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U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202-9034
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONZn and behavior in...Zn and behavior in...Zn and behavior in...Zn and brain electrophysiology...Methodology issues relevant to...SUMMARYREFERENCES |
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KEY WORDS: • zinc nutrition • humans • cognition • brain function • methods
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONZn and behavior in...Zn and behavior in...Zn and behavior in...Zn and brain electrophysiology...Methodology issues relevant to...SUMMARYREFERENCES |
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) and
developed (Sandstead 1995
) countries. Despite
substantial evidence from animal experiments showing that Zn
deprivation during periods of rapid development impairs behavior and
brain development in animals (Golub et al. 1995
,
Halas and Eberhardt 1987
), few studies have investigated
Zn deficiency effects on behavior or brain function of children. |
Zn and behavior in infants |
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TOPABSTRACTINTRODUCTIONZn and behavior in...Zn and behavior in...Zn and behavior in...Zn and brain electrophysiology...Methodology issues relevant to...SUMMARYREFERENCES |
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supplemented very-low-birth-weight U.S. infants
with either 6.7 or 11 mg Zn/L from birth to 5 mo and found better motor
development on the Griffiths developmental assessment in the infants
receiving higher Zn. In a study of Egyptian infants, a relationship was
found between mothers’ consumption of foods high in available Zn and
attention measured by the Brazelton Neonatal Development Assessment
Scales administered shortly after birth (Kirksey et al. 1991
), and with
motor development measured by the Bayley Scales of Infant Development
administered at 6 mo (Kirksey et al. 1994
). Sazawal et al. (1996)
found increased activity, particularly among boys, after
6 mo of repletion with 10 mg Zn/d added to a multivitamin mixture in
Indian infants and toddlers initially aged 6–17 mo, compared with
children given only multivitamins. Similarly, in 6- to 9-mo-old
Guatemalan infants, Bentley et al. (1997)
observed
increased activity after 7 mo of supplementation with 10 mg Zn/d,
compared with control infants. In a recent study of Brazilian infants
(aged 6–12 mo), repletion with 5 mg Zn/d increased responsiveness and
decreased problem behaviors associated with low birth weight, but had
no effect on mental or psychomotor function measured by the Bayley
Scales of Infant Development (Ashworth et al. 1998
). |
Zn and behavior in school-aged children |
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TOPABSTRACTINTRODUCTIONZn and behavior in...Zn and behavior in...Zn and behavior in...Zn and brain electrophysiology...Methodology issues relevant to...SUMMARYREFERENCES |
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reported a positive correlation between hair Zn
and reading ability in elementary school children living in the
Baltimore, MD area. However, Zn repletion (10 mg/d) studies with
Canadian boys (aged 5–7 y) and Guatemalan boys (aged 6–7 y) failed to
find changes in performance on a subset of tests from the Detroit Test
of Learning Abilities (Cavan et al. 1993
,
Gibson et al. 1989
). More recently, Zn intakes of
Egyptian children (aged 7–10 y) were found to correlate with social
behavior of girls and activity level of boys, but not with cognitive
function (Wachs et al. 1995
).
Penland et al. (1997
and 1998
) and Sandstead et al. (1998)
used a more extensive neuropsychologic test battery
(Cognition Psychomotor Assessment System-Revised;
Penland 1994
) to measure cognitive and psychomotor
function of 740 urban and 540 rural Chinese children (aged 6–9 y) in
response to repletion with 20 mg Zn/d (Zn), a micronutrient mixture
(M), or a combination of the two (ZnM). Findings in the urban phase of
this project were as follows. Compared with M, ZnM resulted in greater
improvement in recognition memory (delayed design matching), reasoning
(oddity) and psychomotor function (tapping and tracking). Zn also
resulted in greater improvement than M in attention (continuous
performance), perception (design matching), reasoning (oddity) and
psychomotor function (tapping). Findings in the rural phase were as
follows. Compared with M, ZnM resulted in greater improvement in
attention (object pair search), recognition memory (delayed object
search) and reasoning (oddity). Zn also resulted in greater improvement
than M in recognition memory and reasoning. There were no treatment
effects on performance of tasks emphasizing perceptual processes. The
consistent finding among both urban and rural children was that Zn
supplementation resulted in greater improvement than control treatments
in performance on tasks assessing visual recognition memory and
reasoning.
This research with Chinese children was the first to find a
relationship between Zn intake and cognition and psychomotor function
in older children. The failure of previous intervention studies by
Gibson (Cavan et al. 1993
, Gibson et al. 1989
) to show this relationship may be explained by differences
in intervention and performance assessment. The particulars of
Penland’s studies (Penland et al. 1997
and 1998
) are as
follows: 1) the Zn treatments provided twice the Zn used
in Gibson’s studies (20 vs. 10 mg/d); 2) treatment with
Zn alone was compared with treatment with a multiple micronutrient
supplement and with Zn treatment that was simultaneous with
micronutrients to control for possible effects of other limiting
nutrients (Ronaghy et al. 1974
); 3)
CPAS-R (Penland 1994
) was configured to assess all
neurocognitive domains, except language processing, deemed necessary
for a comprehensive neuropsychologic evaluation of school-aged
children (Taylor and Fletcher 1990
); thus, a larger
number of cognitive domains were assessed than in the Gibson study; and
4) cognitive measures assessed both speed and accuracy
to detect performance trade-offs made to compensate for nutritional
stressors (Wickelgren 1977
). These differences exemplify
several methodological issues that must be considered when designing
studies of the behavioral and cognitive sequellae of Zn nutrition.
Penland et al. (1999)
recently measured the beneficial
effects of short-term Zn repletion of 240 low income
Mexican-American children (aged 6–9 y) at risk for Zn deficiency
because their usual diets were high in phytate. Because iron deficiency
commonly coexists with Zn deficiency (Allen 1998
,
Darnell and Sandstead 1991
), the effects of iron
supplementation were also examined. Treatments were a micronutrient
mixture (M; Sandstead et al. 1998
), 20 mg Zn/d plus
micronutrients (ZnM), 24 mg Fe/d iron plus micronutrients (FeM), or a
placebo (P) administered 5 d each week for 10 wk in a
double-blind control trial. CPAS-R (Penland 1994
) was again configured to assess all cognitive domains
except language processing. Examiners received both training and
practice in administering the battery, and were instructed on when and
how to motivate effectively and reassure children to perform at their
best. Testing was done in rooms free of visual as well as auditory
distraction. Children were given thorough instructions and a practice
session before data collection. The Child Behavior CheckList and
Teacher Report Form (Achenback and Edelbrock 1986a
and 1986b
) were administered to assess psychoeducational
performance, behavioral problems and social competencies.
Compared with the other treatments and placebo, ZnM resulted in significantly (P < 0.05) greater improvements in reasoning, indicated by the fact that fewer trials were needed to learn simple concepts (M ± SEM: M = -14 ± 5; ZnM = -28 ± 5; FeM = -12 ± 4, P = -12 ± 4). Although significant effects of treatment with Zn were few, finding a beneficial effect of Zn supplementation on reasoning is noteworthy because it represents the third time this effect has been observed.
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Zn and behavior in adults |
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TOPABSTRACTINTRODUCTIONZn and behavior in...Zn and behavior in...Zn and behavior in...Zn and brain electrophysiology...Methodology issues relevant to...SUMMARYREFERENCES |
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reported increased emotional lability and perceptual and
memory deficits in patients with progressive systemic sclerosis after
administration of histidine, a Zn chelating agent. Tucker and Sandstead (1984)
found that men with low Zn intakes (<4 mg/d)
had faster, but less accurate performance on a memory for digits task
and several perceptual tasks. Darnell and Sandstead (1991)
found that 30 mg Zn/d added to a vitamin-mineral
supplement improved visual memory in sideropenic women, whereas the
vitamin-mineral supplement alone did not. In a highly controlled
6-mo, live-in metabolic study, Penland (1991)
found
poorer performance on 9 of 15 cognitive and psychomotor tasks
administered to men fed 1, 2, 3 or 4 mg Zn/d during each of four
consecutive 35-d Zn deprivation periods assigned in a random,
double-blind manner, compared with when they were fed a control
diet containing 10 mg Zn/d. |
Zn and brain electrophysiology in humans |
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TOPABSTRACTINTRODUCTIONZn and behavior in...Zn and behavior in...Zn and behavior in...Zn and brain electrophysiology...Methodology issues relevant to...SUMMARYREFERENCES |
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reported low hair Zn concentrations in 55
women with epilepsy. Using a more controlled approach, Goldstein and Pfeiffer (1978)
administered Zn or a placebo to
schizophrenics and recorded their electroencephalogram (EEG) 4 h
after treatment; they found a greater reduction in EEG amplitude
(toward normal) in treated subjects compared with controls. Findings
from these studies suggest that low Zn is associated with cortical
hyperexcitability; however, the reports were incomplete and did not
specify the specific EEG frequencies affected. At least three studies
have investigated Zn effects on brain electrophysiology of healthy
individuals. Henrotte et al. (1977)
found that healthy
subjects who showed decreased frequency responses in the EEG during
hyperventilation also had lower red blood cell Zn concentrations than
controls. Sandstead et al. (1983)
found a correlation
between plasma Zn and EEG activity in three of five subjects
participating in a metabolic study of Zn depletion. The principal
finding was increased left and decreased right hemisphere amplitudes in
the occipital lobes in the lower frequencies of the EEG.
Thatcher et al. (1984)
reported that hair Zn
concentrations of elementary school children were correlated with EEG
coherence involving the frontal lobe. That study also found that both
hair Zn and EEG coherence were related to reading ability. Studies with
healthy individuals seem to suggest that low Zn intakes or status are
associated with highly specific effects involving specific areas of the
brain and specific EEG frequencies and characteristics. |
Methodology issues relevant to research on Zn and behavior |
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TOPABSTRACTINTRODUCTIONZn and behavior in...Zn and behavior in...Zn and behavior in...Zn and brain electrophysiology...Methodology issues relevant to...SUMMARYREFERENCES |
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) produced several excellent reviews
of these issues (e.g., Grantham-McGregor 1995
); more
recent discussions can be found in Allen (1998)
and
Black (1998)
. Several of these issues were addressed in
the review noted above. Some specific points and suggestions for future
research follow.
Individual differences, sex and age are extremely important
concerns when designing research and analyzing results to assess
relationships between Zn nutriture and behavior and brain function
(Gorman 1995
). Effects may be detected only by designs
that yield relative response measures (i.e., changes in scores) and
statistical analyses that differentiate outcomes by sex and age
(Black 1998
). Zn deficiency research involving children
is implemented in the context of ongoing developmental changes, and the
selection of interventions, outcome measures and statistical analyses
must always reflect this fact.
As appears to be the case with general malnutrition, effects on motor development, activity level, exploratory activities and play, social skills and emotional states may mediate observed effects of Zn deficiency or supplementation on cognition and school achievement. Therefore, these potential mediating variables must be assessed. Further, ability to deal effectively with stressors may be another active intervening variable requiring assessment. Stress responses are highly compensatory in nature, acting to conserve the integrity of responses (e.g., performance) by drawing on other available resources. Because Zn deficiency itself is a stressor, its effect on neuropsychologic functions may be missed unless evaluated by means of a challenge test. Such tests are easy to contrive and may consist simply in the addition of a secondary task or stressor (e.g., noise) to the test situation. Properly devised, a challenge test may reveal whether the inability to compensate for the challenge is due to Zn deficiency or some other factor such as fatigue, impaired emotionality or poor problem-solving skills.
Do we seek consistent changes on a specific measure or consistent changes in a class of measures assessing a meaningful underlying function? The answer must consider the powerful compensatory mechanisms that are always available to reallocate resources to produce and preserve a desired outcome. Further, there must be a balance between the need to use highly focused tasks to assess specific neuropsychologic processes and the need to ensure that experimental tasks are sufficiently valid ecologically that they yield findings that generalize to the real world. Rather than seek consistency on a single experimental and sometimes arbitrary measure, I suggest we seek a convergence of evidence from varying approaches, interventions, populations and outcomes to discover the true picture of how Zn nutriture relates to behavior.
Given findings that infant and toddler activity may be impaired by Zn deficiency, objective assessment of activity should be considered for inclusion in studies of older children. Monitoring activity via electronic device is simple and relatively inexpensive, and permits determination of sleep patterns as well as gross motor activity during waking. Inadequate amounts of sleep and poor sleep quality can lead to fatigue, decreased performance efficiency and impaired social interactions. Last, addition of electrophysiologic measures of brain function as outcomes is proposed to expand assessment of functional sequellae of Zn deficiency and perhaps provide insight into the mechanisms responsible for Zn effects on behavior.
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SUMMARY |
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TOPABSTRACTINTRODUCTIONZn and behavior in...Zn and behavior in...Zn and behavior in...Zn and brain electrophysiology...Methodology issues relevant to...SUMMARYREFERENCES |
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FOOTNOTES |
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2 Sponsored by an educational grant from National Cattlemen’s Beef Association and the American Society for Nutritional Sciences.
3 The U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area, is an equal opportunity/affirmative action employer and all agency services are available without discrimination.
4 Mention of a trademark or proprietary product does not constitute a guarantee or warranty of the product by the U.S. Department of Agriculture and does not imply its approval to the exclusion of other products that may also be suitable.
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TOPABSTRACTINTRODUCTIONZn and behavior in...Zn and behavior in...Zn and behavior in...Zn and brain electrophysiology...Methodology issues relevant to...SUMMARYREFERENCES |
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