Inertia on folic acid has caused thousands of unnecessary deaths
BMJ 2003; 326 doi: https://doi.org/10.1136/bmj.326.7398.1054-c (Published 15 May 2003) Cite this as: BMJ 2003;326:1054
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
During the ‘70s, I was research director of the Steinberg Corporation
in Canada, one of the largest integrated agribusinesses at the time. Not
only did we own more than 300 large supermarkets, but the production and
processing infrastructure for many of the retail products as well. In the
case of bakery products, we had our own flour mill and the largest bakery
under one roof in the world. Because the business was family-owned, the
relationship to consumers and the commitment to social responsibility were
very strong. A great number of the positive actions we took were never
advertised because we did not want to turn them into a form of underhanded
marketing as is often seen today.
During the mid-‘70s, the Nutrition Canada Survey reported a shortfall
in folic acid and biotin intakes. We immediately petitioned the
Government to allow us to include these two nutrients in all our bread
products. We had no intention of making a major issue out of it, but
simply intended to list these two ingredients in their proper order on the
label ingredient listing. We felt that it was the right thing to do and
as the cost of these nutrients were next to nothing in the overall scheme
of things, we had no plan to change product pricing. The Government
regulators refused to permit us to do this as there was no allowance in
the bread standard for these micro-nutrients. However, we felt that the
Nutrition Canada evidence was compelling and decided to defy the
Government. By 1978, all our bread products were supplemented with folic
acid and biotin. The Government wisely decided not to prosecute us.
Descriptions of our products containing folic acid were made in a
number of trade magazines – two decades before the rest of the world
decided to add it. Most of the industry, has long known the nutritional
benefits of folic acid supplementation, but refused to do anything about
it until compelled. It is a pity, because consumers really deserve a bit
more responsibility than that.
Morton Satin
Competing interests:
None declared
Competing interests: No competing interests
With interest we read the considerations by A. Ellis, who criticized
the inertia of the UK government regarding fortification of food with
folate. Whereas it is well established that folate is effective in
preventing neural tube defects in pregnancy, the statement that thousands
of unnecessary deaths due to cardiovascular disease could have been
prevented by folic acid supplementation, is still rather speculative. In
this context the protective role of folate against vascular dysfunction
was based primarily on its efficacy to lower homocysteine in
hyperhomocysteinaemic and normohomocysteinaemic individuals. However, data
that homocysteine by itself induces vascular damage by enforcing oxidative
stress are mainly derived from in vitro experiments, applying much higher
homocysteine concentrations than detectable in the blood of patients.
Moreover, gene expression studies indicate that homocysteine itself is
unable to elicit an oxidative stress response in vitro, rather it is able
to enhance it once established (1). Although folate administration
efficiently lowers homocysteine concentrations and in parallel ameliorates
vascular function (2), a causal relationship remains to be elucidated.
E.g., a recent study shows (3), that endothelial function already improved
within 2-4 hours after folate administration, rather independently from
changes of homocysteine concentrations which declined with some delay.
Studies demonstrating folate administration to inhibit the
progression/development of coronary artery disease are still scarce, and
larger clinical trials are needed to confirm that folate is the key player
preventing this process. Notably, not only folate administration but also
supplementation with other vitamins, e.g. antioxidants vitamin C and E,
can be beneficial to reduce lipid peroxidation (4). Immune activation is
deeply involved in the pathogenesis of several chronic disorders, like
neurodegenerative, autoimmune and malignant diseases in addition to
cardiovascular disease. Overwhelming production of antimicrobial and
cytocidal compounds may cause oxidative stress and enhance the demand for
vitamins in patients with so-called “consuming diseases” (5). Thus,
vitamin supplementation in general could effectively slow-down the long-
term consequences of chronic immune system activation in patients,
compensate for enhanced vitamin consumption thereby reducing, e.g.,
vascular complications. Also anti-inflammatory medication like aspirin
could be of benefit for patients, as the protective role of non-steroidal
anti-inflammatory drugs has already been established in many diseases
associated with immune chronic immune activation like cardiovascular and
neurodegenerative diseases. To conclude, additional vitamins will
certainly be beneficial in chronic disorders going along with immune
activation and oxidative stress. One the one hand, this does not
necessarily allow the conclusion that vitamin supplementation is also of
benefit in “healthy” individuals. On the other hand, a more specific role
of homocysteine and folate still remains to be unequivocally demonstrated.
Schroecksnadel Katharina, Frick Barbara, Dietmar Fuchs
Institute of Medical Chemistry and Biochemistry, University of Innsbruck,
A-6020 Innsbruck, Austria
1. Outinen PA, Sood SK, Liaw PC, Sarge KD, Maeda N, Hirsh J, et al.
Characterization of the stress-inducing effects of homocysteine.
Biochem J 1998;332:213-21.
2. Doshi SN, McDowell IF, Moat SJ, Payne N, Durrant HJ, Lewis MJ, et al.
Folic acid improves endothelial function in coronary artery disease via
mechanisms largely independent of homocysteine lowering. Circulation
2002;105:22-6.
3. Woo KS, Chook P, Chan LL, Cheung AS, Fung WH, Qiao M et al. Long-term
improvement in homocysteine levels and arterial endothelial function after
1-year folic acid supplementation. Am J Med 2002;112:535-9.
4. Huang HY, Appel LJ, Croft KD, Miller ER 3rd, Mori TA, Puddey IB.
Effects of vitamin C and vitamin E on in vivo lipid peroxidation: results
of a randomized controlled trial. Am J Clin Nutr 2002;76:549-55.
5. Fuchs D, Jaeger M, Widner B, Wirleitner B, Artner-Dworzak E, Leblhuber
F. Is hyperhomocysteinemia due to the oxidative depletion of folate rather
than to insufficient dietary intake? Clin Chem Lab Med 2001;39:691-4.
Competing interests:
None declared
Competing interests: No competing interests
I agree with Dr Ellis and I feel the widespread use of folic acid as
a supplement or in food fortification could effectively circumvent a
growing public health care issue. Folic acid, especially combined with
other B-Nutrients has been continuously shown to lower the risk of
developing a host of diseases such as atherosclerosis, cervical dysplasia,
NTD, colon cancer,and maybe even Alzheimer's. Certainly the data assessing
the impact this inexpensive vitamin has upon the development of heart
disease, stokes, peripheral vascular disease and NTD should compell all
providers to fully endorse the use of this preventative strategy.
Competing interests:
None declared
Competing interests: No competing interests
There is documented evidence that folic acid prevents upto 70%
recurrence of neural tube defects.Many health care providers are aware of
this. But the fact that it is to be given preconceptionally is known only
to few. Efforts are required to include this in the undergraduate
curriculum in th must know area of learning objectives. In the community
use of supplemental folic acid at the right time inright doses can be
increased through media. This should be a part of marriage counselling
Though fortification will take care of most of folic acid requirment but
it may not be possible in many countries.As we discover role of different
micronutrients and vitamins how are we going to supplement these in the
right quantity for different individuals. "Food for thought" -ultimately
healthy eating habits, good quality natural food, awareness and selective
supplementation is the answer for such problems.If we supplement iron,
zinc , folic acid etc together will it be possible? Will the food be
palatable? Won't they interfere with each others absorption.
Competing interests:
None declared
Competing interests: No competing interests
Dietary Folates are not enough
Dietary folates are not enough
The authors, who contributed the Italian data (1) to the WHO/EUROCAT
report quoted in the News roundup article, would like to contribute
further to the case supporting compulsory folic acid fortification of
essential food.
In Italy diet has traditionally been considered an adequate source of
folates and neural tube defect (NTD) prevalence low compared to Northern
European countries. This has placed folic acid supplementation low on the
public health agenda. Awareness of the preventative effect of folic acid
for birth defects is also low. In a recent study only 3% of pregnant women
took FA supplements correctly (2).
Data from the Emilia Romagna registry of birth defects (IMER)
clearly shows that dietary folates are not enough to prevent (NTD) with a
prevalence of 7 per 10,000 as total cases in 2000 (see graph).
Legalisation of termination of pregnancy (the registry started collecting
data in 1996) shows terminations following prenatal diagnosis of NTD were
6 per 10,000 in 2000 (see graph).
The factors underlying this trend are currently under investigation.
Demographic change in the region with immigration from countries outside
of the European Community could perhaps indicate a socio-economically
deprived group. 15 to 18% of births in our region are to immigrants (3).
Compulsory folic acid fortification of essential food - cheap,
effective and proven - as a primary prevention policy for NTD is required
across Europe. Only this policy can prevent socio-economic inequality and
ensure birth defect prevention to those who need it most. Reliance on a
secondary prevention policy based on the termination of affected
pregnancies - a heartbreaking alternative in a wanted pregnancy - is no
longer ethical given the body of evidence now available regarding the
preventative effects of folic acid.
Sincerely
E Calzolari
A J Neville
G Cocchi
References
1. Calzolari E, Cocchi G, Neville AJ. Report on periconceptional
folic acid supplementation for Italy EUROCAT Special Report: Prevention of
Neural tube defects by periconceptional Folic acid supplementation in
Europe. pp52-55 May 2003 in print.
2. Cocchi G., Gualdi S.,Mammoliti PMA., Piccolo C . Primary prevention of
Neural tube defects: lack of information about folic acid in Italy: Emilia
Romagna region. Fontiers of Fetal Health Vol 2, pp9-11 Sept. 2000
3. ERMES (statistics regarding the Emilia Romagna region)
www.regione.emilia-romagna.it
Competing interests: �
None declared
Competing interests: No competing interests