12th May 2017, Volume 130 Number 1455

Yusuf Ozgur Cakmak

High exposure of hydrogen sulfide (H2S) gas is toxic to the human nervous system, and effects such as necrosis of the cerebral cortex in addition to the basal ganglia have been demonstrated.1 In ambient air, the respiratory system is the main path for absorption.2 Toxication reports underline the relationship between H2S concentrations and related different organ system problems: 1,000,000–2,000,000ppb of H2S exposure results in immediate respiratory paralysis, 530,000–1,000,000ppb of H2S causes respiratory arrest, 320,000–530,000ppb of H2S exposure includes a risk of death as a result of pulmonary oedema, 150,000–250,000ppb of H2S blocks the olfactory sense and 50,000–100,000ppb can cause serious eye damage. Concentrations of H2S for eye and respiratory irritation are reported in the range of 10,000–50,000ppb.1–3

Hydrogen sulfide intoxications are most often caused by occupational exposure events, up to 100,000ppb. Industrial sites with high risk for potential exposure and associated health problems include Kraft mills and viscose rayon plants, where concentrations are within the range of 3,000–20,000ppb. An accidental release of H2S in Mexico, Poza Rica, exposed people to concentrations of 1,000,000–2,000,000ppb, and was claimed to be the cause of deaths and hospitalisations.1,2 The concentration of H2S occurring naturally in nature is much lower. Most likely, locations for naturally occurring H2S gas concentrations in ambient air are those near sulfur springs and lakes in geothermally active areas. In a geothermal area, mean concentrations of up to 1,400ppb have been reported.2 In contrast, maximum clean air concentrations in cities like London are dramatically lower at 0.1ppb.1,2

Rotorua city is within an active geothermal region in New Zealand. Exposure analysis in a Rotorua population group demonstrated H2S concentrations to be only 20.8ppb (mean) for residences and 27ppb (mean) in workplaces.4 The highest concentration obtained, 64 ppb, is too low for intoxication levels, but certainly relatively high compared to non–geothermal regions like London (0.1ppb).1 Overall, ambient air chronic exposure levels in the Rotorua region where 80,000 people live are measured as among the highest in the world.

These relatively high H2S concentrations in the Rotorua region have been a focus of toxicology research in recent years. One study focused on examining links between asthma and chronic obstructive pulmonary disease (COPD) and H2S concentrations for 1,204 participants. No evidence of reduction in lung functions or increased risk of COPD was found.5 Another study surveyed 1,637 long-term adult residents and undertook neuropsychological tests, including visual and verbal episodic memory, attention, fine motor skills, psychomotor speed and mood.4 Results showed no association between H2S exposure and cognition. However, a small association was observed between higher H2S exposure and improved simple reaction time, including finger tapping scores.

Two other observations were made regarding finger tapping scores. Firstly, that better performance was associated with higher H2S exposure defined as the long-term exposure metric based on maximum exposures at home or work, and secondly that “there was some evidence of an interaction between age and the H2S exposure metric for tapping with the non-dominant hand and this was in the direction of improved performance by older people associated with higher H2S exposures”.4

These associations could have been due to a positive bias effect of multiple testing as suggested by Reed et al, however, other research findings in the literature suggest they might be worth further investigating. There is no data in the published literature that chronic exposure to safe concentrations of H2S is beneficial to cognitive function of the human brain, but examination of animal studies using PD models as well as indirect evidence in humans, including microbiota differences in PD patients, suggests there may be a biological basis for health benefits related to the prevention of degradation of dopaminergic neurons, associated with PD.

The number of dopaminergic neurons in the brain decreases as Parkinson’s disease progresses and in PD animal models, H2S as a gaseous neurotransmitter has been proven to have protective effects on dopaminergic neuron loss when inhaled.6 In addition, it has been demonstrated that H2S as a neuromodulator regulates striatal neurotransmission.7 In humans, naturally low levels of H2S gas occur in the body. This gas is synthesized by gut microbiota flora as well by enzymes in tissues where L-cysteine is metabolised, derived from alimentary sources or liberated from proteins in addition to synthesisation from L-methionine.8 These enzymes are predominantly in nervous system, liver and kidney tissue.8 Hydrogen sulphide functions as a gaseous neurotransmitter and helps maintain homeostasis of cellular energetics, vascular and anti-inflammatory processes. If certain levels of H2S are necessary for healthy homeostasis of dopaminergic neurons, it may be that findings from a study on the abundance of a particular H2S secreting Prevotellaceae, which showed that, relatively, abundance in gut microbiota of PD patients presents an interesting link.9,10

It may be that the observation of a small positive association between higher H2S exposure and improved simple reaction time, including finger tapping scores, was not due to multiple testing (which all participants were subject to) but due to a higher concentration of H2S in dopaminergic neurons. This is a speculative but tantalising idea that is worth further examining. Presently there is no normalised report for PD diagnosis and progression in Rotorua. Detailed and normalised (including ethnicity, smoking habits, age) survey studies are needed to investigate if there is a statistically significant difference of PD rates and symptom severities of Rotorua residents in comparison to other regions of New Zealand. This research question needs to be carefully developed. Improved finger tapping reports obtained in Rotorua residents exposed to higher chronic levels of H2S give no clarity to potential benefical effects of H2S exposure on Parkinson’s disease. The PD animal models studies, where eight days of H2S inhalation showed prevention of neurodegeneration,6 showed results for acute rather than chronic exposure, so are limited in relevance to the chronic exposure model that Rotorua provides. However, available knowledge that chronic exposure levels of H2S inhalation in Rotorua are not harmful and possibly beneficial to motor functions is positive for any further studies that might be proposed to focus on the potential beneficial effects of H2S on PD. In addition, the potential bottleneck of future studies is to determine the optimal inhalation dosages of H2S for human PD studies. The H2S levels in Rotorua (20.8–27ppb) would be the key to overcome the underlined bottleneck of the future human PD studies.

In conclusion, Rotorua with its unique, safe and relatively high concentration of ambient H2S warrants closer examination to clarify whether there is a definite, positive correlation of inhalation of H2S on human PD symptoms and pathophysiology.

Summary

Rotorua city (New Zealand) is known for its ‘rotten egg’ smell, due to high levels of hydrogen sulphide (H2S) concentrations emitted from local geothermal vents. Studies have shown H2S as potentially toxic if too high in concentration. However, research on H2S on health postulates whether ambient air inhalation levels of H2S in Rotorua might have a therapeutic role in the management of motor symptoms in Parkinson’s disease (PD). An observed beneficial link between chronic H2S inhalation in PD animal models and improved finger tapping scores in a sample of the Rotorua population, linked to dopaminergic nerve function, is worth investigating further.

Abstract

Aim

Rotorua city (New Zealand) is known for its ‘rotten egg’ smell, due to high levels of hydrogen sulphide (H2S) concentrations emitted from local geothermal vents. Studies have shown H2S as potentially toxic if too high in concentration. However, some health benefits have been observed at lower concentrations. This article summarises what is known about effects of H2S on health and postulates whether ambient air inhalation levels of H2S in Rotorua might have a therapeutic role in the management of motor symptoms in Parkinson’s disease (PD).

Results

Chronic H2S inhalation has been shown to have a protective factor on dopaminergic neurons of animal models of PD. A large-scale survey of long-term Rotorua residents showed no evidence of health detriment nor impairment of cognitive functions. Intriguingly, however, participants in higher H2S exposures showed a tendency for faster motor response times in a finger tapping test. One of the PD Motor Rating Scale examination tests for PD is finger tapping speed, as this is associated with motor performance. Might it be that relatively high, but safe, H2S levels in Rotorua could help protect the degradation of dopaminergic neurons associated with PD?

Conclusion

An observed beneficial link between chronic H2S inhalation in PD animal models and improved finger tapping scores in a sample of the Rotorua population, linked to dopaminergic nerve function, is worth investigating further.

Author Information

Yusuf Cakmak, Senior Lecturer, Otago University, School of Medicine, Department of Anatomy, Dunedin.

Correspondence

Dr Yusuf Ozgur Cakmak, Senior Lecturer, Otago University, School of Medicine, Department of Anatomy, Dunedin.

Correspondence Email

yusuf.cakmak@otago.ac.nz

Competing Interests

Nil.

References

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  2. WHO, 1981 World Health Organization, 1981 Hydrogen sulfide. Geneva, (Environmental Health Criteria, No. 19). 
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  7. Wang M, Zhu J, Pan Y, Dong J, Zhang L, Zhang X, Zhang L. 2015. Hydrogen sulfide functions as a neuromodulator to regulate striatal neurotransmission in a mouse model of Parkinson’s disease. J Neurosci Res 93(3):487–94. 
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  9. Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola-Rautio J, Pohja M, Kinnunen E, Murros K, Auvinen P. 2014. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord 30(3):350–8.
  10. Cakmak YO. 2015. Provotella-derived hydrogen sulfide, constipation, and neuroprotection in Parkinson’s disease. Mov Disorders 30(8):1151.