Krueger and Reed (1976) reviewed key reports published in that period on the biological effects of NAIs. They proposed the serotonin hypothesis of NAI biological actions. Serotonin is a very powerful and versatile neurohormone. It functions in inducing profound neurovascular, endocrinal, and metabolic effects in humans or animals. It plays important roles in basic patterns of life including sleep and mood regulation. Evidence has shown that NAIs could significantly reduce the level of serotonin in blood or brain, etc. Subsequent evidence showed that superoxide ions have been involved in the biological effects of NAIs and in vitro experiments demonstrated that serotonin could be oxidized into tryptamine-4,5-dione by superoxide ions. Thus, some of the biological effects of NAIs were related to the reduction of serotonin. However, others reported no significant effect of NAIs on the concentration or turnover of serotonin in rats under their exposure conditions. Bailey et al. (2018) carried out a comprehensive review on the effects of air ions on serotonin and other neurotransmitters and their analysis indicated some modest or strong evidence to support no effect hypothesis.

 

There are many references to report the possible biological effects

them were listed in Table S2. The negative oxygen ion concentration exceeding 1000 ions/cm3 has been regarded as the threshed value for fresh air and the concentration should be higher for boosting the human immune system ( and references therein). Exposure to NAIs exhibit wide effects on animal/human health, anti-microorganisms and plant growth (Table S2). The effects of NAIs on human/animal health mainly focused on the cardiovascular and respiratory system as well as on mental health (Table S2). The effects of NAIs on the cardiovascular system included improving erythrocyte deformability and aerobic metabolism as well as decreasing blood pressure. However, no effect was also reported on blood pressure or heart rate and related data on cardiovascular function studies were not quantitatively evaluated. On mental health, exposure to NAIs showed highly significant increase in performance of all tested tasks (mirror drawing, rotary pursuit, visual reaction time, and auditory), alleviating symptoms of seasonal affective disorder (SAD). Similar effects of NAIs on relieving symptoms in mood disorders to antidepressant nonpharmacotherapy trials were observed. NAIs also showed effective treatment of chronic depression. On the contrary, no effect of NAIs on mental health was reported in other studies. Comprehensive analysis on literatures showed no conclusive results on the potential therapeutic effects of NAIs on depression. As for the effect of NAIs on respiratory function, exposure to negative or positive air ions does not appear to play an appreciable role in respiratory function. In addition, some reports also showed the effects of NAIs on inhibiting cancer cells. For example, water-generated NAIs activated natural killer (NK) cell and inhibit carcinogenesis in mice. The presence of NAIs is credited for increasing psychological health, productivity, and overall well-being. Reports also showed that NAIs attached themselves to particles such as dust, mold spores, and other allergens. As a result, people in the NAI atmosphere relieved symptoms of allergies to these particles. Generally, although some reports showed that air enriched with NAIs have multiple beneficial therapeutic effects in normalizing arterial pressure and blood rheology, supporting tissue oxygenation, easing stress conditions, and augmenting resistance to adverse factors, a systematic review suggested no consistent or reliable effects of NAIs on cardiovascular and respiratory system as well as on mental health.

 

Similarly, there are lots of research articles to present the effects of NAIs on the growth of microorganism (Table S2). The majority of the studies focused on bacteria and the presence of high concentration of NAIs inhibited the growth of bacteria. An early study showed that NAIs caused a significant amount of biological decay of the bacterium Serratia marcescens [95]. Exposure to NAIs showed inactivation or growth inhibition of the bacteria E. coli, Candida albicans, Staphylococcus aureus, P. fluorescens and has a lethal effect on starved Pseudomonas veronii cells. NAIs prevented 60% of tuberculosis (TB) infection and 51% of TB disease [102]. Except for the inhibition effect of NAIs on bacteria, reports also showed that NAIs inhibited the growth of fungi and viruses. For example, NAIs could inhibit the growth of Penicillium notatum [103]; the use of NAI generators reduced airborne transmission of Newcastle disease virus [104]. However, some controversial results have been reported on the growth inhibition of NAIs on microorganisms. For example, Fan et al. (2007) reported that NAIs had a very limited effect on E. coli that were inoculated on mung bean seed and apples [105]. In another report, seven bacterial species (Staphylococcus aureus, Mycobacterium parafortuitum, Pseudomonas aeruginosa, Acinetobacter baumanii, Burkholderia cenocepacia, Bacillus subtilis, and Serratia marcescens) were exposed to NAIs and only the growth Mycobacterium parafortuitum was inhibited.

 

Besides animals/humans and microorganisms, plants might also be affected by NAI exposure. After NAI treatment of Avena sativa, the fresh and dry weight were increased and mean stem length and integral elongation were also increased. Oxygen consumption was increased in barley seedlings after exposure to NAIs. Plant height increased by 13–15% and dry weight increased by 18% under the growth environment with high concentrations of NAIs [110]. Lettuce plants exposed to NAIs showed vigorous growth with increased leaf area and fresh weight. NAI treatment improved sprout growth and bacterial control during plant development. NAIs have a positive effect on kale growth by improving fresh weight, macroelements and microelements. However, no significant difference was observed between control and NAI-treated tobacco plants in nicotine and total alkaloid; the total nitrogen content in NAI-treated plants was slightly increased when compared with control plants.