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EDITORIAL
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The Importance of Food
I
T HAS BEEN FIRMLY ESTABLISHED THAT LOW MA-
ternal intake of folate creates a fetal nutrient deficiency that leads to incomplete development
of the fetal nervous system. The critical period
for maternal folate intake seems to be the first
few weeks of fetal development. Ensuring adequate folate intake during this period is a vexing problem because the fact of pregnancy may not be known even to
the mother at this early stage. The confluence of the problem of getting women of childbearing age to eat an adequate amount of folate with the observation that adequate folate helps prevent neural tube defects (NTDs)
led to the addition of folic acid to grain foods in the US
food supply starting in 1998.1 This strategy has been effective in getting folate to young potential mothers and
also in reducing NTDs. 2 However, the strategy enhances an otherwise nutrient-poor food (refined grain
foods are the primary focus of fortification; whole grain
foods are naturally rich in folate) and increases folic acid
in purified form to the total population.
See also page 121
Despite the success of folate fortification in decreasing NTDs, in the broader context of a variety of dietary
supplements, we are generally pessimistic about the value
of purified supplements.3 Mursu et al3 studied consumption of 15 dietary supplements in 38 772 women initially aged 55 to 69 years with a median follow-up period of 19 years; after adjustment for lifestyle variables,
14 of the supplements were unassociated with total mortality or were associated with increased mortality. There
is considerable evidence from randomized clinical trials
(RCTs) that isolated supplements do not yield expected
benefits and may even do harm.4 Of particular concern
in regard to folic acid is the extended follow-up (median duration, 38 months) after 2 Norwegian RCTs that
provided folate, pyridoxine hydrochloride (vitamin B6),
and cyanocobalamin (vitamin B12) (median duration of
treatment, 39 months) to men and women with ischemic heart disease.5 The pooled findings for these studies
found a hazard ratio of 1.18 (95% CI, 1.04-1.33) for total
mortality, 1.38 (95% CI, 1.07-1.79) for cancer mortality, and 1.21 (95% CI,1.03-1.41) for cancer incidence comparing the 3411 participants who were treated with folic acid plus cyanocobalamin and pyridoxine
hydrochloride or folic acid plus cyanocobalamin with the
3426 participants who were treated with pyridoxine hydrochloride or placebo. Folate is a growth promoter, which
is of benefit in the early fetal situation, but may be a detriment in cancer. Of great interest, given this conundrum of competing benefits (reduced NTDs) and risks
(increased cancer or other chronic disease), Carmichael
et al6 show that certain dietary patterns are strongly inversely related to reduced NTDs.
Carmichaeletal6 appliedthedietpatternsconcepttoNTDs,
although this approach has most commonly been used to
study chronic diseases, such as cancer and cardiovascular
disease,7-9 and has been used in other contexts, such as hypospadias.10 The importance of the findings of Carmichael
et al6 lies in showing that women obtain benefit from the consumption of a high-quality diet, beyond the benefits derived
throughgrainfortification.Thisraisesthequestionofwhether
ahigh-qualitydietalonemaybesufficienttopreventNTDs—a
strategy that would also remove the potential harm from fortification.5 Furthermore, a high-quality diet will contribute
additional nutrients that may contribute to human development in as-yet unrecognized ways. Along these lines of
thought, Carmichael et al6 contend that other constituents
in food besides folate help to prevent NTDs, a notion supported by their data and in need of further investigation. For
example, a living organism would likely activate a complementarypathwaytoinhibitfolate-inducedundesirablegrowth
promotion. Such a complementary substance might be available in a food but not in folic acid as a supplement or added
to food.
We believe that a high-quality diet could have even
greater benefits than those documented by Carmichael
et al,6 in whose study diet patterns did not satisfy some
optimality conditions. In particular, the authors did not
separate whole-grain from refined-grain foods, nor dairy
products by fat content, nor foods by predominant type
of fat. We and others have made such distinctions,7-9 consistent with dietary recommendations. It would be interesting for Carmichael et al to use a dietary pattern score
in the National Birth Defects Prevention Study that better reflects current nutritional knowledge. In addition,
other databases might be queried to study data acquired
prior to folate fortification; the point would be to examine the effect on NTDs of a high-quality diet in the absence of any form of folate supplementation.
Food, deriving as it does from formerly living organisms, is a complex, nonrandom mixture of constituents that
works well in keeping the organism alive.11 Nutrients repair deficiency conditions, such as folate in the case of NTD
(deficient at least for the fetus). The fetus perhaps “doesn’t
care” whether folate comes from food or supplements.
Foods, however, are a balanced combination of nutrients
and prevent a wide variety of chronic conditions, even in
ARCH PEDIATR ADOLESC MED/ VOL 166 (NO. 2), FEB 2012
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the absence of deficiencies. The biologic systems involved
in nutrition and disease are complex and not completely
understood. We do know, however, that the human body
did not evolve in the presence of a fortified food supply,
and that some of the healthiest populations on the planet
subsist, even thrive, on a whole food diet. Thus, we feel
that it is reasonable to call for further exploration of the
health effects, whether positive or negative, of adding isolated compounds to the food supply.
The lesson from the article by Carmichael et al6 is an
important one: people, including women of childbearing age, should eat good food. A good diet may be described as simply as the aphorism, “Eat food, not too
much, mostly plants.”12 At the same time, we are reminded that more of a good thing is not always better. A
nutrient may correct a deficiency condition but not necessarily be of benefit at higher doses in well-nourished
people. The implication, based on many clinical trials of
supplements, is that supplementation and its hidden partner in food, fortification, may have some dangers. Reduction of NTDs may be achievable by diet alone, at the
same time reducing potential risk for other chronic diseases in the rest of the population.
David R. Jacobs Jr, PhD
Jaakko Mursu, PhD
Katie A. Meyer, MPH, ScD
Published Online: October 3, 2011. doi:10.1001
/archpediatrics.2011.184
Author Affiliations: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis.
Correspondence: Dr Jacobs, Division of Epidemiology
and Community Health, School of Public Health, Uni-
versity of Minnesota, 1300 S Second St, Ste 300, Minneapolis, MN 55454 ([email protected]).
Financial Disclosure: None reported.
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3. Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR. Dietary supplements and
mortality rate in older women: the Iowa Women’s Health Study. Arch Intern Med.
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5. Ebbing M, Bønaa KH, Nygård O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA. 2009;302(19):2119-2126.
6. Carmichael SL, Yang W, Feldkamp ML, et al; National Birth Defects Prevention
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8. Jacobs DR Jr, Sluik D, Rokling-Andersen MH, Anderssen SA, Drevon CA. Association of 1-y changes in diet pattern with cardiovascular disease risk factors and
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11. Jacobs DR Jr, Gross MD, Tapsell LC. Food synergy: an operational concept for
understanding nutrition. Am J Clin Nutr. 2009;89(5):1543S-1548S.
12. Pollan M. In Defense of Foods. New York, NY: Penguin Press; 2008.
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