Since the late 18th century, molecular hydrogen (H₂) has been shown to be well tolerated, firstly in animals, and then in humans. However, although research into the beneficial effects of molecular hydrogen in both plant and mammalian physiology is gaining momentum, the idea of utilising this electrochemically neutral and non-polar diatomic compound for the benefit of health has yet to be widely accepted by regulatory bodies worldwide. Due to the precise mechanisms of H₂ activity being as yet undefined, the lack of primary target identification, coupled with difficulties regarding administration methods (e.g., dosage and dosage frequencies, long-term effects of treatment, and the patient’s innate antioxidant profile), there is a requirement for H₂ research to evidence how it can reasonably and most effectively be incorporated into medical practice. This review collates and assesses the current information regarding the many routes of molecular hydrogen administration in animals and humans, whilst evaluating how targeted delivery methods could be integrated into a modern healthcare system.

Molecular hydrogen (H₂) has been suggested to be a beneficial treatment for a range of species, from humans to plants. Hydrogenases catalyze the reversible oxidation of H₂, and are found in many organisms, including plants. One of the cellular effects of H₂ is the selective removal of reactive oxygen species (ROS) and reactive nitrogen species (RNS), specifically hydroxyl radicals and peroxynitrite. Therefore, the function of hydrogenases and the action of H₂ needs to be reviewed in the context of the signalling roles of a range of redox active compounds. Enzymes can be controlled by the covalent modification of thiol groups, and although motifs targeted by nitric oxide (NO) can be predicted in hydrogenases sequences it is likely that the metal prosthetic groups are the target of inhibition. Here, a selection of hydrogenases, and the possibility of their control by molecules involved in redox signalling are investigated using a bioinformatics approach. Methods of treating plants with H₂ along with the role of H₂ in plants is also briefly reviewed. It is clear that studies report significant effects of H₂ on plants, improving growth and stress responses, and therefore future work needs to focus on the molecular mechanisms involved.

Molecular hydrogen (H₂) is now considered part of the suite of small molecules that can control cellular activity. As such, H₂ has been suggested to be used in the therapy of diseases in humans and in plant science to enhance the growth and productivity of plants. Treatments of plants may involve the creation of hydrogen-rich water (HRW), which can then be applied to the foliage or roots systems of the plants. However, the molecular action of H₂ remains elusive. It has been suggested that the presence of H₂ may act as an antioxidant or on the antioxidant capacity of cells, perhaps through the scavenging of hydroxyl radicals. H₂ may act through influencing heme oxygenase activity or through the interaction with reactive nitrogen species. However, controversy exists around all the mechanisms suggested. Here, the downstream mechanisms in which H₂ may be involved are critically reviewed, with a particular emphasis on the H₂ mitigation of stress responses. Hopefully, this review will provide insight that may inform future research in this area.

Molecular hydrogen (H₂) is a low-molecular-weight, non-polar and electrochemically neutral substance that acts as an effective antioxidant and cytoprotective agent, with research into the effects of H₂ incorporation into the food chain, at various stages, rapidly gaining momentum. H₂ can be delivered throughout the food growth, production, delivery and storage systems in numerous ways, including as a gas, as hydrogen-rich water (HRW), or with hydrogen-donating food supplements such as calcium (Ca) or magnesium (Mg). In plants, H₂ can be exploited as a seed-priming agent, during seed germination and planting, during the latter stages of plant development and reproduction, as a post-harvest treatment and as a food additive. Adding H₂ during plant growth and developmental stages is noted to improve the yield and quality of plant produce, through modulating antioxidant pathways and stimulating tolerance to such environmental stress factors as drought stress, enhanced tolerance to herbicides (paraquat), and increased salinity and metal toxicity. The benefits of pre- and post-harvest application of H₂ include reductions in natural senescence and microbial spoilage, which contribute to extending the shelf-life of animal products, fruits, grains and vegetables. This review collates empirical findings pertaining to the use of H₂ in the agri-food industry and evaluates the potential impact of this emerging technology.

Hydrogen gas (molecular hydrogen, H₂) has significant effects in a range of organisms, from plants to humans. Many inert gases have been reported to have similar effects, and such responses may be most pronounced when cells are stressed. Xenon (Xe), for example, is a well-known anesthetic. The direct targets of these gases, in most cases, remain elusive. Myoglobin and hemoglobin are known for their roles in the transport of gases through coordinate interactions with metals (O₂, NO, CO) and covalent modifications of thiols (NO, H₂S) and amines (CO₂). These are well exemplified in biotrophic reactions of NO with heme iron (to form iron nitrosyl heme) and cysteine (to form bioactive S-nitrosothiols) essential for tissue oxygenation. Here, we consider an alternative “third mode” of gas transport in what have been dubbed “Xenon pockets”, whereby inert gases may have functional effects. Many proteins have similar cavities, and possible effects include alterations in allosteric properties of proteins (potentially altering protein hydration). Here, it is suggested that similar to other inert gases, H₂ also has biological effects by utilizing these protein structures. This ought to be investigated further, in a range of species, to determine if this is the mode of action of H₂.

Despite being trialed in other regions of the world, the use of molecular hydrogen (H₂) for enhanced plant growth and the postharvest storage of crops has yet to be widely accepted in the UK. The evidence that the treatment of plants and plant products with H₂ alleviates plant stress and slows crop senescence continues to grow. Many of these effects appear to be mediated by the alteration of the antioxidant capacity of plant cells. Some effects seem to involve heme oxygenase, whilst the reduction in the prosthetic group Fe³⁺ is also suggested as a mechanism. Although it is difficult to use as a gaseous treatment in a field setting, the use of hydrogen-rich water (HRW) has the potential to be of significant benefit to agricultural practices. However, the use of H₂ in agriculture will only be adopted if the benefits outweigh the production and application costs. HRW is safe and relatively easy to use. If H₂ gas or HRW are utilized in other countries for agricultural purposes, it is tempting to suggest that they could also be widely used in the UK in the future, particularly for postharvest storage, thus reducing food waste.