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Hydrogen’s Health Potential for Epilepsy

In this blog article, I am going to share an email correspondence where I discuss how the biomedical research of molecular hydrogen has revealed that hydrogen gas may have “HEALTH POTENTIAL” for Epilepsy. I highlighted the phrase “health potential” because we need far more medical research on hydrogen and Epilepsy before we can start discussing its health effects, in the same way we can with other disease models (E.g. Metabolic syndrome). That being said, I wanted to help this client see that, although molecular hydrogen research for therapeutic use is in its infancy, the research is elucidating the precursors needed to confirm that hydrogen gas may have health effects or potential for Epilepsy. Thus, in the correspondence, I deal heavily with the etiological (causal) factors that are linked to Epilepsy and its progression. Furthermore, I shared some data that demonstrated that molecular hydrogen reduces the incidents of seizures in particular disease models. Therefore, the article will cover indirect data and direct data showing molecular hydrogen or hydrogen therapy may in deed have Health Potential For Epilepsy. This email is rather technical, but I do believe it’s informative, impactful, and that everyone can enjoy it or appreciate the data that is shared.

Note: I did include in this email some information on H2 and Autism. I will write an article on the subject in the future as well.

H2 and Epilepsy

“Hello,

Thank you for contacting us. I reviewed your email and will gladly address your inquiries.

First, there are many disease models that have been investigated with molecular hydrogen (>170 human and animal diseases) but the medical or biomedical research into molecular hydrogen is still in its infancy. We need far more research before we can start taking more definitive stands on hydrogen therapy, especially for particular disease models. Therefore, in this email, as I do with every other email, I will speak of molecular hydrogen’s therapeutic potential or promise regarding your current situation.

Now, the potential therapeutic targets hydrogen regulates based on etiological (causal) factors I am sharing may not apply to all forms of epilepsy but there are common ictogenesis characteristics or mechanisms they shared that are part of the pathophysiology of epilepsy or seizures. These targets include, but are not limited to, Astrocytes (Astrogliosis), Glutamate (excitotoxicity), GABA, Oxidative stress, Neuro-inflammation, Mitochondrial dysfunction, gut microbiome, etc. As stated, this list is not exhaustive; I left out Ghrelin (hunger hormone), Leptin (full hormone), and Lipid Peroxidation, all of which have been linked to Epilepsy, and all regulated by hydrogen gas to produce therapeutic effects. I decided to go through the effort of compiling some of the data to help you see that molecular hydrogen appears to regulate, modulate, or influence many of these targets that have emerged as central players in the possible cause and progression of epilepsy disorders. The quotations on the causal markers provide indirect evidence that supports the idea that molecular hydrogen may have therapeutic potential for Epilepsy. Furthermore, I gathered a couple of molecular hydrogen studies that focus on disease models that can lead to or exhibit seizures or epilepsy. These sources provide more direct evidence that molecular hydrogen may offer promise for your child’s situation. Lastly, I grabbed some studies on hydrogen and autism. The same process can be done for autism and more and more studies are being done in these areas due to the promising preliminary studies.

Note: Even if the entirety of this information was not provided to you, the sheer fact that we have a growing body of human evidence that molecular hydrogen is safe to use, reduces oxidative stress systemically, reduces inflammations systemically, and is advantageous for the mitochondria and immune system makes it a noteworthy candidate for your kiddo’s situation.

H2 and Epilepsy

Possible Etiological Markers:

Oxidative stress:
Oxidative stress, the dysregulation of our free radical/antioxidant system appears to have a direct link to the onset, initiation, and progression of epilepsy. Molecular hydrogen can reduce oxidative stress due to its antioxidant-like properties.

Epilepsy:
Oxidative stress is involved in the pathogenesis of a number of neurologic conditions and neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and epilepsy (Perry et al., 2002; Migliore et al., 2005; Ashrafi et al., 2007).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606551/

“Epilepsy is a highly prevalent serious brain disorder, and oxidative stress is regarded as a possible mechanism involved in epileptogenesis. Experimental studies suggest that oxidative stress is a contributing factor to the onset and evolution of epilepsy.”
https://pubmed.ncbi.nlm.nih.gov/22848783/

“Epilepsy, characterized by a long-term predisposition to epileptic seizures, is one of the most common of the neurological disorders associated with OS (oxidative stress). Evidence shows that increased neuronal excitability-the hallmark of epilepsy-is accompanied by neuroinflammation and an excessive production of ROS; together, these factors are likely key features of seizure initiation and propagation.”
https://pubmed.ncbi.nlm.nih.gov/35052661/

Molecular Hydrogen:

“Our results indicated that low concentration of H2 in drinking water can reduce oxidative stress in the brain.”
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007247

“Recently it was also shown that drinking H2-saturated water, instead of inhaling H2 gas, prevents cognitive impairment by reducing oxidative stress [3]. According to Nagata et al. [3], even in drinking water, H2 can be delivered to the blood in minutes.”
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007247

“Inhalation of molecular hydrogen (H2) gas ameliorates oxidative stress-induced acute injuries in the brain. Consumption of water nearly saturated with H2 also prevents chronic neurodegenerative diseases including Parkinson’s disease in animal and clinical studies.”
https://pubmed.ncbi.nlm.nih.gov/28467497/

“The consumption of H2-rich water inhibits oxidative stress and thereby inhibits the onset of stress-induced brain damage.(43)”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525017/

Neuroinflammation:
Molecular hydrogen is a gaseous signaling molecule and is also being recognized as a gasotransmitter that can regulate a host of cellular systems by activating gene expression. This is how hydrogen gas can exhibit so many different therapeutic effects, such as its potent anti-inflammatory effects. Since neuroinflammation is a characteristic of Epilepsy, it stands to reason that molecular hydrogen may aid in reducing neuroinflammation and benefit Epilepsy.

Epilepsy:

“In the process of epileptogenesis, neuroinflammation commonly occurs after acute brain injuries and lowers the seizure threshold, thereby contributing to a persistent state of neuronal network hyperexcitability.”
https://www.nature.com/articles/s41582-019-0217-x#:~:text=In%20the%20process%20of%20epileptogenesis,state%20of%20neuronal%20network%20hyperexcitability.

“Based on evidence that neuroinflammation contributes to set seizure threshold and occurs before the onset of epilepsy in animals exposed to status epilepticus, neurotrauma, or hyperthermia, pharmacological studies targeted potentially pathogenic inflammatory pathways during epileptogenesis.”
https://journals.sagepub.com/doi/10.1177/1535759720948900

“Blocking neuroinflammation can be especially effective in counteracting the cascade mechanisms of recurrent seizures. As a future perspective, it would be important to explore if a pretreatment with anti-inflammatory drugs could block the emergence of seizures in subjects that are prone to epilepsy because of genetic diseases, brain trauma, tumors, infections, or SARS-COV2.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267969/

“Many studies have explored the interaction between neuroinflammation and neurological disorders, particularly with epilepsy [7,8]. Epilepsy can be a primary pathology, due to structural or genetic reasons, or a secondary effect. In the latter case, it can be a consequence of traumatic brain injuries and brain tumors; then, it can be related to an infectious, metabolic, immune or unknown etiology, as summarized in the last ILAE classification of the epilepsies [9]. Undoubtedly, the presence of certain chronic inflammatory diseases facilitates epilepsy or other neurological manifestations. Indeed, in most autoimmune diseases, there is a five-fold increased risk of epilepsy in children and a four-fold increased risk in non-elderly adults (aged < 65) [10,11]. Even though the impaired regulation of the inflammatory response in injured neuronal tissue is a critical factor to the development of epilepsy, it is still unclear how this unbalanced regulation of inflammation contributes to epilepsy [8]. On the other hand, several studies have shown that epileptogenesis produces long-term effects on neuroinflammation, worsening the progression and outcome of epilepsy [7,8,12,13,14].”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267969/

“Neuroinflammation is proposed to contribute to the neurobiology of both autism and epilepsy (14-17). Recently, anti-inflammatory and immunosuppressive drugs have showed promising therapeutic effects in autism (18) and epilepsy.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322506/

Molecular Hydrogen:

“HS treatment prevented neuro-inflammation and behavioral dysfunction following HI insult.”
https://link.springer.com/article/10.1186/s12974-019-1488-2

“One of hydrogen’s greatest potentials is the exciting findings indicating it may act as a potential prophylactic neurodegenerative agent. Research on therapeutic Hydrogen has gathered considerable evidence demonstrating results in neurodegenerative diseases such as a 52 week human trial on mild cognitive impairment68, Alzheimer’s6970 and Parkinson’s717273, benefits in protection from cognitive impairment/decline747576777879808182, rodent models on central nervous system diseases such as ALS83 and MS84, reduction of neuroinflammation8586 and recovery from stroke878889 and traumatic brain injuries90. Hydrogen has also been shown to induce secretion of ghrelin91 which has demonstrated neuroprotective capabilities.9293 On top of Hydrogen’s ability to protect against both long-term deterioration in our brain, as well as acute injury, it has shown to positively affect mood, anxiety, and depression both in rodent and human models,949596 as well as reducing autistic-like behaviors in mice.97”

“Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis.”
https://pubmed.ncbi.nlm.nih.gov/25251596/

“Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice.”
https://pubmed.ncbi.nlm.nih.gov/22860058/

“Biological gaseous molecules, also referred as gasotransmitters, including nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and molecular hydrogen (H2), also serve critical roles in mammals’ physiological and pathological conditions (Zhou et al., 2012). They can easily cross the blood–brain barrier (BBB) and spread through brain tissue due to their smaller molecular weights compared with chemically formulated drugs (Zhou et al., 2012; Deng et al., 2014). Accumulating evidence has demonstrated that these gaseous molecules provide neuroprotection in many diseases of the central nervous system (CNS) through different mechanisms and administration regimens (Ren et al., 2010; Charriaut-Marlangue et al., 2012; Zhan et al., 2012; Otterbein, 2013).”
https://www.frontiersin.org/articles/10.3389/fnins.2018.00392/full

Astrocytes (Astrogliosis) – Glial cells in the CNS or Brain:
Astrocytes are the most numerous cell type within the central nervous system and perform a variety of tasks. Their excessive activation and proliferation (increases in numbers or Astrogliosis) are key mediators of epilepsy or epileptic episodes. Molecular hydrogen has been shown to reduce the excessive activation of astrocytes and inhibit astrogliosis, presenting therapeutic potential to a variety of CNS or brain disorders.

Epilepsy:

“Recent studies have implicated that astrocytes play important roles in physiology, but these cells also emerge as crucial actors in epilepsy.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355248/

“These findings suggest that dysfunctional astrocytes are crucial players in epilepsy and should be considered as promising targets for new therapeutic strategies.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355248/

“The pivotal role played by astrocytes in regulating normal brain functions clearly extends to a pathophysiologic role in epilepsy. As is discussed above, astrocytes play a number of essential roles in brain function, including regulation of K+ and glutamate homeostasis, as well as in the supply of neurotransmitter precursors for reuse at excitatory and inhibitory synapses. These normal functions are all significantly perturbed in epilepsy. Associated with the development of gliosis (e.g. Astrogliosis) in the brains of patients with epilepsy and in animal models of this disorder, there is accumulating evidence for loss of appropriate K+ homeostasis and accompanying changes in aquaporin, gap-junction expression and function, compromised uptake and metabolism of glutamate in astrocytes, and disrupted neurotransmitter supply, particularly in inhibitory neurons. In addition to being potentially linked with gliosis, these biochemical changes have significant functional consequences, contributing to the circuit hyperexcitability that is the hallmark of epilepsy. This further implicates compromised astrocyte dysfunction in the pathophysiology of epilepsy. In addition to providing new information about causal factors in epilepsy development and expression, this role of astrocytes suggests new avenues for therapeutic interventions with significant promise.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355248/

“Changes in astrocyte channels, transporters, and metabolism play a critical role in seizure generation and epilepsy. In particular, alterations in astrocyte potassium, glutamate, water and adenosine homeostasis and gap junctional coupling have all been associated with hyperexcitability and epileptogenesis (largely in temporal lobe epilepsy). Distinct astrocytic changes have also been identified in other types of epilepsy, such as tuberous sclerosis, tumor-associated epilepsy and post-traumatic epilepsy. Together, the emerging literature on astrocytes and epilepsy provides powerful rationale for distinct new therapeutic targets that are astrocyte-specific.”
https://link.springer.com/article/10.1007/s11064-021-03236-x

“Furthermore, excessive astrocyte activation may cause other detrimental effects that were not investigated in this study, involving damnifying blood-brain barrier function by vascular endothelial growth factor (VEGF) production, releasing excitotoxic glutamate, inducing cytotoxic edema through AQP4 over activity, and contributing to chronic pain and seizures 1,”
https://onlinelibrary.wiley.com/doi/full/10.1111/cns.12258

Molecular Hydrogen:

“The above results verified that molecular hydrogen could suppress the astrogliosis and related inflammation after SCI and oxidative injury. Anti-astrogliosis may be a neuroprotective mechanism of molecular hydrogen.” https://onlinelibrary.wiley.com/doi/full/10.1111/cns.12258

“These results further demonstrated that the functional activation of astrocytes, due to H2O2‐induced oxidative injury, was decreased by hydrogen‐rich medium.”
https://onlinelibrary.wiley.com/doi/full/10.1111/cns.12258

“H2 suppresses expression of S100 calcium-binding protein B (S100B), phosphorylation of C-Jun N-terminal kinase (JNK), and reactive astrogliosis through reduction of ROS and lower neuronal cell damage in several rat disease models”
https://www.nature.com/articles/s41598-020-69028-5.pdf?origin=ppub

“We found that HS (hydrogen saline) could reduce the content of IL‐1β, IL‐6, and TNF‐α in the spinal cord during the acute period (POD 3; HS vs. NS, P < 0.01, P < 0.01, and P < 0.05, respectively; Figure 1A). This means that triggers of astrogliosis can be attenuated by HS.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493038/

“We also showed that the analgesic effect of hydrogen-rich normal saline was associated with decreased activation of astrocytes and microglia, attenuated expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the spinal cord.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032255/

“HS could inhibit the major signaling pathway of astrogliosis.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493038/

Mitochondrial dysfunction:
The mitochondria is central for bioenergetics and without properly functioning mitochondrial in the cells the cell will not function accordingly or properly. Mitochondria dysfunction is appearing to be a hallmark of Epilepsy. Research shows that the Mitochondria may be a direct target for molecular hydrogen and how it mediates the vast majority of its therapeutic effects. Molecular hydrogen is being proposed as a novel therapeutic agent for virtually all mitochondrial disorders. This includes epilepsy disorders.

Epilepsy:

“The role of mitochondrial dysfunction arising from mitochondrial DNA mutation/depletion has been shown to be the cause of certain types of epilepsy.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606551/

“The brain is particularly susceptible to oxidative damage due to its high aerobic metabolic demand and high iron load (Halliwell, 1992). The brain is rich in mitochondria, the principal source of cellular superoxide (O2-) formed during respiration (Turrens et al., 1982). It is plausible that prolonged seizures result in sufficient O2- production to overwhelm the endogenous mitochondrial antioxidant defenses by a cascade of events initiated by increased neuronal firing, excessive glutamate release, N-methyl-D-aspartate (NMDA) receptor activation, cytosolic and mitochondrial calcium influx, and increased ATP consumption.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606551/

Molecular hydrogen:

“Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases”
https://pubmed.ncbi.nlm.nih.gov/21621588/

“HS (Hydrogen saline) markedly increased the antioxidant potential of mitochondria, as evidenced by elevated adenosine triphosphate levels, mitochondrial respiratory function, and increased levels of active Bcl‑2. In conclusion, HS attenuates mitochondrial oxidative stress and dysfunction, and inhibits mitochondrial-mediated apoptosis in the livers of BDL mice.”
https://pubmed.ncbi.nlm.nih.gov/26936224/

“Our study showed that hydrogen-rich saline was able to attenuate neuronal I/R injury, probably by protecting mitochondrial function in rats.”
https://pubmed.ncbi.nlm.nih.gov/24969549/

“Collectively, the results demonstrated that H2 alleviated mitochondrial dysfunction and cytokine release via autophagy-mediated NLRP3 inflammasome inactivation.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713420/

“Preliminary clinical trials show that drinking hydrogen-dissolved water seems to improve the pathology of mitochondrial disorders.”
https://pubmed.ncbi.nlm.nih.gov/21621588/

Glutamate – Neurotransmitter:
Glutamate is an excitatory neurotransmitter, and its excessive release has been found to induce neurodegeneration and is critical to Epilepsy. In abnormal conditions, glutamate may behave as a neurotoxin. As a neurotoxin, it is believed to be involved in the pathogenesis of a variety of neurodegenerative disorders including Epilepsy. Molecular hydrogen may regulate Glutamate in the brain and has been shown to improve Glutamate homeostasis and reduce its excessive levels which leads to brain injuries and disorders.

Epilepsy:

“Glutamate is the principal excitatory neurotransmitter in the brain and, as such, it inevitably plays a role in the initiation and spread of seizure activity. It also plays a critical role in epileptogenesis.”
https://pubmed.ncbi.nlm.nih.gov/7970002/

“This imbalance is related to increased extracellular glutamate in the brain and/or reduction in GABA concentrations, leading to excitotoxicity, seizures, and cell death.”
https://pubmed.ncbi.nlm.nih.gov/34233236/

“Glutamatergic synapses (synapses that produce Glutamate) play a critical role in all epileptic phenomena”
https://www.sciencedirect.com/science/article/abs/pii/S0079612308604495?via%3Dihub

Molecular hydrogen:

“The current study further revealed that ERW (Hydrogen water) significantly suppresses cell death caused by glutamate or SNP-induced stresses although it does not have direct NO scavenging activity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212634/

“ERW (hydrogen water) significantly suppressed glutamate-induced cell death which is closely correlated with reduced Ca2+ influx.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212634/

“ERW was also reported to possess reducing activities because of the presence of dissolved molecular hydrogen [57, 58].”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212634/

“Based on these studies, it is highly probable that hydrogen molecules in ERW can reach and deliver a neuroprotective effect in the brain.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212634/

GABA – Neurotransmitter:
Glutamate is the highest-ranking neurotransmitter in the brain and CNS (central nervous system) but GABA is a close second. GABA is a neurotransmitter that inhibits nerve cell impulses in the brain. Lower levels of GABA have been linked to Anxiety /mood disorders, Epilepsy, and Chronic pain. Molecular hydrogen may indirectly regulate GABA in the brain via its direct regulation of secondary messengers or molecules (TNF-a, H2S, etc). It has been demonstrated that TNF-a (Tumor Necrosis Factor Alpha) an inflammatory molecule and mediator (over-expression initiates neuroinflammation) regulates GABA in the brain. Additionally, hydrogen sulfide (H2S: toxic at a high level) appears to regulate GABA in the brain reducing brain damage. Molecular hydrogen (H2) modulates both of these biomolecules, therefore, it may have an impact on GABA levels in the brain.

Epilepsy:

“Our results suggest that glutamatergic and GABAergic synapses are synergistically regulated by TNF-α, strengthening and weakening glutamatergic and GABAergic synapses, respectively, which leads to a synaptic imbalance.”
https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3000307&type=printable

“Hydrogen sulfide (H2S) is recognized as a new neuromodulator in regulating various brain functions. Some of our recent studies showed that H2S alleviates the hippocampal damage induced by recurrent febrile seizures (FS). In the present study, we used a rat model of recurrent FS and found that sodium sulfhydrate (NaHS, a donor of H2S) down-regulated the expression of c-fos and increased the expression of gamma-aminobutyric acid B receptor subunits 1 (GABABR1) and 2 (GABABR2).” https://pubmed.ncbi.nlm.nih.gov/16122826/

“gamma-Aminobutyric acid (GABA) is considered to be the major inhibitory neurotransmitter in the brain and loss of GABA inhibition has been clearly implicated in epileptogenesis.”
https://pubmed.ncbi.nlm.nih.gov/11475940/

“These recent findings indicate that the GABA transporter plays a much more dynamic role in control of brain excitability than has previously been recognized.”
https://pubmed.ncbi.nlm.nih.gov/15250587/

Molecular hydrogen:

“Furthermore, HRW administration significantly reversed the alternation of serum levels of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), but without any effects on the BDNF levels in maternal VPA-exposed mice offspring. These data suggest the need for additional research on HRW as a potential preventive strategy for autism and related disorders.”
https://www.frontiersin.org/articles/10.3389/fnbeh.2018.00170/full

“In addition, hydrogen water reduced levels of TNF-α and IL-6, which mediate inflammatory responses. Therefore, hydrogen water is efficacious in the treatment of neonatal HIE.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329859/

“Our results showed that hydrogen (H2) up-regulated H2S levels via promoting the expression of CBS in the hippocampus, and its treatment alleviated oxidative stress via activating the expression of Nrf2 and HO-1, and then cell apoptosis reduced, furthermore, brain function improved by down-regulating the levels of S100-βand NSE.”
https://ijbms.mums.ac.ir/article_14868.html

Gut Microbiome:
In recent years, it has become more evident that gut flora may have a significant impact on neurological disorders and may be central to their cause or development. There have been quite a few studies that have been conducted demonstrating the connection between the dysregulation of the gut microbiome and Epilepsy. On the other hand, molecular hydrogen is naturally produced in the human gut (one of the ways we know it is safe for humans) and appears to mediate several of its therapeutic effects on the human body by acting on the gut flora. Hydrogen may have the potential for Epilepsy by regulating the gut microbiome, benefiting those with Epilepsy.

Epilepsy:

“The close relationship between epilepsy and autoimmune diseases and the fact that the cause of epilepsy is idiopathic in 60% of cases suggest that intestinal microbiota may play a role in the etiology of epilepsy.”
https://www.sciencedirect.com/science/article/abs/pii/S0882401019304917?via%3Dihub

“Normalization of the intestinal microbiota may be a new treatment for epilepsy.”

“On the contrary, in many neurological diseases, such as in ASD and epilepsy, an alteration in gut microbiota has been shown [129,130,131,132,133,134].”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267969/

“Moreover, several alterations in gut microbiota associated with intestinal problems have been found in other neuropsychiatric disorders of potential neurodevelopmental origins, such as schizophrenia [128,135,136,137], bipolar disorder [138] and depression [139,140], where the balance between excitation and inhibition is impaired [141].”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267969/

“Recently, evidence from both animal studies and human cases has emerged that a dysbiosis in the gut may be associated with certain forms of epilepsy.”
https://pubmed.ncbi.nlm.nih.gov/31160269/

“Several studies demonstrate a microbiota-gut-brain bidirectional connection via neural, endocrine, metabolic and immune pathways.”
https://pubmed.ncbi.nlm.nih.gov/31626816/

“Accordingly, the gut microbiota has a crucial role in modulating intestinal permeability, to alter local/peripheral immune responses and in production of essential metabolites and neurotransmitters. Its alterations may consequently influence all these pathways that contribute to neuronal hyper-excitability and mirrored neuroinflammation in epilepsy and similarly other neurological conditions. Indeed, pre- and clinical studies support the role of the microbiome in pathogenesis, seizure modulation and responses to treatment in epilepsy. Up to now, researchers have focused attention above all on the brain to develop antiepileptic treatments, but considering the microbiome, could extend our possibilities for developing novel therapies in the future.”
https://pubmed.ncbi.nlm.nih.gov/31626816/

Molecular hydrogen:

“Exogenous H2 (hydrogen water, H2 inhalation, etc) reprograms colonocyte metabolism by regulating the H2–gut microbiota–SCFAs axis and strengthens the intestinal barrier by modulating specific mucosa-associated mucolytic bacteria, wherein improved microbial hydrogen economy alleviates colitis.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759589/

“Taken together, the evidence indicates that HRW administration helps maintain permeability, mucosal structure and barrier function in the intestine and improves the gastrointestinal microenvironment for bacteria that protect against EtOH-induced liver injury.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526762/

“Hydrogen inhalation significantly improved bowel motility 24 h after reperfusion (N = 6 each group) (B)”
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-6143.2008.02359.x?regionCode=US-KS&identityKey=c982340a-0b86-4c68-80c5-6d4cf231264a&wol1URL=%2Fdoi%2F10.1111%2Fj.1600-6143.2008.02359.x%2Ffull

“These findings suggest that H2 improves LPS-induced hyperpermeability of the intestinal barrier and disruptions of TJ and AJ by moderating RhoA-mDia1 signaling.”
https://pubmed.ncbi.nlm.nih.gov/26529665/

“These results suggest luminal administration of hydrogen-rich saline, which prevents intestinal dysbiosis, hyperpermeability, and bacterial translocation, could potentially be a new therapeutic strategy in critical illness.”
https://pubmed.ncbi.nlm.nih.gov/29293174/

“Furthermore, the consumption of hydrogen-rich water improved the diversity and abundance of the gut flora in athletes.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352569/

“Thus, the consumption of hydrogen-rich water for two months might play a role modulating in the gut flora of athletes based on its selective antioxidant and anti-inflammatory activities.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352569/

“These results suggest that saturated hydrogen could improve intestinal structural integrity and lipid metabolism disorders by inhibiting the glyoxylic acid cycle of the intestinal flora.”
https://pubmed.ncbi.nlm.nih.gov/31910652/

H2 and Epilepsy

Molecular hydrogen studies that have demonstrated that hydrogen gas may reduce or is suggested to reduce incidents of seizures:

“They added 2.4 percent hydrogen gas to the animals’ usual ventilation gases during and after arrested blood flow and hypoxia. Compared with controls, the treated animals did significantly better on neurologic evaluations. They had fewer seizures, smaller areas of tissue injury on brain MRI and decreased chemical markers of brain and kidney injury in their blood.”
https://www.sciencedaily.com/releases/2019/04/190429140617.htm

“Two swine in the control group exhibited refractory status epilepticus and were sacrificed at 32 and 36 h post-injury following a failed trial of extubation; no hydrogen-treated animals exhibited seizures.”

“We have shown that the perioperative administration of 2.40% H2 is safe and diminishes neurologic injury in an experimental model of circulatory arrest. Although the combination of temperature and duration of circulatory arrest used is not used clinically, the model did successfully establish the degree of neurologic injury manifested in the most severely affected neonates, including perioperative seizures and radiographically apparent injury. In that setting, the perioperative administration of H2 improved clinical neurologic scores, decreased serum markers of brain injury, decreased radiographically apparent volumes of brain injury, and lessened the degree of histopathologic injury. In addition, H2-treated swine exhibited a significantly lower concentration of serum creatinine during the survival period, suggesting that hydrogen may diminish the effects of renal ischemia.” https://basictranslational.onlinejacc.org/content/4/2/176

“Because most CA patients may not get advanced life support immediately, we applied the 2-hour 60% H2 treatment starting 1 hour after resuscitation. This approach tended to reduce the incidence of seizures and improve neurological deficit scores in the resuscitated rats. However, the time of H2 administration seems to play an important role in that early administration has been shown to be associated with more significant benefits in previous studies.[18],[22],[23]
https://www.medgasres.com/article.asp?issn=2045-9912;year=2018;volume=8;issue=3;spage=73;epage=78;aulast=Huang

Closing

Studies for Hydrogen and Autism: 

Physical exercise and intermittent administration of lactulose may improve autism symptoms through hydrogen production
https://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-2-19

http://www.ncbi.nlm.nih.gov/pubmed/?term=22846252

Hydrogen-rich water ameliorates autistic-like behavioral abnormalities in valproic acid-treated adolescent mice offspring (Jul 2018)
https://www.frontiersin.org/articles/10.3389/fnbeh.2018.00170/abstract

Ghanizadeh, A., Hydrogen as a novel hypothesized emerging treatment for oxidative stress in autism.European Review for Medical and Pharmacological Sciences, 2012. 16(9): p. 1313-4.
https://www.researchgate.net/publication/232225514_Hydrogen_as_a_novel_hypothesized_emerging_treatment_for_oxidative_stress_in_autism

The neuroprotective effects of electrolyzed reduced water and its model water containing molecular hydrogen and Pt nanoparticles – autism
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285010/

Oxidative stress in autism
http://www.sciencedirect.com/science/article/pii/S0928468006000538

Oxidative and environmental stress
http://link.springer.com/article/10.1007/s13273-012-0029-1

Hydrogen as a novel hypothesized emerging treatment for oxidative stress in autism
http://www.europeanreview.org/article/1469

I hope this gives you enough information on molecular hydrogen and its potential for your kiddos. I know a lot of it may be hard to understand, but I wanted to give you a genuine look at the data to understand its potential. I cannot imagine what you have been through trying to love on your kids and help them with their health challenges, but I do believe molecular hydrogen holds potential for your family. You mentioned your budget is limited, but without a ballpark dollar amount, it’s hard to recommend a particular H2 product. Based on the research it would be best to have them consume both hydrogen water and hydrogen inhalation, as they both have their unique advantages and disadvantages. Hydrogen water will be better for gut health and H2 inhalation for increasing H2 in the brain and CNS.

So with that being said here are a couple of recommendations. 

H2 water: 

https://h2hubb.com/drinkhrw-hydrogen-tablets/

https://h2hubb.com/q-life-q-cup-max/

H2 Inhalation: 

https://h2hubb.com/q-life-h2-respire-150/

https://h2hubb.com/hydrogen-for-health-hx600-falcon/

https://h2hubb.com/hbs10brownsgasinhaler/

These are some of the more budget-friendly options. 

I hope this blesses you. 

Let me know how I can help you further.

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