Autism Prevention and Recovery

Research & Studies

Hydrogen as a novel hypothesized emerging treatment for oxidative stress in autism

 

“According to the mentioned above evidence, there is an increased level of oxidative stress, and a decreased antioxidant capacity in autism. In addition, there is a lack of evidenced-based research into treatments to address this issue. Considering the apparent usefulness of hydrogen as a non-toxic antioxidant that can readily cross the blood-brain barrier and cellular membrane, it is worthwhile to conduct studies to examine the possible therapeutic role of molecular hydrogen for the treatment of autism.”

 

Ghanizadeh, A. (2012). Hydrogen as a novel hypothesized emerging treatment for oxidative stress in autism. European Review for Medical and Pharmacological Sciences, 16(9), 1313-1314. Retrieved from http://www.europeanreview.org/wp/wp-content/uploads/1469.pdf
 


Physical exercise and intermittent administration of lactulose may improve autism symptoms through hydrogen production

 

“Autism is neuro-developmental disorder. Oxidative stress is enhanced in some children with autism. Hydrogen is a gas with anti-oxidative effects suggested for treating or prevention of some medical problems. It is hypothesized that lactulose or hydrogen water may provide hydrogen to reduce oxidative stress in autism.”

 

Ghanizadeh, A. (2012). Physical exercise and intermittent administration of lactulose may improve autism symptoms through hydrogen production. Medical Gas Research, 2(1), 1-3. doi: 10.1186/2045-9912-2-19

 

Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications

 

“H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2. H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. Moreover, H2 passes through the blood brain barrier, although most antioxidant compounds cannot; this is also an advantage of H2.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

 

Downregulation of the expression of mitochondrial electron transport complex genes in autism brains

 

“Mitochondrial dysfunction (MtD) and abnormal brain bioenergetics have been implicated in autism, suggesting possible candidate genes in the electron transport chain (ETC). This could have been induced by oxidative stress due to impaired ATP synthesis. We report new candidate genes involved in abnormal brain bioenergetics in autism, supporting the hypothesis that mitochondria, critical for neurodevelopment, may play a role in autism.”

 

Anitha, A., Nakamura, K., Thanseem, I., Matsuzaki, H., Miyachi, T., Tsujii, M., . . . Mori, N. (2012). Downregulation of the expression of mitochondrial electron transport complex genes in autism brains. Brain Pathology, 23(3), 294-302. doi: 10.1111/bpa.12002

 


Mitochondrial dysfunction in autism spectrum disorders: A systematic review and meta-analysis

 

“A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD.”

 

Rossignol, D. A., & Frye, R. E. (2011). Mitochondrial dysfunction in autism spectrum disorders: A systematic review and meta-analysis. Molecular Psychiatry, 17(3), 290-314. doi: 10.1038/mp.2010.136

 


Molecular hydrogen and its potential application in therapy of brain disorders

 

“A possible cause for the neuroprotective effect of hydrogen may be related to its high diffusibility. Hydrogen molecules can readily cross the blood-brain barrier and penetrate biomembranes smoothly to diffuse into the cytosol, nucleus and mitochondria. This is particularly important, as mitochondria is the major source of ROS and notoriously difficult to target. The protective effect of molecular hydrogen on the mitochondria have also been found in our study.”

 

Ma, F. X. (2015). Molecular hydrogen and its potential application in therapy of brain disorders. Brain Disorders & Therapy, 4(1), 1-2. doi: 10.4172/2168-975x.1000154

 

Mitochondrial dysfunction in autism spectrum disorders: A systematic review and meta-analysis

 

“Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD.”

 

Rossignol, D. A., & Frye, R. E. (2011). Mitochondrial dysfunction in autism spectrum disorders: A systematic review and meta-analysis. Molecular Psychiatry, 17(3), 290-314. doi: 10.1038/mp.2010.136

 


Brain region-specific altered expression and association of mitochondria-related genes in autism

 

“Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted.”

 

Anitha, A., Nakamura, K., Thanseem, I., Yamada, K., Iwayama, Y., Toyota, T., . . . Mori, N. (2012). Brain region-specific altered expression and association of mitochondria-related genes in autism. Molecular Autism, 3(1), 1-12. doi: 10.1186/2040-2392-3-12

 


Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases

 

“Hydrogen has many advantages for therapeutic and preventive applications, and shows not only anti-oxidative stress effects, but also has various anti-inflammatory and anti-allergic effects. Preliminary clinical trials show that drinking hydrogen-dissolved water seems to improve the pathology of mitochondrial disorders.”

 

Ohta, S. (2012). Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases. Biochimica et Biophysica Acta, 1820(5), 586-594. doi: 10.1016/j.bbagen.2011.05.006

 

Mitochondrial disease in autism spectrum disorder patients: A cohort analysis

 

“These and prior data suggest a disturbance of mitochondrial energy production as an underlying pathophysiological mechanism in a subset of individuals with autism.”

 

Weissman, J. R., Kelley, R. I., Bauman, M. L., Cohen, B. H., Murray, K. F., Mitchell, R. L., . . . Natowicz, M. R. (2008). Mitochondrial disease in autism spectrum disorder patients: A cohort analysis. PLOS ONE, 3(11), 1-6. doi: 10.1371/journal.pone.0003815
 


Evidence of mitochondrial dysfunction in autism and implications for treatment

 

“Classical mitochondrial diseases occur in a subset of individuals with autism and are usually caused by genetic anomalies or mitochondrial respiratory pathway deficits.”

 

Rossignol, D. A., & Bradstreet, J. J. (2008). Evidence of mitochondrial dysfunction in autism and implications for treatment. American Journal of Biochemistry and Biotechnology, 4(2), 208-217. doi: 10.3844/ajbbsp.2008.208.217

 

Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

 

Brain region-specific glutathione redox imbalance in autism

 

“Recently, we reported a brain region-specific increase in lipid peroxidation, and deficits in mitochondrial electron transport chain complexes in autism, suggesting the role of oxidative stress and mitochondrial dysfunction in the pathophysiology of autism. These findings indicate that autism is associated with deficits in glutathione antioxidant defense in selective regions of the brain. We suggest that disturbances in brain glutathione homeostasis may contribute to oxidative stress, immune dysfunction and apoptosis, particularly in the cerebellum and temporal lobe, and may lead to neurodevelopmental abnormalities in autism.”

 

Chauhan, A., Audhya, T., & Chauhan, V. (2012). Brain region-specific glutathione rox imbalance in autism. Neurochemical Research, 37(8), 1681-1689. doi: 10.1007/s11064-012-0775-4

 

A review of hydrogen as a new medical therapy

 

“In the past few years many initial and subsequent clinical studies have demonstrated that hydrogen can act as an important physiological regulatory factor to cells and organs on the antioxidant, anti-inflammatory, anti-apoptotic and other protective effects. So far several delivery methods applied in these studies have proved to be available and convenient, including inhalation, drinking hydrogen-dissolved water and injection with hydrogen-saturated saline.”

 

Zhang, J., Liu, C., Zhou, L., Qu, K., Wang, R., Tai, M., . . . Wang, Z. (2012). A Review of hydrogen as a new medical therapy. Hepatogastroenterology, 59(116), 1026-1032. doi: 10.5754/hge11883

 

Oxidative stress in autism

 

“Taken together, these studies suggest increased oxidative stress in autism that may contribute to the development of this disease. A mechanism linking oxidative stress with membrane lipid abnormalities, inflammation, aberrant immune response, impaired energy metabolism and excitotoxicity, leading to clinical symptoms and pathogenesis of autism is proposed.”

 

Chauhan, A., & Chauhan, V. (2006). Oxidative stress in autism. Pathophysiology, 13(3), 171-181. doi: 10.1016/j.pathophys.2006.05.007

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“In the clinic, oral administration of H(2)-saturated water is reported to improve lipid and glucose metabolism in subjects with diabetes or impaired glucose tolerance; promising results have also been obtained in reducing inflammation in haemodialysis patients and treating metabolic syndrome. These studies suggest H(2) has selective antioxidant properties, and can exert antiapoptotic, antiinflammatory and antiallergy effects.

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

 

Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism

 

“A significant increase in the levels of lipid hydroperoxides, an oxidative stress marker, was also observed in the cerebellum and temporal cortex in the children with autism. These results suggest that the expression of ETC complexes is decreased in the cerebellum and the frontal and temporal regions of the brain in children with autism, which may lead to abnormal energy metabolism and oxidative stress.”

 

Chauhan, A., Gu, F., Essa, M. M., Wegiel, J., Kaur, K., Brown, W. T., & Chauhan, V. (2011). Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism. Journal of Neurochemistry, 117(2), 209-220. doi: 10.1111/j.1471-4159.2011.07189.x

 

The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance

 

“Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell.”

 

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance. Medical Gas Research, 3(10), 1-12. doi: 10.1186/2045-9912-3-10

 

Urinary oxidative stress markers in children with autism

 

“The study observed a significant elevation in the level of oxidative stress markers in autistic children when compared with normal children. The level of antioxidants excreted in urine was found to be significantly low in autistic children. These findings when correlated with the degrees of severity, oxidative stress markers showed positive correlation with increasing order of severity (LFA>MFA>HFA), whereas antioxidants showed negative correlation.”

 

Damodaran, L. P., & Arumugam, G. (2011). Urinary oxidative stress markers in children with autism. Redox Report, 16(5), 216-222. doi: 10.1179/1351000211y.0000000012

 

Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

 

Glutathione-related factors and oxidative stress in autism, a review

 

“The current literature suggests an imbalance of oxidative and anti-oxidative stress systems in autism. Glutathione is involved in neuro-protection against oxidative stress and neuro-inflammation in autism by improving the anti-oxidative stress system. Decreasing the oxidative stress might be a potential treatment for autism.”

 

Ghanizadeh, A., Akhondzadeh, S., Hormozi, M., Makarem, A., Abotorabi-Zarchi, M., & Firoozabadi, A. (2012). Glutathione-related factors and oxidative stress in autism, a review. Current Medicinal Chemistry, 19(23), 4000-4005. doi: 10.2174/092986712802002572

 


Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine

 

“The numerous publications on its biological and medical benefits revealed that H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism.”

 

Ohta, S. (2014). Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine. Pharmacology & Therapeutics, 144(1), 1-11. doi: 10.1016/j.pharmthera.2014.04.006

 

Mast cells, brain inflammation and autism

 

“CRF and NT are significantly increased in serum of ASD children compared to normotypic controls further strengthening their role in the pathogenesis of autism. There are no clinically affective treatments for the core symptoms of ASDs, but pilot clinical trials using natural-antioxidant and anti-inflammatory molecules reported statistically significant benefit.”

 

Theoharides, T. C., Stewart, J. M., Panagiotidou, S., & Melamed, I. (2016). Mast cells, brain inflammation and autism. European Journal of Pharmacology, 778, 96-102. doi: 10.1016/j.ejphar.2015.03.086

 

Hydrogen therapy: From mechanism to cerebral diseases

 

“Inhalation of 2% H2 can significantly decrease the damage of cerebral ischemia/reperfusion caused by oxidative stress via selective elimination of hydroxyl freebase (OH) and peroxynitrite anion (ONOOˉ). Subsequently, there have been numerous experiments on H2. Most research and trials involving the mechanisms underlying H2 therapy show the effects of antioxygenation, anti-inflammation, and anti-apoptosis.”

 

Chen, G., Liu, C., & Zhang, K. (2016). Hydrogen therapy: From mechanism to cerebral diseases. Medical Gas Research, 6(1), 48-54. doi: 10.4103/2045-9912.179346

 

Relevance of neuroinflammation and encephalitis in autism

 

“In recent years, many studies indicate that children with an autism spectrum disorder (ASD) diagnosis have brain pathology suggestive of ongoing neuroinflammation or encephalitis in different regions of their brains. Evidence of neuroinflammation or encephalitis in ASD includes: microglial and astrocytic activation, a unique and elevated proinflammatory profile of cytokines, and aberrant expression of nuclear factor kappa-light-chain-enhancer of activated B cells. A conservative estimate based on the research suggests that at least 69% of individuals with an ASD diagnosis have microglial activation or neuroinflammation.”

 

Kern, J. K., Geier, D. A., Sykes, L. K., & Geier, M. R. (2016). Relevance of neuroinflammation and encephalitis in autism. Frontiers in Cellular Neuroscience, 9(519), 1-10. doi: 10.3389/fncel.2015.00519

 

A review of research trends in physiological abnormalities in autism spectrum disorders: Immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures

 

“A large percentage of publications implicated an association between ASD and immune dysregulation/inflammation, oxidative stress, mitochondrial dysfunction and toxicant exposures. The strongest evidence was for immune dysregulation/inflammation and oxidative stress followed by toxicant exposures and mitochondrial dysfunction.”

 

Rossignol, D. A., & Frye, R. E. (2011). A review of research trends in physiological abnormalities in autism spectrum disorders: Immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Molecular Psychiatry, 17(4), 389-401. doi: 10.1038/mp.2011.165

 

Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice

 

“We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- α and upregulation of IL-10). In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation.”

 

Spulber, S., Edoff, K., Hong, L., Morisawa, S., Shirahata, S., & Ceccatelli, S. (2012). Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice. PLOS ONE, 7(7), 1-12. doi: 10.1371/journal.pone.0042078

 

Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain

 

“Together, these results indicate that decreased GSH/GSSG redox/antioxidant capacity and increased oxidative stress in the autism brain may have functional consequence in terms of a chronic inflammatory response, increased mitochondrial superoxide production, and oxidative protein and DNA damage.”

 

Rose, S., Melnyk, S., Pavliv, O., Bai, S., Nick, T. G., Frye, R. E., & James, S. J. (2012). Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Translational Psychiatry, 2(7), 1-8. doi: 10.1038/tp.2012.61

 

Hydrogen resuscitation, a new cytoprotective approach

 

“Recent evidence indicates that hydrogen is a potent anti-oxidative, anti-apoptotic and anti-inflammatory agent and so may have potential medical application. Studies have shown that hydrogen resuscitation has cytoprotective effects in different cell types and disease models, including ischaemia-reperfusion injury, inflammation, toxicity, trauma and metabolic disease. The underlying mechanism may be the selective elimination of hydroxyl radicals, although other mechanisms may also be involved (e.g. hydrogen functioning as a gaseous signalling molecule). Hydrogen resuscitation may have several potential advantages over current pharmacological therapies for oxidative injuries.”

 

Zheng, X., Sun, X., & Xia, Z. (2011). Hydrogen resuscitation, a new cytoprotective approach. Clinical and Experimental Pharmacology and Physiology, 38(3), 155-163. doi: 10.1111/j.1440-1681.2011.05479.x

 

Evaluation of oxidative stress in autism: Defective antioxidant enzymes and increased lipid peroxidation

 

“We concluded that children with autism are more vulnerable to oxidative stress in the form of increased lipid peroxidation and deficient antioxidant defense mechanism especially at younger children. We highlight that autistic children might benefit from antioxidants supplementation coupled with polyunsaturated fatty acids. Moreover, early assessment of antioxidant status would have better prognosis as it may decrease the oxidative stress before inducing more irreversible brain damage.”

 

Meguid, N. A., Dardir, A. A., Abdel-Raouf, E. R., & Hashish, A. (2011). Evaluation of oxidative stress in autism: Defective antioxidant enzymes and increased lipid peroxidation. Biological Trace Element Research, 143(1), 58-65. doi: 10.1007/s12011-010-8840-9

 

Beneficial biological effects and the underlying mechanisms of molecular hydrogen - Comprehensive review of 321 original articles

 

“A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases.”

 

Ichihara, M., Sobue, S., Ito, M., Ito, M., Hirayama, M., & Ohno, K. (2015). Beneficial biological effects and the underlying mechanisms of molecular hydrogen - Comprehensive review of 321 original articles. Medical Gas Research, 5(12), 1-21. doi: 10.1186/s13618-015-0035-1

 

Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism

 

“Evidence is accumulating that ASD is characterized by certain physiological abnormalities, including oxidative stress, mitochondrial dysfunction and immune dysregulation/inflammation.”

 

Rossignol, D. A., & Frye, R. E. (2014). Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Frontiers in Physiology, 5(150), 1-15. doi: 10.3389/fphys.2014.00150

 

Recent advances in hydrogen research as a therapeutic medical gas

 

“Recent basic and clinical research has revealed that hydrogen is an important physiological regulatory factor with antioxidant, anti-inflammatory and anti-apoptotic protective effects on cells and organs.”

 

Huang, C., Kawamura, T., Toyoda, Y., & Nakao, A. (2010). Recent advances in hydrogen research as a therapeutic medical gas. Free Radical Research, 44(9), 971-982. doi: 10.3109/10715762.2010.500328 

 

Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain

 

“Together, these results indicate that decreased GSH/GSSG redox/antioxidant capacity and increased oxidative stress in the autism brain may have functional consequence in terms of a chronic inflammatory response, increased mitochondrial superoxide production, and oxidative protein and DNA damage.

 

Rose, S., Melnyk, S., Pavliv, O., Bai, S., Nick, T. G., Frye, R. E., & James, S. J. (2012). Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Translational Psychiatry, 2(7), 1-8. doi: 10.1038/tp.2012.61

 


Molecular hydrogen: A therapeutic antioxidant and beyond

 

“Although the underlying mechanisms were initially proposed as selective extinctions of hydroxyl radical and peroxynitrite, the signaling pathway regulation effect of molecular hydrogen by modulating a various molecules expressions/activities, gene expression and microRNA may also account for the ultimate effects of anti-reperfusion injury, anti-infammation, anti-apoptosis, anti-metabolic disorders, anti-allergy, anti-radiation injury, anti-dementia as well as anti-aging.”

 

Huang, L. (2016). Molecular hydrogen: A therapeutic antioxidant and beyond. Medical Gas Research, 6(4), 219–222. doi: 10.4103/2045-9912.196904 
 

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