Food
additives and hyperactivity: Feingold was right
One hundred fifty-three three-year-old children and 144 children
aged eight or nine years consumed a diet free of food colorings
and sodium benzoate for six weeks. During weeks 2, 4, and 6, they
were randomly assigned to receive, in double-blind fashion, a daily
drink containing 1) placebo or 2) sodium benzoate plus one of two
mixtures of artificial food colors and additives. Mix A contained
sunset yellow, carmoisine, tartrazine, and ponceau 4R. Mix B contained
sunset yellow, carmoisine, quinoline yellow, and allura red AC.
Doses for mixes A and B for three-year-old children were roughly
the same as the amount of food coloring in two 56 g bags of sweets.
For eight-year-old and nine-year-old children, the dose for mix
A was equal to about two bags of sweets per day and for mix B about
four bags of sweets per day. In three-year-old children, compared
with placebo, Mix A had a significant adverse effect on the main
outcome measure (a global hyperactivity score; p < 0.05), whereas
Mix B had a nonsignificant adverse effect (p = 0.09). In eight-
and nine-year-old children, a significant adverse effect was seen
for Mix A (p < 0.03) and Mix B (p = 0.001) when the analysis
was restricted to children who consumed at least 85% of the study
drinks.
Comment: More then 30 years ago, Dr.
Ben Feingold reported that ingestion of artificial colors or large
amounts of naturally occurring salicylates was an important contributing
factor to hyperactive behavior. Feingold's initial report stimulated
a great deal of research, some of which supported his observations,
but much of which did not. Most of the negative studies had important
flaws. In one study, for example, the effect of a chocolate cookie
containing artificial colorings was compared with that of a placebo
chocolate cookie. Since many of the children were presumably sensitive
to sugar or chocolate, a chocolate cookie was not an appropriate
placebo. The results of the present study confirm Feingold's original
observations by demonstrating that consumption of artificial colors
or sodium benzoate (or both) resulted in increased hyperactivity
in three-year-old and eight- and nine-year-old children in the general
population.
McCann D, et al. Food additives and hyperactive behaviour in 3-year-old
and 8/9-year-old children in the community: a randomised, double-blinded,
placebo-controlled trial. Lancet.
2007;370:1560-1567.
Omega-3 fatty acids
and hyperactivity
Nine children (aged eight to 16 years) with attention deficit hyperactivity
disorder (ADHD) received, in open-label fashion, an omega-3 fatty
acid supplement for eight weeks. The initial dosage was 30 ml/day,
which provided 16.2 g/day of omega-3 fatty acids (10.8 g of eicosapentaenoic
acid [EPA] and 5.4 g of docosahexaenoic acid [DHA]). The dosage
was adjusted after four weeks based on the ratio of arachidonic
acid (AA) to EPA in plasma phospholipids. If the ratio was <
1.0, the dosage was decreased to 15 ml/day. If the ratio was between
1.0 and 1.5, the dosage was decreased to 20 ml/day. After eight
weeks, significant improvements were seen in inattention, hyperactivity,
oppositional/defiant behavior, and conduct. The mean Clinical Severity
of Illness score improved from 4.4 (moderately symptomatic) to 3.3
(mildly symptomatic). There was a significant correlation between
the reduction in the AA:EPA ratio and Clinical Severity of Illness
score.
Comment: In most previous studies,
omega-3 fatty acids were not beneficial for patients with ADHD.
The present study, which demonstrated improved behavior in children
with ADHD, used substantially higher doses of omega-3 fatty acids
than did the earlier studies. Placebo-controlled trials are needed
to confirm a beneficial effect of high-dose EPA/DHA in children
with ADHD.
Sorgi PJ, et al. Effects of an open-label pilot study with high-dose
EPA/DHA concentrates on plasma phospholipids and behavior in children
with attention deficit hyperactivity disorder. Nutr
J. 2007;6:16.
Iron deficiency as a
factor in ADHD
Twenty-three non-anemic children (aged five to eight years) with
ADHD and a serum ferritin level less than 30 ng/ml (indicating mild
iron deficiency) were randomly assigned in a 3:1 ratio to receive
80 mg/day of iron (as ferrous sulfate; n = 18) in a single morning
dose or placebo (n = 5) for 12 weeks. The mean score on the ADHD
Rating Scale improved significantly (p < 0.01) in the iron group
and became nonsignificantly worse in the placebo group. There was
a nonsignificant trend toward greater improvement on the Conners'
Parent Rating Scale in the iron group compared with the placebo
group. The mean Clinical Global Impression-Severity score improved
significantly (p < 0.01) in the iron group and did not change
in the placebo group. The magnitude of the improvement with iron
was said to be comparable to that achievable with stimulant medications.
Iron therapy was well-tolerated, with the exception of gastrointestinal
side effects (constipation, nausea, abdominal pain) in some patients.
Comment: Iron deficiency can cause
a wide range of mood and behavioral abnormalities. In previous studies,
a low serum ferritin concentration without anemia was found to be
common in children with ADHD, with a prevalence as high as 84% in
one study. The results of the present study indicate that iron deficiency
is an important contributing factor to ADHD in some children. In
order to reduce the incidence of side effects from iron therapy,
it should probably be administered in divided doses throughout the
day. In addition, iron status should be monitored periodically in
patients receiving iron supplements, both to assure that iron deficiency
has been corrected and to reduce the possibility of causing iron
overload.
Konofal E, et al. Effects of iron supplementation on attention deficit
hyperactivity disorder in children. Pediatr
Neurol. 2008;38:20-26.
Omega-3 fatty acids
and autism
Thirteen children (aged five to 17 years) with autistic disorders
accompanied by severe tantrums, aggression, or self-injurious behavior
were randomly assigned to receive, in double-blind fashion, menhaden
oil (providing 840 mg/day of eicosapentaenoic acid and 700 mg/day
of docosahexaenoic acid) or placebo for six weeks. The outcome measure
was the Aberrant Behavior Checklist (ABC) at six weeks. There was
no significant difference in outcome between groups. However, there
was a trend in favor of menhaden oil over placebo for the ABC subscales
of hyperactivity (p < 0.1) and stereotypy, each with a large
effect size.
Comment: Omega-3 fatty acids have been
reported to be beneficial for patients with various psychiatric
conditions, including unipolar depression, bipolar disorder, postpartum
depression, and schizophrenia. In a case report, an 11-year-old
male with autism experienced a marked improvement in anxiety after
receiving a fish oil supplement (J Clin
Psychiatry. 2003;64:848-849). In the present study, clinically
significant improvements were seen in hyperactive and stereotypic
behavior in autistic children who received fish oil. However, because
of the small sample size, the results were not statistically significant.
A larger study is needed to confirm these preliminary observations.
Amminger GP, et al. Omega-3 fatty acids supplementation in children
with autism: a double-blind randomized, placebo-controlled pilot
study. Biol Psychiatry. 2007;61:551-553.
Zinc prevents infections
in elderly people
Fifty healthy volunteers (mean age, 66 years) were randomly assigned
to receive, in double-blind fashion, 45 mg/day of zinc (as zinc
gluconate) or placebo for 12 months. The proportion of people having
one or more infections during the study was significantly lower
in the zinc group than in the placebo group (29% vs. 88%; p <
0.001). The proportion of subjects having more than one infection
was 0% in the zinc group and 36% in the placebo group.
Comment: Zinc enhances immune function
through several different mechanisms. The typical Western diet,
with its high proportion of refined and processed foods, contains
suboptimal amounts of zinc. The results of the present study indicate
that zinc supplementation can reduce the incidence of infections
in healthy elderly people. Long-term zinc supplementation should
be accompanied by a copper supplement (1-4 mg per day, depending
on the zinc dose), to prevent zinc-induced copper deficiency. For
a person taking 45-50 mg of supplemental zinc per day, a reasonable
dose of supplemental copper would be 2-3 mg per day.
Prasad AS, et al. Zinc supplementation decreases incidence of infections
in the elderly: effect of zinc on generation of cytokines and oxidative
stress. Am J Clin Nutr. 2007;85:837-844.
Beta-carotene prevents
cognitive decline
Participants in the Physicians' Health Study, which began in 1982,
were randomly assigned to receive, in double-blind fashion, 50 mg
of beta-carotene every other day or placebo for a mean of 18 years.
Participants in the Physicians' Health Study II, which was begun
in 1998, were also randomly assigned to receive beta-carotene or
placebo for a mean of one year until the beta-carotene arm of the
study was terminated. Among participants from the Physicians' Health
Study (mean treatment duration, 18 years), the mean global score
that assessed cognitive function was significantly higher in the
beta-carotene group than in the placebo group (p = 0.03). On verbal
memory, the beta-carotene group also performed significantly better
than the placebo group (p = 0.007). No difference in cognitive function
was seen between the beta-carotene and placebo groups among participants
in the Physicians' Health Study II (mean treatment duration, one
year).
Comment: Oxidative stress contributes
to brain aging. Because beta-carotene is an antioxidant, it has
the potential to slow the aging process, thereby slowing the normal
decline in cognitive function. The results of the present study
indicate that long-term beta-carotene supplementation prevented
cognitive decline, but short-term supplementation did not. Smokers
should not take beta-carotene supplements, because this compound
has been shown to increase the incidence of lung cancer in smokers.
It is probably best to obtain beta-carotene mostly from foods (i.e.,
fruits and vegetables) rather than from supplements, because foods
that contain beta-carotene are also rich in many other beneficial
nutrients.
Grodstein F, et al. A randomized trial of beta carotene supplementation
and cognitive function in men: The Physicians' Health Study II.
Arch Intern Med. 2007;167:2184-2190.
Papaya seeds eradicate
intestinal parasites
Sixty asymptomatic Nigerian children with evidence of intestinal
parasites on stool microscopic examination were randomly assigned
to receive 20 ml of an elixir containing air-dried and blended Carica
papaya seeds (0.2 g/ml; 4 g of seeds) and honey or honey alone (placebo).
Seven days after the treatment, stool examination was negative for
parasites in 76.7% of the children receiving active treatment and
in 16.7% of those receiving placebo (p < 0.00002). The stool
clearance rates for the various types of parasites were 71.4%-100%:
A. lumbricoides, 11 of 13; E. histolytica, 5 of 7; N. americanus,
4 of 5; S. stercoralis, 4 of 4; T. trichiura, 3 of 3; G. lamblia,
2 of 2; and T. saginata, 1 of 1. No adverse effects were seen.
Comment: Seeds of the tropical fruit,
Carica papaya, have antihelminthic and anti-amoebic activities and
have been used in folk medicine to treat helminthiasis. The results
of the present study indicate that this treatment can eradicate
most of the common intestinal parasites. Further studies should
compare the effectiveness of papaya seeds to that of conventional
medications used to treat parasites.
Okeniyi JAO, et al. Effectiveness of dried Carica papaya seeds against
human intestinal parasitosis: a pilot study. J
Med Food. 2007;10:194-196.
D-Pinitol improves glycemic control in diabetics
Twenty patients (mean age, 65.5 years; mean body mass index, 26.3
kg/m2) with type 2 diabetes that was poorly controlled on sulfonylurea,
Metformin, and/or insulin therapy received D-pinitol at a dose of
20 mg per kg of body weight per day for 12 weeks, while continuing
their usual medication. The mean fasting plasma glucose concentration
decreased from 200 mg/dl at baseline to 169 mg/dl after 12 weeks
(15.5% decrease; p < 0.05). The mean hemoglobin A1c concentration
decreased from 9.8% to 8.3% (15.3% decrease; p < 0.05).
Comment:
D-chiro-inositol, a stereoisomer of myo-inositol (commonly known
as inositol), is a component of an endogenous phosphoglycan that
has been reported to mediate the action of insulin. D-Pinitol (3-O-methyl-
D-chiro-inositol) occurs naturally in several foods such as legumes
and citrus fruits and has a chemical structure and biochemical actions
similar to those of D-chiro-inositol. In addition, D-pinitol is
probably converted to D-chiro-inositol in vivo, as demonstrated
by a 14-fold increase in the mean serum concentration of D-chiro-inositol
after administration of D-pinitol to diabetic patients. The results
of the present study confirm an earlier report (Eur
J Clin Nutr. 2005;59:456-458)
showing that supplementation with D-pinitol improves glycemic control
in patients with type 2 diabetes. Since D-pinitol appears to mediate
the action of insulin, rather than enhance the binding of insulin
to its receptor, D-pinitol's effects on glycemic control might
be additive to those of chromium, which is believed to work by facilitating
insulin binding to its receptor.
Kim MJ, et al. Effect of pinitol on glucose metabolism and adipocytokines
in uncontrolled type 2 diabetes. Diabetes
Res Clin Pract. 2007;77(Suppl
1):S247-S251.
Alan R. Gaby, MD
drgaby@earthlink.net
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