There’s Something in the Air: Empirical Evidence for the Effects of Negative Air Ions (NAI) on Psychophysiological State and Performance

Abstract

Numerous reports document advances made in our understanding of the effects of negative air ions on physiological functions and human health. Collectively, these reports demonstrate an increasing awareness of their mechanisms, and reflect contrasting findings about their influence. The purpose of the present paper was to review the evidence base for the beneficial effects of negative air ions (NAI) in improving neuropsychological performance and treating mood disorders. Underlying mechanisms, treatments parameters and the extent to which negative air ionization can represent a valuable treatment for affective disturbances are reported together with experimental data gathered from our laboratory. The analysis, particularly with randomized, controlled trials suggests that NAI treatment for mood disorders is in general effective with effects almost equivalent to those in other antidepressant non pharmacotherapy trials. Despite the growth in clinical research, there remained a substantial gap in mental health services to translate state-of-the-art treatments and incorporate them into mainstream practice.

Full text

Research in Psychology and Behavioral Sciences, 2013, Vol. 1, No. 4, 48-53
Available online at http://pubs.sciepub.com/rpbs/1/4/1
© Science and Education Publishing
DOI:10.12691/rpbs-1-4-1
There’s Something in the Air: Empirical Evidence for
the Effects of Negative Air Ions (NAI) on
Psychophysiological State and Performance
Olimpia Pino
1,*
, Francesco La Ragione
2
1
Department of Neurosciences, University of Parma, Italy
2
Microengineering, Caserta, Italy
*Corresponding author: olimpia.pino@unipr.it
Received December 18, 2012; Revised June 10, 2013; Accepted June 12, 2013
Abstract Numerous reports document advances made in our understanding of the effects of negative air ions on
physiological functions and human health. Collectively, these reports demonstrate an increasing awareness of their
mechanisms, and reflect contrasting findings about their influence. The purpose of the present paper was to review
the evidence base for the beneficial effects of negative air ions (NAI) in improving neuropsychological performance
and treating mood disorders. Underlying mechanisms, treatments parameters and the extent to which negative air
ionization can represent a valuable treatment for affective disturbances are reported together with experimental data
gathered from our laboratory. The analysis, particularly with randomized, controlled trials suggests that NAI
treatment for mood disorders is in general effective with effects almost equivalent to those in other antidepressant
non pharmacotherapy trials. Despite the growth in clinical research, there remained a substantial gap in mental
health services to translate state-of-the-art treatments and incorporate them into mainstream practice.
Keywords: negative air ion, depressive symptoms, performance, environment
1. Introduction
Meteorological conditions are one of the factors
influencing the morbidity and mortality of a population.
Sudden changes in the weather may represent a risk factor,
mainly to individuals with an existing chronic condition,
e.g. cardiovascular, cerebrovascular or respiratory disease.
Schneider et al. [1] showed that a change in weather
parameters (such as a decrease/increase in air temperature
and water vapour pressure) was associated with significant
changes in heart rate and electrocardiography parameters.
Ischeamic heart disease mortality in winter in the UK is
related to air mass changes; the types of weather
associated with increased mortality are (1) anticyclonic
systems with advection of cold dry continental air, and (2)
well-developed and deepening North Atlantic storm
systems moving towards or over the UK with rapidly
moving fronts [2]. Blood pressure may also be affected by
changes in weather: transitions from an anticyclonic air
mass (a day with settled weather conditions, high
atmospheric pressure, low air temperature, and prevalently
clear sky) to a cyclonic air mass (a day with opposite
weather characteristics) were found to be characterized by
a significant increase in ambulatory blood pressure in
winter in Italy [3]. Finally, the periods around weather
changes are associated with pronounced patterns in
mortality: a significant increase in mortality is found after
large temperature increases and on days of large pressure
drops; a decrease in mortality occurs after large
temperature drops, pressure increases, and passages of
strong cold fronts. Temperature generally plays the most
important role in day-to-day variations in mortality, and
the sudden pressure changes should be considered in
models for predicting excess mortality [4]. Therefore, it is
important to study links between changes in weather and
human health. The purpose of the present paper is to
provide a review of the evidence for the effects of
negative air ions (NAI), and their effectiveness as
treatment of mood disturbances revealing underlying
mechanisms.
There was some evidence that air ion concentrations an
ion polarity ratio result in physiological effects [5,6,7,8].
Ions are charged particles that are formed in nature when
enough energy acts upon a molecule such as carbon
dioxide, oxygen, water, or nitrogen to eject an electron
from the molecule leaving a positively charged Ion. The
displaced electron attaches itself to a nearby molecule,
which then becomes a negatively charged ion. The
atmosphere we breathe contains positive and negative ions.
The light atmospheric ions are represented by a group of
10-30 neutral molecules aggregated around the particle
with electric charge. Their life time is not longer than few
minutes. These particles perform chaotic motion which is
generally known as the Brownian motion. In the case of
sufficiently high concentration of ions (n ≈ 10
3
cm
–3
) and
uni-polarity coefficient P (ratio of positive n
+
and negative
n
–
ions concentration) tends to 1, the micro-climate is
taken as suitable for therapeutic usage. Roughly one-third
of the population seems to be particularly sensitive to
negative-ion depletion [9,10]. The normal count in fresh

Research in Psychology and Behavioral Sciences 49
country air is 2,000 to 4,000 negative ions per cubic
centimeter. The concentration of atmospheric ions in a
given environment depends on a multiplicity of factors. In
an outdoor rural setting the air may contain 2000 positive
and 1500 NAI per cubic centimeter. These levels can be
modified both by natural factor (e.g. levels of background
radiation, short-wave UVA light) and environmental
factors (e.g. industrial pollution, air conditioning). Their
main action seems to be through entry through the
respiratory system.
There are two types of generating methods: one is by
corona discharge, and the other is by water shearing
similar to the Lenard’s effect. The former method charges
every substance in the air negatively, generating ozone as
a by-product. The latter method only generates superoxide
ions attached to microclusters of water and is essentially
considered a natural source of negative air ions [11]. High
levels of negative air ions created by water shearing are
observed near waterfalls, ranging from 2000 to 10,000
ions/cm
3
. Superoxide causes oxidative damage to various
tissues and is suppressed by superoxide dismutase (SOD).
However, an interesting study reported a low intensity of
superoxide increasing SOD activity, whereas a high
intensity decreased SOD activity [12]. Only recently it
was suggested that their biological action is somehow
related to free radicals [13]. Negative air ions function as
“sparks”, initiating and sustaining processes in which
reactive oxygen species (ROS) participated accompanied
by production of high grade electronic excitation. This
energy can be used for bionergetic and bio-regulatory
functions [9,14].
At present, two lines of empirical evidence suggest that
NAI can affect organisms. The first of these involves
epidemiological data. The possibility that air ions may
influence human health has been suggested since the
beginning of the 20
th
century. Studies in the 1950's and
1960's indicated that human well-being was affected by
weather conditions. Warm dry winds such as the
Siroccoco (Italy), Sharkije (Egypt), Santa Ana (California),
Hamsin or Sharav (Middle East) or the Foehn (Central
Europe) are associated with a sudden increase in
morbidity. With such winds, related to elevated levels of
positive ions, about 30% of the general population
reported migraine, depression, irritability, lethargy or
respiratory symptoms. Physiological and neurological
changes resulted in an increase in human errors. Sulman
and Kreuger's work led to the hypothesis that serotonin
was involved in a mechanism of interaction between air
ions (concentrations and polarity ratio) and biological
systems [15,16,17]. Because of NAI suppress serotonin
levels in the same way that natural sunlight suppresses
melatonin, evidence for the impact of ions on psycho-
physiological status is provided by the findings of
naturalistic and laboratory studies. Over the years, it has
been claimed that NAI can influence, in several
mammalian species, growth, metabolism, immunological
responses, and reactions to environmental stressors [8].
This controversial literature has been reviewed by Kotaka
[6]
. NAI have been proved to slow growth of bacterial
cultures and reduce viable cell count in bacterial aerosols
[5,18]. In addition, a study found that negative ions
significantly enhanced the cytotoxic activity of natural
killer (NK) cells, and significantly decreased the incidence
of cancer and inhibited tumor growths [19]. Anti-tumor
effects were attributed to enhancement of NK activity, as
showed by the efficacy of the Shinki Bioclean Room ®
for preventing infection in neutropenic patients with acute
leukemia who received intensive chemotherapy [20]. The
decreased production of stress hormones may also
partially contribute to the increased NK activity.
Nevertheless, the use of ion generator was used mostly as
a tool for bacterial and chemical decontamination in
biological, genetic and food industries [5,7]. To
investigate the effect of air quality on well-being and
longevity, the Chinese Gerontological Society carried out
a study in Zhongxiang, a city located in the Southeast of
China in which historically had many residents with long
life spans. Air quality values in both indoor and outdoor
air samples resulted much greater than those typically
present in an urban enclosed housing area [21]. All the
negative ions contents in the selected sites were >300
ion/cm3, and almost all the positive to negative ion ratios
were between 1 and 3. The SO
2
and the inhalable
particulate levels in the air of Zhongxiang were within the
grade I air quality standard suggesting that air quality can
be considered a relevant factor for health and longevity.
The main reason for the poor and unfortunate use of
NAI for clinical purposes was the lack of knowledge of
the primary mechanisms of their action [12,14]. A second
reason was that research about NAI effects suffered for
methodological shortcomings, including failure to control
NAI concentration, humidity, or temperature, and
differences in apparatus used. Finally, the decrease of their
application to clinical settings can be attributed at the
appearance of numerous drugs, attractive to both
physicians and patients.
2. Hypothesized Mechanisms of Influence
and Preliminary Data
Kreuger [15] reported that in laboratory subjects
serotonin could be affected by the polarity and
concentration of air ions breathed. Serotonin produces
neurovascular, endocrinal, and metabolic effects and plays
an important role in mood and sleep patterns. Sulman and
colleagues have reported that individuals suffering Sharav
wind sensitivity have been successfully treated by
inhalation of air containing excess negative ions, or by
administration of serotonin blocking drugs [16]
. The first
pioneering observations have shown that levels of cerebral
and tracheal 5-HT, a metabolite of serotonin (5-
hydroxytriptamine) was decreased and the urinary level of
5-hydroxyindoleacetic acid (5-HIAA) was increased in
rats following exposure to negative ions [13,17].
Alterations in 5-HT concentrations were implicated in
sleep, activity level, pain, anxiety, somatic complaints and
changes in the circadian rhythm [22,23].
Systems for NAI generation can be broadly divided into
water-generated NAI arrangements based on the Lenard
effect and electrically-generated NAI using corona
discharge. It has been suggested that water-generated NAI
have a longer lifetime and more beneficial effects on
autonomic regulation, immunologic activation, and
aerobic metabolism [14]. Is the gas-phase superoxide of
atmospheric air (GS) that plays a key role in the biological
activity of NAI [9]. The activation of the hypothalamic-
pituitary complex and increase in ACTH secretion, which

50 Research in Psychology and Behavioral Sciences
may result in the increase in the sensitivity of the
hypothalamic neurons to the signals and shortened latent
period of responses, are considered as one of the principal
physiological mechanisms underlying the effect of GS. A
similar process was showed for NAI. Other structures and
biochemical systems are in the basal ganglia, which are
functionally connected with the hypothalamus and
represent the subcortical link between the association and
motor areas of the brain cortex involved in the modulation
of activity of the serotonergic system and activation of
endogenous opiod production.
2.1. First Empirical Evidence
In rats exposed to NAI hippocampal pyramidal neurons
were more sensitive to microiontophoretically applied 5-
HT than those of control rats. Recent data suggest a
potential molecular mechanism within the serotonergic
system by which a reduced capacity for negative feedback
regulation of 5-HT release is associated with increased
amygdala reactivity and, in turn may contribute to both the
risk for major depression and the therapeutic effects of
antidepressant drugs [22,23].
In addition, power spectral analysis of beat-to-beat
intervals of heart rate (heart rate variability; HRV) it was
performed, and the high-frequency component (HF
component, 0.8-3.0 Hz) in the power spectrum of HRV
was calculated in rats exposed to NAI or normal air. Since
it has been suggested that HF power of the HRV spectrum
is a measure of parasympathetic modulation of sinus node
function, it was used as a tool to assess effects of NAI on
parasympathetic control of heart rate. Data indicated that
NAI exposure decreased HR and increased HF power of
the HRV spectrum, suggesting that NAI could be effective
in inhibiting sympathetic nervous activity and/or
activating parasympathetic nervous activity. Focusing on
neuronal activity in three brain regions responsible for
autonomic regulation, findings indicated that exposure to
NAI could decrease neuronal activity in paraventricular
nucleus of the hypothalamus (PVN) and locus coeruleus
(LC) and increase the activity of nucleus ambiguus (NA)
neurons [25].
3. Evidence-based Effects on Neuropsychological
Performance and Mood Disorders
The effect of NAI , on depressive symptoms or mood
disturbances has initially yielded rather variable results
[15,26,27,28]. Sometimes faulty experimental design has
allowed the influence of extraneous factors, and results
have been wrongly attributed to NAI action. Major factors
causing errors of observation can be the neglect of the
effect of ozone and nitrogen oxides produced by corona
discharge ion sources, failure in monitoring ion densities,
temperature and humidity of air containing particulate or
gaseous pollutants or failure to hold experimental subjects
at electrical ground potential [26].
It is well known in research design that evidence
grading is highest for a systematic review with meta-
analysis of randomized controlled trials (RCTs). Although
many studies have reported the effects of NAI, there is no
systematic review of the evidence of their effectiveness.
The objective of the present paper was to summarize the
evidence on the human health enhancement effects of NAI,
and to assess the quality of those trials. PubMed, PsycLit
and the Cochrane Library were searched using a list of
terms available on request. The literature was searched up
to 1980 for the earliest searches and 2012 for the latest
ones. Articles were included if they reported treatment of
individuals selected as having an anxiety disorder or a
high level of anxiety symptoms, mood disturbances or
depressive symptoms, performances in neuropsychological
tasks in clinical and non-clinical samples. All research or
review articles were considered for analysis, while
historical articles, editorials, expert opinions and
proceedings of congresses were excluded. Articles
published in supplements or special issues and patents
were not reviewed. Letters to the editor were included if
they explicitly reported the results of a study (e.g. case
reports). The selection and assessment of articles were
based on analysis of the abstract.
The evidence was evaluated according to the modified
Sackett’s system [29]: randomized controlled trials (RCT)
(Level I) and non-randomized controlled trials (CCT)
(Level II) at the top, observational studies in the middle
(Level III), and uncontrolled studies at the bottom (Level
IV). Expert opinion was not included in this study. Studies
with historical controls were included within the CCT
category. Cross-sectional studies, case-control studies,
cohort studies and studies without interventions were
included in the Level III category. Further article
categories were literature reviews (containing systematic
reviews and reviews, Level V). It should be noted that
these levels relate to the quality of the evidence, not the
effectiveness of the NAI administration. A treatment could
have been evaluated by rigorous methodologies and found
to be ineffective or, conversely, evaluated by weaker
methodologies, but found to be highly effective.
There was no restriction on participants (patients or
healthy participants). Studies included at least one
treatment group in which NAI treatment was applied for
empirical investigations. Disagreements and uncertainties
were resolved by discussion with other colleagues. Studies
were selected when (a) the design was with humans
participants, (b) one of the interventions was a form of
NAI administration, and (c) contained relevant literature.
The literature searches included 20 relevant articles.
Nine publications were excluded because they did not
meet the eligibility criteria. The language of the eligible
publications was English. A meta-analysis could not be
performed as the main outcome measures were different
and could not be compared between the eligible papers.
For Level I a total of sixteen articles was reviewed.
Three of them showed the effects of NAI on improving
selective attention, incidental memory and cerebral
activation in learning impaired participants
[30,31] but
amplifying a time-phased information processing disorder
in mentally retarded individuals [32]. There have been
five randomized placebo-controlled studies of the effect of
NAI on heart rate (HR) and temperature [33], reaction
times [34], salivary chromogranin A (CgA), cortisol,
reported anxiety [12,35,36] showing that NAI are
effective for the reduction of and the prompt recovery
from stress. The peripheral limbs of the stress system are
the hypothalamic-pituitary-adrenal (HPA) axis and the
sympathetic/adrenomedullary (S/A) system. The activities
of the HPA axis and the S/A system can be biochemically

Research in Psychology and Behavioral Sciences 51
evaluated by measuring the catecholamines and cortisol,
respectively. Examining the effects of NAI on computer
operation using the salivary chromogranin A-like
immunoreactivity (CgA-like IR) and self-report
questionnaire (State-Trait Anxiety Inventory, Anxiety
State- STAI-S), il was demonstrated that NAI attenuated
CgA-like IR level that had increased after the task [35].
A placebo-controlled study [36] showed that musically
based auditory stimuli, bright light and high-density ions
produced rapid mood changes in healthy subjects. While
both serotonergic and catecholaminergic activation may
mediate response to light therapy, NAI effects may be
mediated by both central and peripheral serotonergic
activity but the mechanism of action of the specific
auditory stimulus has not been investigate.
There have been a total of eight randomized controlled
trials carried out by Terman’s research group. In Seasonal
Affective Disorder [37,38,39], the reduction in depression
rating scale scores was significantly greater at the NAI
higher dose, with a large effect size. No emergent side
effects were identified [37]. High ion flow rate (e.g., 4.5 ×
10
14
ions/second
13
), as used in the studies described above,
may be needed to override uncontrolled modulating
environmental factors such as relative humidity, room size,
and the proximity of grounded objects. The antidepressant
effect of high-density negative air ions has also been
observed in patients with chronic depression >2 years in a
5-week randomized, controlled trial [40]. Both bright light
and NAI treatments were found to be superior to placebo
control, and the remission rates were similar to those for
SAD, but without showing a seasonal dependency or
mediation by circadian rhythm phase shifts. Background,
treatment method and detailed description are reported in
a United Stated Patent paper [41]. Although the
antidepressant effect of NAI in Seasonal Affective
Disorder has been independently replicated using post-
awakening administration, the result for administration
during sleep remains a novel observation [39]. Basing on
higher levels of evidence, there was promising evidence
(Level I) for high-density air ionization also as a treatment
for acute mania phase [42] and bipolar depression [43].
Moreover, other investigators provided evidence for the
effects of NAI in treating SAD [44].
In Level II of evidence category there have been a total
of four articles. Three of them reported experiments
carried out with undergraduate students. Their results
suggested that moderate concentrations of NAI increased
performance on cognitive tasks (baron 1) while high
concentrations enhanced physiological arousal and errors
[45], and interpersonal aggression by Type A individual
[46]. With male healthy subjects a paper (Level II)
Buckalew and Rizzuto [47] reported that the exposition to
NAI for 6 hours increased subjective perception of
relaxation. In a second paper Buckalew and Rizzuto [48]
failed to found significant effect on cognitive or
psychomotor performance and physiological condition
with the same procedure. Finally, in two reviews (Level V
of evidence) environmental aspects [49] and mechanisms
of physiological action of exogenous reactive oxygen
species are illuminated [9].
As expected, there was a tendency for a beneficial
impact of NAI administration and articles reviewed show
high level of evidence. RCTs are traditionally the gold
standard for judging the benefits of treatments, because
they are more able to attribute effects to causes. However,
the use of RCTs may be limited by ethical, or practical
factors. In fact, RCTs generally require more resources
than other studies, sometimes there may be problems with
randomization or recruitment, and the treatment of
patients with an intervention believed to be ineffective is
often considered to be unethical.
4. Data Gathered in Our Laboratory
4.1. Pilot Study
Using 10 male Wistar albino rats we investigated in our
laboratory if air ion affect learning in a maze. All animals
were kept in standard rat cages, 5 rats per cage and housed
in an air-conditioned room with controlled lighting (12hr
light/dark). Rats were divided into the control and
experimental groups at random. All rats were allowed free
access to water and rat chow. Our results indicated that as
consequence of two weeks of 15 min. NAI exposition (the
animals rested under constant temperature of 24±1°C and
humidity of 47±1%) the experimental group show a
significant reduction in error and time scores, confirming
almost in part previous data [50].
4.2. Clinical Trials with Mood Disordered
Participants
The proposal of our research plan was designed to
evaluate the antidepressant effect of NAI as a potential
treatment modality for mood disorders and also for
patients who discontinue or cannot tolerate antidepressants,
fail to maintain positive response, or are drug non-
responders. The experimental equipment is based also on
Prioré pioneer experimental work [51]. Our prototype
consisted in a grounded box containing ion generators and
lamp where many intervening variables are controlled
(byproducts by the majority air ionizers, temperature, and
air humidity). Basically, the fundamental part of the
device are: a) air ionizers installed in a box of 2.20 x 2.70
x 2.70 m
2
that neutralize effect of ozone and nitrogen
oxides produced by corona discharge included in the
device; b) UV- lamp for producing artificial NAI at
concentrations close to the natural background which do
not affect the level of anti-oxidative protection of the
organism, c) reader unit. Generally, the equipment is
adjusted so that the ion level is approximately of 7.0-8.0 x
10
4
/cm
3
. Production of ozone and nitrous oxides is
reduced to a minimum. The tests were conducted in the
box with a temperature of 24 ± 1°C and relative humidity
of 45 ± 2% was maintained by an air-conditioning system.
Upper-room UV light efficacy depends on adequate
mixing of lower- and upper-room air through simple
convection currents that may be augmented by mechanical
ventilation systems, or inexpensive mixing fans, as in the
current study. The devices contained a fan to re-circulate
chamber air through the negative ionic air purifier. Design
is according to international and European safety
standards. The casing of the room is grounded which
guarantees a stable and continuous ion flux.
The first study was designed to evaluate the effects of
NAI on anxiety and depressive symptoms in asthmatic
female patients. Twenty-height clinically stable adult
patients (age range, 18-43 years) with persistent asthma

52 Research in Psychology and Behavioral Sciences
were randomly allocated to NAI treatment or placebo
group (self-management of symptoms). The inclusion
criteria were: a) ages of participants, b) a continuous use
of inhaled steroids for at least last 1 year, c) stable phase
of disease during the last 3 months. The exclusion criteria
were: 1) smoking history of 10 or more years, and 2) other
diseases that could influence bronchial symptoms and/or
lung function.
Patients were instructed to measure their PEF three
times every morning using a peak flow meter, and to
record daily symptom scores (based on presence of cough,
expectoration, wheeze, breathing difficulties, and
nocturnal awakening) using a scale from 0 to 3. Patients
were also requested to document if a supplemental beta-2
agonist was used. Self-management training required the
implementation of an action plan and recording
information on a diary. All participants who received NAI
treatment (3 weeks of 25 min exposition) had improved
scores on assessments of depression (Beck Depression
Inventory, BCI) and anxiety (STAI-X) and showed a
significant reduction on asthma outcomes (number of
asthma exacerbation, doubling dose of inhaled
corticosteroids, use of oral prednisolone and antibiotics,
and asthma symptoms).
Zhang and Zu [52]
confirmed that 254 nm UV
irradiation conduces to high negative AIC (NAIC) [18],
[53]. UV radiation is also responsible for cutaneous
synthesis of vitamin (vit) D3, a substance that is then
sequentially hydroxylated in the liver and kidney to yield
1,25 (OH) 2 vit D, a hormone critical for calcium
homeostasis and skeletal maintenance. Several studies
suggested an association between vit D deficiency and
executive cognitive functions, depression, bipolar disorder,
and schizophrenia. Vitamin D activates receptors on
neurons in regions implicated in the regulation of behavior,
stimulates neurotrophin release, and protects the brain by
buffering antioxidant and anti-inflammatory defenses
against vascular injury and improving metabolic and
cardiovascular function. The second study was a
randomized controlled, parallel group clinical trial.
Inclusion criteria were: single depressive episodes,
seasonal affective disorder (SAD), major depressive
episode with dystymia, chronic depression, bipolar
disorder, atypical depression etc. Thirty-two patients
participated and were diagnosed by trained psychiatrists
basing on the Structured Clinical Interview for DSM-IV
Axis I Disorders (SCID) according to the DSM-IV [54].
Subjects were randomized in different exposure conditions.
Group 1: NAI on/lamp on; Group 2: NAI off/lamp on;
Group 3: NAI on/lamp off, and Control Group a placebo
treatment (with NAI device disabled).
Treatments were taken in the early morning for 30 min
over 21 days, followed by withdrawals. Short term
outcomes immediately post-treatment were evaluated and
compared across groups. Post-treatment session occurred
at the end of treatment with the aim to evaluate Depressive
symptoms (Hamilton Rating Scale for Depression –
HAMS) [55]. Data showed group 1 and 2 treatments to be
more effective. Negative air ionization with or without
UV lamp both appear to act as specific antidepressants for
man and women and appear to influence performance on
cognitive tasks (self-report data on everyday activities and
simple tasks). Although we may not be certain of the
mechanism of vitamin D action on mood and cognition, it
seems prudent to ensure that all adults receive an adequate
intake of vitamin D. Additional understanding of these
mechanisms are necessary.
5. Conclusions
Application of NAI in clinical e non-clinical settings
was decreased during last years. Heterogeneity among
studies and lack of standard approaches to NAI treatment
procedure (parameters of active versus control conditions,
NAI generation device and exposition duration) and
rigorous designs (adequate group size, randomized
assignment, inherent challenges in creating an acceptable
placebo.
The limitation in much of the literature on NAI may
have created the unsubstantiated impression that the
treatment itself has limitations in terms of its efficacy.
When we analyzed the data from all available studies,
particularly in randomized, controlled trials a significant
reduction in symptoms severity was demonstrated
together with an increasing performance in healthy
participants. While pharmaceutical industry has devoted
considerable resources for potential new antidepressant
pharmacotherapies, there has not been a similarly
endowed industry to support the development and testing
of NAI.
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