Respiratory symptoms and atopy in children in Aberdeen: questionnaire studies of a defined school population repeated over 35 years
BMJ 2004; 329 doi: https://doi.org/10.1136/bmj.38139.666447.F7 (Published 26 August 2004) Cite this as: BMJ 2004;329:489All rapid responses
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Dr Grant's comments are, as always, interesting and provocative, but
on the basis of our questionnaire-based study, we are able to comment only
on exposure to environmental tobacco smoke, which fell significantly
between 1989 and 1999.
Our questionnaires were not designed to examine the rôle of diet in
asthma, but we agree with her that there are numerous reasons why dietary
insufficiency might be important. It is however important to distinguish
between factors that might be involved in the pathogenesis of asthma, the
correction of which might prevent the development of asthma, and factors
that might be involved in the perpetuation of asthma, correction of which
might be useful in the management of established asthma. Although large
numbers of studies have shown associations between asthma and a wide
variety of dietary insufficiencies, particularly of antioxidant vitamins
and minerals, dietary modification and supplementation have not so far
been convincingly successful in the management of asthma.[1-3] We must
therefore be cautious in assuming that dietary modification or
supplementation will be useful in the management of asthma; it may even be
dangerous.[4]
The failure of dietary modification to produce clinical improvement
in established asthma suggests that diet may be more important in
initiating than in the perpetuating asthma, an effect that may begin
before birth. Studies in Aberdeen have suggested associations between
maternal antioxidant intake during pregnancy and wheezing illness in the
first year of life,[5] as well as effects of maternal vitamin E intake on
cord blood mononuclear cell function.[6]
References
1. Allam MF, Lucane RA. Selenium supplementation for asthma.
Cochrane.Database.Syst.Rev. 2004;CD003538.
2. Thien FC, Woods R, de Luca S, Abramson MJ. Dietary marine fatty
acids (fish oil) for asthma in adults and children.
Cochrane.Database.Syst.Rev. 2004;2.
3. Kaur B, Rowe BH, Ram FS. Vitamin C supplementation for asthma.
Cochrane.Database.Syst.Rev. 2004;2.
4. Milner JD, Stein DM, McCarter R, Moon RY. Early infant
multivitamin supplementation is associated with increased risk for food
allergy and asthma. Pediatrics 2004;114:27-32.
5. Martindale S, McNeill G, Devereux G, Seaton A. Antioxidant intake
in pregnancy in relation to wheeze and eczema in the first two years of
life. Eur Respir J 2003;24(suppl 48):665s.
6. Devereux G, Barker RN, Seaton A. Antenatal determinants of
neonatal immune responses to allergens. Clin.Exp.Allergy 2002;32:43-50.
Competing interests:
None declared
Competing interests: No competing interests
EDITOR- Thank you Dr Nehrlich for your kind comments about my
responses. I did not provide a comprehensive review of the many
nutritional deficiencies found in children with asthma. My intention was
to emphasise the fall in “healthy” children’s sweat zinc levels in the
decade of the 1980s, which saw the largest increase in the diagnosis of
important childhood illnesses, following the largest increase of in
prolonged use of hormones by young women before pregnancy.
The recent Australian evidence, for a significant association between
the ratio of n-6:n-3 fatty acids and risk for current asthma in children,
is based on dietary questionnaires and not on RBC EFA assessments.1 Diets
higher in n-3 EFAs may also be higher in zinc, if a lot of fish is eaten.
My experience, with monitoring red blood cell EFA levels in patients not
already taking supplements, is that females are more likely to be
deficient in red cell n-6 EFAs and males in n-3 EFAs but delta desaturase
blocks are common in both pathways. Unless zinc, copper, magnesium and B
vitamin deficiencies are also treated, EFA supplementation can fail to
improve EFA pathway deficiencies.
Pub Med cites16 papers mentioning zinc deficiency and asthma starting
with Colquhoun and Bunday, the founders of the Hyperactive Children’s
Support Group (HCSG), who hypothesised that many hyperactive children also
have eczema, allergies and asthma and EFA supplements seemed to help.2
Also zinc deficiency and adverse reactions to wheat and milk, foods are
known to give rise to exorphins in the gut which can block conversion of
EFAs to prostaglandins, were common. The HCSG advises mothers to avoid
giving their children colours, additives and harmful medications, and
instead provide low allergy diets with extra nutritional supplements
including zinc and EFAs.
In 2001 Truong-Tran and colleagues mapped zinc in the respiratory
epithelium to elucidate its role in regulating caspase-3 activated
apoptosis. They proposed that zinc, being a major dietary anti-oxidant
has a protective role for the airway epithelium against oxyradicals and
other noxious agents. Zinc acts as: (i) an anti-oxidant; (ii) an organelle
stabilizer; (iii) an anti-apoptotic agent; (iv) an important cofactor for
DNA synthesis; (v) a vital component for wound healing; and (vi) an anti-
inflammatory agent.3 They considered zinc may have important implications
for asthma and other inflammatory diseases where the physical barrier is
vulnerable and compromised.
Some studies in asthmatic children have found significantly lower
serum and hair zinc levels (but a one hour collection of passive sweat
gives a more accurate assessment because zinc is actively conserved in
sweat in zinc deficiency).
In 2002 the ADAM33 (a disintegrase and metalloproteinase 33) gene, a
novel member of the ADAM family of zinc-dependent metalloproteases, was
identified as a risk factor for the development of asthma and bronchial
hyper-responsiveness.4,5 When zinc is deficient gene function, messenger
RNA and protein synthesis and repair enzymes may be impaired.
Powell and colleagues write that new approaches are needed as the
incidence of asthma worldwide is increasing and the disease has a large
unmet clinical need because of persisting morbidity and mortality, despite
the availability of anti-inflammatory and bronchodilator medication.6
Ensuring adequate nutritional status by monitored supplementation,
especially before conception and during growth, seems an excellent way to
start.
1 Oddy WH, de Klerk NH, Kendall GE, Mihrshahi S, Peat JK. Ratio of
omega-6 to omega-3 fatty acids and childhood asthma. J Asthma. 2004; 41:
319-26.
2 Colquhoun I, Bunday S. Med Hypotheses. A lack of essential fatty
acids as a possible cause of hyperactivity in children. Med Hypotheses.
1981; 7: 673-9.
3 Truong-Tran AQ, Carter J, Ruffin R, Zalewski PD. New insights into
the role of zinc in the respiratory epithelium. Immunol Cell Biol. 2001;
79:170-7.
4. Yoshinaka T, Nishii K, Yamada K, Sawada H, Nishiwaki E, Smith K,
Yoshino K, Ishiguro H, Higashiyama S. Identification and characterization
of novel mouse and human ADAM33s with potential metalloprotease activity.
Gene. 2002; 282: 227-36.
5 Van Eerdewegh P, Little RD, Dupuis J, Del Mastro RG, Falls K, Simon
J, et al. Association of the ADAM-33 gene with asthma and bronchial
hyper-responsiveness. Nature 2002;418:426-30.
6 Powell RM, Hamilton LM, Holgate ST, Davies DE, Holloway JW.
ADAM33: a novel therapeutic target for asthma. Expert Opinion on
Therapeutic Targets 2003; 7: 485- 494.
Competing interests:
None declared
Competing interests: No competing interests
I greatly enjoy most of Dr. Grant's comments as they contain little
in the way of filler or paddings, it's almost all substance.
She laments the sharp increase in some of the modern illnesses, these are
called "the modern nutritional diseases" by Drs Alice and Fred Ottoboni in
their book of the same title.
A small omission seems to have ocurred, however: the fact that most of us
lack omega-3 essential fatty acids, that is, the balance between n-6 and n
-3 is badly out of kilter.
Rudin and Horrobin have carried on from the original Johanna Budwig of
Freudenstadt, Germany and it is very good to see that cardiologists and
others are beginning to implement these life-improving and often life-
saving procedures.
Leaving the subject of cardiac arrhythmias for a future discussion, I
would like to mention the clinical use of n-3 for various conditions, such
as Attention Deficit problems,
skin diseases, schizophrenia and manic depressive illness and a multitude
of other ailments (including malignancies) of modern man.
The best results I have observed are those that can be achieved with
asthma and eczema.
Rudin talks about Dietary Deviations and Disease Correlations and his book
"The Omega-3 Phenomenon" is good reading.
Some clouds, however are on the horizon: Fish is set to become inedible in
our lifetime in many parts of the world.
Competing interests:
None declared
Competing interests: No competing interests
EDITOR - Anne Devenny and colleagues report that over the past 15
years the prevalence of childhood asthma, and symptoms suggestive of
asthma, have risen with a quarter of primary school children being
diagnosed as having asthma at some time in their lives.1 Their Table shows
huge increases in childhood allergies over the past 35 years, mostly
between 1964 and 1989. By 1999 asthma diagnoses had increased six fold and
shortness of breath, eczema and hay fever had increased four to five fold.
What happened to cause such large increases in childhood illnesses?
Similar increases seem to have occurred in dyslexia, hyperactivity and
autism. Why has the sex ratio of childhood allergies changed from being
twice as common in boys to equal prevalence in girls?
A single cohesive explanation may be the increasing use by younger
women of hormonal contraceptives, and also smoking and alcohol before
conception. Hormone use lowers zinc and magnesium levels and causes copper
imbalances. It is important to correct these abnormalities before
conception to prevent unexplained infertility or recurrent miscarriages,
or health problems in future children.2,3 Low maternal zinc levels during
early pregnancy can impair homeostatic mechanism and stress-coping
mechanisms throughout future growth and development in animals. It is
likely that the increases in allergic illnesses in children could be
stemmed if hormonal contraception, smoking and alcohol use were avoided by
young women before conception. Monitored nutritional supplementation for
parents before conception, mothers during pregnancy and children when
growing is very useful.
In 1989 we found that the average sweat zinc level of a group of
dyslexic children was only 358 ug/l. Their matched controls had a bottom
reference range average of only 520 ug/l. In contrast in 146 healthy
children tested in the early 1979, the average sweat zinc level for boys
was 719 ug/l and for girls was 704 ug/l. These differences are highly
significant.2,3 In 1971 only one in ten single women had used oral
contraceptives but this had increased to nine out of ten by 1981. The
effect of this change in maternal hormone use would be seen among 7 to 13
year olds during the 1980s and 1990s.
Boys need more zinc during development than girls, which may explain
the previous double risk of asthma in boys. As zinc deficiency has become
more common, more girls are also likely to be zinc deficient. As with
dyslexia, asthma tends to be more common in younger boys but after puberty
becomes more problematic for girls. The effect of endogenous sex hormone
production after puberty is to lower zinc and raise copper levels in
girls, who would then become more likely to be zinc deficient.
1 Devenny A, Wassall H, Ninan T, Russell G. Respiratory symptoms and
atopy in children in Aberdeen: questionnaire studies of a defined school
population repeated over 35 years. BMJ 2004; 329: 489-490 (28 August),
doi:10.1136/bmj.38139.666447.F7 (published 24 June 2004)
2 Grant ECG. Nutritional supplements to prevent pregnancy
complications.
http://bmj.com/cgi/eletters/329/7458/152#67502, 16 Jul 2004
3 Grant ECG. Monitored nutritional supplements to prevent pregnancy
complications. http://bmj.com/cgi/eletters/329/7458/152#70176, 6 Aug 2004
4 Grant ECG, Howard JM, Davies S, Chasty H, Hornsby B, Galbraith J.
Zinc deficiency in children with dyslexia: concentrations of zinc and
other minerals in sweat and hair. BMJ 1989 ; 296: 607-9.
5 Howard JM. Serum, leucocyte, sweat and hair zinc levels – a
correlation study. J Nutr Environ Med 1990; 1:119-126.
Competing interests:
None declared
Competing interests: No competing interests
Studies of nutritional supplementation, in asthma or other diseases, which fail to monitor nutritional status, are unscientific.
Professor Russell and colleagues confirm that parental tobacco
smoking and nutritional status may be an important cause of childhood
asthma. While tobacco smoking has declined in both men and women overall,
it has caused some alarm that tobacco smoking and alcohol drinking has
increased in the youngest age groups.
The excellent work of Devereaux and colleagues in Aberdeen showed
that the magnitude of cord blood mononuclear cells (CBMC)-proliferative
responses to allergens increased significantly in association with a
family history of atopic disease or maternal smoking, and decreased
significantly with increasing birth order and high maternal dietary intake
of vitamin E. They concluded that the epidemiological association between
birth order and atopy may be a consequence of antenatal influences rather
than of protective effects of childhood infections and that diet during
pregnancy may influence the fetal immune system in such a way as to
modulate the risk of childhood atopy.1
However, studying unmonitored supplementation with single or group
nutrients is not particularly scientific.
Allam and colleagues found only one trial with a total of 24 patients
suffering from chronic asthma who were supplemented with selenium.2 Those
supplemented had a significant clinical improvement in terms of a
'clinical evaluation.' Either fish oils or vitamin C or multivitamins were
supplemented in the other 3 studies quoted.3-5
The conclusions of Milner study were that early vitamin
supplementation is associated with increased risk for asthma in black
children and food allergies in exclusively formula-fed children. Is
supplementation not more likely in families with a history of allergies
and asthma because so many studies have shown for many years that such
children do indeed have a range of nutritional deficiencies?
We demonstrated in the 1970s that the numbers of foods causing
adverse reactions, in response to re-introduction after exclusion dieting,
was greater in migraine patients with higher serum copper/zinc ratios.6,7
The overwhelming fundamental importance of verifying normal zinc,
copper, and magnesium status before conception, during pregnancy and
during growth and development in children is still not fully recognised.
Such mineral deficiencies block essential fatty acid pathways and impair
the function of B vitamins, even if dietary intake of these is adequate.
I do not see that it is a cautious approach to leave important
nutritional deficiencies undiagnosed and untreated in asthma or in any
other condition.
1. Devereux G, Barker RN, Seaton A. Antenatal determinants of
neonatal immune responses to allergens. Clin.Exp.Allergy 2002;32:43-50.
2. Allam MF, Lucane RA. Selenium supplementation for asthma.
Cochrane.Database.Syst.Rev. 2004;CD003538.
3. Thien FC, Woods R, de Luca S, Abramson MJ. Dietary marine fatty
acids (fish oil) for asthma in adults and children.
Cochrane.Database.Syst.Rev. 2004;2.
4. Kaur B, Rowe BH, Ram FS. Vitamin C supplementation for asthma.
Cochrane.Database.Syst.Rev. 2004;2.
5. Milner JD, Stein DM, McCarter R, Moon RY. Early infant
multivitamin supplementation is associated with increased risk for food
allergy and asthma. Pediatrics 2004;114:27-32.
6. Capel ID, Grant ECG, Dorrell HM, Pinnock MH, Clifford Rose F, Williams
DC. Disturbed liver function in migraine patients. Headache 1979;19:270-
272
7.Grant ECG. The pill, hormone replacement therapy, vascular and mood
over-reactivity , and mineral imbalance. J Nutr Environ Med 1998;8:105-116
Competing interests:
None declared
Competing interests: No competing interests