "Until public health agencies fortify our diet with sufficient folic acid, people should consider taking an 800 µg supplement each day, especially if they have coronary heart disease.

The Medical Research Council vitamin study was published in 1991 and gave compelling evidence that taking folic acid prevents up to three quarters of neural tube defects, such as spina bifida (Lancet 1991;338:132-7). Despite the publicity that the report generated, the incidence of neural tube defects has not declined in the United Kingdom over the last decade, despite quite a steep decline between 1970 and 1992.

The government recommends that women who are trying to conceive take 400 µg of folic acid a day. But experts point out that about half of pregnancies are unplanned, meaning that many women start taking the vitamin only once they find out they are pregnant or not at all. Specialists say that the optimal time for women to take the vitamin is from stopping contraception to 12 weeks after conception.

Public health doctors and charities such as the Association of Spina Bifida and Hydrocephalus have called on the UK government many times to fortify flour with folic acid. They point out that 39 countries around the world, including the United States and Canada, now either fortify flour or have agreed to do so, and that the rate of neural tube defects has fallen in these countries. In Nova Scotia, where fortification was implemented in 1998, the incidence fell from 2.58 per thousand people in 1991-7 to 1.17 per thousand people in 1998-2000 (Canadian Medical Association Journal 2002;167:241-5).

No country in the European Union, however, has yet decided to fortify flour. The folic acid working group of the European Surveillance of Congenital Anomalies is soon to publish a report, concluding that most women in Europe do not take folic acid around the time of conception, despite education programmes in some countries encouraging them to do so.

The group collated data from 17 countries showing that the overall incidence of neural tube defects in Europe has not declined over the 1990s. Even women who do take folic acid often do not start until after conception. The report will recommend that EU countries adopt a policy of fortifying flour with folic acid.

If flour were fortified at the recommended level on a worldwide scale 100 000 pregnancies resulting in neural tube defect would be prevented each year, according to Professor Nick Wald, of the St Bartholomew's and the Royal London School of Medicine and Dentistry.

He said, "There is no evidence or reason to regard fortification at any of the doses proposed as a risk to health, and there is compelling evidence that failure to fortify causes considerable harm."

The meeting was held the day before the UK's Food Standards Agency issued a report warning people against taking too many vitamin supplements. The Birth Defects Foundation issued a press release urging women to keep taking folic acid, after receiving a flood of calls to its telephone helpline from worried women in the wake of the report.

More information can be accessed at

Posted by: Josef Hasslberger on June 2, 2003 06:03 PM


The molecular biology of folic acid and public health issues surrounding the role of the vitamin in human health and disease are extremely complex as evidenced by the contrasting views of experts in the field noted here. However, I'm afraid there is an additional level of complexicity that I think is quite is important but virtually ignored by most investigators in the field and that is the extreme sensitivity of serum (and presumably rbc) folate to photolysis by sunlight. In one study 30-50% of serum folate was destroyed following 1h of exposure to full spectrum solar light (Branda RF 1978 Science 201:625-6). As you have pointed out here, folate deficency is widespread in human populations especially in Europe and I would suggest that the problem may be exacerbated in fair skinned individuals by significant exposure to the sun. We have found that folate is essential for at least two types of DNA repair in cells and our results in human subjects over the past several years has suggested that a folate derivative also acts as a natural sunfilter. Folate supplementation results in greatly decreased rates of sunburning. Taken as a whole, these data add increased skin cancer risk to the many consequences of deficiency in this important micronutrient.

Posted by: Dr Barry J Barclay on July 27, 2003 10:34 AM


Dear Dr. Barclay,

thank you for commenting on my post regarding folic acid. I find your research intriguing as it adds new understanding to the workings of some of the vital substances that are part of the B complex. Let me provide a link for my readers who would like to follow this trail of discovery, a page devoted to your work which I found on Innnovation Alberta

Thanks for the contribution.

Kind regards

Posted by: Josef Hasslberger on July 27, 2003 11:48 AM


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