Physical exercise and intermittent administration of lactulose may improve autism symptoms through hydrogen production
© Ghanizadeh; licensee BioMed Central Ltd. 2012
Received: 12 June 2012
Accepted: 26 July 2012
Published: 30 July 2012
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.
Autism and oxidative stress
Autism is a neurodevelopmental disorder that its diagnosis is increased in recent decade. In addition to increasing professionals and public awareness regarding autism, its diagnostic concept is broaden . According to parents’ report and DSM-IV diagnostic criteria, about 1.9% of a sample of school aged children in Iran meet the screening cutoff scores for possible autistic disorder . The neurobiology and genetics of autism is not clearly known .
Oxidative stress probably plays a significant role in the neurobiology of autism . Some symptoms of autism are mediated by oxidative stress . Urinary oxidative stress markers levels in autism are more than that of the controls and these levels are associated with the severity of autism . Lipid peroxidation is increased in autism . The vulnerability of children with autism to oxidative stress is higher than that of the controls . For example, the total and reduced levels of glutathione are decreased in some children with autism, while reactive oxygen species and oxidized glutathione level are increased . Moreover, the activity levels of glutathione- s-transferase and catalase are decreased . Besides, the serum levels of transferrin and ceruloplasmin as significant antioxidant proteins are decreased in autism .
Brain-derived neurotrophic factor (BDNF) in brain in some children with autism is reduced . Sonic hedgehog (SHH) protein and brain-derived neurotrophic factor (BDNF) are associated with oxidative stress in autism . This association might be mediated by Malondialdehyde, Bcl-2, superoxide dismutase and glutathione peroxidase .
The increased oxidative stress is suggested as a treatment target to improve the function of mitochondria [13–15]. Many of the suggested treatments targeted neuro-inflammation [16, 17]. Already, some uncontrolled studies reported that hyperbaric oxygen is beneficial for some children with autism. However, there are not enough evidence for its efficacy for treating autism . There is a limited number of FDA approved medications for treating autism. Finally, while there is no curative treatment for autism, alternative medications are highly required.
Hydrogen and oxidative stress
Hydrogen molecule defenses against oxidative stress . There are two advantages for hydrogen molecule. First, it decreases the hydroxyl radical which is a potent cytotoxic reactive oxygen species. Secondly, Hydrogen does not react with other reactive oxygen species. This is very important because some of the reactive oxygen species have physiological roles . The therapeutic effects of hydrogen is reported for some problems, such as hepatic injury , atherosclerosis prevention , and isplatin-induced ototoxicity . Recently, it has been suggested that hydrogen may decrease some symptoms of autism .
Lactulose and hydrogen
Lactulose is not absorbed from intestine in humans but this synthetic sugar can be used by some intestinal bacteria to produce hydrogen. Hydrogen in breath air is increased after taking lactulose . However, intermittent hydrogen administration more than continually increased level of hydrogen is effective for protection against Parkinson disease . The effect of hydrogen water is more effective than administering lactulose or continually administration of 2% hydrogen gas . In fact, the effect of intermittent administration of hydrogen is more than continually administration of hydrogen. In other words, the dose of hydrogen is not important as much as being administered intermittently . Bacteria in human gut can produce hydrogen from lactulose that exercise exacerbates this hydrogen production .
In addition, about 42% of children with autism suffer from gastrointestinal problems . Both constipation and diarrhea are the most common problems . The incidence rate of constipation in autism is 33.9% while this rate for the control group is 17.6% . Not only constipation is a common gastrointestinal problem in children with autism but also constipation is associated with increased social impairment and lack of expressive language . Therefore, there is a need for treating constipation in autism . It is supposed that there is a common genetic factor for intestinal and behavioral problems in autism that targeting both problems is recommended for treating autism . Lactulose is a osmotic laxative which is used for treating constipation .
Physical exercise and autism
While the physical activity of children with autism is lesser than the controls , physical exercise decreases some of the symptoms of autism. Exergaming which is a simultaneous combine of physical and mental exercise decreases stereotypies in autism . Moreover, exergaming enhances their cognitive function . In addition, aerobic exercise improves academic function of children with autism . Besides, the improved motor proficiency and sensory integrative functions after physical activity are sustained for long term .
There are many reports about the role of oxidative stress in autism. Moreover, hydrogen is a gas with anti-oxidative stress effects. There are some resources for hydrogen, such as hydrogen water and lactulose. Lactulose administration enhances hydrogen production in intestines. Considering that oxidative stress is a target for treating autism, it is hypothesized that lactulose may target both oxidative stress in brain and constipation in autism. Therefore, it is worthy to investigate the possible effect of lactulose or hydrogen water on autism. Taking into account that continues hydrogen is less effective than intermittent hydrogen administration, intermittent lactulose administering should be considered.
- Elsabbagh M, Divan G, Koh YJ, Kim YS, Kauchali S, Marcin C, Montiel-Nava C, Patel V, Paula CS, Wang C, et al: Global Prevalence of Autism and Other Pervasive Developmental Disorders. Autism Res. 2012, 5 (3): 160-179.PubMed CentralView ArticlePubMedGoogle Scholar
- Ghanizadeh A: A preliminary study on screening prevalence of pervasive developmental disorder in schoolchildren in Iran. J Autism Dev Disord. 2008, 38 (4): 759-763.View ArticlePubMedGoogle Scholar
- Anagnostou E, Taylor MJ: Review of neuroimaging in autism spectrum disorders: what have we learned and where we go from here. Mol Autism. 2011, 2 (1): 4-PubMed CentralView ArticlePubMedGoogle Scholar
- Essa MM, Guillemin GJ, Waly MI, Al-Sharbati MM, Al-Farsi YM, Hakkim FL, Ali A, Al-Shafaee MS: Increased markers of oxidative stress in autistic children of the sultanate of oman. Biol Trace Elem Res. 2012, 147 (1–3): 25-27.View ArticlePubMedGoogle Scholar
- Ghanizadeh A: Oxidative stress may mediate association of stereotypy and immunity in autism, a novel explanation with clinical and research implications. J Neuroimmunol. 2011, 232 (1–2): 194-195.View ArticlePubMedGoogle Scholar
- Damodaran LP, Arumugam G: Urinary oxidative stress markers in children with autism. Redox Rep. 2011, 16 (5): 216-222.View ArticlePubMedGoogle Scholar
- Chauhan A, Chauhan V, Brown WT, Cohen I: Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin–the antioxidant proteins. Life Sci. 2004, 75 (21): 2539-2549.View ArticlePubMedGoogle Scholar
- Meguid NA, Dardir AA, Abdel-Raouf ER, Hashish A: Evaluation of oxidative stress in autism: defective antioxidant enzymes and increased lipid peroxidation. Biol Trace Elem Res. 2011, 143 (1): 58-65.View ArticlePubMedGoogle Scholar
- Ghanizadeh A, Akhondzadeh S, Hormozi , Makarem A, Abotorabi M, Firoozabadi A: Glutathione-related Factors and Oxidative Stress in Autism, a Review. Curr Med Chem. 2012, [Epub ahead of print]Google Scholar
- Hashimoto K, Iwata Y, Nakamura K, Tsujii M, Tsuchiya KJ, Sekine Y, Suzuki K, Minabe Y, Takei N, Iyo M, et al: Reduced serum levels of brain-derived neurotrophic factor in adult male patients with autism. Prog Neuropsychopharmacol Biol Psychiatry. 2006, 30 (8): 1529-1531.View ArticlePubMedGoogle Scholar
- Al-Ayadhi LY: Relationship between Sonic hedgehog protein, brain-derived neurotrophic factor and oxidative stress in autism spectrum disorders. Neurochem Res. 2012, 37 (2): 394-400.PubMed CentralView ArticlePubMedGoogle Scholar
- Ghanizadeh A: Malondialdehyde, Bcl-2, superoxide dismutase and glutathione peroxidase may mediate the association of sonic hedgehog protein and oxidative stress in autism. Neurochem Res. 2012, 37 (4): 899-901.View ArticlePubMedGoogle Scholar
- Ghanizadeh A: Targeting Mitochondria by Olesoxime or Complement 1q Binding Protein as a Novel Management for Autism: A Hypothesis. Mol Syndromol. 2011, 2 (1): 50-52.PubMed CentralPubMedGoogle Scholar
- Ghanizadeh A: Nuclear factor kappa B may increase insight into the management of neuroinflammation and excitotoxicity in autism. Expert Opin Ther Targets. 2011, 15 (6): 781-783.View ArticlePubMedGoogle Scholar
- Ghanizadeh A: Gold implants and increased expression of metallothionein-I/II as a novel hypothesized therapeutic approach for autism. Toxicology. 2011, 283 (1): 63-64.View ArticlePubMedGoogle Scholar
- Ghanizadeh A: Methionine sulfoximine may improve inflammation in autism, a novel hypothesized treatment for autism. Arch Med Res. 2010, 41 (8): 651-652.View ArticlePubMedGoogle Scholar
- Ghanizadeh A: Targeting neurotensin as a potential novel approach for the treatment of autism. J Neuroinflammation. 2010, 7: 58-PubMed CentralView ArticlePubMedGoogle Scholar
- Ghanizadeh A: Hyperbaric oxygen therapy for treatment of children with autism: a systematic review of randomized trials. Med Gas Res. 2012, 2 (1): 13-PubMed CentralView ArticlePubMedGoogle Scholar
- Sun Y, Shuang F: Chen DM. 2012, Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats. Osteoporos Int, Zhou RBGoogle Scholar
- Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S: Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007, 13 (6): 688-694.View ArticlePubMedGoogle Scholar
- Fukuda K, Asoh S, Ishikawa M, Yamamoto Y, Ohsawa I, Ohta S: Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia/reperfusion through reducing oxidative stress. Biochem Biophys Res Commun. 2007, 361 (3): 670-674.View ArticlePubMedGoogle Scholar
- Ohsawa I, Nishimaki K, Yamagata K, Ishikawa M, Ohta S: Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem Biophys Res Commun. 2008, 377 (4): 1195-1198.View ArticlePubMedGoogle Scholar
- Qu J, Li X, Wang J, Mi W, Xie K, Qiu J: Inhalation of hydrogen gas attenuates cisplatin-induced ototoxicity via reducing oxidative stress. Int J Pediatr Otorhinolaryngol. 2012, 76 (1): 111-115.View ArticlePubMedGoogle Scholar
- Ghanizadeh A: Hydrogen as a novel hypothesized emerging treatment for oxidative stress in autism. Eur Rev for Med and Pharmacol Sci. Under PressGoogle Scholar
- Ito M, Hirayama M, Yamai K, Goto S, Ichihara M, Ohno K: Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson's disease in rats. Med Gas Res. 2012, 2 (1): 15-PubMed CentralView ArticlePubMedGoogle Scholar
- Ehrenpreis ED, Swamy RS, Zaitman D, Noth I: Short duration exercise increases breath hydrogen excretion after lactulose ingestion: description of a new phenomenon. Am J Gastroenterol. 2002, 97 (11): 2798-2802.View ArticlePubMedGoogle Scholar
- Wang LW, Tancredi DJ, Thomas DW: The prevalence of gastrointestinal problems in children across the United States with autism spectrum disorders from families with multiple affected members. J Dev Behav Pediatr. 2011, 32 (5): 351-360.View ArticlePubMedGoogle Scholar
- Ibrahim SH, Voigt RG, Katusic SK, Weaver AL, Barbaresi WJ: Incidence of gastrointestinal symptoms in children with autism: a population-based study. Pediatrics. 2009, 124 (2): 680-686.PubMed CentralView ArticlePubMedGoogle Scholar
- Gorrindo P, Williams KC, Lee EB, Walker LS, McGrew SG, Levitt P: Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism Res. 2012, 5 (2): 101-108.PubMed CentralView ArticlePubMedGoogle Scholar
- Pang KH, Croaker GD: Constipation in children with autism and autistic spectrum disorder. Pediatr Surg Int. 2011, 27 (4): 353-358.View ArticlePubMedGoogle Scholar
- Carlin A, Justham D: A literature review of two laxatives: lactulose and polyethylene glycol. Br J Community Nurs. 2011, 16 (12): 588-590. 584, 586Google Scholar
- Macdonald M, Esposito P, Ulrich D: The physical activity patterns of children with autism. BMC Res Notes. 2011, 4: 422-PubMed CentralView ArticlePubMedGoogle Scholar
- Anderson-Hanley C, Tureck K, Schneiderman RL: Autism and exergaming: effects on repetitive behaviors and cognition. Psychol Res Behav Manag. 2011, 4: 129-137.PubMed CentralView ArticlePubMedGoogle Scholar
- Oriel KN, George CL, Peckus R, Semon A: The effects of aerobic exercise on academic engagement in young children with autism spectrum disorder. Pediatr Phys Ther. 2011, 23 (2): 187-193.View ArticlePubMedGoogle Scholar
- Wuang YP, Wang CC, Huang MH, Su CY: The effectiveness of simulated developmental horse-riding program in children with autism. Adapt Phys Activ Q. 2010, 27 (2): 113-126.PubMedGoogle Scholar
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