自闭症的饮食、营养和医疗治疗总结-基于超过150项已发表的研究2013年
RIA出版物40 - 2013版本
Summary of Dietary, Nutritional, and Medical Treatments for Autism自闭症的饮食、营养和药物治疗总结– based on over 150 published research studies——基于150多项已发表的研究成果By James B. Adams, Ph.D.作者:詹姆斯·亚当斯,博士 2013 Version2013年版see http://autism.asu.edu or www.autism.com for future updates.看见http://autism.asu.edu 或者www.autism.com 供将来更新。 Overview 概观This document is intended to provide a simple summary for families and physicians of the major dietary, nutritional, and medical treatments available to help children and adults with autism spectrum disorders. The discussion is limited to those treatments which have scientific research support, with an emphasis on nutritional interventions. This report excludes psychiatric medications for brevity. The dietary, nutritional, and medical treatments discussed here will not help every individual with autism, but they have helped thousands of children and adults improve, usually slowly and steadily over months and years, but sometimes dramatically.本文件旨在为自闭症谱系障碍儿童和成人的家庭和医生提供主要饮食、营养和医疗治疗的简单总结。讨论仅限于有科学研究支持的治疗,重点是营养干预。为简洁起见,本报告不包括精神药物。这里讨论的饮食、营养和医疗治疗不会对每个自闭症患者都有所帮助,但它们已经帮助成千上万的儿童和成人得到改善,通常是在数月或数年内缓慢而稳定地改善,但有时会显著改善。 This summary is primarily based on review of the scientific literature, and includes over 150 references to peer-reviewed scientific research studies. It is also based on discussions with many physicians, nutritionists, researchers, and parents. This summary generally follows the philosophy of the Autism Research Institute (ARI), which involves trying to identify and treat the underlying causes of the symptoms of autism, based on medical testing, scientific research, and clinical experience, with an emphasis on nutritional interventions. Many of these treatments have been developed from observations by parents and physicians.本摘要主要基于对科学文献的综述,包括150多篇对同行评议的科学研究的参考文献。它还基于与许多医生、营养学家、研究人员和家长的讨论。本总结通常遵循自闭症研究所(ARI)的理念,即根据医学检测、科学研究和临床经验,尝试识别和治疗自闭症症状的根本原因,重点是营养干预。其中许多治疗方法都是根据父母和医生的观察制定的。 ARI Survey of Parent Ratings of Treatment Efficacy and Safety家长对治疗疗效和安全性评分的ARI调查Most of the treatments listed on the following pages were evaluated as part of the Autism Research Institute (ARI) survey of over 27,000 parents on their opinion of the effectiveness of various treatments for children with autism. For a full copy of the latest ARI Survey, see the last page. (For Asperger’s see www.autism.com).以下各页所列的大多数治疗方法都是作为自闭症研究所(ARI)对超过27,000名家长进行的调查的一部分进行评估的,该调查旨在了解他们对自闭症儿童各种治疗方法有效性的看法。有关最新ARI调查的完整副本,请参阅最后一页。(阿斯伯格综合症参见www.autism.com).Almost all the treatments listed here generally have a much lower rate of adverse effects than psychiatric medications, according the ARI Survey of Parent Ratings. However, adverse effects are possible with any treatment, and in a few cases special Safety Notes are mentioned for particular treatments.根据ARI家长评分调查,此处列出的几乎所有治疗方法的不良反应发生率通常都远低于精神药物。然而,任何治疗都可能产生不良作用,在少数情况下,会针对特定治疗提及特殊安全注意事项。 Other Interventions:其他发言:Behavioral interventions, such as Applied Behavior Analysis (ABA), can also be very helpful to children with autism, and are recommended to be used in conjunction with dietary, nutritional, and medical treatments. Similarly, speech therapy, sensory integration, physical therapy, occupational therapy, and a good educational program can be very important. Finally, social interventions such as play with parents/siblings, play dates and social groups can be very helpful in building social understanding, relationships and skills. Dietary, nutritional, and medical therapy may help improve the efficacy of these other interventions, by improving brain and body health and making it easier for the child to learn.行为干预,如应用行为分析(ABA),对自闭症儿童也很有帮助,建议与饮食、营养和医疗治疗结合使用。同样,语音治疗、感觉整合、物理治疗、职业治疗和良好的教育计划也非常重要。最后,社会干预,如与父母/兄弟姐妹玩耍、游戏约会和社交团体,对建立社会理解、关系和技能非常有帮助。饮食、营养和药物治疗可以通过改善大脑和身体健康以及让儿童更容易学习来帮助提高这些其他干预措施的疗效。 Note about Author: James Adams is a President’s Professor at Arizona State University, where he directs the ASU Autism/Asperger’s Research Program (http://autism.asu.edu), which focuses on researching the biological causes of autism and how to treat and prevent it. He has published over作者简介:詹姆斯·亚当斯是亚利桑那州立大学的校长教授,负责亚利桑那州立大学自闭症/阿斯伯格研究项目(http://autism.asu.edu),重点研究自闭症的生物学原因以及如何治疗和预防自闭症。他发表了超过
25 articles on autism, including studies of vitamins, minerals, essential fatty acids, amino acids, carnitine, neurotransmitters, toxic metals, detoxification, oxidative stress, glutathione, sulfation, gastrointestinal bacteria, immune system regulation, seizures, and sleep disorders in children and adults with autism. He has a Ph.D. in Materials Engineering and is Program Chair of Materials Engineering at ASU, but now focuses his research on autism due to having a daughter with autism. He is a member of the graduate faculty in Chemistry and Biochemistry at ASU. He also serves as the President of the Autism Society of Greater Phoenix since 2000, and co-leader of the Scientific Advisory Committee of the Autism Research Institute.25篇关于自闭症的文章,包括维生素、矿物质、必需脂肪酸、氨基酸、肉碱、神经递质、有毒金属、解毒、氧化应激、谷胱甘肽、硫酸盐化、胃肠细菌、免疫系统调节、癫痫发作以及自闭症儿童和成人睡眠障碍的研究。他拥有材料工程博士学位,是亚利桑那州立大学材料工程系的项目主席,但由于有一个患有自闭症的女儿,他现在专注于自闭症的研究。他是亚利桑那州立大学化学和生物化学研究生院的成员。自2000年以来,他还担任过大凤凰城自闭症协会主席,以及自闭症研究所科学咨询委员会的共同主席。 Reviewers:审阅者:We thank the many experts who reviewed different sections of this Summary (see list below), and special thanks to Stephen Edelson and Jane Johnson for reviewing the entire Summary.我们感谢许多专家审阅了本总结的不同部分(见下表),特别感谢斯蒂芬·埃德尔森和简·约翰逊审阅了整个总结。Tapan Audhya, Ph.D. – Vitamins/Minerals, High-Dose B6/Mg Kelly Barnhill, CN, CCN (Nutritionist) – Healthy DietsTapan Audhya,ph . d .–维生素/矿物质,高剂量B6/Mg Kelly Barnhill,CN,CCN(营养学家)——健康饮食Gordon Bell, Ph.D. – Essential Fatty Acids Marvin Boris, M.D. – Immune System Regulation戈登·贝尔,博士–必需脂肪酸马文·鲍里斯,医学博士–免疫系统调节Richard Frye, M.D., Ph.D. – Carnitine; Melatonin; Thyroid; HBOT Jill James, Ph.D. – Methylation/Glutathione/Oxidative Stress Harumi Jyonouchi, Ph.D. – Food Sensitivities, GFCF DietRichard Frye,M.D .,ph . d .–肉碱;褪黑素;甲状腺;HBOT·吉尔·詹姆斯,博士–甲基化/谷胱甘肽/氧化应激Harumi Jyonouchi,博士–食物敏感性,GFCF饮食Rafail Kushak, Ph.D., Dr.Sc. – Digestive EnzymesRafail Kushak,Ph.D .,dr . sc .–消化酶David Quig, Ph.D. – Gut Treatments – Antifungals, Probiotics; Amino Acids Rosemary Waring, Ph.D. – SulfationDavid Quig,ph . d .–肠道治疗–抗真菌药物、益生菌;氨基酸迷迭香Waring,ph . d .–硫酸盐化 Additional Reading额外阅读Nutritional Supplement Use for Autistic Spectrum Disorder, by Jon B. Pangborn, Ph.D., published by Autism Research Institute 2012.营养补充剂用于自闭症谱系障碍,由Jon B. Pangborn博士撰写,自闭症研究所出版,2012年。 Acknowledgements 承认I would like to thank the many ARI doctors, nutritionists, researchers, parents, and others who have helped provide information on treatments for autism, with special thanks to Jon Pangborn, Ph.D., and Tapan Audhya, Ph.D.我要感谢许多ARI医生、营养师、研究人员、父母和其他人,他们帮助提供了自闭症治疗方面的信息,我尤其要感谢Jon Pangborn博士和Tapan Audhya博士。 Dedication 奉献 This summary is dedicated to the memory of Bernard Rimland, Ph.D., for his pioneering work on autism research and advocacy, and for inspiring many others to follow in his footsteps. Thank you Bernie.本总结旨在纪念伯纳德·林兰德博士,感谢他在自闭症研究和宣传方面的开创性工作,并激励许多其他人追随他的脚步。谢谢你,伯尼。 Donations 捐款 I encourage you to support research on new treatments for autism by donating to the Autism Research Institute at www.autism.com – your donations can make a difference.我鼓励你们通过向自闭症研究所捐款来支持自闭症新疗法的研究www.autism.com –您的捐赠会有所作为。
Changes to the 2013 Edition 对2013年版的更改 We have made many updates to this version based on new research, but the general list of treatments is very similar to the original 2007 Edition (Summary of Biomedical Treatments for Autism).基于新的研究,我们对该版本进行了多次更新,但总的治疗列表与2007年版(自闭症生物医学治疗总结)非常相似。 The major changes are more research studies on treatments listed previously, and the addition of new therapies including:主要变化是对之前列出的治疗方法进行了更多的研究,并增加了新的治疗方法,包括: Carnitine (for mitochondrial support to make energy) NADH (for oxidative stress/glutathione/methylation) Ribose (for oxidative stress/glutathione/methylation) N-Acetyl-Cysteine肉碱(用于线粒体支持以产生能量)NADH(用于氧化应激/谷胱甘肽/甲基化)核糖(用于氧化应激/谷胱甘肽/甲基化)N-乙酰半胱氨酸Hyperbaric Oxygen Therapy高压氧治疗 Also, each section was reviewed by an expert in that area (see Reviewer list above).此外,每个部分都由该领域的专家进行审查(见上文的审查人员名单)。 Finally, the section on Detoxification has been moved to a separate document, which will be available from http://autism.asu.edu in spring 2013. You can also find more information on this topic from ACAM (www.acamnet.org).最后,关于戒毒的一节已被移至另一份文件,该文件可从以下网址获得http://autism.asu.edu 2013年春天。您也可以从ACAM找到更多关于这个主题的信息(www.acamnet.org). Disclaimers 放弃This summary is not intended as individual medical advice, and people should consult their physician or nutritionist for how to best treat their individual child. Autism is a spectrum disorder, and a treatment that helps one individual may not help others. This summary represents the personal views of James B. Adams, and does not necessarily represent the views of Arizona State University, Autism Research Institute, Autism Society, or any other organization.本总结并非作为个人医疗建议,人们应咨询他们的医生或营养师,了解如何最好地治疗他们各自的孩子。自闭症是一种谱系障碍,对一个人有帮助的治疗可能对其他人没有帮助。本摘要代表James B .亚当斯的个人观点,不一定代表亚利桑那州立大学、自闭症研究所、自闭症协会或任何其他组织的观点。 The Autism Research Institute's mission is to provide scientific information about evidence-based treatments to parents and professionals. However, ARI does not endorse any specific intervention described in this summary paper or referred to in other sources.自闭症研究所的任务是向父母和专业人士提供循证治疗的科学信息。然而,ARI不认可本总结文件中所述或其他来源中提及的任何特定干预措施。file:///C:/Users/liang/AppData/Local/Temp/ksohtml12396/wps568.pngfile:///C:/Users/liang/AppData/Local/Temp/ksohtml12396/wps569.png
Treatment Order 治疗令 We have listed the various treatments in approximate order of what is typically recommended, but every child is different, and initial assessment by a physician and/or nutritionist may suggest a different order. Also, some physicians and nutritionists have their own preferences as to order of treatment. The key point to remember is to assess the effect of each treatment on each individual, by careful assessment of behavioral symptoms and through testing if possible.我们已按通常建议的大致顺序列出了各种治疗方法,但每个儿童都不同,医生和/或营养师的初步评估可能会建议不同的顺序。此外,一些医生和营养学家对治疗顺序有自己的偏好。记住的要点是,通过仔细评估行为症状并在可能的情况下进行检测,评估每种治疗对每个人的影响。 This Summary includes the following sections:此摘要包括以下部分:· Improve Diet· 改善饮食· Food Sensitivities· 食物过敏· GFCF Diet· GFCF饮食· Vitamin/Mineral Supplements· 维生素/矿物质补充剂· High-Dose Vitamin B6 and Magnesium· 高剂量维生素B6和镁· Essential Fatty Acids· 必需脂肪酸· Gut Treatments· 肠道治疗o Antifungalso 抗真菌药o Probioticso 益生菌o Digestive Enzymeso 消化酶· Amino Acids· 氨基酸· Carnitine· 肉碱· Melatonin· 褪黑激素· Thyroid Supplements· 甲状腺补充剂· Sulfation· 硫酸盐化作用· Methylation/Glutathione/Oxidative Stress· 甲基化/谷胱甘肽/氧化应激· Immune System Regulation· 免疫系统调节· Hyperbaric Oxygen Therapy· 高压氧治疗 Finding a Physician 查找医生Some of the treatments listed here do not require physician oversight, such as shifting to a healthier diet or beginning a vitamin/mineral supplement. However, it is helpful to work with a knowledgeable physician, especially for medical testing and prescription medications. This Summary is designed to be taken to your physician so you can discuss tests and treatments with them. A knowledgeable nutritionist can also be very helpful.此处列出的一些治疗方法不需要医生的监督,例如转向更健康的饮食或开始补充维生素/矿物质。但是,与学识渊博的医生合作很有帮助,尤其是在医疗检测和处方药方面。本总结旨在提供给您的医生,以便您与他们讨论检查和治疗。一位知识渊博的营养师也很有帮助。There are some clinicians who specialize in treating individuals on the autism spectrum. Some of them are excellent, some are reasonable, and others are questionable. Several organizations post lists of clinicians by geographic area, including the Autism Society of America, Autism Speaks, and MAPS. We recommend asking other parents in your local community to help you find the most appropriate clinician for your child. In addition, ARI posts a list of questions to ask when interviewing potential clinicians.有一些临床医生专门治疗自闭症谱系障碍患者。其中一些是优秀的,一些是合理的,还有一些是值得怀疑的。一些组织按地理区域发布临床医生名单,包括美国自闭症协会、自闭症之声和MAPS。我们建议询问您当地社区的其他父母,以帮助您为您的孩子找到最合适的临床医生。此外,ARI还发布了一份在采访潜在临床医生时要问的问题清单。
Example of a Personal Checklist for Biomedical Treatments生物医学治疗个人检查表示例The treatments are listed in the order we generally recommend, but the order can be tailored to the individual and their specific needs and symptoms.治疗方法按我们通常推荐的顺序列出,但顺序可根据个人及其具体需求和症状定制。
Currently Doing It – whateffects?Tried It In Past – what effect?Considering for Future – anyquestions?Treatments
Healthy Diets
Food Sensitivities
GFCF Diet
Vitamin/Mineral Supplements (or Juicing)
High-Dose Vitamin B6 & Magnesium
Essential Fatty Acids
Gut Treatments Antifungals ProbioticsDigestive Enzymes
Amino Acids
Carnitine
Melatonin
Thyroid Testing/Supplementation
Sulfation
Methylation/Glutathione/Oxidative Stress
Immune System Regulation
Hyperbaric Oxygen Therapy
当前正在做——什么效果?过去试过——什么效果?考虑未来——任何有问题吗?治疗
健康饮食
食物过敏
GFCF饮食
维生素/矿物质补充剂(或榨汁)
高剂量维生素B6和镁
必需脂肪酸
肠道治疗抗真菌益生菌消化酶
氨基酸
肉碱
褪黑激素
甲状腺检测/补充
硫酸盐化作用
甲基化/谷胱甘肽/氧化应激
免疫系统调节
高压氧治疗
Understanding Research理解研究We still need a lot more research on the causes of autism and how to treat it. However, we believe that there is now enough evidence for the treatments listed in this Summary that it is reasonable to consider them as treatment options, since they are likely to be beneficial to some individuals with autism and generally have a low risk of adverse effects.我们仍然需要对自闭症的病因以及如何治疗进行更多的研究。然而,我们认为,目前有足够的证据证明本总结中所列的治疗方法是合理的,可以将其视为治疗方案,因为它们可能对某些自闭症患者有益,且通常产生不良影响的风险较低。 In this Summary we cite over 150 published research studies. In a few places we also cite some unpublished work which we think provides additional insight, but is not as rigorous.在本总结中,我们引用了超过150篇已发表的研究论文。在一些地方,我们还引用了一些未发表的作品,我们认为这些作品提供了额外的见解,但并不严格。 Placebo-controlled treatment studies安慰剂对照治疗研究For treatment studies, the highest quality studies are randomized, double-blind, placebo-controlled studies. This means that the researchers took a group of subjects and randomly assigned half to a treatment and half to a placebo (no treatment), but neither the participants nor the researchers knew who was in each group. Evaluations are done at the beginning and end of the study, and then the code is broken to determine if the treatment group did better than the placebo group.对于治疗研究,质量最高的研究是随机、双盲、安慰剂对照研究。这意味着研究人员抽取了一组受试者,随机分配一半进行治疗,另一半使用安慰剂(不进行治疗),但受试者和研究人员都不知道每组中的人员。在研究开始和结束时进行评估,然后对代码进行分解,以确定治疗组是否比安慰剂组做得更好。“Single-blind” studies are similar in design and quality, except that only the evaluators (and“单盲”研究在设计和质量上相似,除了只有评估者(和not the participants) are blinded as to which group they are in.而不是参与者)不知道他们属于哪一组。 Open Label treatment studies开放标签治疗研究An “open label” study is a lower quality study. It means that everyone receives the treatment, and knows that they received it. Unfortunately, due to the “placebo effect,” behavioral scores usually improve just by the hope involved in being in a study, and so it is usually unclear if improvements from open-label studies are real or imagined. Open label studies are useful to demonstrate safety, to determine the type of possible benefit, and sometimes they are used to gather data on changes in medical test results (biomarkers). If an open label study has very promising results, it is then useful to follow up with a placebo-controlled study.“开放标签”研究是质量较低的研究。这意味着每个人都接受了治疗,并知道自己接受了治疗。不幸的是,由于“安慰剂效应”,行为评分的改善通常只是因为参与研究的希望,因此通常不清楚来自非盲研究的改善是真实的还是想象的。开放标签研究有助于证明安全性和确定可能的获益类型,有时也用于收集医学检测结果(生物标志物)变化的数据。如果开放标签研究有非常有希望的结果,那么随访安慰剂对照研究是有用的。 ARI Survey DataARI调查数据Survey data is subject to both the placebo-effect and possible biases in collecting the data. However, an advantage of the ARI Survey of Parent Ratings of Treatment Efficacy and Safety is that it includes responses from over 27,000 families, and it involves comparisons of many different treatments (which is rarely done in traditional studies). So, although there is some “placebo effect” such that benefits may be somewhat over-estimated, it can provide useful insight into potential relative benefits of one type of study vs. another.调查数据受安慰剂效应和数据收集中可能存在的偏差的影响。然而,ARI父母治疗疗效和安全性评分调查的一个优势在于,它包括了来自27,000多个家庭的应答,还包括了许多不同治疗方法的比较(这在传统研究中很少进行)。因此,尽管存在一些“安慰剂效应”使得获益可能被高估,但它可以为了解一种研究类型相对于另一种研究类型的潜在相对获益提供有用的信息。 Individuality个人It is important to remember that autism is a heterogeneous condition, and recent research suggests there are probably several subtypes of autism. There are likely different genetic and environmental factors associated with each subgroup. So, it is unlikely that any one treatment will apply to everyone with autism. However, most of the treatments here will probably help many children and adults with autism. In some cases medical testing or nutritional assessment can be very helpful as a guide as to whether or not a treatment is likely to be helpful.重要的是要记住,自闭症是一种异质性疾病,最近的研究表明,自闭症可能有几种亚型。每个亚组可能有不同的遗传和环境因素。因此,任何一种疗法都不可能适用于所有自闭症患者。然而,这里的大多数治疗可能对许多自闭症儿童和成人有所帮助。在某些情况下,医疗检查或营养评估非常有助于指导您确定治疗是否可行。 Pediatric Reference Ranges小儿参考范围In interpreting personal lab results for children, it is important that the lab use pediatric reference ranges, not adult reference ranges. Otherwise, the test results are usually invalid and misleading, and it is better to not do the test. It is very important to check this, as many labs do NOT have pediatric reference ranges. Ideally, the lab should have multiple pediatric reference ranges, as a 3- year-old is very different from a 16-year-old for most medical tests.在解读儿童的个人实验室检测结果时,重要的是实验室应使用儿科参考范围,而不是成人参考范围。否则,检测结果通常是无效和误导的,最好不要进行检测。检查这一点非常重要,因为许多实验室没有小儿参考范围。理想情况下,实验室应具有多个儿科参考范围,因为在大多数医学检查中,3岁儿童与16岁儿童有很大不同。
Healthy Diets健康饮食Rationale: Humans need certain essential nutrients for their bodies to function, including vitamins, minerals, essential fatty acids, and amino acids (from protein). A balanced diet rich in vegetables, fruits, protein, and certain fats is important to help provide those key nutrients.基本原理:人类需要某些身体功能所必需的营养物质,包括维生素、矿物质、必需脂肪酸和氨基酸(来自蛋白质)。富含蔬菜、水果、蛋白质和某些脂肪的均衡饮食对于帮助提供这些关键营养非常重要。 Explanation of Diet:饮食说明:· Consume 3-4 servings of nutritious vegetables and 1-2 servings of fruit each day. (Corn is not a vegetable, it is a grain; potatoes have only limited nutritional value, especially if fried). Fruit juice is less healthy than eating the whole fruit, but better than soda.· 每天食用3-4份营养蔬菜和1-2份水果。(玉米不是蔬菜,它是谷物;土豆只有有限的营养价值,尤其是如果油炸的话)。果汁不如吃整个水果健康,但比苏打水好。· Consume at least 1-2 servings/day of protein (meat, chicken, eggs, nuts, beans). If child shows periods of irritability between protein meals, consider smaller protein snacks given more frequently.· 每天至少摄入1-2份蛋白质(肉、鸡、蛋、坚果、豆类)。如果孩子在蛋白质餐之间表现出烦躁不安,考虑更频繁地吃少量蛋白质零食。· Greatly reduce or avoid added sugar (soda, candy, etc.).· 大大减少或避免添加糖(苏打、糖果等)).· Avoid “junk food” – cookies, fried chips, etc. – they contain empty calories.· 避免“垃圾食品”——饼干、薯条等。-它们含有空的卡路里。· Greatly reduce or avoid fried foods or foods containing transfats.· 大大减少或避免油炸食物或含有反式脂肪酸的食物。· Avoid artificial colors, artificial flavors, and preservatives.· 避免使用人工色素、人工香料和防腐剂。· If possible, eat organic foods as they contain lower levels of pesticides. Organic milk and chicken contain higher levels of essential omega-3 fats. If eating non-organic food, wash fruit and vegetables well if eating the outside, and consider peeling the outer layer.· 如果可能,吃有机食物,因为它们含有较低水平的杀虫剂。有机牛奶和鸡肉含有较高水平的必需ω-3脂肪。如果吃非有机食物,如果在外面吃,要好好清洗水果和蔬菜,并考虑剥去外层。 Benefits:保障利益:· Vegetables and fruits contain essential vitamins, minerals, and phytonutrients to improve and maintain mental and physical health.· 蔬菜和水果含有必需的维生素、矿物质和植物营养素,可改善和维持身心健康。· Protein is needed to provide amino acids, which are the building blocks for neurotransmitters and many other key amino acids and proteins in the body.· 蛋白质是提供氨基酸所必需的,氨基酸是神经递质和体内许多其他关键氨基酸和蛋白质的组成部分。· Reduction in sugar intake can prevent rapid rises and falls in blood sugar, which can cause irritability and difficulty concentrating.· 减少糖的摄入可以防止血糖快速上升和下降,这会导致烦躁和注意力难以集中。Kohlboeck G, et al. Food intake, diet quality and behavioral problems in children: results from the GINI- plus/LISA-plus studies. Ann Nutr Metab. 2012;60(4):247-56.儿童的食物摄入、饮食质量和行为问题:来自GINI- plus/LISA-plus研究的结果。Ann Nutr Metab。2012;60(4):247-56.· Artificial colors and flavors can irritate some sensitive individuals, causing behavioral and other problems.· 人工色素和香料会刺激一些敏感的个体,引起行为和其他问题。· Organic foods have lower levels of pesticides, and one study found that people living near areas with higher usage of agricultural pesticides had a significantly higher risk of having a child with autism. Pesticide use inside the home is probably a similar concern.· 有机食品的杀虫剂含量较低,一项研究发现,生活在农业杀虫剂使用量较高地区附近的人生自闭症儿童的风险明显较高。家庭内部的农药使用可能也是一个类似的问题。Roberts EM et al., Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley. Environ Health Perspect. 2007 Oct;115(10):1482-9.Roberts EM等人,Maternal residence near agricultural pesticide applications and autism spectrumdisorders among children in the California Central Valley. 环境健康视角。2007年10月;115(10):1482-9.Shelton et al., Tipping the balance of autism risk: potential mechanisms linking pesticides and autism. Environ Health Perspect. 2012 Jul;120(7):944-51.Shelton等人,《打破自闭症风险的平衡:农药与自闭症之间的潜在联系》。环境健康视角。2012年7月;120(7):944-51. Duration: Lifelong healthy diet.持续时间:终身健康饮食。 Research:研究:Most children in the US consume insufficient amounts of vegetables and fruits, leading to decreased levels of many essential vitamins and minerals.美国大多数儿童对蔬菜和水果的消费不足,导致许多必需维生素和矿物质的水平下降。 ARI Survey of Parent Ratings of Treatment Efficacy:父母对治疗疗效评定的ARI调查:
% Worse% No Change% BetterNumber of Reports
Removed Sugar2%46%52%4589
Feingold Diet2%40%58%1041
%更糟%无更改%更好报告数量
除去的糖2%46%52%4589
费恩戈尔德饮食2%40%58%1041
A randomized, double-blind, placebo-controlled study of food additives found that they increased hyperactivity in typical children. This was a large study of 153 3-year-old and 144 8/9-year-old typical children, and found that either artificial colors or sodium benzoate (a food preservative) at levels typically found in foods caused hyperactivity.一项随机、双盲、安慰剂对照的食品添加剂研究发现,它们会增加典型儿童的多动症。这是一项针对153名3岁和144名8/9岁典型儿童的大型研究,发现人工色素或食品中常见水平的苯甲酸钠(一种食品防腐剂)都会导致多动症。McCann et al, Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Lancet. 2007 Nov 3;370(9598):1560-7. Erratum in: Lancet. 2007 Nov 3;370(9598):1542McCann等人,Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in thecommunity: a randomised, double-blinded, placebo-controlled trial. 柳叶刀。2007年11月3日;370(9598):1560-7.勘误表:柳叶刀。2007年11月3日;370(9598):1542Individuals with autism appear to be more sensitive than the general population, since they often lack the sulfate needed to detoxify food additives and preservatives (see Sulfation section).自闭症患者似乎比一般人群更敏感,因为他们通常缺乏解毒食物添加剂和防腐剂所需的硫酸盐(参见“硫酸盐化”部分)。 A major study reviewed the reported benefits of organic foods. It analyzed a total of 17 studies in humans and 223 studies of food content/contamination. The major differences were:一项主要研究回顾了有机食品的益处。该研究共分析了17项人体研究和223项食物含量/污染研究。主要差异是:1) Organic foods rarely had detectable levels of pesticides (7%) compared to conventional foods (37%). Two studies found that children on organic diets had lower levels of pesticides in their urine.2) 与传统食品(37%)相比,有机食品很少含有可检测水平的农药(7%)。两项研究发现,采用有机饮食的儿童尿液中的农药含量较低。3) Organic milk and organic chicken had higher amounts of certain essential omega-3 fatty acids. Similarly, two studies of mothers found that those who ate mostly organic dairy and meat products had higher levels of beneficial essential fatty acids in their breast milk compared to mothers on more conventional diets.4) 有机牛奶和有机鸡肉中某些必需的ω-3脂肪酸含量较高。同样,两项针对母亲的研究发现,与采用更传统饮食的母亲相比,那些主要食用有机乳制品和肉制品的人,其母乳中的有益必需脂肪酸含量更高。5) Vitamins and most minerals were present in similar amounts in organic foods vs. conventional foods. However, organic foods had higher levels of phosphorus, an essential mineral.6) 与传统食物相比,有机食物中维生素和大多数矿物质的含量相似。然而,有机食品的磷含量更高,磷是一种必不可少的矿物质。Smith-Spangler C et al., Are Organic Foods Safer or Healthier Than Conventional Alternatives? A Systematic Review, Ann Intern Med. 2012;157 Crystal Smith-Spangler,Smith-Spangler C等人,有机食品比传统替代品更安全还是更健康?系统综述,Ann Intern Med。2012;157 Crystal Smith-Spangler, For more information on diets avoiding unsafe food additives, go to: www.feingold.org有关避免使用不安全食品添加剂的饮食的更多信息,请访问:www.feingold.org
Food Sensitivities and A lergies食物过敏和过敏Rationale: Many children with autism have food sensitivities, due to abnormalities in their digestive and/or immune systems. If food is not fully digested into individual sugars, amino acids, etc., then the partly digested food can cause the immune system in the gut to react to those foods. This reaction is much more likely to occur if there is inflammation of the gut.理由:许多自闭症儿童因其消化和/或免疫系统异常而对食物过敏。如果食物没有完全消化成单个的糖、氨基酸等。,那么部分被消化的食物就会引起肠道中的免疫系统对那些食物作出反应。如果存在肠道炎症,则更可能发生这种反应。Immune reactions can involve an immediate allergic reaction (mediated by IgE antibodies), or they can be delayed by several hours to 1-2 days due to other parts of the immune system being involved (so-called non-IgE mediated food allergy).免疫反应可能涉及立即过敏反应(由IgE抗体介导),也可能由于涉及免疫系统的其他部分而延迟数小时至1-2天(所谓的非IgE介导的食物过敏)。Immediate-type responses can range from mild to severe, and may involve hives, respiratory problems such as choking/wheezing, diarrhea, vomiting, dizziness/feeling faint, or even severe reactions such as anaphylaxis.立即型反应的范围可从轻度到重度,可能涉及荨麻疹、呼吸问题(如窒息/喘息、腹泻、呕吐、头晕/晕厥),甚至严重的反应(如过敏反应)。For delayed-type food allergy, symptoms are typically limited to GI tract, but may involve headaches, migraines, or other reactions. For example, some patients with celiac disease (immune reaction to wheat mediated by IgA antibodies) may develop migraines in addition to severe gut inflammation.对于迟发型食物过敏,症状通常限于胃肠道,但可能涉及头痛、偏头痛或其他反应。例如,一些乳糜泻患者(IgA抗体介导的对小麦的免疫反应)除了严重的肠道炎症外,还可能发生偏头痛。 Testing:测试: Observation (clinical diagnosis):观察(临床诊断):According to the 2010 US Guidelines for food allergy testing (Boyce et al 2010) and the European Food Allergy Diagnostic Criteria (Burks et al 2012), the gold standard for diagnosis of food allergy is observation, involving two steps:根据2010年美国食物过敏试验指南(Boyce等人,2010年)和欧洲食物过敏诊断标准(Burks等人,2012年),食物过敏诊断的黄金标准是观察,包括两个步骤:1) Resolution of chronic symptoms after elimination of the offending food from the diet, which may take several days to 2-3 weeks for delayed-type food allergy, and2) 将违规食物从饮食中清除后,慢性症状消退,对于迟发型食物过敏,可能需要数天至2-3周的时间,以及3) Recurrence of symptoms with reintroduction of the offending food.4) 重新引入违规食物后症状复发。For children with autism, symptoms may include changes in behavior, which may be due to pain and discomfort caused by reactions to food allergens.对于自闭症儿童,症状可能包括行为改变,这可能是由于对食物过敏原的反应引起疼痛和不适。Safety Note: If the food causes a severe reaction or anaphylaxis shock, then reintroduction of foods should only be done in a physician’s clinic or hospital.安全注意事项:如果食物引起严重反应或过敏休克,则应仅在医生的诊所或医院重新引入食物。Boyce, J.A., et al. (2010). Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report. J Allergy Clin Immunol 126, 1105- 1118.Boyce,J.A .,et al. (2010年)。美国食物过敏诊断和治疗指南:NIAID赞助的专家小组报告总结。j过敏临床免疫126,1105- 1118。Burks, A.W., et al. (2012). ICON: Food allergy. J Allergy Clin Immunol 129, 906-920.Burks,A.W .,et al. (2012)。图标:食物过敏。j过敏临床免疫129,906-920。 Diet Log: Keep a diet log, and look for a pattern between symptoms and foods eaten in the last 1-2 days. For delayed-type food allergies, the association between intake of the food allergens and clinical symptoms are much less evident, so a diet log is helpful to recognize associations in饮食日志:记录饮食日志,并在症状和过去1-2天所吃食物之间寻找规律。对于迟发性食物过敏,食物过敏原摄入量与临床症状之间的关联不太明显,因此饮食记录有助于识别delayed-type food allergies.迟发型食物过敏。 Blood and skin testing: Food allergen specific IgE testing by blood testing (called RAST) or skin prick testing can be helpful to detect immediate-type food allergies. These tests are readily available but have a high frequency of false positive results (i.e., many safe foods will be falsely reported as being allergens), so they should only be used as a guide as to possible foods to consider removing and then reintroducing. These tests do NOT help diagnose delayed-type food allergies. Blood IgG testing for food allergens is available but is of questionable reliability.血液和皮肤测试:通过血液测试(称为RAST)或皮肤点刺测试进行的食物过敏原特异性IgE测试有助于检测即时型食物过敏。这些检测很容易获得,但具有高频率的假阳性结果(即,许多安全食品将被错误地报告为过敏原),因此它们应仅用作可能考虑移除然后重新引入的食品的指南。这些检查无助于诊断迟发型食物过敏。可进行食物过敏原的血液IgG检测,但其可靠性值得怀疑。 Patch testing: This involves use of a special patch to hold the food on the skin on the back for 48- 72 hours, to check for delayed reactions – this may correlate with delayed-type cellular immune贴片测试:使用特殊贴片将食物贴在背部皮肤上48- 72小时,以检查是否有延迟反应——这可能与延迟型细胞免疫相关
reactivity to food proteins. However, validity of skin patch testing to food allergens is unclear, so it is best used as a possible guide of foods to consider removing.对食物蛋白质的反应性。然而,皮肤贴片检测对食物过敏原的有效性尚不清楚,因此最好将其作为考虑去除的食物的可能指南。 Again, commercially available laboratory testing is limited, especially for delayed-type food allergies. For delayed-type food allergies, the current gold standard for diagnosis is removal of the suspect food, followed by reintroduction, as discussed above.同样,市售实验室检测也有局限性,尤其是对迟发型食物过敏。对于迟发型食物过敏,目前的诊断金标准是去除可疑食物,然后再引入,如上所述。 In severe cases of food allergy, the diagnosis procedure can involve an elimination diet of the most common reactive foods. For non-IgE-mediated food allergies, soy and milk products are the most common. For IgE-mediated food allergies, egg, milk, and peanuts are the most common. Grains such as wheat, rye, barley, oats, and corn can sometimes be allergens also. If there is improvement after removing several foods, then try challenging with one suspect food every 4 days, to see if any can be added back in. Some children may also be sensitive to artificial colors, flavors, and preservatives, and sensitivity to those can be assessed in the same way.在严重的食物过敏病例中,诊断程序可包括消除饮食中最常见的反应性食物。对于非IgE介导的食物过敏,大豆和奶制品最为常见。对于IgE介导的食物过敏,鸡蛋、牛奶和花生最为常见。小麦、黑麦、大麦、燕麦和玉米等谷物有时也可能是过敏原。如果在去除几种食物后有所改善,那么每4天尝试挑战一种可疑食物,看看是否有任何食物可以添加回去。有些儿童可能对人工色素、香料和防腐剂敏感,对这些物质的敏感性也可以用同样的方法评估。 Explanation of treatment:治疗说明:· Avoid foods that cause allergic reactions or symptoms· 避免食用会引起过敏反应或症状的食物· Consider other methods to heal the gut – many food allergies will disappear when gut inflammation is healed.· 想想其他治愈肠道的方法——许多食物过敏会在肠道炎症治愈后消失。· May consider using a 4-day diet rotation, in which a given food is only eaten 1 day every four days, so that there is less likelihood of developing an allergy to it (this is a method typically used for patients with eosinophilic esophagitis and some patients with severe reactions to food proteins, but there is not a good scientific rationale and this method is still controversial).· 可考虑采用4天一次的饮食轮换制,即每四天只吃一天给定的食物,因此对其产生过敏的可能性较小(这是一种通常用于嗜酸性食管炎患者和一些对食物蛋白有严重反应的患者的方法,但没有良好的科学依据,且该方法仍有争议)。 Benefits:保障利益:Removing allergic foods can result in a wide range of improvements in some children, including gastrointestinal and improvements in behavior and attention.去除过敏食物可使一些儿童获得广泛的改善,包括胃肠功能以及行为和注意力的改善。 ARI Survey of Parent Ratings of Treatment Efficacy:父母对治疗疗效评定的ARI调查:
% Worse% No Change% BetterNumber of Reports
Food Allergy Treatment2%31%67%1294
Rotation Diet2%43%55%1097
Removed Chocolate2%46%52%2264
Removed Eggs2%53%45%1658
%更糟%无更改%更好报告数量
食物过敏治疗2%31%67%1294
轮换饮食2%43%55%1097
取出的巧克力2%46%52%2264
取出的鸡蛋2%53%45%1658
Duration: Some food allergies (like peanuts) seem to be lifelong, whereas others can disappear when gut inflammation is healed and/or the gut immune system develops tolerance to the offending food.持续时间:一些食物过敏(如花生)似乎是终身的,而另一些则可以在肠道炎症治愈和/或肠道免疫系统对违规食物产生耐受性时消失。 Research:研究:A study by Vojdani et al. found that many children with autism have food allergies.沃达尼等人的一项研究发现,许多自闭症儿童有食物过敏。Vojdani A, et al., Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism. Nutr Neurosci. 2004 Jun;7(3):151-61.Vojdani a,等,自闭症儿童对膳食蛋白质、神经胶蛋白和小脑肽的免疫反应。Nutr Neurosci。2004年6月;7(3):151-61. There are also 3 studies by Jyonouchi et al, which found that children with autism had more hypersensitivities to food allergens than did typical children, which seemed to contribute to gut problems.Jyonouchi等人还进行了3项研究,发现自闭症儿童对食物过敏原的过敏反应比一般儿童更多,这似乎导致了肠道问题。
Jyonouchi et al., Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention.Jyonouchi等,自闭症谱系障碍幼儿先天性免疫应答失调:与胃肠道症状和饮食干预的关系。Neuropsychobiology. 2005;51(2):77-85.神经心理生物学。2005;51(2):77-85.Jyonouchi et al., Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders.Jyonouchi等,评估自闭症谱系障碍儿童的胃肠道症状与针对常见膳食蛋白的细胞因子产生之间的相关性。J Pediatr. 2005 May;146(5):605-10.j儿科。2005年5月;146(5):605-10.Jyonouchi et al., Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder. Neuropsychobiology. 2002;46(2):76-84.Jyonouchi等人,与自闭症谱系障碍患者针对常见膳食蛋白的炎性反应和细胞因子产生相关的先天免疫。神经心理生物学。2002;46(2):76-84. A study by Lucarelli et al found that an 8-week diet that avoided allergic foods resulted in benefits in an open study of 36 children.Lucarelli等人的一项研究发现,在一项针对36名儿童的开放性研究中,8周饮食避免过敏食物对儿童有益。Lucarelli et all, Food allergy and infantile autism. Panminerva Med. 1995 Sep;37(3):137-41.食物过敏和婴儿自闭症。Panminerva Med。1995年9月;37(3):137-41. Three studies have demonstrated that children and adults with autism often have low levels of digestive enzymes for sugars and carbohydrates, especially the sugar in milk, which reduces the ability to digest those foods (see section on Digestive Enzymes).三项研究表明,自闭症儿童和成人的糖和碳水化合物消化酶水平通常较低,尤其是牛奶中的糖,会降低消化这些食物的能力(参见“消化酶”一节)。 Three studies have demonstrated that some individuals have increased intestinal permeability, so that large sugar molecules that normally would not be absorbed are able to pass through the三项研究表明,一些个体的肠道通透性增加,因此通常不会被吸收的大糖分子能够通过intestinal wall into the blood stream. This “leaky gut” may allow other partly digested foods to pass into the body, potentially causing an allergic or immune response to those foods. It is unclear if this test for sugars is relevant to proteins since they are absorbed by a different mechanism.肠壁进入血流。这种“漏肠”可能会让其他部分消化的食物进入体内,潜在地对这些食物产生过敏或免疫反应。目前尚不清楚这项糖检测是否与蛋白质相关,因为它们是通过不同的机制吸收的。de Magistris L et al., Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr. 2010 Oct;51(4):418-24.de Magistris L等人,Alterations of the intestinal barrier in patients with autism spectrum disorders and intheir first-degree relatives.j儿科胃肠营养品。2010年10月;51(4):418-24.D'Eufemia P, Celli M, Finocchiaro R, et al.: Abnormal intestinal permeability in children with autism. Acta Paediatr 1996,85:1076–1079.D'Eufemia P,Celli M,Finocchiaro R,等:自闭症儿童的异常肠道通透性。《儿科学报》1996,85:1076–1079。Horvath K, Zielke H, Collins J, et al.: Secretin improves intestinal permeability in autistic children. J Pediatr Gastroenterol Nutr 2000, 31(suppl 2):S30–S31.霍瓦特K,席尔克H,科林斯J,等:分泌素改善自闭症儿童肠道通透性。J Pediatr胃肠病学Nutr 2000,31(Suppl 2):S30–S31。 There are many studies of gastrointestinal problems in children and adults with autism (see reviews by Buie et al 2010 and Coury et al 2012), and inflammation of the gut will greatly increase the likelihood that the immune cells in the gastrointestinal tract will react to foods.有许多关于自闭症儿童和成人胃肠道问题的研究(参见Buie等人2010年和Coury等人2012年的综述),肠道炎症会大大增加胃肠道免疫细胞对食物产生反应的可能性。Buie, T., et al. (2010). Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 125 Suppl 1, S1-18.Buie,t .,等人(2010年)。自闭症谱系障碍患者胃肠疾病的评估、诊断和治疗:一份共识报告。儿科125 Suppl 1,S1-18。Coury DL et al (2012) Gastrointestinal Conditions in children with Autism Spectrum Disorder: Developing a Research Agenda, Pediatrics V130, Supplement 2 pp S160-168.Coury DL等人(2012)《自闭症谱系障碍儿童的胃肠状况:制定研究议程》,儿科V130,补编2,PP . S160-168。 Limitations of IgG blood testingIgG血液检测的局限性Two studies found that IgG blood testing was not clinically relevant to the general population for identification of food allergies.两项研究发现,IgG血液检测与一般人群的食物过敏识别没有临床相关性。Hochwallner, H et al. (2011). Patients suffering from non-IgE-mediated cow's milk protein intolerance cannot be diagnosed based on IgG subclass or IgA responses to milk allergens. Allergy 66, 1201-1207.Hochwallner,H等人(2011年)。非IgE介导的牛乳蛋白不耐受患者不能根据对牛乳过敏原的IgG亚类或IgA应答进行诊断。过敏反应66,1201-1207。Mitchell, N., (2011). Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches. Nutr J 10, 85. (NEGATIVE RESULTS)Mitchell,n .(2011)。基于IgG抗体的消除食物饮食预防偏头痛样头痛的随机对照试验。Nutr J 10,85。(阴性结果)
Gluten-Free, Casein-Free Diet (and often corn-free and soy-free)无谷蛋白、无酪蛋白饮食(通常不含玉米和大豆)Rationale: It is important to note that human digestive systems have not evolved on a diet containing high amounts of wheat and dairy products. Humans are the only animal who drink milk as adults, and the only ones to drink the milk of another animal. Cow’s milk is a perfect food for baby cows, but not for humans or infants.原理:需要注意的是,人类的消化系统并不是在含有大量小麦和乳制品的饮食中进化而来的。人类是唯一成年后喝牛奶的动物,也是唯一喝另一种动物的牛奶的动物。牛奶是乳牛的理想食物,但不适用于人类或婴儿。 Over the last several hundred years, wheat has been bred to greatly increase its gluten content, and a typical US diet contains far higher amounts of wheat than humans were eating 1000-10,000 years ago. Gluten (in wheat, rye, barley, and possibly oats) and cow’s milk proteins (including casein, β lactoglobulin, α-lactoalbumin which are present in all dairy products, including milk, yogurt, cheese, ice cream, caseinate) can cause several problems:在过去的几百年里,人们培育小麦来大大增加其谷蛋白含量,典型的美国饮食中小麦的含量比1000-10,000年前的人类要高得多。谷蛋白(小麦、黑麦、大麦,可能还有燕麦中的谷蛋白)和牛乳蛋白(包括所有乳制品(包括牛奶、酸奶、奶酪、冰淇淋、酪蛋白酸盐)中存在的酪蛋白、β-乳球蛋白和α-乳白蛋白)会导致几个问题:1. They are common food allergens (see previous section), causing both immediate- and delayed- type food reactions.2. 它们是常见的食物过敏原(见上一节),引起立即型和延迟型食物反应。3. Many individuals with autism have low levels of lactase, the enzyme needed to digest lactose (the sugar in milk). This results in bacteria consuming the lactose, resulting in painful gas, bloating, and diarrhea.4. 许多自闭症患者的乳糖酶水平较低,乳糖酶是消化乳糖(牛奶中的糖)所需的酶。这会导致细菌消耗乳糖,导致胀气、腹胀和腹泻。5. Certain peptides from gluten and casein can bind to opioid-receptors in the brain, and can have a potent effect on behavior (like heroin or morphine), causing problems including sleepiness,6. 来自谷蛋白和酪蛋白的某些肽可以结合到大脑中的阿片样物质受体,并且可以对行为具有有效的作用(如海洛因或吗啡),引起问题,包括嗜睡,giddiness, inattention/”zoning out,” and aggressive and self-abusive behavior. Like opioids, they can be highly addictive, and a lack of them can cause severe behaviors. This problem appears to be due to an inability to fully digest the gluten and casein peptides into single amino acids, and due to inflammation of the gut, which allows the gluten and casein peptides to enter the bloodstream and reach opioid receptors in the brain. However, the evidence for this “opioid hypothesis” is limited.眩晕、注意力不集中/“区域划分”以及攻击性和自虐行为。像阿片样物质一样,它们会高度成瘾,缺乏它们会导致严重的行为。该问题似乎是由于无法将谷蛋白和酪蛋白肽完全消化为单一氨基酸,以及由于肠道炎症,使得谷蛋白和酪蛋白肽进入血流并到达大脑中的阿片受体。然而,这一“阿片样物质假说”的证据有限。7. Consumption of dairy products can cause the immune system to create antibodies against a similar protein in the body, the folate transport receptor, which carries folic acid into the brain. Individuals with cerebral folate deficiency have benefitted from a dairy-free diet.8. 食用乳制品会导致免疫系统产生针对体内类似蛋白质的抗体,该蛋白质是叶酸转运受体,可将叶酸转运到大脑中。脑叶酸缺乏症患者已从无乳制品饮食中获益。 Explanation of Treatment:治疗说明:· Total, 100% avoidance of all gluten products and all dairy products. Even small amounts, like a bite of a cookie, can cause allergic problems if the individual has immediate-type IgE-mediated food allergy. Symptoms caused by delayed-type food allergy may be more dependent on dose. Many foods have trace contamination with gluten; e.g., French fries and raisins are dusted with wheat powder to keep them from sticking, so it can be very difficult to avoid all foods and contaminated foods. In recent studies, extensively heated proteins (milk and egg) can be better tolerated in patients with immediate-type milk and egg allergy.· 完全、100%避免食用所有麸质产品和所有乳制品。如果患者患有即时型IgE介导的食物过敏,即使是少量的食物,如咬一口饼干,也可能导致过敏问题。迟发型食物过敏引起的症状可能更依赖于剂量。许多食物都有麸质的微量污染;例如,炸薯条和葡萄干撒上小麦粉以防止它们粘在一起,所以很难避免所有的食物和被污染的食物。在最近的研究中,广泛加热的蛋白质(牛奶和鸡蛋)在速发型牛奶和鸡蛋过敏患者中可以更好地耐受。 · Digestive enzymes may be helpful, especially if there is an accidental exposure, for delayed type food allergy, although efficacy is not well proven. In case of immediate type food allergy, digestive enzymes will not be effective.· 消化酶可能对迟发型食物过敏有帮助,特别是在意外接触的情况下,尽管疗效尚未得到充分证明。如果发生直接型食物过敏,消化酶将不起作用。 · Children with autism may also benefit from removing corn and/or soy products. It is of note that soy protein is highly immunogenic. In children with Food Protein Induced Enterocolitis Syndrome (FPIES, a condition in which food proteins cause inflammation of the gut) the most common causative food proteins are cow’s milk protein and soy protein.· 自闭症儿童也可从去除玉米和/或大豆制品中受益。值得注意的是,大豆蛋白具有高度免疫原性。在食物蛋白诱导的小肠结肠炎综合征(FPIES,一种食物蛋白导致肠道炎症的疾病)患儿中,最常见的致病食物蛋白是牛奶蛋白和大豆蛋白。 Benefits:保障利益:
Children who most crave dairy and/or wheat, and who eat a lot of it, are most likely to benefit. Casein-free diets usually produce benefits within a month, and sometimes within a week. Gluten free diets usually take 1-3 months to produce benefits. In some children there is a worsening of symptoms for a few days (similar to a drug withdrawal) followed by improvement.最渴望牛奶和/或小麦并大量食用的儿童最有可能受益。无酪蛋白饮食通常在一个月内产生效益,有时在一周内。无谷蛋白饮食通常需要1-3个月才能产生效益。在一些儿童中,症状会恶化几天(类似于停药),然后好转。 ARI Survey of Parent Ratings of Treatment Efficacy:父母对治疗疗效评定的ARI调查:
% Worse% No Change% BetterNumber of Reports
Gluten- and Casein-Free Diet3%28%69%3593
Casein-Free Diet2%44%55%6950
Wheat-Free Diet2%43%55%4340
%更糟%无更改%更好报告数量
无谷蛋白和酪蛋白饮食3%28%69%3593
无酪蛋白饮食2%44%55%6950
无小麦饮食2%43%55%4340
Duration: At least until problems in the gut are addressed, and possibly lifelong.持续时间:至少到肠道问题得到解决,可能终身。 Safety Note: It is important that a calcium-and-vitamin-D supplement be taken while on a dairy-free diet unless a child has an exceptionally nutritious diet rich in calcium. (Vitamin D is essential for calcium absorption from the gut).安全注意事项:食用无乳制品饮食时,摄入钙和维生素D补充剂很重要,除非儿童的饮食特别营养,富含钙。(维生素D是肠道吸收钙所必需的)。 Testing:测试:A trial of the GFCF diet is the best test, as it is the only way to determine if the diet will help a particular individual. At least one month of avoiding dairy and 3 months of avoiding gluten is recommended.GFCF饮食试验是最好的测试,因为这是确定饮食是否对特定个体有帮助的唯一方法。建议至少一个月不吃乳制品,三个月不吃谷蛋白。 Immediate-type food allergies to milk proteins and gluten can be detected by ELISA in the blood or by prick skin testing, but the testing often yields false positive results, and does NOT test for delayed-type food allergies.对乳蛋白和谷蛋白的直接型食物过敏可通过ELISA法在血液中或通过点刺皮肤试验进行检测,但这种检测通常会产生假阳性结果,且不能检测迟发型食物过敏。 In patients with celiac disease, IgA antibody against deaminated gliadin (wheat protein) and anti- IgA antibody against tissue transglutaminate (autoantigen cross-reactive to deaminated gliadin) can be detected in the blood.在乳糜泻患者中,可在血液中检测到针对脱氨基醇溶蛋白(小麦蛋白)的IgA抗体和针对组织转谷氨酰胺(与脱氨基醇溶蛋白交叉反应的自身抗原)的抗IgA抗体。 Research:研究:Reichelt has conducted several studies that have found abnormal peptides in the urine of people with autism, and he has conducted long-term treatment studies that found significant improvement from a GF/CF diet. Cade found that long-term use of digestive enzymes was beneficial, but that the GFCF diet was even more helpful.赖歇尔特进行了多项研究,发现自闭症患者尿液中存在异常肽。他还进行了长期治疗研究,发现GF/CF饮食可显著改善自闭症。凯德发现,长期使用消化酶是有益的,但GFCF饮食更有帮助。 Cade’s large study of 150 children with autism found that 87% had IgG antibodies (allergy) to gluten, vs. 1% of the age and gender-matched controls, and 90% had IgG antibodies to casein, vs. 7% of the controls. (Note that IgG testing may yield false positives, and is of limited validity, but the difference between the two groups was striking). He also studied 70 autistic children who followed a GFCF diet for 1-8 years, and found that 81% improved significantly by the third month, with improvements continuing over the next 12 months. Large improvements were observed in social isolation, eye contact, mutism, learning skills, hyperactivity, stereotypic activity, and panic attacks. Among the 19% who did not improve, about 1/3 of them were not following the GFCF diet, and had lots of gluten and casein peptides still in their blood.Cade对150名自闭症儿童进行的大型研究发现,87%的儿童对谷蛋白有IgG抗体(过敏),而年龄和性别匹配的对照组中这一比例为1%;90%的儿童对酪蛋白有IgG抗体,而对照组中这一比例为7%。(请注意,IgG检测可能会产生假阳性,且有效性有限,但两组之间的差异非常显著)。他还对70名遵循GFCF饮食1-8年的自闭症儿童进行了研究,发现81%的儿童在第三个月时有显著改善,在接下来的12个月里改善仍在继续。观察到社交孤立、眼神接触、缄默、学习技能、多动、刻板活动和恐慌发作有很大改善。在19%没有改善的受试者中,约1/3的受试者没有遵循GFCF饮食,并且他们的血液中仍然含有大量的谷蛋白和酪蛋白肽。Cade R, Privette M et al. "Autism and Schizophrenia: Intestinal Disorders" Nutr. Neurosci 3 (2000) 57-72. Published by Overseas Publishers Association, (OPA) N.V.Cade R,Privette M等,“自闭症和精神分裂症:肠道疾病”nut。Neurosci 3 (2000) 57-72。由海外出版商协会(OPA) N.V .出版Knivsberg AM, Reichelt KL, Nodland M. Reports on dietary intervention in autistic disorders. Nutr Neurosci. 2001;4(1):25-37. Review.Knivsberg AM, Reichelt KL, Nodland M. 自闭症障碍的饮食干预报告。Nutr Neurosci。2001;4(1):25-37.回顾一下。
Single-blind study of 10 children with autism found that 8 benefitted from a GFCF diet.对10名自闭症儿童的单盲研究发现,其中8名受益于GFCF饮食。Knivsberg et al. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci. 2002 Sep;5(4):251-61.Knivsberg et al.自闭症综合征饮食干预的随机对照研究。Nutr Neurosci。2002年9月;5(4):251-61. A 12-week, double-blind, cross-over study of a GFCF diet in 15 children with autism did not find significant benefits, but parents reported benefits that were not identified by the testing.一项在15名自闭症儿童中进行的为期12周的GFCF饮食双盲交叉研究未发现显著益处,但父母报告了检测未发现的益处。Elder et al, The gluten-free, casein-free diet in autism: results of a preliminary double blind clinical trial. J Autism Dev Disord. 2006 413-420.Elder等,“孤独症患者的无谷蛋白、无酪蛋白饮食:一项初步双盲临床试验的结果”。j自闭症发展障碍。2006 413-420. A 12-month, randomized, single-blind, placebo-controlled GFCF diet involving 54 children with autism found statistically significant benefits in communication subscores (ADOS evaluation) in the GFCF diet group compared to the control group. The parents (who were not blinded) also reported benefits in social interaction, daily living skills, inattention, and hyperactivity.一项涉及54名自闭症儿童的12个月、随机、单盲、安慰剂对照GFCF饮食研究发现,与对照组相比,GFCF饮食组的沟通分量表(ADOS评估)具有统计学意义的益处。父母(非盲)也报告在社会互动、日常生活技能、注意力不集中和多动症方面受益。Whitely et al, The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders. Nutr Neurosci. 2010 Apr;13(2):87-100.Whitely等,ScanBrit一项针对自闭症谱系障碍儿童的无谷蛋白和无酪蛋白饮食干预的随机、对照、单盲研究。Nutr Neurosci. 2010年4月;13(2):87-100. Overall, most of the above studies (except a small, short one by Elder et al) found that the GCFC diet was beneficial for children with autism. More research is needed to determine if the primary problem with these foods is immediate-allergy, delayed allergy, lactose intolerance, possible opioid effect, or other factors, since in all these studies, characterization of food sensitivities in the study subjects were lacking.总体而言,上述大多数研究(除了Elder等人的一项小型、简短研究外)发现,GCFC饮食对自闭症儿童有益。由于在所有这些研究中均缺乏对研究受试者食物敏感性的描述,因此需要进行更多研究以确定这些食物的主要问题是否是直接过敏、延迟过敏、乳糖不耐受、可能的阿片样物质效应或其他因素。 Other Diets:其他饮食:Several other diets are being investigated currently. One alternative diet is the Specific Carbohydrate Diet (SCD), which involves avoiding all carbohydrates and most sugars (except monosaccharides in fruit). This diet is reasonable to consider in patients who do not respond well to a gfcf diet because some individuals with autism have low levels of digestive enzymes for certain sugars and carbohydrates (see Digestive Enzyme section). For more information on this diet, see www.pecanbread.com. It is recommended that an experienced nutritionist assist you with implementing the diet, as some individuals have done poorly on a poorly-implemented version of the diet.目前正在研究其他几种饮食。一种替代饮食是特定碳水化合物饮食(SCD),即避免所有碳水化合物和大多数糖(水果中的单糖除外)。对于gfcf饮食反应不佳的患者,考虑这种饮食是合理的,因为一些自闭症患者的某些糖和碳水化合物的消化酶水平较低(参见“消化酶”部分)。有关这种饮食的更多信息,请参见www.pecanbread.com。建议有经验的营养师帮助您实施该饮食,因为一些人在实施不当的饮食版本中表现不佳。 For more information on GFCF and other diets, go to:有关GFCF和其他饮食的更多信息,请访问: Autism Network for Dietary Intervention: www.autismndi.com自闭症饮食干预网络:www.autismndi.com Books on how to implement GFCF and other Special Diets关于如何实施GFCF和其他特殊饮食的书籍 Special Diets for Special Kids, by Lisa Lewis丽莎·刘易斯为特殊儿童设计的特殊饮食 The Kid-Friendly ADHD & Autism Cookbook, Updated and Revised: The Ultimate Guide to the Gluten-Free, Casein-Free Diet by Pamela Compart M.D., Dana Laake R.D.H. M.S. L.D.N., Jon B. Pangborn Ph.D. F.A.I.C. and Sidney MacDonald Baker M.D. (Apr 1, 2012)The Kid-Friendly ADHD & Autism Cookbook, Updated and Revised: The Ultimate Guide to theGluten-Free, Casein-Free Diet 作者:Pamela Compart M.D .,Dana Laake R.D.H. M.S. L.D.N .,Jon B. Pangborn Ph.D. F.A.I.C .和Sidney MacDonald Baker m . d .(2012年4月1日) Nourishing Meals by Alissa Segersten and Tom Malterre Digestive Wellness by Elizabeth LipskiAlissa Segersten和Tom Malterre的营养餐伊丽莎白·利普斯基的消化保健
Vitamin/Mineral Supplements维生素/矿物质补充剂Rationale: In order to be classified as a “vitamin” or “essential mineral,” many studies were conducted that showed that the lack of that vitamin or mineral resulted in disease or even death. The RDA is the minimum amount required to prevent disease, but may be less than the amount needed for optimal mental and physical health. Most people in the US consume less than the Required Daily Allowance (RDA) of one or more vitamins and minerals. For example, many women lack enough calcium and iron, leading to osteoporosis and anemia, respectively.理由:为了归类为“维生素”或“必需矿物质”,进行了许多研究,表明缺乏该维生素或矿物质会导致疾病甚至死亡。RDA是预防疾病所需的最低剂量,但可能低于最佳身心健康所需的剂量。美国大多数人一种或多种维生素和矿物质的消耗量低于每日必需摄入量(RDA)。例如,许多女性缺乏足够的钙和铁,分别导致骨质疏松症和贫血。Explanation of Treatment:治疗说明:Vitamins and minerals are available in vegetables, fruits, meat, and other sources. However, the typical U.S. diet is lacking in key vitamins and minerals, so many people need to take a supplement. Juicing: One option is to use a juicer to make fresh vegetable/fruit juice, and storing it for up to a few days in an airtight glass container. Fresh vegetable/fruit juice is a rich source of vitamins,蔬菜、水果、肉类和其他来源均含有维生素和矿物质。然而,典型的美国饮食缺乏关键的维生素和矿物质,因此许多人需要服用补充剂。榨汁:一种方法是使用榨汁机制作新鲜蔬菜/果汁,并在密封的玻璃容器中储存几天。新鲜蔬菜/果汁是维生素的丰富来源,minerals, and other nutrients. Commercial juices are “pasteurized” or heated to destroy bacteria,矿物质和其他营养物质。商业果汁被“巴氏杀菌”或加热以消灭细菌,which also causes a loss of some nutrients, especially vitamins.这也会导致一些营养物质的损失,尤其是维生素。Typical juicing grinds the vegetables/fruit and strains out the pulp. Grinding vegetables/fruit one time provides only about half of the original vitamins/minerals, so after the first juicing it is useful to soak the pulp for about 15 minutes in a small amount of pure water (about 10% of the amount of liquid initially squeezed out), and then grind the pulp again – this will yield most of the remaining vitamins/minerals. The disadvantage to juicing is a loss of fiber (the soluble fiber remains, but the insoluble fiber is removed, and both are beneficial).典型的榨汁会将蔬菜/水果磨碎,滤出果肉。一次性研磨蔬菜/水果仅提供了约一半的原始维生素/矿物质,因此第一次榨汁后,将果肉浸泡在少量纯水(约为最初挤出液体量的10%)中约15分钟是有用的,然后再次研磨果肉——这将产生大部分剩余的维生素/矿物质。榨汁的缺点是纤维损失(可溶性纤维保留,但不溶性纤维被去除,两者都是有益的)。An alternative method is to use a special blender which grinds the pulp into very small chunks, resulting in no loss of fiber. This results in a thicker consistency (which can be addressed by adding water). Vitamix is one popular brand.另一种方法是使用特殊的搅拌机,将纸浆研磨成非常小的块,不会造成纤维损失。这会产生更稠的稠度(可以通过加水来解决)。Vitamix是一个受欢迎的品牌。The advantage of juicing is that it is often a very easy and tasteful way to get healthy nutrients into children who don’t eat fruits/vegetables. Some of the healthiest vegetables to use include cabbage, spinach, carrots, broccoli, parsley, and oregano, mixed with a small amount of fresh fruit for flavor and other nutrients. Organic vegetables and fruits are preferred, as they have less toxic pesticides. 8 ounces/day should be enough for most children and adults, depending on their intake of other vegetables and fruits.榨汁的优势在于,它通常是一种非常容易和有品味的方式,为不吃水果/蔬菜的儿童获得健康营养。一些最健康的蔬菜包括卷心菜、菠菜、胡萝卜、西兰花、欧芹和牛至,混合少量新鲜水果以增加味道和其他营养。首选有机蔬菜和水果,因为它们的杀虫剂毒性较低。8盎司/天应该足够大多数儿童和成人,这取决于他们摄入的其他蔬菜和水果。 Supplements: Vitamin/mineral supplements are largely unregulated, and some supplements do not contain what they claim, contain impurities, and/or use forms that are poorly absorbed. Some companies choose to participate in the Dietary Supplement Verification Program (DSVP) of the United States Pharmacopeia (USP) - that program verifies that the contents of the supplement match the label. Check for a USP or DSVP label, or go to http://www.usp.org/USPVerified/ to check a product.补充剂:维生素/矿物质补充剂在很大程度上不受监管,一些补充剂不含其声称的成分,含有杂质,和/或使用吸收不良的形式。一些公司选择参加美国药典(USP)的膳食补充剂验证计划(DSVP)——该计划验证补充剂的内容与标签相符。检查是否有美国药典或DSVP标签,或访问http://www.usp.org/USPVerified/ 检查产品。· Most supplements do not contain all the essential vitamins and minerals, or do not contain enough of them.· 大多数补充剂不含所有必需的维生素和矿物质,或含有的维生素和矿物质不够。· Several good choices for broad-spectrum vitamin/mineral supplements include the following, listed in alphabetical order:· 广谱维生素/矿物质补充剂有多种选择,按字母顺序排列如下:Awaken Nutrition’s Agape唤醒营养的魅力Brainchild’s Spectrum Support (used in the Adams et al 2004 study)Brainchild频谱支持(用于亚当斯等人2004年的研究)Kirkman’s Super Nu Thera (very high in vitamin B6), and Kirkman’s Spectrum Complete.柯克曼超级Nu Thera(维生素B6含量非常高)和柯克曼全谱。Yasoo’s Syndion (used in the Adams et al 2011 study).Yasoo 's Syndion(用于亚当斯等人2011年的研究)。However, some of those supplements do not contain enough calcium or magnesium, which is also very important to supplement, and they do not contain iron, which some young children and teen girls/women may need.然而,其中一些补充剂不含足够的钙或镁,而钙或镁对补充剂来说也非常重要,而且这些补充剂不含一些幼儿和少女/妇女可能需要的铁。
· Either folinic acid or methyl-tetra-hydrofolate should be used for supplying vitamin B - folic acid is not sufficient for children with autism, according to one research study.· 根据一项研究表明,叶酸或甲基四氢叶酸都应该用于提供维生素B。叶酸对自闭症儿童来说是不够的。James SJ, Cutler et al., Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism.Am J Clin Nutr. 2004, 80(6):1611-7.James SJ,Cutler等,自闭症儿童氧化应激增加和甲基化能力受损的代谢生物标志物。Am J Clin Nutr。2004, 80(6):1611-7.· Calcium supplements are especially important if a person is on a dairy-free diet.· 如果一个人采用无乳制品饮食,钙补充剂尤为重要。· Iron supplements are needed by some typical children as well as children with autism, but should only be given if a test indicates a need, as too much iron can also be a problem.· 一些典型的儿童以及自闭症儿童都需要铁补充剂,但只有在检测表明需要时才应给予,因为铁过多也可能是一个问题。· In general, nutritional supplements are a good way to boost key nutrients lacking in the diet, and to provide extra amounts that may be needed to overcome metabolic problems.· 一般来说,营养补充剂是促进饮食中缺乏的关键营养的好方法,并提供克服代谢问题可能需要的额外量。Testing:测试:Most vitamin and mineral levels can be tested using blood samples taken while fasting. Health Diagnostics is one of very few companies that can measure the level of all vitamins. Many commercial labs can measure the level of most minerals, most of which can be measured reliably in Red Blood Cells (RBC). Calcium is best measured in the urine, preferably with a 24-hour urine collection. Some laboratories also offer functional assessments of the need for vitamins and minerals based on blood and/or urine testing. Measure iron with serum ferritin.大多数维生素和矿物质水平可通过空腹时采集的血液样本进行检测。健康诊断是为数不多的几家能够测量所有维生素水平的公司之一。许多商业实验室可以测量大多数矿物质的含量,其中大部分可以在红细胞(RBC)中可靠地测量。钙最好在尿液中测定,最好是24小时尿液采集。一些实验室还根据血液和/或尿液检测对维生素和矿物质的需求进行功能评估。用血清铁蛋白测定铁。 Recommended Dosages:推荐剂量:We recommend the following dosages for people with autism as a reasonable level to start with. However, some individuals may need more or less depending on their diet and metabolic needs, and testing can help determine optimal supplement levels.我们建议自闭症患者从以下剂量开始,作为一个合理的水平。然而,有些人可能会根据他们的饮食和代谢需求增加或减少所需量,检测有助于确定最佳的补充剂水平。Note that vitamins and minerals can have a potent effect on body function and behavior, so start at a low dose (1/10 of that below) and then gradually increasing over 3-4 weeks.请注意,维生素和矿物质对身体功能和行为有很强的影响,所以从低剂量(以下剂量的1/10)开始,然后在3-4周内逐渐增加。 Iron should be added only if a test indicates a need for iron – this is a common problem in children under 5 years. Low iron is a leading cause of mental retardation in the US, and 40% of infants under the age of 2 have low iron (and so do 40% of women of child-bearing age). Most girls/women who are menstruating should take supplemental iron. However, too much iron can be harmful, so testing is important.只有在检测显示需要铁时才应添加铁——这是5岁以下儿童的常见问题。在美国,缺铁是导致智力低下的主要原因,40%的2岁以下婴儿缺铁(40%的育龄妇女也是如此)。大多数来月经的女孩/妇女应该补充铁。然而,过多的铁可能是有害的,所以检测很重要。 The dosage below should be adjusted up or down by bodyweight; ie, half for a 30-lb child, and double for 120 pounds and above.以下剂量应根据体重上下调整;也就是说,30磅重的孩子体重减半,120磅及以上的孩子体重加倍。 The following recommendations are based on the results of a published study that measured the effect of a multi-vitamin/mineral supplement on children with autism.以下建议基于一项已发表的研究结果,该研究测量了多种维生素/矿物质补充剂对自闭症儿童的影响。Adams JB et al., Effect of a Vitamin/Mineral Supplement on Children with Autism, BMC Pediatrics 2011, 11:111亚当斯JB等,维生素/矿物质补充剂对自闭症儿童的影响,BMC儿科2011,11:111The recommendations are similar to what was used in the Adams et al 2011 study, but slightly modified based on the results of that study. We recommend starting at a low dose, and gradually increasing over several weeks – some individuals may be better with half or ¾ dose.这些建议与亚当斯等人2011年研究中使用的建议相似,但根据该研究的结果进行了轻微修改。我们建议从低剂量开始,并在几周内逐渐增加——部分个体服用一半或更少剂量可能会更好。
VITAMINSRecommendedSupplement (for 60 lb child)RDA (4-8 yr)Upper Limit
Vitamin A(as mixed carotenoids)6000 IU carotenoidsa (equivalent to 3000 IU Vit. A)400 mcg (1333 IU)900 mcg (3000 IU)
Vitamin C (ascorbic acid)500 mg25 mg650 mg
Vitamin D1000 IU(some individuals may need more, especially if littleexposure to direct sunlight)5 mcg (200 IU)Children - 50 mcg (2000 IU)Teens/Adults –100 mcg (4000 IU)
维生素被推荐的补充保险(适用于60磅重的儿童)RDA (4-8岁)上限
维生素a(作为混合类胡萝卜素)6000国际单位类胡萝卜素sa(相当于3000国际单位维生素。a)400微克(1333国际单位)900微克(3000国际单位)
维生素C(抗坏血酸)500毫克25 mg650 mg
钙化醇1000国际单位(有些人可能需要更多,尤其是如果很少的话暴露于阳光直射下)5微克(200国际单位)儿童- 50微克(2000国际单位)青少年/成人–100微克(4000国际单位)
Vitamin E(including mixed tocopherols)250 IU7 mg (10.5 IU)300 mg (450 IU)
Vitamin K55 mcg55 mgND
B1(thiamin HCl)30 mg0.6 mgND
B2(riboflavin)40mg0.6 mgND
B3(niacin/niacinamide)15 mg niacin20 mg niacinamide8 mg15 mg
B525 mg3 mgND
B640 mgb0.640 mg
B12 (methylcobalamin or cyanocobalamin)600 mcg1.2 mcgND
Folic Acid800 mcg of folinic acid or methyltetrahydrofolate (not folic acid, which is insufficientfor children with autism)200 mcg400 mcg
Biotin(d-biotin)300 mcg12 mcgND
Choline250 mg250 mg1000 mg
Inositol100 mgn/an/a
MINERALS
Calcium300 mg (may need more if on dairy-free diet)800 mg2500 mg
Chromium70 mcg15 mcgND
Copper0-400 mcgc440 mcg3000 mcg
Iodine100 mcg90 mcg300 mcg
Iron0d10 mg40 mg
Lithium300 mcgen/a****n/a
Magnesium250 mg130 mg110 mgf
Manganese0-1 mgg1.5 mg3 mg
Molybdenum100 mcg22 mcg600 mcg
Phosphorus0 (eat fruits & vegetables)500 mg3000 mg
Potassium50 mg1500 mgn/a
Selenium40 mcg30 mcg150 mcg
Sulfur (MSM)500 mg; or, take Epsom Salt bathsn/an/a
Zinc10-20 mg5 mg12 mg
生育酚(包括混合生育酚)250国际单位7 mg (10.5 IU)300毫克(450国际单位)
维生素k55 mcg55 mg钕
B1(盐酸硫胺素)30 mg0.6 mg钕
B2(核黄素)40mg0.6 mg钕
B3(烟酸/烟酰胺)15 mg烟酸20 mg烟酰胺8 mg15 mg
B525 mg3 mg钕
B640 mgb0.640 mg
B12(甲基钴胺素或氰钴胺素)600微克1.2 mcg钕
叶酸800微克叶酸或甲基四氢叶酸(不是叶酸,这是不够的对于患有自闭症的儿童)200微克400微克
生物素(d-生物素)300微克12 mcg钕
胆碱250 mg250 mg1000 mg
肌糖100 mg不适用的不适用的
矿物
钙300毫克(如果在无乳制品饮食中,可能需要更多)800毫克2500 mg
铬70微克15 mcg钕
铜0-400 mcgc440 mcg3000微克
碘100微克90微克300微克
熨斗0d10 mg40 mg
锂300 mcgen/a****不适用的
镁250 mg130 mg110 mgf
锰0-1mg1.5 mg3 mg
钼100微克22 mcg600微克
磷0(吃水果和蔬菜)500毫克3000毫克
钾50 mg1500 mg不适用的
硒40微克30微克150微克
硫(MSM)500毫克;或者,洗个爱普生盐浴不适用的不适用的
锌10-20毫克5 mg12 mg
a) Carotenoids are only converted to vitamin A as needed, so this level is safe even though it is at the Tolerable Upper Limitb) 类胡萝卜素仅在需要时转化为维生素A,因此即使处于容许上限,该水平也是安全的c) Some children and adults may benefit from much higher dosages, see section on High Dose Vitamin B6.d) 一些儿童和成人可能受益于更高的剂量,参见“高剂量维生素B6”一节。e) Some children with autism have slightly elevated copper, so either low or no supplementation is sufficient for most children with autism.f) 一些自闭症儿童的铜含量略有升高,因此对大多数自闭症儿童来说,低水平或不补充铜就足够了。g) Iron should be added on an individual basis only if serum ferritin tests reveal a need for iron, or for girls/women who are of menstruation age. Suggest 5-10 mg of iron chelate for 4 weeks, followed by half that dosage afterwardsh) 只有在血清铁蛋白检测显示需要铁或处于月经年龄的女孩/妇女需要铁时,才应逐个添加铁。建议服用5-10毫克铁螯合物4周,然后服用一半剂量
i) For magnesium, the UL is the amount for supplements and does not count food sourcesj) 对于镁,UL是补充剂的量,不计算食物来源k) Estimated daily intake of lithium in food is 1900 mcg/day for adults.l) 成年人食物中锂的估计日摄入量为1900 mcg/天。m) One study found that children with autism have slightly elevated manganese, so either low or no supplementation is sufficient for most children with autism.n) 一项研究发现,自闭症儿童的锰含量略有升高,因此对大多数自闭症儿童来说,低锰或不加锰就足够了。 Duration: Lifelong, although improving diet and healing gut may reduce the need for supplementation.持续时间:终身,但改善饮食和愈合肠道可减少对补充药物的需求。 Safety Note: Most vitamins are water soluble, and excess amounts of them will be safely excreted in the urine. Some vitamins (vitamins A, D, E, K) are fat soluble, and excess amounts of those can build up in the body and cause toxicity if taken at high levels (above what we recommend) for a long time.安全注意事项:大多数维生素是水溶性的,过量则会安全地通过尿液排出。一些维生素(维生素A、D、E、K)是脂溶性的,如果长期以高水平(高于我们建议的水平)摄入,过量的维生素会在体内积聚并导致毒性。Excess amounts of minerals can cause problems, and the upper limits listed above should not be exceeded without consultation with a physician or nutritionist.矿物质过量会引起问题,未经医生或营养师咨询,不得超过上述上限。Start with a low dose (1/5 of that listed above), and gradually increase over 1 month.从较低剂量(上述剂量的1/5)开始,并在1个月内逐渐增加。 ARI Survey of Parent Ratings of Treatment Efficacy:父母对治疗疗效评定的ARI调查:
% Worse% No Change% BetterNumber of Reports
Vitamin A2%54%44%1535
CalciumE:3%60%36%2832
Folic Acid5%50%45%2505
Magnesium6%65%29%301
P5P (Vit. B6)13%37%51%213
Vitamin B34%51%45%1192
Vitamin B6 alone8%63%30%620
Vitamin B6 with Magnesium4%46%49%7256
Vitamin B12 (methyl, subcut.)6%22%72%899
Vitamin C2%52%46%3077
Zinc2%44%54%2738
%更糟%无更改%更好报告数量
维生素a2%54%44%1535
钙用量:3%60%36%2832
叶酸5%50%45%2505
镁6%65%29%301
P5P (Vit。B6)13%37%51%213
维生素B34%51%45%1192
维生素B6单独8%63%30%620
含镁的维生素B64%46%49%7256
维生素B12(甲基,皮下注射。)6%22%72%899
维生素c2%52%46%3077
锌2%44%54%2738
Research – Vitamins:研究——维生素:One large comprehensive study found that children with autism had lower levels of several vitamins (especially biotin) and some minerals (lithium, calcium, and magnesium) and impairments in sulfation, methylation, glutathione, ATP, and oxidative stress, compared to neurotypical children of the same age. The severity of autism was strongly associated with the level of certain vitamins and minerals.一项大型综合研究发现,与同龄典型神经系统儿童相比,自闭症儿童的几种维生素(尤其是生物素)和一些矿物质(锂、钙和镁)水平较低,硫酸盐化、甲基化、谷胱甘肽、ATP和氧化应激受损。自闭症的严重程度与某些维生素和矿物质的水平有很大关系。Adams JB et al., Nutritional and Metabolic Status of Children with Autism vs. Neurotypical Children, and the Association with Autism Severity, Nutr. Metab (Lond) 2011 Jun 8:8(1):34.亚当斯JB等人,“自闭症儿童与神经典型儿童的营养和代谢状态,以及与自闭症严重程度的关系”,Nutr。Metab (Lond) 2011年6月8:8(1):34。 One study in China found that most children with autism had inadequate intake of folic acid, vitamin B6, calcium, vitamin A, vitamin C, and zinc, based on estimating dietary intake from diet logs (not as accurate as blood measurements).中国的一项研究发现,大多数自闭症儿童的叶酸、维生素B6、钙、维生素A、维生素C和锌的摄入量不足,这是根据饮食记录(不如血液测量准确)估计的饮食摄入量得出的。Xia W et al., A preliminary study on nutritional status and intake in Chinese children with autism. Eur J Pediatr 2010, 69(10):1201-6.夏伟等。中国孤独症儿童营养状况及摄入量的初步研究。Eur J Pediatr 2010,69(10):1201-6。 One study in Romania found normal levels of vitamin B12 and folate in children with autism compared to controls, but low levels of plasma glutathione, consistent with the Adams et al 2011 study. In other words, it seems that children with autism need extra amounts of vitamin B12 and folate to have normal glutathione.罗马尼亚的一项研究发现,与对照组相比,自闭症儿童的维生素B12和叶酸水平正常,但血浆谷胱甘肽水平较低,与亚当斯等人2011年的研究一致。换句话说,似乎自闭症儿童需要额外的维生素B12和叶酸来获得正常的谷胱甘肽。
Paşca SP et al., One carbon metabolism disturbances and the C677T MTHFR gene polymorphism inpaca SP等,一碳代谢紊乱与中的C677T MTHFR基因多态性children with autism spectrum disorders. J. Cell. Mol. Med. 2009, 13(10):4229-4238.自闭症谱系障碍儿童。J. Cell。摩尔。医学。2009, 13(10):4229-4238. One study found that children with autism had high levels of plasma vitamin B6 pre- supplementation, and this finding was confirmed in a follow-up study (Adams 2006), suggesting a metabolic imbalance in B6. (See section on High-Dose Vitamin B6 for more info.)一项研究发现,自闭症儿童在补充维生素B6前血浆水平较高,这一发现在一项后续研究中得到证实(亚当斯,2006),表明B6存在代谢失衡。(更多信息请参见“高剂量维生素B6”一节。)Adams JB, Holloway C.J: Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. Altern Complement Med. 2004, 10(6):1033-9.Adams JB,Holloway C.J:一项针对自闭症谱系障碍儿童的中等剂量多种维生素/矿物质补充剂的试点研究。Altern补体Med。2004, 10(6):1033-9.Adams JB, George F, Audhya T: Abnormally high plasma levels of vitamin B6 in children with autism not taking supplements compared to controls not taking supplements. J Altern Complement Med. 2006, 12(1):59-63.Adams JB,George F,Audhya T:与未服用补充剂的对照组相比,未服用补充剂的自闭症儿童的维生素B6血浆水平异常高。J Altern补体Med。2006, 12(1):59-63. One study of vitamin D status in Egypt found that young children with autism had lower levels of vitamin D compared to age-matched controls. However, the Adams et al 2011 study did not find any difference between vitamin D levels in children with autism in the US and neurotypical children in the US. Low levels of vitamin D are a concern for the general population, since vitamin D is made by the body only when exposed to direct sunlight, and nowadays people spend more time inside or shielded from the sun.一项关于埃及维生素D状况的研究发现,与同龄对照组相比,自闭症幼儿的维生素D水平较低。然而,亚当斯等人2011年的研究没有发现美国自闭症儿童与美国神经典型儿童的维生素D水平有任何差异。维生素D水平低是普通人群关注的问题,因为维生素D只有在暴露于阳光直射下时才会由身体生成,而如今人们在室内或避光处的时间更长。Meguid NA, Hashish AF, Anwar M, Sidhom G: Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in Egyptian children with autism. J Altern Complement Med. 2010, 16(6):641-5.Meguid NA,Hashish AF,Anwar M,Sidhom G:埃及自闭症儿童血清中25-羟基和1,25-二羟基维生素D水平降低。J Altern补体Med。2010, 16(6):641-5. One study in Slovakia found that children with autism had significantly higher levels of vitamin C and beta-carotene, but normal levels of vitamin A and vitamin E, compared to older teen controls. This is consistent with the Adams et al 2011 study.斯洛伐克的一项研究发现,与年龄较大的青少年对照组相比,自闭症儿童的维生素C和β-胡萝卜素水平显著较高,但维生素A和维生素E水平正常。这与亚当斯等人2011年的研究一致。Krajkovicova-Kudlackova M et al. Plasma concentration of selected antioxidants in autistic children and adolescents. Bratisl Lek Listy 2009, 110(4): 247-250.krajkovicova-kudrackova M等.自闭症儿童和青少年中选定抗氧化剂的血浆浓度.Bratisl Lek Listy 2009,110(4): 247-250。 Many studies have demonstrated that children with autism have substantial oxidative stress, suggesting either a low level of key antioxidants or an increased need for them. (See section on oxidative stress.)许多研究表明,自闭症儿童有很大的氧化应激,这表明要么关键抗氧化剂水平低,要么对它们的需求增加。(参见“氧化应激”一节。) Research – Minerals研究-矿物 One large comprehensive study found that children with autism had lower levels of some minerals (lithium, calcium, and magnesium) compared to neurotypical children of the same age. The severity of autism was strongly associated with the level of certain vitamins and minerals.一项大型综合研究发现,与同龄神经典型儿童相比,自闭症儿童的某些矿物质(锂、钙和镁)水平较低。自闭症的严重程度与某些维生素和矿物质的水平有很大关系。Adams JB et al., Nutritional and Metabolic Status of Children with Autism vs. Neurotypical Children, and the Association with Autism Severity, Nutr. Metab (Lond) 2011 Jun 8:8(1):34.亚当斯JB等人,“自闭症儿童与神经典型儿童的营养和代谢状态,以及与自闭症严重程度的关系”,Nutr。Metab (Lond) 2011年6月8:8(1):34。 Another study also found that young US children with autism (and their mothers) had unusually low levels of lithium compared to neurotypical children and their mothers. Lithium is receiving increasing recognition as possibly being an essential mineral, as low levels are associated with psychiatric and immunological disorders.另一项研究还发现,与神经典型儿童及其母亲相比,美国自闭症幼儿(及其母亲)的锂含量异常低。锂被越来越多的人认为可能是一种重要的矿物质,因为低水平的锂会导致精神和免疫疾病。Adams JB et al., Biol Tr El Res 2006, 110:193-209.Adams JB等,Biol Tr El Res 2006,110:193-209。 Two large studies of iron status found that young US and Canadian children with autism had anemia in 8% and 16% of cases, respectively.两项关于铁状况的大型研究发现,美国和加拿大自闭症幼儿中贫血的比例分别为8%和16%。Latif A et al., Iron Deficiency in Autism and Asperger Syndrome. Autism 2002, 6:103.Latif A等,自闭症和阿斯伯格综合征中的铁缺乏。自闭症2002,6:103。Dosman CF et al., Ferritin as an indicator of suspected iron deficiency in children with autism spectrum disorder: prevalence of low serum ferritin concentration. Dev Med Child Neurol. 2006, 48(12):1008-9.Dosman CF 铁蛋白作为自闭症谱系障碍儿童疑似缺铁的指标:低血清铁蛋白浓度的患病率。Dev Med Child Neurol。2006, 48(12):1008-9.
One small study of minerals in red blood cells found that young Canadian children with autism had lower levels of RBC selenium and RBC molybdenum than neurotypical children of the same age , but similar levels of most other minerals.一项关于红细胞中矿物质的小型研究发现,加拿大自闭症幼儿的RBC硒和RBC钼水平低于同龄神经典型儿童,但大多数其他矿物质的水平相似。Jory J and McGinnis W: Red-Cell Trace Minerals in Children with Autism. American Journal of Biochemistry and Biotechnology 2008, 4(2):101-104.Jory J和McGinnis W:自闭症儿童的红细胞微量矿物质。美国生物化学和生物技术杂志2008,4(2):101-104。 A small study of zinc and copper in plasma found that British children with autism had similar levels to neurotypical children.一项针对血浆中锌和铜的小型研究发现,英国自闭症儿童的锌和铜水平与神经典型儿童相似。Jackson MJ and Gerard PJ: Plasma Zinc, Copper, and Amino Acid Levels in the Blood of Autistic Children. J Autism Childhood Schizophrenia 1978, 8(2):203-208Jackson MJ和Gerard PJ:自闭症儿童血液中的血浆锌、铜和氨基酸水平。j自闭症儿童精神分裂症1978,8(2):203-208In contrast, a study of Turkish children with autism found that they had lower levels of zinc in plasma and RBC compared to neurotypical children.相比之下,一项针对土耳其自闭症儿童的研究发现,与神经典型儿童相比,他们的血浆和红细胞中锌的含量较低。Yorbik O, Akay C, Sayal A, Cansever A, Sohmen T, Cavdar AO: Zinc Status in Autistic Children J. Trace Elements Experimental Medicine 2004, 17:101-107.Yorbik O,Akay C,Sayal A,Cansever A,Sohmen T,Cavdar AO:自闭症儿童的锌状况j .微量元素实验医学2004,17:101-107 . Research – Treatment研究–治疗 A large, randomized, double-blind placebo-controlled study found that a similar strong, balanced multi-vitamin/mineral supplement resulted in modest but statistically significant improvements in the Average Change of all symptoms on the Parent Global Impressions-Revised, and significant improvements in subscores in expressive language, tantrumming, hyperactivity, and overall symptoms. The supplement improved the level of many vitamins and minerals. There were also many improvements in metabolism, including improvements in oxidative stress, methylation, glutathione, sulfation, plasma ATP. The children with low levels of vitamin K and biotin (both made by gut bacteria) improved the most.一项大型、随机、双盲、安慰剂对照研究发现,一种类似的强效、平衡的多种维生素/矿物质补充剂在“母体总体印象-修订版”上的所有症状的平均变化方面取得了适度但具有统计学意义的改善,在表达性语言、焦虑、多动症和总体症状方面的分量表也取得了显著改善。该补充剂提高了许多维生素和矿物质的水平。代谢方面也有许多改善,包括氧化应激、甲基化、谷胱甘肽、硫酸化、血浆ATP等方面的改善。维生素K和生物素(均由肠道细菌制造)水平低的儿童改善最多。Adams JB et al., Effect of a Vitamin/Mineral Supplement on Children with Autism, BMC Pediatrics 2011, 11:111亚当斯JB等,维生素/矿物质补充剂对自闭症儿童的影响,BMC儿科2011,11:111 One open-label study found that micronutrient supplementation was comparable or more effective than treatment with pharmaceuticals in terms of improvements in the Childhood Autism Rating Scale, Childhood Psychiatric Rating Scale, Clinical Global Impressions, and Self-Injurious Behavior.一项开放标签研究发现,在改善儿童孤独症评定量表、儿童精神病学评定量表、临床总体印象和自我伤害行为方面,微量营养素补充剂与药物治疗相当或更有效。Mehl-Madrona L et al., Micronutrients versus standard medication management in autism: a naturalistic casecontrol study. J Child Adolesc Psychopharmacol 2010, 20(2):95-103.Mehl-Madrona L等,《自闭症中微量营养素与标准药物管理的比较:一项自然主义病例对照研究》。J Child Adolesc精神病药物学2010,20(2):95-103。 One small randomized, double-blind, placebo-controlled study published found that a strong, balanced multi-vitamin/mineral supplement resulted in improvements in children with autism in sleep and gut function, and possibly in other areas.已公布的一项小型随机、双盲、安慰剂对照研究发现,一种强效、平衡的多种维生素/矿物质补充剂可改善自闭症儿童的睡眠和肠道功能,可能在其他方面也有所改善。Adams JB et al., Pilot study of a moderate dose multivitamin-mineral supplement for children with autistic spectrum disorder. J Altern Complement Med. 2004 Dec;10(6):1033-9.亚当斯JB等人,中度剂量多种维生素矿物质补充剂用于自闭症谱系障碍儿童的试点研究。J Altern补体Med。2004年12月;10(6):1033-9. One study found that high-dose vitamin C (1.1 g per 10 kg bodyweight) helped children with autism.一项研究发现,高剂量维生素C(每10公斤体重1.1克)对自闭症儿童有帮助。Dolske MC et al., A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry 1993 Sep;17(5):765-74.Dolske MC等,抗坏血酸作为自闭症补充疗法的初步试验。Prog神经心理药物生物学精神病学1993年9月;17(5):765-74.
High-Dose Vitamin B6 and Magnesium高剂量维生素B6和镁Rationale: There are over 20 studies of vitamin B6 with Magnesium for autism, including 12 double-blind, placebo-controlled studies, making it one of the most studied nutritional treatments for autism. Almost all of these studies found that 30-40% of children and adults with autism benefited from high-dose supplementation of vitamin B6 with magnesium. Vitamin B6 is required for over 1113 enzymatic reactions, including the production of major neurotransmitters (serotonin, dopamine, and others), glutathione (needed for detoxification), and hemoglobin (carries oxygen in blood). Magnesium is used to prevent the possibility of hyperactivity, which can occur if the vitamin B6 is taken by itself.理由:有超过20项关于维生素B6联合镁治疗自闭症的研究,包括12项双盲、安慰剂对照研究,使其成为研究最多的自闭症营养治疗方法之一。几乎所有这些研究都发现,30-40%的自闭症儿童和成人受益于高剂量补充镁的维生素B6。超过1113个酶促反应需要维生素B6,包括产生主要神经递质(血清素、多巴胺等)、谷胱甘肽(解毒所需)和血红蛋白(携带血液中的氧气)。镁用于预防多动症的可能性,如果维生素B6单独服用,则可能发生多动症。Most of the studies used dosages of about 8-15 mg/pound of B6 (maximum of 1000 mg).大多数研究使用的剂量约为8-15毫克/磅B6(最大1000毫克)。Only 1 study used a lower dosage (1.3 mg/pound), and that is one of the few studies that found no benefit.只有1项研究使用了较低的剂量(1.3mg/磅),这是少数没有发现益处的研究之一。An unpublished study by Audhya steadily increased the dosage of vitamin B6 from 1 to 10 mg/pound. They found that at least 3 mg/pound was needed to begin to see benefits, and 6 mg/pound was enough for most children to see benefit.由Audhya进行的一项未发表的研究将维生素B6的剂量从1稳步增加到10毫克/磅。他们发现,至少需要3mg/kg剂量才能开始受益,6mg/kg剂量足以让大多数儿童受益。The reason why many children and adults benefit from high-dose vitamin B6 is still unclear, but a possible explanation is that some children and adults with autism have both 1) a decreased ability to convert vitamin B6 to its active form, and 2) defective enzymes for making key neurotransmitters that require an unusually high amount of the active form of vitamin B6.许多儿童和成人受益于高剂量维生素B6的原因仍不清楚,但一个可能的解释是,一些自闭症儿童和成人既有1)将维生素B6转化为其活性形式的能力下降,又有2)制造关键神经递质的酶缺陷,这些神经递质需要异常大量的活性形式维生素B6。Adams JB, Holloway C.J: Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. Altern Complement Med. 2004, 10(6):1033-9.Adams JB,Holloway C.J:一项针对自闭症谱系障碍儿童的中等剂量多种维生素/矿物质补充剂的试点研究。Altern补体Med。2004, 10(6):1033-9.Adams JB, George F, Audhya T: Abnormally high plasma levels of vitamin B6 in children with autism not taking supplements compared to controls not taking supplements. J Altern Complement Med. 2006, 12(1):59-63.Adams JB,George F,Audhya T:与未服用补充剂的对照组相比,未服用补充剂的自闭症儿童的维生素B6血浆水平异常高。J Altern补体Med。2006, 12(1):59-63. Treatment: Based on a review of all the research, Dr. Bernard Rimland recommended a dosage of about 8 mg/pound of vitamin B6 (maximum of 1000 mg) and half as much magnesium. However, he emphasized that some individuals with autism need somewhat more or less.治疗:根据对所有研究的回顾,Bernard Rimland医生建议服用约8mg/磅的维生素B6(最高1000 mg)和一半的镁。然而,他强调说,一些自闭症患者或多或少需要一些治疗。 Test: There is not yet a lab test to determine who will benefit from high-dose vitamin B6, although measurements of low neurotransmitters might be a possible clue. The best test is simply a 2-month trial, slowly increasing the dose from 1 mg/pound bodyweight to 8 mg/pound bodyweight of B6, and half as much magnesium.测试:目前还没有实验室测试来确定谁将受益于高剂量维生素B6,尽管测量低神经递质可能是一个可能的线索。最好的试验只是一个为期2个月的试验,将剂量从1毫克/磅体重慢慢增加到8毫克/磅体重的B6,并加入一半的镁。A test for B6-deficiency is a measurement of 4-pyridoxic acid in urine. Normally about 50% of dietary vitamin B6 is excreted as 4-pyridoxic acid. Vitamin B6-deficient subjects have undetectable levels of 4-pyridoxic acid in their urine, making it a useful diagnostic test of vitamin B6 status; on a B6-deficient diet, levels drop to <5% within 5 days.B6缺乏症检测是测量尿液中的4-吡哆酸。通常情况下,约50%的膳食维生素B6以4-吡哆酸的形式排出体外。维生素B6缺乏受试者的尿液中检测不到4-吡哆酸水平,这使其成为维生素B6状态的有用诊断检测;在B6缺乏的饮食,水平下降到< 5%在5天内。 Absorption of vitamin B6维生素B6的吸收Only non-phosphated forms can be absorbed orally. Luckily, phosphated forms are converted into non-phosphated forms by alkaline phosphatase in the intestinal membrane.只有非磷酸盐形式才能口服吸收。幸运的是,磷酸化形式被肠膜中的碱性磷酸酶转化为非磷酸化形式。Non-phosphated forms are then absorbed by passive diffusion, primarily in the jejunum (gut). Absorption is non-saturable (very large amounts can be absorbed).然后,非磷酸盐形式通过被动扩散吸收,主要是在空肠(肠)中。吸收是不可饱和的(可以吸收非常大量的物质)。Physicians Desk Reference (PDR) on Nutritional Supplements 2001.《2001年营养补充剂医师案头参考》(PDR)。
Forms of vitamin B6维生素B6的形式There are six different forms of vitamin B6, including three unphosphated forms and their corresponding phosphated forms. All forms can be converted to one another, and should result in increases in the active forms (PLP and (for a few reactions) PMP).维生素B6有六种不同的形式,包括三种未磷酸化形式及其相应的磷酸化形式。所有形式都可以相互转化,并应导致活性形式(PLP和(对于少数反应)PMP)的增加。The six forms of vitamin B6 are:维生素B6的六种形式是:Pyridoxine (PN) & Pyridoxine 5-Phosphate (PNP) Pyridoxal (PL) & Pyridoxal 5-Phosphate (PLP) Pyridoxamine (PM) and Pyridoxamine 5-Phosphate (PMP)吡哆醇(PN)和吡哆醇5-磷酸(PNP)吡哆醛(PL)和吡哆醇5-磷酸(PLP)吡哆胺(PM)和吡哆胺5-磷酸(PMP) ARI survey data reports a slightly higher rate of adverse effects for PLP (11%) than for other forms of B6 (8%, or 4% if given with Mg). Analysis of their survey data suggests that some children do better on unphosphated forms (pyridoxine HCL), and some do better on the phosphated forms (PLP). Both forms should be well absorbed and have similar effects.ARI调查数据显示,PLP的不良反应发生率(11%)略高于其他形式的B6 (8%,如果与Mg一起给药,则为4%)。对调查数据的分析表明,一些儿童在服用非磷酸盐类药物(盐酸吡哆醇)时表现更好,而一些儿童在服用磷酸盐类药物(PLP)时表现更好。两种形式都应该被很好地吸收,并且具有相似的效果。So, we suggest first starting with pyridoxine HCL; if it is not effective, consider switching to PLP. All research studies to date have only investigated high-dose pyridoxine HCL for autism, and none have involved high-dose PLP.因此,我们建议首先从盐酸吡哆醇开始;如果无效,请考虑切换到PLP。到目前为止,所有研究都只对高剂量盐酸吡哆醇治疗自闭症进行了研究,没有一项研究涉及高剂量PLP。 ARI Survey of Parent Ratings of Treatment Efficacy:父母对治疗疗效评定的ARI调查:
% Worse% No Change% BetterNumber of Reports
Magnesium6%65%29%301
Vitamin B6 (pyridoxine HCl)8%63%30%620
Vitamin B6 with Magnesium4%46%49%7256
P5P (Vit. B6)11%40%48%920
%更糟%无更改%更好报告数量
镁6%65%29%301
维生素B6(盐酸吡哆醇)8%63%30%620
含镁的维生素B64%46%49%7256
P5P (Vit。B6)11%40%48%920
Safety: High dose B6 should always be taken with magnesium to prevent possible hyperactivity (which occurs in about 20% of cases when high dose B6 is taken without magnesium).安全性:高剂量B6应始终与镁一起服用,以防止可能出现的多动症(约20%的病例在不含镁的情况下服用高剂量B6时会出现多动症)。High dose supplementation of vitamin B6 with Mg in children and adults with autism appears to be very safe.高剂量补充维生素B6与镁在儿童和成人自闭症似乎是非常安全的。In very rare cases (less than 1 in 1000) high dose vitamin B6 can cause temporary numbness in fingers and toes. Stopping supplementation generally results in full recovery.在非常罕见的情况下(低于1/1000),高剂量维生素B6可导致手指和脚趾暂时麻木。停止补充通常会导致完全康复。 For more info: A summary of vitamin B6 studies in autism is available at www.autism.com更多信息:自闭症维生素B6研究总结见www.autism.com
Essential Fatty Acids必需脂肪酸Rationale: Essential fatty acids (EFAs) are critical nutrients for humans. They exist in the cell membrane of every cell, and roughly 20% of an infant’s brain is composed of essential fatty acids. Mother’s milk is very rich in essential fatty acids, but some infant formulas lack this key ingredient needed for brain development.原理:必需脂肪酸(EFA)是人类的关键营养素。它们存在于每个细胞的细胞膜中,大约20%的婴儿大脑由必需脂肪酸组成。母乳富含必需脂肪酸,但一些婴儿配方奶粉缺乏大脑发育所需的这一关键成分。Two general categories of essential fatty acids are omega-3 and omega-6. Omega-3 fatty acids have relatively short shelf lives, so commercial food processing often hydrogenates or partially hydrogenates them, which provides long shelf life but eliminates their nutritional value. Thus, over 80% of the US population has low levels of omega-3 fatty acids – this is one of the most widespread nutritional problems in the US.必需脂肪酸的两个一般类别是ω-3和ω-6。ω-3脂肪酸的保质期较短,因此商业食品加工通常会对其进行氢化或部分氢化,从而延长保质期,但会消除其营养价值。因此,超过80%的美国人ω-3脂肪酸水平低——这是美国最普遍的营养问题之一。Low levels of EFAs are associated with a wide range of psychological disorders, including depression, post-partum depression, bipolar disorder (manic/depression), and Rett’s syndrome (similar to autism). Most importantly, four published studies have found that children with autism have lower levels of omega–3 fatty acids than the general population.低水平的EFA与多种心理障碍有关,包括抑郁症、产后抑郁症、双相情感障碍(躁狂/抑郁)和雷特氏综合征(类似于自闭症)。最重要的是,四项已发表的研究发现,自闭症儿童的ω-3脂肪酸水平低于普通人群。• S. Vancassel et al., Plasma fatty acid levels in autistic children, Prostaglandins Leukot Essent Fatty Acids 2001 65:1-7.• 南Vancassel等,自闭症儿童的血浆脂肪酸水平,前列腺素类,白细胞,精华脂肪酸2001 65:1-7。• Bell et al Essential fatty acids and phospholipase A2 in autistic spectrum disorders. Prostaglandins Leukot Essent Fatty Acids. 2004 Oct;71(4):201-4.• Bell等.自闭症谱系障碍中的必需脂肪酸和磷脂酶A2 .前列腺素类,白细胞,精华脂肪酸类。2004年10月;71(4):201-4.• Wiest et al Plasma fatty acid profiles in autism: a case-control study Prostaglandins Leukot Essent Fatty Acids. 2009 Apr;80(4):221-7.• Wiest等自闭症患者的血浆脂肪酸谱:一项前列腺素类、白细胞类、Essent脂肪酸类的病例对照研究。2009年4月;80(4):221-7.• Bell et al 2010, 7The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake. Br. J. Nutri. 103 1160-7.• Bell等人,2010,7自闭症儿童、发育迟缓或典型发育对照儿童的红细胞和血浆极性脂质的脂肪酸组成以及鱼油摄入的影响。大不列颠的J. Nutri。103 1160-7. Explanation of Treatment:治疗说明:One of the best sources of omega-3 fatty acids is fish, which obtain them from algae and plankton in the sea. Unfortunately, many fish are high in mercury and other toxins, especially the large predators (shark, swordfish, and tuna) that are at the top of the food chain and consume smaller fish. Smaller fish with shorter lifespans, such as salmon and shrimp, have lower levels of mercury, but it depends where they come from. So, it is generally safer for children to obtain essential fatty acids from fish oil from small fish, since little mercury is stored in the oil. Because fish oil (and fish) spoil readily, it is important to obtain a high-quality oil that does not smell or taste rancid, and it should be kept refrigerated. A high-quality fish oil should have only a mild taste.ω-3脂肪酸的最佳来源之一是鱼,鱼从海洋中的藻类和浮游生物中获取ω-3脂肪酸。不幸的是,许多鱼类的汞和其他毒素含量很高,尤其是食物链顶端的大型食肉动物(鲨鱼、剑鱼和金枪鱼),它们会吃掉体型较小的鱼类。寿命较短的较小鱼类,如鲑鱼和虾,其汞含量较低,但这取决于它们来自何处。因此,一般来说,儿童从小鱼的鱼油中获取必需脂肪酸更安全,因为鱼油中储存的汞很少。因为鱼油(和鱼)容易变质,所以获得无异味或无酸败味道的优质油很重要,并且应保存在冷藏条件下。高质量的鱼油应该只有一个温和的味道。 Two of the major omega-3 fatty acids are eicosapentaenoic acid (EPA) & docosahexaenoic acid (DHA). DHA is critical for early brain development, and EPA is useful for later development and is an important anti-inflammatory mediator.两种主要的ω-3脂肪酸是二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)。DHA对早期大脑发育至关重要,而EPA对后期发育有用,是一种重要的抗炎介质。 Recommended dosages (based on the amount of omega-3’s, not the total amount of oil which推荐剂量(基于ω-3的量,而不是will contain other oils):将含有其他油类):Omega-3: 20-60 mg/kg (600-1800 mg for a 30 kg, or 60 lb, child). For younger children, use a supplement richer in DHA, and for older children and adults, use a supplement richer in EPA. Omega 6: ¼ as much omega-6 as omega-3; so, if taking 1000 mg of omega-3’s, then 250 mg of omega-6. It is important to maintain a balance of omega-3 and omega-6. Most people eating a typical western diet receive sufficient omega-6 but are lacking in omega-3; however, some may need a little extra omega-6 when taking an omega-3 supplement.ω-3:20-60mg/kg(30kg或60 lb儿童为600-1800 mg)。对于年龄较小的儿童,使用富含DHA的补充剂;对于年龄较大的儿童和成人,使用富含EPA的补充剂。ω6:ω6和ω3一样多;所以,如果服用1000毫克的ω-3,那么服用250毫克的ω-6。保持ω-3和ω-6的平衡很重要。大多数人吃典型的西方饮食获得足够的ω-6,但缺乏ω-3;然而,有些人在服用ω-3补充剂时可能需要一点额外的ω-6。 Flax seed oil is also a source of omega-3 fatty acids, but the form it provides (alpha linolenic acid) must be converted by the body to the active form (EPA and DHA), and that conversion process is亚麻籽油也是ω-3脂肪酸的来源,但是它提供的形式(α亚麻酸)必须被身体转化为活性形式(EPA和DHA),并且这种转化过程是
slow in humans. There have been some reports that children with autism respond poorly to flax seed oil, so we generally recommend fish oil instead.对人类来说很慢。有一些报道称,自闭症儿童对亚麻籽油的反应很差,所以我们通常建议改用鱼油。 Cod liver oil (or other fish liver oil) is a good source of omega-3 fatty acids, and also provides good amounts of vitamin A and vitamin D. However, vitamin A intake from all supplements should not greatly exceed the RDA intake (see vitamin/mineral section) for extended periods, since excess amounts will be stored in the liver and could affect liver function. (Carotenes are pre-vitamin A and are not a problem.)鱼肝油(或其他鱼肝油)是ω-3脂肪酸的良好来源,也提供了大量的维生素A和维生素d。但是,所有补充剂中的维生素A摄入量不应长时间大大超过RDA摄入量(见维生素/矿物质部分),因为过量会储存在肝脏中并可能影响肝功能。(胡萝卜素是维生素A前体,不是问题。) Testing: The level of essential fatty acids can be measured in the red blood cell membrane. However, because most people in the US have low levels of omega-3’s, it is desirable to reach levels at the top of the “normal” range. Also, it is better to measure the absolute amount of each fatty acid, rather than just the percentage of each.检测:可在红细胞膜上测定必需脂肪酸的含量。然而,因为美国大多数人的ω-3脂肪酸水平较低,所以希望达到“正常”水平。此外,最好测量每种脂肪酸的绝对含量,而不仅仅是其百分比。 ARI Survey of Parent Ratings of Treatment Efficacy:父母对治疗疗效评定的ARI调查:
% Worse% No Change% BetterNumber of Reports
Fatty Acids2%39%59%1680
%更糟%无更改%更好报告数量
脂肪酸2%39%59%1680
Safety:安全:One unpublished study by Audhya of 400 children with autism found that about 1-2% had a severe behavioral reaction to fish oil within a few days, resulting in extreme behavioral problems. These symptoms disappeared within a few days after stopping intake. Blood testing revealed that these children had a carnitine deficiency (see section on Carnitine), which is needed to carry long-chain fatty acids into the mitochondria, and to transport short and medium chain fatty acids out of the mitochondria. Supplementation with low dose carnitine (about 200 mg/day) allowed the children to tolerate fish oil without any problem. Since the major source of carnitine is beef and pork, people who avoid those foods may want to start with very low doses of fish oil, and if there is a problem add a carnitine supplement or eat beef or pork regularly.Audhya对400名自闭症儿童进行的一项未发表的研究发现,约1-2%的儿童在几天内对鱼油产生严重的行为反应,从而导致极端的行为问题。这些症状在停止摄入后几天内消失。血液检查显示,这些儿童存在肉碱缺乏症(参见“肉碱”部分),需要肉碱将长链脂肪酸带入线粒体,并将短链和中链脂肪酸带出线粒体。补充低剂量肉碱(约200毫克/天)使儿童能够耐受鱼油,没有任何问题。由于肉碱的主要来源是牛肉和猪肉,避免这些食物的人可能想从非常低剂量的鱼油开始,如果有问题,添加肉碱补充剂或定期食用牛肉或猪肉。 Research:研究:There are a huge number of scientific studies showing that humans need EFAs, and that most people in the US do not consume enough. As mentioned above, 4 studies found that children with autism have lower levels of omega-3 fatty acids than do typical children, many of whom are not consuming enough.大量科学研究表明,人类需要全民教育,而美国大多数人消费不足。如上所述,4项研究发现,自闭症儿童的ω-3脂肪酸水平低于普通儿童,其中许多儿童摄入不足。 There have been nine treatment studies for children/adults with autism, six positive and three inconclusive or negative. Most of the studies have been short, and did not pre-screen for children with low EFA levels. It is likely that fish oil will be most beneficial to children who do not eat fish regularly, and it could be that long treatment (12 months) is needed for full benefits to be observed.已有九项针对自闭症儿童/成人的治疗研究,六项为阳性,三项为非决定性或阴性。大多数研究都很短,没有对低EFA水平的儿童进行预筛选。鱼油可能对不经常吃鱼的儿童最有益,也可能需要长期治疗(12个月)才能观察到全部益处。 Positive studies积极的研究A 90-day open trial of essential fatty acids in 18 children with autism found significant increases in language and learning skills.在18名自闭症儿童中进行的为期90天的必需脂肪酸开放试验发现,他们的语言和学习技能显著提高。Patrick L and Salik R, The Effect of Essential Fatty Acid Supplementation on Language Development and Learning Skills in Autism and Asperger’s syndrome. Autism/Asperger’s Digest: Research Article – Jan/Feb 2005.补充必需脂肪酸对自闭症和阿斯伯格综合症患者语言发展和学习技能的影响。自闭症/阿斯伯格综合症文摘:研究文章–2005年1月/2月。 One unpublished study by Adams et al. found that 2 months supplementation of fish oil (rich in DHA) led to significant improvements in sociability and other areas, especially in children and adults who consumed 0-1 servings of fish/month.亚当斯等人一项未发表的研究发现,补充2个月鱼油(富含DHA)可显著改善社交和其他方面,尤其是在每月食用0-1份鱼的儿童和成人中。
One unpublished open study by Audhya et al. was a 9-month treatment study of several hundred children. They found little improvement by 6 months, but substantial improvements by 9 months. The largest improvement was in gut function (verified by pre and post endoscopies in many cases), but also improvements in other areas.Audhya等人的一项未发表的开放研究是对数百名儿童进行的9个月治疗研究。他们发现6个月时几乎没有改善,但9个月时有了实质性改善。最大的改善是肠道功能(在许多情况下通过内窥镜检查前和检查后证实),但也有其他方面的改善。 An open-label study of 30 children with autism found that fish oil supplementation led to improvements in EFA levels, and 2/3 of the participants had improvements in their autistic symptoms.一项针对30名自闭症儿童的开放标签研究发现,补充鱼油可改善EFA水平,三分之二的参与者的自闭症症状得到改善。Meguid et al, Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clinical Biochemistry 41 (2008) 1044–1048Meguid等,多不饱和脂肪酸在埃及自闭症儿童治疗中的作用。临床生物化学41(2008)1044-1048 One study found that fish oil supplementation improved omega-3 levels in children with autism.一项研究发现,鱼油补充剂改善了自闭症儿童的ω-3水平。Bell JG et al, The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake. Br J Nutr. 2010 Apr;103(8):1160-7.贝尔·JG等人,The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism,developmental delay or typically developing controls and the effect of fish oil intake. Br J Nutr。2010年4月;103(8):1160-7. One small randomized, double-blind, placebo-controlled 16-week treatment study found that the combination of DHA (an omega 3 EFA) and arachidonic acid (an omega 6 EFA) led to significant improvements in communication and social withdrawal. (There is a concern that western diets already contain sufficient arachidonic acid.)一项为期16周的小型随机、双盲、安慰剂对照治疗研究发现,DHA(一种ω3 EFA)和花生四烯酸(一种ω6 EFA)联合用药可显著改善沟通和社交退缩。(有人担心西方饮食已经含有足够的花生四烯酸。)Bent et al.,. Effects of large doses of arachidonic acid added to docosahexaenoic acid on social impairment in individuals with autism spectrum disorders: a double-blind, placebo-controlled, randomized trial. J Clin Psychopharmacol. 2012 Apr;32(2):200-6.Bent等人。在二十二碳六烯酸中添加大剂量花生四烯酸对自闭症谱系障碍患者社会功能损害的影响:一项双盲、安慰剂对照、随机试验。J Clin Psychopharmacol. 2012年4月;32(2):200-6. Negative/Inconclusive studies阴性/非决定性研究One small double-blind, placebo-controlled treatment study by Amminger et al. found that fish oil might have some benefit in reducing hyperactivity, but the numbers were too small to be statistically significant.Amminger等人进行的一项小型、双盲、安慰剂对照治疗研究发现,鱼油可能在减少多动症方面有一定益处,但其数量太少,不具有统计学意义。Amminger et al. Omega-3 Fatty Acids Supplementation in Children with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study. Biol Psychiatry. 2006 Aug 22.Amminger et al.自闭症儿童补充ω-3脂肪酸:一项双盲、随机、安慰剂对照的试点研究。Biol精神病学。2006年8月22日。 In an open-label 6-week study of 19 young adults with severe autism, there was no benefit of EFA supplementation on autistic symptoms or problem behaviors.在一项对19名患有严重自闭症的年轻人进行的6周开放标签研究中,补充EFA对自闭症症状或问题行为没有任何益处。Politi et al, Behavioral Effects of Omega-3 Fatty Acid Supplementation in Young Adults with Severe Autism: An Open Label Study Archives of Medical Research 39 (2008) 682-685Politi等,补充ω-3脂肪酸对严重自闭症青年的行为影响:医学研究开放标签研究档案39 (2008) 682-685 In a small randomized, double-blind, placebo-controlled 12-week treatment study of young children with autism, the treatment group did not improve significantly more than the placebo group on hyperactivity (the primary outcome measure).在一项针对自闭症幼儿的小型随机、双盲、安慰剂对照12周治疗研究中,治疗组在多动症(主要结局衡量指标)方面的改善并不比安慰剂组明显。Bent et al., A Pilot Randomized Controlled Trial of Omega-3 Fatty Acids for Autism Spectrum Disorder. J Autism Dev Disord. 2011 May;41(5):545-54.Bent等,ω-3脂肪酸治疗自闭症谱系障碍的试点随机对照试验。j自闭症发展障碍。2011年5月;41(5):545-54. For more info on essential fatty acids:如需了解更多关于必需脂肪酸的信息:see www.nordicnaturals.com; www.ghs.co; www.barleans.com看见www.nordicnaturals.com;www.ghs.co;www.barleans.com
Gut Treatments: Digestive Enzymes肠道治疗:消化酶Rationale: The body normally produces a variety of digestive enzymes to break large food molecules into smaller ones that can be absorbed. Different enzymes are needed for different types of protein, carbohydrates, and fats. Children with autism sometimes have low levels of certain enzymes, or less active enzymes, or both – enzyme problems are especially common in children with gut problems (chronic constipation or diarrhea).原理:人体通常会产生各种消化酶,将大的食物分子分解成小的可以被吸收。不同类型的蛋白质、碳水化合物和脂肪需要不同的酶。自闭症儿童有时某些酶的水平较低,或酶活性较低,或两者兼而有之——酶问题在有肠道问题(慢性便秘或腹泻)的儿童中尤为常见。 One digestive enzyme, DPP4, is easily deactivated by small amounts of toxins including mercury and organophosphates (pesticide sprays). DPP4 is needed to digest some peptides from casein and other substances that can have an opioid-like effect.其中一种消化酶DPP4很容易被少量毒素(包括汞和有机磷)灭活(农药喷雾剂)。需要DPP4来消化酪蛋白中的一些肽和其他可能具有类阿片作用的物质。 Treatment: Take a digestive enzyme with each meal, usually at the start of the meal. Use enzymes that are as complete as possible. Proteases are needed for protein, lipases for fats, and disaccharidases and other enzymes for carbohydrates.治疗方法:每餐服用一种消化酶,通常在餐前服用。使用尽可能完整的酶。蛋白质需要蛋白酶,脂肪需要脂肪酶,碳水化合物需要双糖酶和其他酶。Note that we recommend digestive enzymes in addition to special diets, and they should not be used instead of special diets. If a child has a problem digesting wheat or dairy products, it is best to just avoid them, and use the digestive enzymes as a precaution against unknown exposures.请注意,除特殊饮食外,我们还推荐使用消化酶,不应替代特殊饮食使用。如果儿童消化小麦或乳制品有问题,最好避免食用,并使用消化酶作为预防未知暴露的措施。 Testing:测试:Symptoms of pain, gas, and discomfort after eating dairy products is a strong indicator of a lack of digestive enzymes for milk, or a delayed-type food allergy to it.食用乳制品后出现的疼痛、胀气和不适症状强烈表明牛奶缺乏消化酶,或对其产生迟发型食物过敏。If an endoscopy is conducted to investigate chronic gastrointestinal problems, it is highly recommended to include a biopsy to test for digestive enzymes – this is a routine test in most hospitals, and can easily be done as part of the endoscopy.如果进行内窥镜检查是为了检查慢性胃肠道问题,强烈建议进行活检以检测消化酶——这是大多数医院的常规检测,可以很容易地作为内窥镜检查的一部分进行。A Comprehensive Digestive Stool Analysis may reveal whether some types of foods are not being digested well, suggesting a problem with specific digestive enzymes, but the reliability of the test is limited.全面消化粪便分析可能会揭示某些类型的食物是否消化不良,这表明特定消化酶存在问题,但该检测的可靠性有限。 Research研究 Gut Problems are Common in Autism肠道问题在自闭症中很常见There are many studies of gastrointestinal problems in children and adults with autism (see review by Buie et al 2010), and most of the studies indicate that chronic gastrointestinal problems (constipation, diarhea, abdominal pain, esophagitis, etc.) are common and should be evaluated and treated.关于自闭症儿童和成人的胃肠道问题有很多研究(见Buie等人2010年的综述),大部分研究表明慢性胃肠道问题(便秘、腹泻、腹痛、食管炎等)。)很常见,应进行评估和治疗。Buie, T., et al. (2010). Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 125 Suppl 1, S1-18.Buie,t .,等人(2010年)。自闭症谱系障碍患者胃肠疾病的评估、诊断和治疗:一份共识报告。儿科125 Suppl 1,S1-18。 Lack of Digestive Enzymes消化酶缺乏Studies by Horvath et al. 1999, Williams et al 2011, and Kushak et al 2011 have found that many children with autism and major gastrointestinal problems have low levels of enzymes needed to digest sugars/carbohydrates, especially lactase, the enzyme needed to digest lactose (the sugar in milk). Insufficient lactase would result in gas, pain, and diarrhea after consuming milk products. Their studies involved tissue biopsies taken during an endoscopy, so these were from children/adults with substantial gastrointestinal problems – problems with digestive enzymes are probably less likely in individuals without obvious gastrointestinal symptoms.霍瓦特等人(1999年)、Williams等人(2011年)和Kushak等人(2011年)的研究发现,许多患有自闭症和严重胃肠道问题的儿童消化糖/碳水化合物所需的酶水平较低,尤其是乳糖酶(消化乳糖(牛奶中的糖)所需的酶)。乳糖酶不足会导致食用乳制品后出现气体、疼痛和腹泻。他们的研究涉及内窥镜检查期间的组织活检,因此这些活检来自有严重胃肠道问题的儿童/成人——没有明显胃肠道症状的个体发生消化酶问题的可能性可能更小。
One large study by Horvath, et al (1999) evaluated disaccharidase (sugar) activity from endoscopic biopsies in 90 children with autism. They found that 49% had at least one deficient enzyme霍瓦特等人(1999)的一项大型研究评估了90例自闭症儿童内窥镜活检中的双糖酶(糖)活性。他们发现49%的人至少有一种酶缺陷activity, and 20% had deficiencies in two or more disaccharidase enzymes. “Lactase and maltase deficiencies were the most frequent, followed by low activity of sucrase, palatinase, and glucoamylase. All of the children with low enzyme activity had loose stools and/or gaseousness.”活性,并且20%具有两种或多种二糖酶的缺陷。乳糖酶和麦芽糖酶缺乏最常见,其次是蔗糖酶、帕拉酶和糖化酶活性低。所有酶活性低的儿童均有便溏和/或气肿。”Horvath K et al, Gastrointestinal abnormalities in children with autistic disorder,” J. Pediatrics 135 no. 5霍瓦特K等,“自闭症儿童的胃肠异常”,《儿科杂志》135年第5期(1999) 559-563.(1999) 559-563.Horvath K and Perman JA “Autistic disorder and gastrointestinal disease,” Curr. Opinion in Pediatrics, 14 (2002) 583.霍瓦特K和Perman JA“自闭症和胃肠疾病”,Curr。《儿科意见》,14 (2002) 583。 A small study by Williams et al 2011 also found substantial decreases in disaccharidases, resulting in abnormal gut bacteria.Williams等人2011年的一项小型研究也发现二糖酶大幅减少,导致肠道细菌异常。Williams BL et al., Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS One. 2011;6(9):e24585. Epub 2011 Sep 16.Williams BL等人,Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestinesof children with autism and gastrointestinal disturbances. PLoS One。2011;6(9):e24585。2011年9月16日 A new large study at Harvard Medical School (Kushak et al 2011) involving intestinal biopsy samples of 199 children and adults with autism (ages 22 months to 28 years) found that many had deficiencies in disaccharidases (enzymes for digesting simple sugars). Specifically, they found that 62% had deficiencies in lactase, 16% were deficient in sucrase, and 10% were deficient in maltase. The problems seemed to be equally common in children and adults, suggesting that these problems are lifelong.哈佛医学院的一项新的大型研究(Kushak等人,2011年)涉及199名自闭症儿童和成人(年龄22个月至28岁)的肠道活检样本,发现许多人缺乏二糖酶(消化单糖的酶)。具体而言,他们发现62%的人乳糖酶缺乏,16%的人蔗糖酶缺乏,10%的人麦芽糖酶缺乏。这些问题在儿童和成人中似乎同样常见,表明这些问题是终身的。file:///C:/Users/liang/AppData/Local/Temp/ksohtml12396/wps570.pngKushak RI et al., Intestinal disaccharidase activity in patients with autism: effect of age, gender, and intestinal inflammation. Autism. 2011 May;15(3):285-94. Epub 2011 Mar 17.file:///C:/Users/liang/AppData/Local/Temp/ksohtml12396/wps571.pngKushak RI 自闭症患者的肠道二糖酶活性:年龄、性别和肠道炎症的影响。Autism. 2011年5月;15(3):285-94.Epub 2011年3月17日。 Treatment Studies治疗研究 One open-label treatment study involved a 12-week trial of a digestive enzyme. The digestive enzyme included enzymes for proteins, peptides, casein, and phytic acid. 46 participants started the study, and 17 dropped out, including 6 who stated adverse effects and others for various reasons including lack of benefit. This was a rather high drop-out rate. The 29 who finished the study reported improvements in many areas, especially socialization and hyperactivity, and half reported improvements in digestion.一项开放标签治疗研究涉及一种消化酶的12周试验。消化酶包括蛋白质、肽、酪蛋白和植酸酶。46名受试者开始研究,17名退出,包括6名陈述了不良作用的受试者和其他因各种原因(包括缺乏获益)退出的受试者。这是一个相当高的辍学率。完成研究的29名受试者报告在许多领域有所改善,尤其是社会化和多动症,半数受试者报告消化能力有所改善。Brudnak MA et al. Enzyme-based therapy for autism spectrum disorders -- is it worth another look? Med Hypotheses. 2002 May;58(5):422-8.Brudnak MA 自闭症谱系障碍的酶疗法——值得再看吗?MedHypotheses. 2002年5月;58(5):422-8. However, another digestive enzyme treatment study found no benefit. This was a more rigorous randomized, double-blind, placebo-controlled, cross-over study lasting 6 months and involving 43 participants. It involved a digestive enzyme designed to digest proteins and peptides (small proteins), not carbohydrates or sugars. The digestive enzymes were well tolerated, but there were no statistically significant clinical improvements on any symptoms.然而,另一项消化酶治疗研究发现无益处。这是一项更严格的随机、双盲、安慰剂对照、交叉研究,持续6个月,涉及43名参与者。它涉及一种消化酶,旨在消化蛋白质和肽(小蛋白质),而不是碳水化合物或糖。消化酶耐受良好,但临床症状无统计学意义的改善。Munasinghe et al., Digestive Enzyme Supplementation for Autism Spectrum Disorders: A Double-Blind Randomized Controlled Trial J Autism Dev Disord (2010) 40:1131–1138Munasinghe等,消化酶补充治疗自闭症谱系障碍:一项双盲随机对照试验J自闭症Dev disard(2010)40:1131-1138 The two studies listed above were for digestive enzymes focused on proteins, not sugars and carbohydrates. According to three studies by Horvath et al 1999, Williams et al 2011, and Kushak et al 2011, children with autism have a problem digesting sugars and carbohydrates, and especially milk sugar (lactose). So, there is a need for a treatment study to investigate digestive enzymes designed to digest sugars and carbohydrates, especially lactase.上面列出的两项研究是针对消化酶的,重点是蛋白质,而不是糖和碳水化合物。根据霍瓦特等人1999年、威廉姆斯等人2011年和库沙克等人2011年的三项研究,自闭症儿童在消化糖和碳水化合物方面存在问题,尤其是乳糖。因此,有必要进行一项治疗研究,以研究旨在消化糖和碳水化合物(尤其是乳糖酶)的消化酶。 Finally, the ARI survey data (which involves many different brands of digestive enzymes) suggests that digestive enzymes can be helpful and are generally well-tolerated. The Specific Carbohydrate最后,ARI调查数据(涉及许多不同品牌的消化酶)表明,消化酶可能有帮助,并且通常耐受良好。特定碳水化合物
Diet (which includes avoidance of most sugars and all carbohydrates except for monosaccharides) also seems likely to be beneficial for people lacking digestive enzymes for those foods, but there are no formal research studies on it yet (see ARI survey data below).饮食(包括避免摄入除单糖以外的大多数糖和所有碳水化合物)似乎也可能有益于缺乏这些食物的消化酶的人,但尚未有关于它的正式研究(见下文ARI调查数据)。 ARI Survey of Parent Ratings of Treatment Efficacy:父母对治疗疗效评定的ARI调查:
% Worse% No Change% BetterNumber of Reports
Digestive Enzymes3%35%62%2350
Specific Carbohydrate Diet7%22%71%537
%更糟%无更改%更好报告数量
消化酶3%35%62%2350
特定碳水化合物饮食7%22%71%537
Gut Treatments: Anti-fungals and Probiotics肠道治疗:抗真菌药物和益生菌Rationale: The human gut contains a large number of bacteria (10x more gut bacteria than cells in the entire body). Most of these gut bacteria are beneficial, helping with food digestion and water balance, producing some vitamins, and limiting the growth of harmful bacteria and yeast.原理:人体肠道含有大量细菌(肠道细菌比整个身体的细胞多10倍)。这些肠道细菌大多是有益的,有助于食物消化和水平衡,产生一些维生素,并限制有害细菌和酵母的生长。 One of the most striking differences in the medical history of children with autism is that several studies have reported much higher use of oral antibiotics (usually for ear infections) in infancy of children with autism compared to controls. These oral antibiotics will destroy most of the beneficial gut bacteria, and thus increase the risk of overgrowth of harmful bacteria and/or yeast.自闭症儿童病史中最显著的差异之一是,有几项研究报告称,自闭症儿童婴儿期口服抗生素(通常用于耳部感染)的使用率高于对照组。这些口服抗生素会破坏大部分有益的肠道细菌,从而增加有害细菌和/或酵母过度生长的风险。 Harmful bacteria and yeast produce toxins that can severely affect mental functioning and behavior; alcohol is just one of many toxins that yeast can produce, and is a good example of a yeast toxin that can severely affect behavior. It seems that the best way to treat these problems is with a combination of antifungal diet, antifungal medications (if yeast are present) and probiotics (beneficial bacteria). These can help restore normal gut function. Antibiotics should only be considered as a last resort in most cases, as ARI survey data suggest they are more likely to cause harm than help.有害细菌和酵母产生的毒素会严重影响精神功能和行为;酒精只是酵母能够产生的许多毒素之一,并且是能够严重影响行为的酵母毒素的良好实例。似乎治疗这些问题的最好方法是联合使用抗真菌饮食、抗真菌药物(如果存在酵母)和益生菌(有益菌)。这些可以帮助恢复正常的肠道功能。在大多数情况下,抗生素应仅被视为最后手段,因为ARI调查数据表明,抗生素更可能造成伤害而非帮助。 Treatment:治疗:Anti-fungal Diet: Yeast feed on sugar and simple carbohydrates, so reducing or avoiding those foods is important. Also, it can be helpful to avoid foods containing yeast or yeast products, including fruit juice, vinegar (in ketchup and other foods), leavened foods (bread, pizza, bagels, rolls), cheese, and mushrooms (a type of yeast/fungus).抗真菌饮食:酵母以糖和简单的碳水化合物为食,所以减少或避免这些食物很重要。此外,避免食用含有酵母或酵母制品的食物也很有帮助,包括果汁、醋(在番茄酱和其他食物中)、发酵食物(面包、比萨饼、百吉饼、面包卷)、奶酪和蘑菇(一种酵母/真菌)。Duration: Dr. Sidney Baker recommends a trial for 5-14 days, followed by a high exposure to see if the diet makes a difference. If so, continue long-term.持续时间:悉尼·贝克博士建议进行为期5-14天的试验,然后进行高暴露量试验,观察饮食是否有所不同。如果是,继续长期。 Anti-fungal Medications: There are several prescription and non-prescription anti-fungal treatments, and sometimes several need to be tried before finding an effective one for a given strain of yeast. Nystatin is the safest because it is not absorbed, but many yeast are now resistant to it. Diflucan, Sporanox, Lamisil, and Nizoral are alternatives to which yeast are less likely to be resistant, but since they are absorbed into the body they have a very small chance of overtaxing the liver, and liver enzymes should be checked every few months if they are used long-term. (Note that there is no published research supporting this approach, merely the clinical experience of some MDs.) Some non-prescription antifungal treatments include capryllic acid, oregano concentrate, citrus seed extract, undecylenic acid, and pau d’arco.抗真菌药物:有几种处方药和非处方药抗真菌治疗,有时需要尝试几种,然后才能为给定的酵母菌株找到有效的治疗方法。制霉菌素是最安全的,因为它不被吸收,但许多酵母现在对它有抵抗力。Diflucan、Sporanox、Lamisil和Nizoral是酵母不太可能产生耐药性的替代品,但因为它们被人体吸收,所以使肝脏过度负荷的可能性很小,如果长期使用,应每隔几个月检查一次肝酶。(请注意,没有已发表的研究支持这种方法,仅是一些MDs的临床经验。)一些非处方药物抗真菌治疗包括辛酸、牛至浓缩物、柑橘籽提取物、十一烯酸和pau d'arco。Duration: Dr. Sidney Baker recommends a series of high-dose trials of 2-3 weeks for each antifungal, followed by the next one until you find one that works.持续时间:西德尼·贝克博士建议对每种抗真菌药物进行一系列2-3周的高剂量试验,然后进行下一次试验,直至您发现一种有效。Die-off reaction: When yeast are killed, they can release all their toxins at once. This can cause a temporary “die-off” reaction lasting a few days, followed by good improvement when the toxins leave the body. Activated charcoal can be taken to absorb these toxins and reduce side-effects.死亡反应:酵母被杀死后,可以立即释放出所有的毒素。这可能会导致持续几天的暂时“死亡”反应,随后当毒素离开身体时会有很好的改善。活性炭可以用来吸收这些毒素,减少副作用。 Probiotics: Probiotics are mixtures of one or more beneficial bacteria that are normally present in the gut. Many probiotics contain only a few billion Colony Forming Units (CFU’s), but some strong probiotics contain 30-75 billion CFU’s, and some prescription probiotics contain up to 500 billion CFU’s. The higher-dose products are more likely to be able to reach the gut and recolonize it with good bacteria. If high-dose probiotics continue to be needed, this may suggest pancreatitis or other serious dysfunction is present.益生菌:益生菌是一种或多种通常存在于肠道中的有益菌的混合物。许多益生菌只含有几十亿个菌落形成单位(CFU单位),但一些强效益生菌含有300-750亿个CFU单位,一些处方益生菌含有高达5000亿个CFU单位。较高剂量的产品更有可能到达肠道,并与良好的细菌重新定居。如果继续需要高剂量益生菌,这可能表明存在胰腺炎或其他严重功能障碍。
Duration: Very little is known about optimal types and dosages of probiotics. We recommend gradually increasing to a high dose until benefit is observed, and then consider a lower maintenance dose.持续时间:关于益生菌的最佳类型和剂量知之甚少。我们建议逐渐增加至高剂量,直至观察到获益,然后考虑较低的维持剂量。Testing: One simple and very useful test is to look at the stool, since half of the stool is bacteria. The stool should be a medium/dark brown and well-formed, with 1-3 bowel movements/day.检测:一个简单且非常有用的检测方法是查看粪便,因为粪便中有一半是细菌。大便应为中/深棕色,形态良好,每天排便1-3次。 Use antibiotics only with great caution: One round of oral antibiotics typically kills off over 99% of beneficial gut bacteria, but has little or no effect on yeast or many types of bad bacteria, which then thrive due to lack of competition from beneficial bacteria. Oral antibiotics often cause overgrowths of bad bacteria and yeast, and are suspected as the cause of many of the gut problems in autism. Several studies have shown that children with autism had, on average, a much higher usage of oral antibiotics than typical children in their first few years of life.使用抗生素时要非常小心:一轮口服抗生素通常会杀死99%以上的有益肠道细菌,但对酵母或许多类型的有害细菌几乎没有或没有影响,这些细菌会由于缺乏有益细菌的竞争而茁壮成长。口服抗生素通常会导致有害细菌和酵母过度繁殖,并被怀疑是自闭症许多肠道问题的原因。几项研究表明,自闭症儿童在出生后几年内口服抗生素的使用率平均比一般儿童高得多。 Lab Testing: A Comprehensive Digestive Stool Analysis (available from Genova Diagnostics or Doctor’s Data) will reveal the amount of some types of normal and abnormal bacteria and yeast. Some labs offer individualized susceptibility testing, to determine which anti-fungals are most effective against the patient’s particular yeast.实验室检测:全面的消化粪便分析(可从Genova Diagnostics获得或根据医生数据获得)将揭示某些类型的正常和异常细菌和酵母菌的数量。一些实验室提供个体化的药敏试验,以确定哪些抗真菌药物对患者的特定酵母最有效。Urinary organic acid testing can be done to check for abnormally high levels of metabolites from yeast, although the reliability of this test is unclear.可进行尿有机酸检测,以检查酵母代谢产物的异常高水平,但该检测的可靠性尚不清楚。 Individuals with chronic gastrointestinal problems should consider a consult with a gastroenterologist (a doctor who specializes in gastrointestinal problems), who may recommend an endoscopy or other testing. Endoscopies should include a biopsy to evaluate digestive enzymes (see Digestive Enzyme section) – this testing is now widely available.患有慢性胃肠道问题的个人应考虑咨询消化科医生(专门研究胃肠道问题的医生),他们可能会建议进行内窥镜检查或其他检查。内窥镜检查应包括活检以评估消化酶(参见“消化酶”部分)——该检测现已广泛应用。 ARI Survey of Parent Ratings of Treatment Efficacy:父母对治疗疗效评定的ARI调查:
% Worse% No Change% BetterNumber of Reports
AntifungalsC: Diflucan5%34%62%1214
AntifungalsC: Nystatin5%43%52%1969
Antibiotics (not recommended)33%50%18%2507
Candida diet3%39%58%1141
%更糟%无更改%更好报告数量
抗真菌药物C: Diflucan5%34%62%1214
抗真菌药c:制霉菌素5%43%52%1969
抗生素(不推荐)33%50%18%2507
念珠菌饮食3%39%58%1141
Research – Oral Antibiotics Over-used研究——口服抗生素过度使用Five studies have reported much higher usage of oral antibiotics during infancy of children with autism vs. controls, usually for treating ear infections (possibly suggesting an impaired immune system). Commonly used oral antibiotics eliminate almost all of the normal gut bacteria, which play an important role in the breakdown of plant polysaccharides, promoting gastrointestinal motility, maintaining water balance, producing some vitamins, and competing against harmful bacteria. Loss of normal gut flora can result in the overgrowth of harmful bacteria/yeast, which can in turn cause constipation and other problems.有五项研究报告称,自闭症儿童在婴儿期口服抗生素的使用率高于对照组,通常用于治疗耳部感染(可能表明免疫系统受损)。常用的口服抗生素几乎能清除所有正常肠道细菌,在植物多糖分解、促进胃肠运动、维持水平衡、产生一些维生素以及与有害细菌竞争等方面发挥重要作用。正常肠道菌群的丧失会导致有害细菌/酵母过度生长,进而导致便秘和其他问题。Konstantareas MM, Homatidis S: Ear infections in autistic and normal children. Journal of Autism and Developmental Disorders 1987, 17(4):585-594.Konstantareas MM,Homatidis:自闭症和正常儿童的耳部感染。自闭症和发育障碍杂志,1987,17(4):585-594。Niehus R, Lord C: Early medical history of children with autism spectrum disorders. Journal of Developmental and Behavioral Pediatrics 2006, 27(2):S120-S127.《自闭症谱系障碍儿童的早期病史》。发育与行为儿科杂志2006,27(2):S120-S127。Adams JB et al., Analyses of Toxic Metals and Essential Minerals in the Hair of Arizona Children with Autism and their mothers, Biol Tr El Res 2006, 110:193-209.Adams JB等,亚利桑那自闭症儿童及其母亲头发中有毒金属和必需矿物质的分析,Biol Tr El Res 2006,110:193-209。Adams JB et al., Mercury, Lead, and Zinc in Baby Teeth of Children with Autism vs. Controls J Toxicol Environ Health 2007, 70(12):1046-51.Adams JB等,孤独症儿童乳牙中的汞、铅和锌与对照组的比较J有毒醇环境健康2007,70(12):1046-51。Adams JB et al., Mercury in First-Cut Baby Hair of Children with Autism vs. Typically-Developing Children. 2008, 90(4):739-753.亚当斯JB等人,自闭症儿童与典型发育儿童的第一次剪婴儿头发中的汞。2008, 90(4):739-753.
Research – Treatment研究–治疗A small open-label treatment study by Sandler et al with a potent non-absorbable antibiotic (Vancomycin) found temporary improvement in gut function and behavior, but the gains were lost when the treatment was stopped. These mixed results may be due to the inability for antibiotics to destroy spores produced by clostridia or other bacteria. This study demonstrated the importance of abnormal gut bacteria, and the difficulty in treating them long-term.Sandler等人对强效不可吸收抗生素(万古霉素)进行的一项小型开放标签治疗研究发现,肠道功能和行为暂时得到改善,但当治疗停止时,增益消失。这些混合结果可能是由于抗生素无法破坏梭菌或其他细菌产生的孢子。本研究证明了异常肠道细菌的重要性以及长期治疗的困难。Sander et al, Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000 Jul;15(7):429-35.Sander等,口服万古霉素治疗消退型自闭症的短期获益。j儿童神经。2000年7月;15(7):429-35. Research on Gut Bacteria肠道细菌的研究Historically it has been very difficult to assess gut bacteria, because there are about 1000 different types of bacteria in each person’s gut, and standard culture methods can only assess a few dozen of them.However, new DNA-based methods are rapidly changing the ability to assess gut bacteria.历史上,评估肠道细菌非常困难,因为每个人的肠道中大约有1000种不同类型的细菌,标准培养方法只能评估其中的几十种。然而,基于DNA的新方法正在迅速改变评估肠道细菌的能力。 Two small studies by Finegold, et al found some limited evidence of abnormal anaerobic bacteria, primarily increases in clostridia. They did not test for AGNB. A study by Parracho, et al also found increased amounts of clostridia.Finegold等人的两项小型研究发现了一些有限的厌氧菌异常证据,主要是梭状芽孢杆菌增多。他们未检测AGNB。Parracho等人的一项研究也发现梭菌数量增加。Song Y, Liu C, Finegold SM. Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol. 2004 Nov;70(11):6459-65.Song Y, Liu C, Finegold SM.自闭症儿童粪便中梭菌的实时PCR定量分析。应用环境微生物。2004年11月;70(11):6459-65.Finegold et al, Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis. 2002 Sep 1;35 (Suppl 1):S6-S16.Finegold等,晚发型自闭症的胃肠菌群研究。Clin传染Dis。2002年9月1日;35 (Suppl 1):S6-S16。Parracho HM et al., Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.Parracho HM等,自闭症谱系障碍儿童与健康儿童肠道菌群的差异。j医学微生物学。2005年10月;54(Pt 10):987-91。 One study of 58 children with autism vs. 39 controls found that the severity of gut problems strongly correlated with autism severity. Individuals with gut problems had much worse scores on the ATEC subscales of speech, social, sensory cognitive, and health/physical behavior. That study found some abnormalities in gut bacteria, including decreased levels of bifidobacteria (an important beneficial bacteria) in children with autism compared to controls. However, they did not find elevated yeast (by culture or microscopically) in stool samples.一项针对58名自闭症儿童与39名对照儿童的研究发现,肠道问题的严重程度与自闭症的严重程度密切相关。有肠道问题的个体在言语、社会、感觉认知和健康/身体行为的ATEC分量表中得分更低。该研究发现肠道细菌存在一些异常,包括与对照组相比,自闭症儿童体内的双歧杆菌(一种重要的有益菌)水平下降。然而,他们在粪便样本中未发现酵母(通过培养或显微镜检查)升高。Adams JB et al., Gastrointestinal Flora and Gastrointestinal Status in Children with Autism -- Comparisons to Neurotypical Children and Correlation with Autism Severity, BMC Gastroenterology 2011, 11:22 (16 March 2011).亚当斯JB等人,“自闭症儿童的胃肠道菌群和胃肠道状态——与神经典型儿童的比较及与自闭症严重程度的相关性”,BMC胃肠病学2011,11:22(2011年3月16日)。 Two small studies using DNA-based methods to investigate all gut bacteria have been conducted, but yielded dissimilar results – much larger studies are needed. One study (Finegold et al 2011) found increased levels of desulfovibrio bacteria in children with autism, while another study (Williams et al 2012) found Sutterela bacteria in half of the 23 children with autism but not in any of the 9 controls.已经进行了两项使用基于DNA的方法调查所有肠道细菌的小型研究,但得出的结果不同——需要进行更大规模的研究。一项研究(Finegold等人,2011年)发现自闭症儿童中的脱硫弧菌水平升高,而另一项研究(Williams等人,2012年)在23名自闭症儿童中的一半中发现了萨特累拉菌,但在9名对照儿童中均未发现。Finegold SM et al., Pyrosequencing study of fecal microflora of autistic and control children., Anaerobe. 2010 Aug;16(4):444-53. Epub 2010 Jul 9.Finegold SM等人,Pyrosequencing study of fecal microflora of autistic and control children.厌氧菌。2010年8月;16(4):444-53.Epub 2010年7月9日。Williams BL et al., Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS One. 2011;6(9):e24585. Epub 2011 Sep 16.Williams BL等人,Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestinesof children with autism and gastrointestinal disturbances. PLoS One。2011;6(9):e24585。2011年9月16日
Amino Acids氨基酸Rationale: Protein is made of long strands of individual amino acids. When protein is digested properly, digestive enzymes split the long protein molecule into small peptides and individual amino acids, which the body can absorb. Those amino acids can then be reassembled to make a wide array of critical substances, such as neurotransmitters, hormones, enzymes, antibodies,原理:蛋白质由单个氨基酸的长链组成。当蛋白质被适当消化时,消化酶会将长蛋白质分子分解成小肽和单个氨基酸,供身体吸收。然后,这些氨基酸可以重新组合,形成大量的关键物质,如神经递质、激素、酶、抗体,immunoglobulins, glutathione, and many other substances.Amino acids are the “building blocks” of免疫球蛋白、谷胱甘肽和许多其他物质。氨基酸是life.生活。 Some children with autism have self-limited diets that are low in protein, and some have digestive problems that limit their ability to digest protein into individual amino acids. Either of these problems can lead to insufficient amino acids.一些自闭症儿童有低蛋白的自我限制饮食,一些有消化问题,限制了他们将蛋白消化成单个氨基酸的能力。这些问题中的任何一个都可能导致氨基酸不足。 Treatments:治疗:1) Ensure diet contains sufficient protein (two 4-oz servings/day).2) 确保饮食含有足够的蛋白质(每天两份4盎司)。3) Consider digestive enzymes (with proteases and peptidases) to more completely digest the protein into individual amino acids4) 考虑使用消化酶(包括蛋白酶和肽酶)将蛋白质更完全地消化成单个氨基酸5) Give “free-form” amino acids; “free-form” means that the amino acids exist as individual molecules, rather than part of a large protein molecule that needs to be digested. General amino acid supplements are available, and they can also be customized by a compounding pharmacy.6) 给出“游离形式”的氨基酸;“游离形式”是指氨基酸作为单个分子存在,而不是需要消化的大蛋白质分子的一部分。可提供常规氨基酸补充剂,也可由复合药房定制。 Testing:测试:Amino acids can be tested either from blood (when fasting for 10 hours) or from a urine sample (24 hour is best). Fasting blood plasma reveals circulating levels of amino acids related more to metabolism than to diet/digestion. 24-hour urine amino acid analysis shows what’s in excess or not usable and what’s deficient, if kidney transport is normal. Urine has to be interpreted carefully, as high levels in the urine can indicate “wasting” or excessive excretion, resulting in a low body level. Amino acid levels very greatly with age, so it is important to use a lab that has age-specific reference ranges, or the results will be incorrect and misleading.氨基酸可以通过血液(空腹10小时)或尿液样本(最好在24小时)进行检测。空腹血浆显示循环氨基酸水平与代谢的关系大于与饮食/消化的关系。24小时尿氨基酸分析显示,如果肾脏转运正常,哪些是多余的或不可用的,哪些是不足的。必须仔细解读尿液,因为尿液中的高含量可能表明“消耗”或排泄过量,从而导致低身体水平。氨基酸水平与年龄有很大关系,因此使用具有特定年龄参考范围的实验室很重要,否则结果将是不正确和误导的。 It may also be useful to measure levels of neurotransmitters in platelets (blood), as low levels of neurotransmitters can be treated by supplementing with amino acids and vitamins/minerals, allowing the body to build their own.测量血小板(血液)中的神经递质水平也可能有用,因为低水平的神经递质可以通过补充氨基酸和维生素/矿物质来治疗,让身体建立自己的。 Research:研究: One study of 56 children with autism and 45 neurotypical controls of similar age and gender found that the autism group had significantly lower levels of several amino acids, including tryptophan (needed to make serotonin) and phenylalanine and tyrosine (needed to make dopamine). The children with autism also had higher levels of glutamate, an excitatory neurotransmitter, which may relate to seizures, stimming, and other problems in children with autism. There was a lot of variation within the autism group, so individual testing of amino acids is recommended.一项针对56名自闭症儿童和45名年龄和性别相似的典型神经对照的研究发现,自闭症组的几种氨基酸水平显著较低,包括色氨酸(制造血清素所需)和苯丙氨酸及酪氨酸(制造多巴胺所需)。自闭症儿童的谷氨酸盐(一种兴奋性神经递质)水平也较高,这可能与自闭症儿童的癫痫发作、刺激和其他问题有关。自闭症组中有很多变异,因此建议对氨基酸进行单独检测。Adams JB et al., Nutritional and Metabolic Status of Children with Autism vs. Neurotypical Children, and the Association with Autism Severity, Nutr. Metab (Lond) 2011 Jun 8:8(1):34.亚当斯JB等人,“自闭症儿童与神经典型儿童的营养和代谢状态,以及与自闭症严重程度的关系”,Nutr。Metab (Lond) 2011年6月8:8(1):34。 Several other studies of amino acids in children with autism have been conducted, but they have generally been flawed due to small sample size, lack of an overnight fast, and lack of controls of similar age (plasma amino acid levels vary substantially with age).已对自闭症儿童进行了其他几项氨基酸研究,但由于样本量小、缺乏隔夜快速反应和缺乏类似年龄的对照(血浆氨基酸水平随年龄变化很大),这些研究通常存在缺陷。
Carnitine肉碱 Rationale:理由:Carnitine is a substance in the body that carries fuel (long-chain fatty acids) into the mitochondria (energy-producing organelles inside every cell in the body). It also carries potentially toxic organic acids out of the mitochondria and cell so they can be eliminated from the body. Mitochondria produce ATP, a major fuel for the body and the brain. So, carnitine is important for energy production to fuel the body and the brain.肉碱是体内的一种物质,它将燃料(长链脂肪酸)带入线粒体(体内每个细胞内产生能量的细胞器)。它还会将潜在的有毒有机酸带出线粒体和细胞,以便从体内清除。线粒体产生ATP,这是身体和大脑的主要燃料。因此,肉碱是重要的能源生产,以燃料的身体和大脑。 Carnitine can be made by the body to a limited extent, but much of it comes from our diet, especially beef and pork. People who eat limited amounts of beef and pork are at higher risk of carnitine deficiency. Carnitine is widely used as an over-the-counter nutritional supplement, and it is also available by prescription (it is approved by the FDA for treating carnitine deficiency caused by certain genetic diseases).肉碱可以由身体在有限的程度上,但它的大部分来自我们的饮食,尤其是牛肉和猪肉。吃少量牛肉和猪肉的人患肉碱缺乏症的风险更高。肉碱被广泛用作非处方营养补充剂,也可按处方提供(经FDA批准,用于治疗某些遗传性疾病引起的肉碱缺乏症)。 Testing测试Carnitine levels can be measured in the blood, but for children it is important to have a pediatric reference range. (Many labs do not.)可以测量血液中的肉碱水平,但对于儿童来说,有一个儿科参考范围很重要。(许多实验室没有。) If a person is not eating beef or pork, then they are at higher risk of carnitine deficiency (other protein sources, such as chicken, have only 5% or less of the amount of carnitine present in beef). Vegetarians are especially at risk of carnitine deficiency.如果一个人不吃牛肉或猪肉,那么他们就有更高的风险肉碱缺乏症(其他蛋白质来源,如鸡,只有5%或更少的数额肉碱存在于牛肉)。素食者尤其容易出现肉碱缺乏症。 Treatments治疗Carnitine is available as both l-carnitine and acetyl-l-carnitine. Both forms are useful sources of carnitine, and the body can convert them to one another. However, several double-blind, placebo- controlled studies have found that acetyl-l-carnitine is helpful for improving cognitive functioning and memory in adults with Alzheimer’s, so it is possible that the acetyl-l-carnitine form is more beneficial due to the acetyl group, which can help make acetylcholine, an important neurotransmitter. Acetyl-l-carnitine has also been found to be neuroprotective.肉碱可用作l-肉碱和乙酰-l-肉碱。两种形式都是肉碱的有用来源,身体可以将它们相互转化。然而,几项双盲、安慰剂对照研究发现,乙酰-l-肉碱有助于改善阿尔茨海默病成人患者的认知功能和记忆,因此乙酰-l-肉碱形式可能因乙酰基而更有益,乙酰基有助于生成乙酰胆碱(一种重要的神经递质)。乙酰-l-肉碱也被发现具有神经保护作用。 The amount used in the autism treatment study by Geier et al 2010 (see below) was 50 mg L- carnitine/kg bodyweight/day up to 1 g/day, and dosages of 0.5 to 2 g/day are common. We suggest starting at a lower dosage, and gradually increasing over several weeks.Geier等人2010年的自闭症治疗研究(见下文)中使用的剂量为50 mg L-肉碱/kg体重/天,最高1g/天,常用剂量为0.5至2g/天。我们建议从较低的剂量开始,并在几周内逐渐增加。 About 60% of carnitine in food is absorbed, vs. only about 15% from supplements. So, consuming 9 oz of beef or 1 g of carnitine supplement results in about the same absorption of carnitine.食物中约60%的肉碱被吸收,而补充剂中只有约15%。因此,食用9盎司牛肉或1克肉碱补充剂会导致肉碱的吸收大致相同。Physicians Desk Reference (PDR) for Nutritional Supplements, 2001, P. 255.《营养补充剂的医师案头参考》(PDR),2001年,第255页。 Safety安全A study by Geier et al (2011) found that carnitine supplementation was generally very well- tolerated, with rare side effects of irritability and stomach discomfort, and only 1 of 19 children withdrew due to side-effects. The risk of adverse effects may be reduced by gradually phasing in the dosage over several weeks. A 1-g dose of carnitine is about equivalent to eating a half-poundGeier等人(2011年)的一项研究发现,肉碱补充剂通常具有很好的耐受性,伴有过敏性和胃部不适等罕见副作用,19名儿童中只有1名因副作用而退出。通过在几周内逐渐分阶段增加剂量,可以降低不良作用的风险。1-g剂量的肉碱大约相当于吃半磅
of steak, which is not a significant concern. Common adverse effects include diarrhea and fishy smelling stools.牛排,这不是一个重要的问题。常见的不良反应包括腹泻和有鱼腥味的粪便。 Research研究 Several studies have suggested that mitochondrial disorders are common in children with autism – see review by Rossignol DA and Frye RE, Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry. 2012 Mar;17(3):290-314.几项研究表明线粒体障碍在自闭症儿童中很常见——参见Rossignol DA和Frye RE的综述,Mitochondrial dysfunction in autism spectrum disorders: asystematic review and meta-analysis. Mol精神病学。2012年3月;17(3):290-314. Note that the term “mitochondrial disorders” is used to denote a generalized impairment of请注意,术语“线粒体障碍”用于表示mitochondrial function, and are generally not as severe as “mitochondrial disease,” which involves specific severe genetic abnormalities. One important factor for normal mitochondrial function is carnitine, which transports fatty acids into the mitochondria for energy production. However, mitochondrial disorders can be caused by many factors, and carnitine deficiency is only one possibility.线粒体功能,并且通常不像“线粒体疾病”那样严重,所述“线粒体疾病”涉及特定的严重遗传异常。线粒体功能正常的一个重要因素是肉碱,它将脂肪酸转运到线粒体中以产生能量。然而,线粒体疾病可由多种因素引起,肉碱缺乏只是其中一种可能性。 One study found decreased levels of carnitine in children with autism (Filipek et al 2004); however, that study only compared against laboratory reference ranges, which are of limited validity.一项研究发现自闭症儿童的肉碱水平降低(Filipek等人,2004年);然而,该研究仅与有限有效性的实验室参考范围进行比较。Filipek et al., Relative carnitine deficiency in autism. J Autism Dev Disord. 2004 Dec;34(6):615-23.Filipek等,自闭症中的相对肉碱缺乏症。J Autism Dev Disord. 2004年12月;34(6):615-23. A recent double-blind, placebo-controlled 3-month study (n=30) found that supplementation with carnitine was beneficial. Specifically, that study found significantly greater improvements in the Childhood Autism Rating Scale (CARS) and Clinical Global Impressions (CGI) scores in the treatment group compared to the placebo group. In addition, scores significantly improved in cognition, marginally in speech, and non-significantly in total and sociability scores on the ATEC. L-carnitine therapy significantly increased serum carnitine concentrations, and significant correlations between changes in serum free-carnitine levels and positive clinical changes were observed. Study subjects generally tolerated L-carnitine therapy.最近一项为期3个月的双盲、安慰剂对照研究(n=30)发现,补充肉碱有益。具体而言,该研究发现,与安慰剂组相比,治疗组的儿童孤独症评定量表(CARS)和临床总体印象(CGI)评分有明显更大的改善。此外,在ATEC测验中,认知得分显著提高,言语得分略有提高,总体和社交得分无显著提高。左卡尼汀治疗显著升高了血清肉碱浓度,并且观察到血清游离肉碱水平的变化与阳性临床变化之间存在显著相关性。研究对象普遍耐受左旋肉碱治疗。Geier DA et al., A prospective double-blind, randomized clinical trial of levocarnitine to treat autism spectrum disorders. Med Sci Monit 2011 Jun;17(6):PI15-23.Geier DA等,左卡尼汀治疗自闭症谱系障碍的前瞻性、双盲、随机临床试验。医学科学杂志2011年6月;17(6):PI15-23。 Overall, the literature suggests that mitochondrial disorders are common in autism, and carnitine supplementation may help improve mitochondrial function. Other supplements for mitochondrial therapy include vitamins, minerals, CoEnzyme Q10, and essential fatty acids, which work together to improve mitochondrial function.总的来说,文献表明线粒体疾病在自闭症中很常见,补充肉碱可能有助于改善线粒体功能。线粒体疗法的其他补充剂包括维生素、矿物质、辅酶Q10和必需脂肪酸,它们共同改善线粒体功能。
Melatonin褪黑激素Rationale: Many children and adults with autism have sleep problems, including falling asleep, nighttime waking, and early waking. These sleep problems have a strong correlation with gut problems, and healing the gut seems to reduce many of those sleep problems.理由:许多自闭症儿童和成人有睡眠问题,包括入睡、夜间醒来和早醒。这些睡眠问题与肠道问题有很强的相关性,愈合肠道似乎可以减少许多这些睡眠问题。However, if sleep problems continue, supplementation with melatonin can help. Melatonin is the hormone the body naturally produces at nighttime to regulate sleep. It is formed from the neurotransmitter serotonin, so low serotonin levels can cause low melatonin levels.然而,如果睡眠问题继续存在,补充褪黑素可以有所帮助。褪黑激素是人体在夜间自然产生的调节睡眠的激素。它是由神经递质血清素形成的,因此血清素水平低会导致褪黑素水平低。 Testing: The best test for melatonin is simply a trial of it, if a person has continuing sleep problems not due to other causes (see below).检测:如果一个人持续存在并非由其他原因引起的睡眠问题(见下文),褪黑素的最佳检测方法就是对其进行简单的试验。 Treatment: Melatonin production is reduced by light, and even a simple nightlight can greatly decrease melatonin production. So, first try eliminating all sources of light.治疗:光线会降低褪黑激素的产生,即使是简单的夜灯也能大大降低褪黑激素的产生。所以,首先尝试消除所有光源。 For problems falling asleep, first try a behavioral approach, including a regular nighttime routine (at a fixed time, begin bath/shower, brush teeth, story, etc.). Also, be sure to eliminate caffeine and reduce sugar intake at nighttime.对于入睡问题,首先尝试一种行为方式,包括常规的夜间活动(在固定的时间,开始洗澡/淋浴、刷牙、讲故事等)。).此外,一定要消除咖啡因,减少夜间的糖摄入量。 If sleep problems persist, start with 1 mg of melatonin (0.5 mg for children), and increase up to 2-5 mg if necessary (1-5 mg for children). If waking occurs during the night, then try a time-release form rather than increasing the dose. 2 mg time-release can be better than 5 mg all at once.如果睡眠问题持续存在,从1 mg褪黑激素开始(儿童为0.5 mg),必要时增加至2-5 mg(儿童为1-5 mg)。如果在夜间醒来,则尝试时间释放形式,而不是增加剂量。2 mg的时间释放比5 mg一次释放要好。However, in general it is not effective for night time waking, so other treatments may be necessary if time-release melatonin is not effective.然而,一般来说,它对夜间醒来无效,因此,如果时间释放褪黑激素无效,则可能需要其他治疗。 Safety: Melatonin seems to be exceptionally safe; high dosages in animals produce no toxicity, and a study of 1400 women taking 75 mg/day for up to 4 years with no adverse effects. Children with autism have been documented taking up to 25mg at bedtime without adverse effects. In fact, animal studies suggest that long-term use of melatonin can increase lifespan 20%, presumably due to its strong antioxidant effect.安全性:褪黑素似乎格外安全;在动物中高剂量不产生毒性,并且一项对1400名妇女服用75毫克/天长达4年而没有不良作用的研究。已有记录表明,自闭症儿童在就寝时最多可服用25mg,且无不良作用。事实上,动物研究表明,长期使用褪黑激素可以延长20%的寿命,这大概是由于其强大的抗氧化作用。One study of children with ADHD and insomnia who were followed for approximately 4 years revealed no serious adverse effects associated with long-term use of melatonin; after 4 years, 65% still used it regularly, 12% occasionally, and 9% no longer needed it.一项针对ADHD和失眠儿童的研究(随访约4年)显示,长期使用褪黑激素无严重不良作用;4年后,65%仍定期使用,12%偶尔使用,9%不再需要。Hoebert M, et al. "Long-term follow-up of melatonin treatment in children with ADHD and chronic sleep onset insomnia". J. Pineal Res. 47 (1): 1–7. 2009Hoebert M,等,“褪黑素治疗多动症和慢性睡眠发作性失眠患儿的长期随访”。j . Pineal RES . 47(1):1-7。2009 Research研究Melatonin problems have been extensively studied in children with autism, and there are nine studies that found abnormalities in melatonin levels and/or melatonin cycle in children with autism. Five randomized, double-blind, placebo-controlled trials have been conducted, and Rossignol and Frye conducted a meta-analysis of those five studies. They found that melatonin improved falling asleep and sleep duration (30 minutes more than placebo), but not night-time awakening. The side effects of melatonin were reported to be minimal or none.对自闭症儿童的褪黑激素问题进行了广泛研究,有9项研究发现自闭症儿童的褪黑激素水平和/或褪黑激素周期异常。已经进行了五项随机、双盲、安慰剂对照试验,Rossignol和Frye对这五项研究进行了荟萃分析。他们发现褪黑激素改善了入睡和睡眠时间(比安慰剂多30分钟),但没有改善夜间觉醒。据报告,褪黑激素的副作用很小或没有。 ARI Survey of Parent Ratings of Treatment Efficacy:父母对治疗疗效评定的ARI调查:
% Worse% No Change% BetterNumber of Reports
Melatonin8%26%66%1687
%更糟%无更改%更好报告数量
褪黑激素8%26%66%1687
Overall, melatonin seems like a safe and effective therapy for sleep problems for many children with autism.总的来说,褪黑素似乎是一种安全有效的治疗许多自闭症儿童睡眠问题的药物。
For more info, see the review by Rossignol and Frye, Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev Med Child Neurol 2011 Sep;53(9):783-92.更多信息,请参阅Rossignol和Frye的评论,Melatonin in autism spectrum disorders: asystematic review and meta-analysis. Dev Med Child Neurol 2011年9月;53(9):783-92.
Thyroid Supplementation甲状腺补充剂Rationale: About 5-10% of the general population has a thyroid disorder requiring supplementation, and that percentage may be higher in autism. Poor thyroid function due to lack of iodine is the major cause of mental retardation in the world, resulting in over 80 million cases of mental retardation, and decreased energy level. Poor thyroid function can be caused by other factors as well.基本原理:大约5-10%的普通人群患有需要补充的甲状腺疾病,自闭症患者中这一比例可能更高。碘缺乏导致的甲状腺功能低下是世界范围内智力低下的主要原因,导致8000万以上的智力低下病例,并且能量水平下降。甲状腺功能不良也可由其他因素引起。 Iodine is required for normal thyroid functioning, and a major national study (NHANES) found that levels of iodine fell more than 50% from the early 1970’s to the early 1990’s, presumably due to decreased use of table salt (which is one of the major sources of iodinized salt). Non-iodinized salt is used in most processed foods (potato chips, crackers, etc). Therefore, iodine deficiency is an increasing concern today.碘是正常甲状腺功能所必需的,一项重大国家研究(NHANES)发现,从20世纪70年代初到90年代初,碘的水平下降了50%以上,这大概是由于食用食盐(碘盐的主要来源之一)的减少。大多数加工食品(薯片、饼干等)都使用非碘盐。因此,碘缺乏是一个日益关注的今天。file:///C:/Users/liang/AppData/Local/Temp/ksohtml12396/wps572.pngHollowell, JG et al., ‘Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from National Health and Nutrition Examination Surveys I and III (1971-1974 and 1988- 1994)’, J Clin Endocrinol Metab 83(10): 3401-8 (1998).file:///C:/Users/liang/AppData/Local/Temp/ksohtml12396/wps573.pngHollowell,JG等,“美国的碘营养”。趋势和公共健康意义:来自国家健康和营养检查调查I和III (1971-1974和1988- 1994)的碘排泄数据,J Clin内分泌代谢83(10): 3401-8 (1998)。 Testing:测试:If individuals do not use iodinized salt or take a vitamin/mineral supplement containing iodine, then they are at high risk of iodine deficiency.如果个人不使用碘盐或服用含碘的维生素/矿物质补充剂,那么他们患碘缺乏病的风险很高。 The most accurate testing is a blood measurement of thyroid hormones and iodine level.最准确的检测是对甲状腺激素和碘水平进行血液测量。 Thyroid hormone is measured as part of the newborn screening to rule out congenital hypothyroidism and to start treatment early in life if necessary, in order to prevent mental retardation. If a child has not had a newborn screening test or has symptoms of hypothyroidism in infancy, it is important to check thyroid hormones immediately.测量甲状腺激素是新生儿筛查的一部分,以排除先天性甲状腺功能减退,并在必要时尽早开始治疗,以预防智力低下。如果儿童没有进行新生儿筛查或在婴儿期有甲状腺功能减退症状,立即检查甲状腺激素很重要。 A simple initial assessment can be done by measuring body temperature before waking. A low body temperature is a possible indicator of too low a level of thyroid function. Overall low energy/activity, low muscle tone, constipation, brittle hair, dry hair and developmental delays can also be a possible indicator of a thyroid problem, but could be caused by other factors also.一个简单的初步评估可以通过在醒来之前测量体温来完成。体温过低可能表明甲状腺功能水平过低。总体低能量/活动、低肌张力、便秘、头发脆性、头发干燥和发育迟缓也可能是甲状腺问题的指标,但也可能由其他因素引起。 Treatment:治疗:If iodine levels are low, then one can begin with iodine supplementation. If that does not normalize thyroid levels, then one can consider thyroid supplements. We recommend natural thyroid supplements derived from animals, as they will provide a complete thyroid source (both T3 and T4 hormones). Synthetic thyroid supplements contain only T4.如果碘水平低,那么可以从补碘开始。如果这不能使甲状腺水平正常化,那么可以考虑甲状腺补充剂。我们建议使用动物来源的天然甲状腺补充剂,因为它们可提供完整的甲状腺来源(T3和T4激素)。合成甲状腺补充剂仅含T4。 It is important to treat low thyroid conditions as early as possible, to prevent the risk of mental retardation.尽早治疗甲状腺功能低下非常重要,可预防智力低下的风险。 Some individuals have thyroid dysfunction due to thyroid autoantibodies or congenital abnormalities in thyroid development, so an evaluation by an endocrinologist is important if abnormalities in thyroid function are suspected.有些人因甲状腺自身抗体或先天性甲状腺发育异常而出现甲状腺功能障碍,因此,如果怀疑甲状腺功能异常,内分泌学家的评估很重要。
Duration:持续时间:Usually 1-2 months of supplementation are needed to observe an increase in energy level and body temperature. Supplementation may be needed long term unless the problem with thyroid development is resolved.通常需要1-2个月的补充才能观察到能量水平和体温的升高。除非甲状腺发育问题得到解决,否则可能需要长期补充。 SAFETY CAUTION: Too much thyroid hormone can cause weight loss, anxiety and other problems, so thyroid levels should be monitored regularly if taking a supplement.安全注意事项:过多的甲状腺激素会导致体重减轻、焦虑和其他问题,因此如果服用补充剂,应定期监测甲状腺水平。 Research:研究:. There have been several studies of thyroid function and autism.。已经有几项关于甲状腺功能和自闭症的研究。 One study reported a high incidence of thyroid abnormalities in parents of children with autism一项研究报告了自闭症儿童父母中甲状腺异常的高发生率Megson MN. Is autism a G-alpha protein defect reversible with natural vitamin A? Med Hypotheses. 2000 Jun;54(6):979-83.Megson MN。自闭症是一种G-α蛋白缺陷,使用天然维生素A可以逆转吗?医学假设。2000年6月;54(6):979-83. One study found abnormal thyroid function in young adults with severe autism correlated with impaired verbal communication.一项研究发现,患有严重自闭症的年轻人甲状腺功能异常与言语交流受损相关。Nir I et al., Brief report: circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism. J Autism Dev Disord. 1995 Dec;25(6):641-54.Nir I等人,简要报告:年轻自闭症成人血清中的昼夜褪黑素、促甲状腺激素、催乳素和皮质醇水平。j自闭症发展障碍。1995年12月;25(6):641-54. One study found reduced levels of thyroid hormones (TSH) in children with autism (n=41) vs. controls.一项研究发现,与对照组相比,自闭症儿童(n=41)的甲状腺激素(TSH)水平降低。Hashimoto T et al., Reduced thyroid-stimulating hormone response to thyrotropin-releasing hormone in autistic boys. Dev Med Child Neurol. 1991 Apr;33(4):313-9.桥本等人,自闭症男孩对促甲状腺素释放激素的促甲状腺激素反应降低。Dev Med Child Neurol。1991年4月;33(4):313-9. There was also one small study (n=14) that found normal levels of TSH in children with autism, but that study did not have a control group.还有一项小型研究(n=14)发现自闭症儿童的TSH水平正常,但该研究没有对照组。Abbassi V et al., Triiodothyronine (T3) concentration and therapy in autistic children. J Autism Child Schizophr. 1978 Dec;8(4):383-7.Abbassi V .等,自闭症儿童中三碘甲状腺原氨酸(T3)的浓度和治疗。j自闭症儿童精神分裂症。1978年12月;8(4):383-7. One study found that many children with autism have unusually low levels of iodine in their hair, which possibly suggests a low level in their body and need for more.一项研究发现,许多自闭症儿童头发中的碘水平异常低,这可能表明他们体内的碘水平低,需要更多。Adams JB et al., Analyses of toxic metals and essential minerals in the hair of Arizona children with autism and associated conditions, and their mothers. Biol Trace Elem Res. 2006 Jun;110(3):193-209.亚当斯JB等人,亚利桑那州自闭症和相关疾病儿童及其母亲头发中的有毒金属和必需矿物质分析。Biol Trace Elem Res. 2006 Jun110(3):193-209. One study found that most children with autism had normal levels of iodine in their urine (normalized by creatinine) compared to controls, but 25% of the children with autism had unusually low levels (below the reference range).一项研究发现,与对照组相比,大多数自闭症儿童的尿碘水平(按肌酐标准化)正常,但25%的自闭症儿童的尿碘水平异常低(低于参考范围)。Adams JB et al., Nutritional and Metabolic Status of Children with Autism vs. Neurotypical Children, and the Association with Autism Severity, Nutr. Metab (Lond) 2011 Jun 8:8(1):34.亚当斯JB等人,“自闭症儿童与神经典型儿童的营养和代谢状态,以及与自闭症严重程度的关系”,Nutr。Metab (Lond) 2011年6月8:8(1):34。 Overall, the reports of abnormal thyroid function in most of the studies are consistent with findings of low iodine, and it is possible that impaired thyroid function is a cause of some of the symptoms of autism in some children, especially language impairment and mental retardation.总体而言,大多数研究中关于甲状腺功能异常的报告与低碘的结果一致,甲状腺功能受损可能是某些儿童出现自闭症某些症状的原因,尤其是语言障碍和智力低下。
Sulfation硫酸盐化作用Rationale: Sulfate is used for many functions in the body, including detoxification, maintaining the lining of the gut, and hormone production. Some children with autism have a low level of sulfate in their bodies due to a variety of reasons, including poor absorption in the gut, excess loss in the urine, or poor recycling of sulfate by the kidney, or oxidant stress and inflammation can shut down cysteine dioxygenase, which throttles the cysteine -> sulfate route.基本原理:硫酸盐用于体内的多种功能,包括解毒、维持肠道内壁和产生激素。一些自闭症儿童体内的硫酸盐水平较低,原因有多种,包括肠道吸收不良、尿液流失过多或肾脏对硫酸盐的再循环不良,或者氧化剂应激和炎症可以关闭半胱氨酸双加氧酶,从而抑制半胱氨酸->硫酸盐途径。 Testing: Blood testing can be used to check for levels of free and total plasma sulfate, and this is probably the more reliable test. Plasma cysteine can also be informative. (Urine testing of free and total sulfate may be useful to look for excessive loss of sulfate, but this is only one of several possible causes of low sulfate in the body, and should not be solely relied on to assess sulfate status).检测:血液检测可用于检查游离和总血浆硫酸盐的水平,这可能是更可靠的检测。血浆半胱氨酸也可提供信息。(尿液游离和总硫酸盐检测可能有助于发现硫酸盐的过度损失,但这仅是体内硫酸盐含量低的几个可能原因之一,不应仅依赖于此来评估硫酸盐状态)。 Alternatively, since Epsom salt baths are very safe, one could simply try them for up to several weeks and look for improvements in behavior and functioning (see below).或者,由于爱普生盐浴非常安全,人们可以简单地尝试几周,观察行为和功能的改善(见下文)。 Treatment:治疗:Tapan Audhya evaluated many different ways to increase plasma sulfate levels in children with autism who had low levels. The two most effective methods were oral MSM (500-2000 mg depending on size and sulfate level) and Epsom Salt (magnesium sulfate) baths – 2 cups of Epsom salts in warm/hot water, soak for 20 minutes, 2-3x/week. A few children did not tolerate MSM, but Epsom salt baths are generally very well tolerated.Tapan Audhya评估了提高低水平自闭症儿童血浆硫酸盐水平的多种不同方法。两种最有效的方法是口服MSM (500-2000 mg,取决于大小和硫酸盐水平)和Epsom Salt(硫酸镁)浴-在温水/热水中浸泡2杯Epsom盐20分钟,每周2-3次。少数儿童不耐受MSM,但Epsom盐浴一般耐受良好。T. Audhya, Role of Sulfation, presentation at Autism/Asperger’s Conference in Anaheim, CA, FebruaryT.Audhya,硫酸盐化的作用,在2月于CA Anaheim召开的自闭症/阿斯伯格会议上的发言2007.2007. Many parents and physicians have anecdotally reported that Epsom salt baths were beneficial to their children. However, there is less experience with MSM for children with autism, and more research is needed.许多父母和医生都有轶事报道,爱普生盐浴对他们的孩子有益。然而,针对自闭症儿童的MSM经验较少,需要更多的研究。 Research – Sulfate and Autism研究——硫酸盐与自闭症Sulfur is the fourth most common mineral in the body . Most sulfate is produced in vivo by metabolism of cysteine . Sulfation is important for many reactions, including detoxification, inactivation of catecholamines, synthesis of brain tissue, sulfation of mucin proteins which line the gastrointestinal tract, and more. The measurement of total plasma sulfate involves many substances in the plasma, including neurotransmitters, steroids, glycosaminoglycans, phenols, amino acids, peptides, and other molecules.硫是人体内第四常见的矿物质[常,2007]。大多数硫酸盐是通过半胱氨酸的代谢在体内产生的。硫酸盐化对许多反应都很重要,包括解毒、儿茶酚胺失活、脑组织合成、胃肠道粘蛋白硫酸盐化等。血浆总硫酸盐的测定涉及血浆中的多种物质,包括神经递质、类固醇、糖胺聚糖、酚类、氨基酸、肽类等分子。 Low free and total plasma sulfate in children with autism has been reported in three studies , and is consistent with four studies which found that children with ASD had a significantly decreased sulfation capacity compared to controls, based on decreased ability to detoxify paracetamol (acetaminophen, the active ingredient in Tylenol). The finding of low plasma sulfate is also consistent with a large study that found high sulfate in the urine of children with autism , as sulfate wasting in the urine partly explains low levels in the plasma.三项研究报告了自闭症儿童血浆中低游离和总硫酸盐,该研究发现,与对照组相比,患有ASD的儿童的硫酸盐化能力显著降低,其原因是对乙酰氨基酚(泰诺中的活性成分对乙酰氨基酚)的解毒能力下降。血浆硫酸盐水平低的发现也与一项大型研究一致,该研究发现自闭症儿童的尿液中硫酸盐水平高,因为尿液中的硫酸盐浪费可以部分解释血浆中硫酸盐水平低的原因。
Research – Treatment研究–治疗One study also reported high levels of urinary sulfite in children with autism, suggesting that there was a problem of converting sulfite to sulfate in the mitochondria. In 38% of cases (14/38) urinary sulfite and sulfate levels improved by giving 50 mcg of molybdenum (an essential mineral), presumably since the enzyme for converting sulfite to sulfate (sulfite oxidase) contains molybdenum.一项研究也报告了自闭症儿童尿中高水平的亚硫酸盐,提示线粒体中存在将亚硫酸盐转化为硫酸盐的问题。在38%的病例(14/38)中,通过给予50 mcg钼(一种必不可少的矿物质)改善了尿中的亚硫酸盐和硫酸盐水平,推测是因为将亚硫酸盐转化为硫酸盐的酶(亚硫酸盐氧化酶)含有钼。 One study involved treatment with a multi-vitamin/mineral supplement that included molybdenum and MSM. After three months of treatment, there was a substantial increase in both free and total sulfate in the plasma, but levels were still below normal. This suggests that additional treatment, such as Epsom salt baths, are necessary to normalize sulfate levels.一项研究[亚当斯等人,2011年]涉及多种维生素/矿物质补充剂的治疗,其中包括钼和MSM。治疗3个月后,血浆中游离和总硫酸盐均大幅升高,但水平仍低于正常值。这表明,有必要进行额外治疗,如爱普生盐浴,以使硫酸盐水平正常化。 References参考Chang, Raymond Chemistry, Ninth Edition, 2007. McGraw-Hill. p. 52.常,雷蒙德·化学,第九版,2007。麦格劳-希尔。第52页。Stipanuk MH, Ueki I. Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur. J Inherit Metab Dis. 2011 Feb;34(1):17-32. Epub 2010 Feb 17.Stipanuk MH, Ueki I.处理蛋氨酸/同型半胱氨酸硫:半胱氨酸向牛磺酸和无机硫的代谢。J Inherit Metab Dis. 2011年2月;34(1):17-32.Epub 2010年2月17日Waring RH, Ngong JM, Klovrza L, Green S, Sharp H: Biochemical Parameters in Autistic Children. Dev Brain Dysfunct 1997, 10:40-43.Waring RH,Ngong JM,Klovrza L,Green S,Sharp H:自闭症儿童的生化参数。Dev脑功能障碍1997,10:40-43。Geier DA, Kern JK, Garver CR, Adams JB, Audhya T, Geier MR: A prospective study of transsulfuration biomarkers in autistic disorders. Neurochem Res. 2009, 34(2):386-93. Erratum in: Neurochem Res. 2009, 34(2):394.Geier DA,Kern JK,Garver CR,Adams JB,Audhya T,Geier MR:A prospective study of transsulfurationbiomarkers in autistic disorders.Neurochem Res. 2009,34(2):386-93。勘误表:Neurochem Res. 2009,34(2):394。O’Reilly BA and Warning RH: Enzyme and Sulphur Oxidation Deficiencies in Autistic Children with Known Food/Chemical Sensitivities. J. Orthomolecular Medicine 1993, 8(4):198-200.O'Reilly BA和警告RH:具有已知食物/化学敏感性的自闭症儿童中的酶和硫氧化缺陷。j .正交分子医学1993,8(4):198-200。Alberti A, Pirrone P, Elia M, Waring RH, Romano C, Alberti A, Pirrone P, Elia M, Waring RH, Romano C: Sulphation deficit in "low-functioning" autistic children: a pilot study. Biol Psychiatry. 1999, 46(3):420-4.Alberti A,Pirrone P, Elia M, Waring RH, Romano C,Alberti A,Pirrone P,Elia M,Waring RH,Romano C:“低功能”自闭症儿童的硫酸盐化缺陷:一项试点研究。Biol精神病学。1999, 46(3):420-4.Horvath K and Perman JA: Autistic disorder and gastrointestinal disease. Curr Opin Pediatr 2002, 14:583-587. Waring RH and Klovrza LV: Sulfur Metabolism in Autism. J. Nutritional & Environmental Medicine 2000, 10:25-霍瓦特K和Perman JA:自闭症和胃肠疾病。Curr Opin Pediatr 2002,14:583-587。Waring RH和Klovrza LV:自闭症中的硫代谢。j .营养与环境医学2000,10:25-32.32.
Therapies for Methylation/Glutathione/Oxidative Stress甲基化/谷胱甘肽/氧化应激疗法 Rationale: Many children with autism have impairments in methylation, glutathione, and oxidative stress, which are all closely connected metabolically (see figures 1 and 2).理由:许多自闭症儿童存在甲基化、谷胱甘肽和氧化应激损伤,这些损伤在代谢上密切相关(见图1和图2)。 Methylation is the process of donating a methyl group (CH3, or a carbon atom with three hydrogens attached) to another molecule, like DNA, RNA, proteins, phospholipids, and neurotransmitters, which basically can turn them on or off. The primary methyl donor in the body is SAM (S- adenosylmethionine), and several studies have shown it to be low in autism.甲基化是将一个甲基(CH3,或一个带有三个氢原子的碳原子)提供给另一个分子的过程,如DNA、RNA、蛋白质、磷脂和神经递质,这些分子基本上可以打开或关闭它们。体内主要的甲基供体是SAM (S-腺苷甲硫氨酸),多项研究显示其在自闭症中的水平较低。 Glutathione is the primary antioxidant in the body, and it is also an important defense against toxic metals (it binds to them and is excreted with them in the bile and urine). It also indirectly supports many metabolic reactions, including DNA synthesis/ repair and protein synthesis. Every cell in the body and every system in the body is affected by glutathione, especially the immune system, nervous system, gastrointestinal tract, and lungs. Glutathione is a tri-peptide made from three amino acids – cysteine, glycine, and glutamate, and is the major antioxidant and detoxification system in cells. The amount of cysteine precursor is usually the limiting factor in how much glutathione is made by the body. Some cysteine is made from SAM, so low levels of SAM can result in low levels of cysteine. Several studies have found that children with autism have low cysteine and low glutathione, probably due in part to low SAM.谷胱甘肽是体内主要的抗氧化剂,也是抵抗有毒金属的重要防御物(它与有毒金属结合,随有毒金属排泄到胆汁和尿液中)。它还间接支持许多代谢反应,包括DNA合成/修复和蛋白质合成。谷胱甘肽影响身体的每个细胞和系统,尤其是免疫系统、神经系统、胃肠道和肺。谷胱甘肽是由半胱氨酸、甘氨酸和谷氨酸三个氨基酸组成的三肽,是细胞内主要的抗氧化和解毒系统。半胱氨酸前体的量通常是机体产生多少谷胱甘肽的限制因素。一些半胱氨酸是由SAM制成的,因此SAM水平低时,半胱氨酸水平也会低。几项研究发现,自闭症儿童的半胱氨酸和谷胱甘肽水平较低,部分原因可能是SAM水平较低。 Oxidative stress occurs when too many free radicals are produced and glutathione antioxidant capacity is insufficient. Free radicals are highly-reactive molecules that can attack any cell in the body, interfering with their function and causing damage. One common cause is when mitochondria (energy-producing organelles in every cell of the body) are functioning incorrectly when they “burn” oxygen when it reacts with “fuel” (sugars, fats, etc) to make energy. Glutathione and other anti-oxidants can reduce oxidative stress by quenching free radicals, but they need to be recycled after each time they act. Several studies have demonstrated that children with autism often have impaired mitochondrial function, impaired glutathione recycling, and increased oxidative stress.氧化应激发生在自由基生成过多,谷胱甘肽抗氧化能力不足的时候。自由基是高反应性分子,可以攻击体内任何细胞,干扰其功能并造成损害。一个常见的原因是,当线粒体(身体每个细胞中产生能量的细胞器)在与“燃料”(糖、脂肪等)反应产生能量时“燃烧”氧气,从而导致功能不正常。谷胱甘肽和其他抗氧化剂可以通过淬灭自由基来减少氧化应激,但它们在每次作用后都需要回收。几项研究表明,自闭症儿童通常具有线粒体功能受损、谷胱甘肽再循环受损和氧化应激增加的情况。 Treatment:治疗:There are many ways to improve SAM, glutathione, and oxidative stress, but some are more effective than others. They include:有很多方法可以改善SAM、谷胱甘肽和氧化应激,但有些方法比其他方法更有效。它们包括: Less-effective methods:低效方法:1) Oral glutathione: Only about 10% of oral glutathione is absorbed, so this method is not very effective at raising body levels. One small study of children with autism found that oral doses of 15 mg/kg bodyweight led to a 19% increase in reduced (active) glutathione in plasma, and increased the total level of glutathione in whole blood by 12%. However, it did not improve the level of oxidized glutathione in plasma, so oxidative stress was still high.2) 口服谷胱甘肽:口服谷胱甘肽只有10%左右被吸收,所以这种方法在提高身体水平方面不是很有效。一项针对自闭症儿童的小型研究发现,口服15 mg/kg体重可使血浆中的还原型(活性)谷胱甘肽增加19%,并使全血中的谷胱甘肽总水平增加12%。但并未改善血浆中氧化型谷胱甘肽的水平,故氧化应激仍然较高。Kern JK et al., A clinical trial of glutathione supplementation in autism spectrum disorders. Med Sci Monit 2011 Dec 1;17(12):CR677-682Kern JK等,一项补充谷胱甘肽治疗自闭症谱系障碍的临床试验。Med Sci Monit 2011年12月1日;17(12):CR677-682 3) Transdermal glutathione: Glutathione is a relatively large molecule, and is not easily absorbed through the skin. One small study of 13 children found that a transdermal dose of 350-500 mg4) 经皮谷胱甘肽:谷胱甘肽是一种相对较大的分子,不易通过皮肤吸收。一项针对13名儿童的小型研究发现,350-500毫克
led to an 11% increase in reduced (active) glutathione in plasma, and a 9% increase in the level of total glutathione in whole blood. However, there was little change in the level of oxidized glutathione in plasma (4% decrease).导致血浆中还原型(活性)谷胱甘肽增加11%,全血中总谷胱甘肽水平增加9%。但血浆中氧化型谷胱甘肽水平变化不大(下降4%)。Kern JK, et al., A clinical trial of glutathione supplementation in autism spectrum disorders. Med Sci Monit 2011 Dec 1;17(12):CR677-682Kern JK,等,一项补充谷胱甘肽治疗自闭症谱系障碍的临床试验。Med Sci Monit 2011年12月1日;17(12):CR677-682 5) IV glutathione: One study of high-dose intravenous glutathione found that it did raise levels, but that the half-life in the body was only about 20 minutes, so it does not last long (but the effects probably last longer).6) 静脉注射谷胱甘肽:一项关于大剂量静脉注射谷胱甘肽的研究发现,它确实会升高谷胱甘肽水平,但在体内的半衰期仅为20分钟左右,因此持续时间不长(但影响可能会持续更长时间)。Aebi S et al., High-dose intravenous glutathione in man. Pharmacokinetics and effects on cyst(e)ine in plasma and urine. European Journal of Clinical Investigation 1991, 21:103-110.Aebi S等,人高剂量静脉注射谷胱甘肽。血浆和尿中囊肿(e)ine的药代动力学和影响。欧洲临床研究杂志1991,21:103-110。 More effective methods更有效的方法1) Vitamin C: 500 mg of vitamin C was found to raise RBC glutathione levels 50% in college students.2) 维生素C:发现500毫克维生素C可使大学生的红细胞谷胱甘肽水平提高50%。Johnston et al, Vitamin C elevates red blood cell glutathione in healthy adults. Am J Clin Nutr. 1993 Jul;58(1):103-5.Johnston等,维生素C可升高健康成人的红细胞谷胱甘肽。Am J Clin Nutr。1993年7月;58(1):103-5. 3) Folinic Acid/TMG/methyl-B12: A treatment study of 8 young children with autism found that 800 mcg of folinic acid and 1000 mg of TMG normalized SAM and partially improved levels of cysteine, total glutathione in plasma, and ratio of oxidized to total glutathione. Adding subcutaneous injections of Vitamin B12 (methyl-cobalamin) resulted in normalization of levels of SAM, cysteine, total glutathione in plasma, and the ratio of oxidized to total glutathione levels.4) 亚叶酸/TMG/甲基-B12:一项针对8名自闭症幼儿的治疗研究发现,800 mcg的亚叶酸和1000 mg的TMG使SAM恢复正常,并部分改善了血浆中的半胱氨酸、总谷胱甘肽以及氧化型谷胱甘肽与总谷胱甘肽的比率。增加皮下注射维生素B12(甲基钴胺素)使血浆中SAM、半胱氨酸、总谷胱甘肽的水平以及氧化型谷胱甘肽与总谷胱甘肽的水平比值恢复正常。James SJ, Cutler et al., Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004, 80(6):1611-7.James SJ,Cutler等,自闭症儿童氧化应激增加和甲基化能力受损的代谢生物标志物。Am J Clin Nutr。2004, 80(6):1611-7. A larger treatment study of 48 children with autism involved the use of 800 mcg of folinic acid and subcutaneous injections of vitamin B12 (methylcobalamin), but no TMG. The children were pre-screened to verify that they had methylation and/or glutathione problems (75% of those screened met criteria). The treatment did not significantly improve SAM, but cysteine levels did increase to normal. Total and reduced glutathione increased partially, but remained lower than normal. Oxidized glutathione improved to near-normal levels. The ratio of total glutathione to oxidized glutathione improved partially but was still below normal. This was an open-label study, and some improvements in behavior were mentioned but not reported.一项针对48名自闭症儿童的更大规模治疗研究涉及使用800微克亚叶酸和皮下注射维生素B12(甲基钴胺素),但未使用TMG。对这些儿童进行了预筛选,以确认他们是否存在甲基化和/或谷胱甘肽问题(筛选出的儿童中有75%符合标准)。治疗并未显著改善SAM,但半胱氨酸水平确实升高至正常水平。总谷胱甘肽和还原型谷胱甘肽部分增加,但仍低于正常水平。氧化型谷胱甘肽改善至接近正常水平。总谷胱甘肽与氧化型谷胱甘肽比值虽有部分改善,但仍低于正常值。这是一项开放标签研究,提到了行为方面的一些改善,但未报告。James SJ et al., Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr. 2009, 89(1):425-30.James SJ等人,Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status inchildren with autism.Am J Clin Nutr。2009, 89(1):425-30. So, it appears that the 2004 study, which included TMG, yielded more beneficial results than the 2009 study. TMG, or trimethylglycine, contains three methyl groups that can be donated, and likely supports methylation function and thereby improves SAM (which improved in the 2004 study, but not in the 2009 study).因此,似乎包括TMG在内的2004年的研究比2009年的研究产生了更多有益的结果。TMG,或三甲基甘氨酸,含有三个可捐赠的甲基,可能支持甲基化功能,从而改善SAM(在2004年研究中有所改善,但在2009年研究中没有)。 5) Multi-Vitamin/Mineral Supplement: A randomized, double-blind, placebo-controlled study of 141 children and adults with autism investigated an oral multi-vitamin/mineral supplement designed for individuals with autism. 54 of the children also had measurements of nutritional status at the beginning and end of the study, including measurements of methylation, glutathione, and oxidative stress. The supplement normalized SAM, and substantially improved another biomarker of methylation (plasma uridine). The supplement also partially improved reduced and oxidized glutathione, but the levels remained somewhat abnormal. Another marker of oxidative stress, plasma nitrotryrosine, also improved substantially but remained slightly abnormal.6) 多种维生素/矿物质补充剂:一项针对141名自闭症儿童和成人的随机、双盲、安慰剂对照研究调查了为自闭症个体设计的口服多种维生素/矿物质补充剂。54名儿童在研究开始和结束时还接受了营养状况测量,包括甲基化、谷胱甘肽和氧化应激的测量。补充剂使SAM正常化,并显著改善了甲基化的另一个生物标志物(血浆尿苷)。该补充剂还部分改善了还原型谷胱甘肽和氧化型谷胱甘肽,但水平仍有点异常。氧化应激的另一个标志物,血浆硝基nitrotryrosine,也有显著改善,但仍保持轻微异常。
Behavioral changes were investigated for all participants, and the treatment group improved significantly more than the placebo group as evaluated by the Parent Global Impressions-Revised, including modest but statistically significant improvements in the Average Change of all symptoms on the Parent Global Impressions-Revised, and significant improvements in subscores in expressive language, tantrumming, hyperactivity, and overall symptoms.对所有参与者的行为变化进行了调查,根据母体总体印象-修订版的评估,治疗组的改善显著高于安慰剂组,包括母体总体印象-修订版上所有症状的平均变化有适度但具有统计学意义的改善,以及表达性语言、愤怒、多动症和总体症状的子量表有显著改善。This study also reported that children with autism compared to neurotypical children had significantly lower levels of NADH, the active form of vitamin B3, which is needed to recycle oxidized glutathione to reduced (active) glutathione. The vitamin/mineral supplement normalized levels of NADH, and this at least partially explains the improvement in the ratio of oxidized to reduced glutathione, and improvements in overall oxidative stress本研究还报告称,与神经典型儿童相比,自闭症儿童的NADH(维生素B3的活性形式)水平显著较低,NADH是将氧化型谷胱甘肽再循环为还原型(活性)谷胱甘肽所需的。维生素/矿物质补充剂使NADH水平正常化,这至少部分解释了氧化型谷胱甘肽与还原型谷胱甘肽比值的改善以及总体氧化应激的改善Adams JB et al., Effect of a Vitamin/Mineral Supplement on Children with Autism, BMC Pediatrics 2011, 11:111亚当斯JB等,维生素/矿物质补充剂对自闭症儿童的影响,BMC儿科2011,11:111 7) NADH: NADH is the active form of vitamin B3, and is an important co-factor for many enzymatic reactions in the body. One study found that children with autism had normal levels of vitamin B3, but significantly low levels of NADH (Adams et al 2011). One small treatment study of 8 children with autism investigated the effect of 2 weeks of supplementation with 5-10 mg/day NADH (the active form of vitamin B3). It resulted in significant improvements in SAM to near-normal levels. It significantly improved levels of reduced glutathione, but did not significantly improve levels of oxidized glutathione.8) NADH: NADH是维生素B3的活性形式,是体内许多酶促反应的重要辅因子。一项研究发现,自闭症儿童的维生素B3水平正常,但NADH水平显著较低(亚当斯等人,2011年)。一项针对8名自闭症儿童的小型治疗研究调查了2周补充5-10mg/天NADH(维生素B3的活性形式)的效果。这导致SAM显著改善至接近正常水平。它显著改善了还原型谷胱甘肽的水平,但未显著改善氧化型谷胱甘肽的水平。Freedenfeld S et al., Biochemical Effects of Ribose and NADH Therapy in Children with Autism, Autism Insights, 2011:3 3-13Freedenfeld S等,核糖和NADH治疗对自闭症儿童的生化效应,自闭症见解,2011:3 3-13 9) Ribose: D-ribose is a naturally occurring sugar that is a key structural component of DNA, RNA, NADH, NADPH, and many other important molecules in the body. It is a commonly used nutritional supplement. One small treatment study of 8 children with autism investigated the effect of 2 weeks of supplementation with 5 g/day ribose. It resulted in significant improvements in SAM, but levels were still somewhat low. It slightly improved levels of reduced glutathione, but did not significantly improve levels of oxidized glutathione.10) 核糖:D核糖是一种天然存在的糖,是DNA、RNA、NADH、NADPH和体内许多其他重要分子的关键结构成分。是常用的营养补充剂。一项针对8名自闭症儿童的小型治疗研究调查了为期2周的5g/天核糖补充治疗的效果。这使SAM得到了显著改善,但水平仍较低。它略微改善了还原型谷胱甘肽的水平,但并未显著改善氧化型谷胱甘肽的水平。Overall, the effects of NADH supplementation were similar to the effects of ribose supplementation. Both treatments increased levels of NADH (by 22% and 18%, respectively) and greatly increased levels of ribose (173% and 222%, respectively).总体而言,补充NADH的效果与补充核糖的效果相似。两种治疗均提高了NADH水平(分别提高了22%和18%),并极大地提高了核糖水平(分别提高了173%和222%)。Freedenfeld S et al., Biochemical Effects of Ribose and NADH Therapy in Children with Autism, Autism Insights, 2011:3 3-13Freedenfeld S等,核糖和NADH治疗对自闭症儿童的生化效应,自闭症见解,2011:3 3-13 11) DMSA: Toxic metals such as mercury can greatly decrease the body’s ability to make glutathione, and removing toxic metals seems to normalize glutathione levels. One study investigated treatment with oral DMSA, a medication that is FDA-approved for treating lead poisoning in infants and children. Phase 1 of the study involved giving 3 doses of oral DMSA each day for 3 days (10 mg/kg bodyweight per dose). Levels of glutathione in RBC were measured previous to treatment, and 1-2 months after treatment. Initially, many children with autism had levels that were much below or much above that of the adult reference range, but after treatment they had levels that were almost all within the adult reference range; i.e., those with initially low levels increased towards normal, and those with high levels decreased towards normal. It appeared that high levels of RBC glutathione were associated with high levels of toxic metals (perhaps the body made more glutathione to respond?) and low levels of glutathione were associated with mercury (which inhibits production and decreases levels of glutathione). This treatment was safe and effective, and seemed to improve behavior.12) DMSA:汞等有毒金属会大大降低人体产生谷胱甘肽的能力,去除有毒金属似乎可以使谷胱甘肽水平正常化。一项研究调查了口服DMSA治疗,这是一种经FDA批准用于治疗婴儿和儿童铅中毒的药物。研究的第1阶段包括每天3次口服DMSA,持续3天(每次10 mg/kg体重)。在治疗前和治疗后1-2个月测量RBC中的谷胱甘肽水平。最初,许多自闭症儿童的水平远低于或高于成人参考范围,但治疗后,他们的水平几乎都在成人参考范围内;即具有初始低水平的那些向正常增加,而具有高水平的那些向正常减少。高水平的红细胞谷胱甘肽似乎与高水平的有毒金属有关(也许是身体制造了更多的谷胱甘肽来响应?)和低水平的谷胱甘肽与汞(其抑制谷胱甘肽的产生并降低谷胱甘肽的水平)相关。这种治疗安全有效,似乎改善了行为。
Adams JB et al., Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A-- medical results. BMC Clin Parmacol. 2009 Oct 23:9:16Adams,JB,等.Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A--medical results. BMC Clin Parmacol。2009年10月23日:9:16Adams JB, et al., Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: part B - behavioral results. BMC Clin Pharmacol. 2009 Oct 23;9:17.Adams JB,等,口服DMSA疗法治疗儿童自闭症谱系障碍的安全性和疗效:B部分-行为结果。BMC临床药理学。2009年10月23日;9:17. 13) N-acetyl-cysteine (NAC). NAC is a form of cysteine, an amino acid that is the rate-limiting factor in the production of glutathione. NAC is more resistant to water absorption during storage, so it is often used instead of cysteine. One randomized, double-blind, placebo-controlled study investigated treatment of children with autism with NAC. Dosage was 900 mg every day for the first 4 weeks, then 900 mg twice daily for 4 weeks and 900 mg three times daily for 4 weeks. The treatment group had significantly more improvement in irritability than the placebo-group. There were no measurements of glutathione, but it is a critical component of glutathione and probably raised levels of glutathione.14) n-乙酰半胱氨酸(NAC)。NAC是半胱氨酸的一种形式,半胱氨酸是一种氨基酸,是产生谷胱甘肽的限速因子。NAC在储存过程中更能抵抗水分吸收,因此常被用来代替半胱氨酸。一项随机、双盲、安慰剂对照研究调查了伴有NAC的自闭症儿童的治疗。最初4周的剂量为900mg/天,然后900mg/天两次,持续4周,900mg/天三次,持续4周。治疗组的应激性改善明显多于安慰剂组。未测量谷胱甘肽,但它是谷胱甘肽的关键成分,可能会升高谷胱甘肽的水平。Hardan AY, et al., A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism Biol Psychiatry. 2012 Jun 1;71(11):956-61. Epub 2012 Feb 18.Hardan AY,等,一项在自闭症儿童中口服N-乙酰半胱氨酸的随机对照试验Biol Psychiatry. 2012年6月1日;71(11):956-61.Epub 2012年2月18日 Additional Research:其他研究: Figure 1 shows a schematic of the methionine cycle, which leads to the production of SAM. Methionine is available from most dietary sources of protein (beef, chicken, nuts, etc). It is also made in the body by recycling homocysteine, which requires vitamin B12 and folinic acid.图1显示了导致SAM产生的蛋氨酸循环示意图。蛋氨酸可从大多数蛋白质饮食来源(牛肉、鸡肉、坚果等)中获得。它也是由体内循环的同型半胱氨酸制造的,这需要维生素B12和亚叶酸。Methionine is converted to SAM to SAH to Homocysteine. Homocysteine is then either recycled to methionine or converted into cystathionine, some of which eventually becomes glutathione.甲硫氨酸转化为SAM,SAH转化为同型半胱氨酸。然后,同型半胱氨酸被再循环为蛋氨酸或转化为胱硫醚,其中一些最终转化为谷胱甘肽。
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Figure 2 Reduction of GSSG to GSH (net result of a more complex process which involves FADH).图2 GSSG还原为谷胱甘肽(涉及FADH的更复杂过程的净结果)。NADH is the enzymatic co-factor needed to recycle glutathione.NADH是回收谷胱甘肽所需的酶辅因子。
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Immune System Regulation免疫系统调节Rationale: Several studies have found abnormal immune function in autism, generally with shift to Th-2, and some evidence for auto-immunity.基本原理:几项研究发现自闭症患者的免疫功能异常,通常转变为Th-2,并有一些自身免疫的证据。Molloy et al., Elevated cytokine levels in children with autism spectrum disorder, J. Neuroimmunol 172 (2006) 198-205.Molloy等,自闭症谱系障碍儿童细胞因子水平升高,J. Neuroimmunol 172 (2006) 198-205 . Testing: One standard test (available from any medical laboratory) is a measurement of total immunoglobulins (antibodies) and their subclasses. Decreased levels of IgG or subclasses of IgG provide evidence of immunodeficiency.检测:一项标准检测(可从任何医学实验室获得)是测量总免疫球蛋白(抗体)及其亚类。IgG或IgG亚类水平降低提供了免疫缺陷的证据。 Treatments: More research on effective treatments for normalizing the immune system in children with autism is needed. If lab testing reveals abnormal immune function, current possible treatments include intra-venous immunoglobulins (IVIG), Actos (pioglitazone), and low-dose naltrexone.治疗:需要更多关于自闭症儿童免疫系统正常化有效治疗的研究。如果实验室检查显示免疫功能异常,目前可能的治疗方法包括静脉内免疫球蛋白(IVIG)、Actos(吡格列酮)和低剂量纳曲酮。 Research:研究:IVIG: Gupta et al., found IVIG benefited 4 of 10 children, with 1 case of marked improvement. This is a very expensive treatment, as the immunoglobulins (antibodies) need to be collected from hundreds or thousands of human donors, but it may be covered by insurance if there is evidence of immune deficiency.IVIG: Gupta等人发现,IVIG使10名儿童中的4名受益,1例显著改善。这是一种非常昂贵的治疗方法,因为需要从成百上千的人类供体中采集免疫球蛋白(抗体),但如果有证据表明存在免疫缺陷,这种方法也可能包括在保险范围内。Gupta et al., Treatment of children with autism with intravenous immunoglobulin. J Child Neurol. 1999 Mar;14(3):203-5.Gupta等,静脉注射免疫球蛋白治疗儿童孤独症。j儿童神经。1999年3月;14(3):203-5. Twenty-six autistic children received intravenous gamma globulin (IVIG) every 4 weeks for 6 months at a dose of 400mg/Kg. Aberrant behaviors, speech, hyperactivity, inappropriate stims and social interactions significantly improved. However 22 of the 26 children regressed within 4 months after discontinuing IVIG. Anecdotal reports from clinicians suggest that 12 months or longer therapy is needed for long-term benefits.26名自闭症儿童接受静脉注射丙种球蛋白(IVIG),每4周一次,持续6个月,剂量为400mg/Kg。异常行为、言语、多动、不当刺激和社会互动显著改善。然而,26名儿童中有22名在中断IVIG治疗后4个月内出现退化。临床医生的轶事报告表明,需要12个月或更长时间的治疗才能获得长期益处。Boris m, Goldblatt A, Edelson SM; Improvement in children with autism treated with intravenous gamma globulin. Journal of Nutritional & Environmental Medicine, Dec 2005; 15(4): 169-176.Boris m,Goldblatt A,Edelson SM静脉注射丙种球蛋白治疗儿童自闭症的改善。营养与环境医学杂志,2005年12月;15(4): 169-176. PANS (Pediatric Acute-onset Neuropsychiatric Syndrome, formerly known as PANDAS) is the term used to describe a subset of children and adolescents who have sudden-onset Obsessive Compulsive Disorder (OCD) and/or tic disorders, and in whom symptoms worsen following infections (in the case of streptococcus, the term “PANDAS” is still used). The OCD and tic symptoms are accompanied by a variety of other neuropsychiatric symptoms, including separation anxiety, “anxiety attacks,” irritability, extreme mood swings, temper tantrums, and immature behaviors (like talking “baby talk”), hyperactivity, problems with attention and concentration, handwriting changes, and problems with math, reading and other school subjects. It is present in some children with ASD. The diagnosis is made from symptoms alone; in the case of PANDAS, which comes from strep, elevated ASO (Antistreptolysin Antibodies) and/or antiDNAse antibody levels can be helpful; if the throat culture is positive, a single course of antibiotics will usually get rid of the strep infection and allow the PANDAS symptoms to subside. A treatment for both PANS and PANDAS is IVIG. This therapy is covered by many insurance carriers and may be an additional method for children with ASD to be covered for IVIG. Also, prophylactic antibiotic therapy is sometimes recommended to prevent further strep infections. For more information, see http://intramural.nimh.nih.gov/pdn/web.htmpan(小儿急性发作神经精神综合征,以前称为熊猫)是一个用于描述突发强迫症(OCD)和/或抽动障碍且感染后症状加重的儿童和青少年子集的术语(对于链球菌,仍使用术语“熊猫”)。OCD和tic症状伴有多种其他神经精神症状,包括分离焦虑、“焦虑发作”、易怒、极端情绪波动、脾气暴躁和不成熟行为(如说“婴儿话”)、多动症、注意力和注意力集中问题、笔迹变化以及数学、阅读和其他学校课程问题。它存在于一些自闭症儿童中。仅根据症状作出诊断;对于链球菌引起的熊猫,升高的ASO(抗链球菌溶血素抗体)和/或抗核酸酶抗体水平可能有所帮助;如果咽喉培养结果为阳性,单疗程抗生素通常可消除链球菌感染,并使熊猫症状消退。潘和熊猫都可以在IVIG接受治疗。这种疗法由许多保险公司承保,可能是IVIG将承保的自闭症儿童的另一种方法。此外,有时建议预防性抗生素治疗,以防止进一步的链球菌感染。有关更多信息,请参见http://intramural.nimh.nih.gov/pdn/web.htm ACTOS: ACTOS (pioglitazone) has multiple effects, including the ability to decrease inflammation. An open study of ACTOS in 25 children with autism for 3-4 months found substantial improvementsACTOS: ACTOS(吡格列酮)具有多种作用,包括减轻炎症的能力。在25名自闭症儿童中进行的为期3-4个月的ACTOS开放性研究发现,情况有了实质性的改善
in irritability, lethargy, stereotypy, and hyperactivity, with greater benefits in the younger children. Doses were 30 mg (younger children) and 60 mg (older children).易激惹、嗜睡、刻板印象和多动症,对年龄较小的儿童好处更大。剂量为30 mg(幼儿)和60 mg(大龄儿童)。Boris et al., Effect of pioglitazone treatment on behavioral symptoms in autistic children, accepted in J. Neuroinflammation 2007.Boris等,吡格列酮治疗对自闭症儿童行为症状的影响,发表于《神经炎症杂志》2007年。 However, the ARI survey data (below) suggests that it is only rarely beneficial.然而,ARI调查数据(见下文)表明,其益处很少。 Safety Concern: The FDA has issued a “black box” warning that ACTOS may increase the risk of congestive heart failure, fluid retention, and edema (swelling due to fluid build-up under the skin).安全顾虑:FDA已发出“黑匣子”警告,ACTOS可能增加充血性心力衰竭、液体潴留和水肿(皮肤下液体积聚引起的肿胀)的风险。 Low-dose naltrexone:低剂量纳曲酮:Naltrexone is a medication used to block the opioid receptor in the brain, and therefore is used to treat opioid addiction by preventing the euphoric effect of opioids like morphine and heroin. There have been 14 clinical trials of naltrexone for children with autism. A review paper by Elchaar et al. reported “Naltrexone has been used most commonly at doses ranging from 0.5 to 2 mg/kg/day and found to be predominantly effective in decreasing self-injurious behavior. Naltrexone may also attenuate hyperactivity, agitation, irritability, temper tantrums, social withdrawal, and stereotyped behaviors. Patients may also exhibit improved attention and eye contact. Transient sedation was the most commonly reported adverse event.”纳曲酮是一种用于阻断脑内阿片受体的药物,因此通过防止吗啡和海洛因等阿片类药物的欣快感作用来治疗阿片成瘾。目前已有14项纳曲酮治疗儿童孤独症的临床试验。Elchaar等人的一份综述文件报告说:“纳曲酮最常用的剂量范围为0.5至2mg/kg/天,发现其在减少自残行为方面非常有效。纳曲酮还可减轻多动症、激越、易怒、脾气暴躁、社交退缩和刻板行为。患者的注意力和眼神交流也可能改善。短暂性镇静是最常报告的不良事件。”Elchaar et al., Efficacy and safety of naltrexone use in pediatric patients with autistic disorder. Ann Pharmacother. 2006 Jun;40(6):1086-95. Epub 2006 May 30. Review.Elchaar等,纳曲酮用于自闭症儿童患者的疗效和安全性。安·药理。2006年6月;40(6):1086-95.Epub 2006年5月30日。回顾一下。 It has been suggested that low-dose naltrexone, at about 3-5 mg/day (much lower than the doses mentioned above) may be beneficial to children with autism and may improve the regulation of their immune system. More research is needed.有人建议,约3-5mg/天(远低于上述剂量)的低剂量纳曲酮可能对自闭症儿童有益,并可能改善其免疫系统的调节。需要更多的研究。 ARI Survey of Parent Ratings of Treatment Efficacy:父母对治疗疗效评定的ARI调查:
% Worse% No Change% BetterNumber of Reports
IVIG7%39%54%142
Actos19%60%21%140
Low-dose naltrexone11%52%38%190
%更糟%无更改%更好报告数量
静脉用丙种球蛋白7%39%54%142
爱妥糖19%60%21%140
低剂量纳曲酮11%52%38%190
Based on the ARI Survey Data, IVIG seems the most likely to be beneficial, followed by LDN, with Actos having the lowest % better and the highest % worse. However, this is only survey data from relatively small numbers of families. More research is needed.根据ARI调查数据,IVIG似乎最有可能受益,其次是LDN,Actos的好转率最低,为%且恶化率最高。然而,这只是相对少数家庭的调查数据。需要更多的研究。 TRICHURIS SUIS THERAPY: Eggs of the pig whipworm (Trichuris suis) have been used for treatment of certain immune-system disorders including inflammatory bowel diseases, multiple sclerosis and food allergies, due to their immunomodulatory effects (ability to modulate the immune system). The therapy appears to generally be safe because the worms can only exist for a short time in human digestive tracts. Some physicians have used it for patients with autism, but there is no formal research yet on its use for individuals with autism, so it should be viewed as an experimental therapy for autism.trichori s sui疗法:猪鞭虫卵(trichori s sui)具有免疫调节作用(调节免疫系统的能力),已被用于治疗某些免疫系统疾病,包括炎症性肠病、多发性硬化和食物过敏。这种疗法似乎通常是安全的,因为蠕虫在人体消化道中只能存在很短的时间。一些医生已将其用于自闭症患者,但尚未对其用于自闭症个体进行正式研究,因此应将其视为自闭症的实验性治疗。Summers RW et. al., Trichuris suis therapy in Crohn´s disease, Gut 2005: 54:87-90;Summers RW et .艾尔。,Trichuris suis治疗克罗恩病,Gut 2005:54:87-90;Summer. et al.; Trichuris suis therapy for active ulcerative colitis. a randomized controlled trial gastroenterology april 2005 .夏天。等人;猪三叉杆菌治疗活动期溃疡性结肠炎。随机对照试验胃肠病学2005年4月。Jouvin MH, Kinet JP. Trichuris suis ova: testing a helminth-based therapy as an extension of the hygiene hypothesis., J Allergy Clin Immunol. 2012 Jul;130(1):3-10; quiz 11-2. Review.Jouvin MH,Kinet JP。Trichuris suis ova: testing a helminth-based therapy as an extension of thehygiene hypothesis.过敏,临床免疫。2012年7月;130(1):3-10;测验11-2。回顾一下。
Hyperbaric Oxygen Therapy (HBOT)高压氧治疗(HBOT).。Rationale: There is substantial evidence of decreased blood flow in brains of most children with autism, suggesting a need for more oxygen. HBOT is an effective method to temporarily increase oxygen levels throughout the body. It is effective for improving general wound healing, and might help with gut inflammation, brain inflammation, and similar problems that are common in children with autism.理由:有大量证据表明,大多数自闭症儿童的脑血流量减少,提示需要更多的氧气。HBOT是一个有效的方法,暂时增加氧气水平在整个身体。它可有效促进一般伤口愈合,并可能有助于肠道炎症、脑炎症和自闭症儿童常见的类似问题。 Treatment: Typically 40 1-hour sessions, 1-2x/day, in a chamber with 30% increased air pressure (1.3 atm), which temporarily increases level of oxygen in the body. A face mask with pure oxygen is sometimes used as well (regular air is only 22% oxygen). Higher pressures of 1.5-2 atm are sometimes used, but there is concern regarding excessive oxidative stress at higher partial pressures. Additional treatment hours are sometimes considered if the initial therapy is beneficial.治疗:通常为40次1小时疗程,1-2x/天,在气压升高30%(1.3 ATM)的室内进行,这会暂时增加体内的氧气水平。有时也使用含有纯氧的面罩(常规空气中只有22%的氧)。有时使用1.5-2 atm的较高压力,但担心在较高分压下会产生过度的氧化应激。如果初始治疗有益,有时会考虑额外的治疗时间。 Testing: Currently it is unclear what tests may indicate who is the best candidate for HBOT.测试:目前还不清楚哪些测试可以表明谁是HBOT的最佳候选人。 One small study of 18 children with autism found that HBOT therapy was able to substantially reduce levels of C-Reactive Protein (CRP, a marker of inflammation), primarily in the 3 children with elevated levels. So, this might be a useful biomarker, but more research is needed.一项针对18名自闭症儿童的小型研究发现,HBOT疗法能够显著降低C反应蛋白(CRP,一种炎症标志物)水平,主要是在3名水平升高的儿童中。因此,这可能是一个有用的生物标志物,但还需要更多的研究。Rossignol DA, et al., The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study. BMC Pediatr 2007, 7:36.Rossignol DA,等,高压氧治疗对自闭症儿童氧化应激、炎症和症状的影响:一项开放标签试点研究。BMC Pediatr 2007,7:36。 Safety Concerns:安全顾虑:1) Glutathione: One small study found that HBOT therapy decreased levels of plasma glutathione, which are already low in children with autism, so it is recommended to first normalize glutathione prior to starting HBOT. This is consistent with the notion that HBOT can increase reactive oxygen species, especially at higher partial pressure.2) 谷胱甘肽:一项小型研究发现,HBOT疗法降低了血浆谷胱甘肽的水平,这在自闭症儿童中已经很低了,因此建议在开始HBOT疗法之前首先使谷胱甘肽正常化。这与HBOT可以增加活性氧的概念是一致的,特别是在较高的分压下。Rossignol DA, et al., The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study. BMC Pediatr 2007, 7:36.Rossignol DA,等,高压氧治疗对自闭症儿童氧化应激、炎症和症状的影响:一项开放标签试点研究。BMC Pediatr 2007,7:36。 3) Primary Mitochondrial Disease: A small percent of children with autism also have primary mitochondrial disease. According to an expert on mitochondrial disease, Robert Naviaux, MD, PhD: "Hyperbaric oxygen therapy is contraindicated in children with primary mitochondrial disease and has led to serious injury and death in some patients. Primary mitochondrial disease is characterized by gene defects that make cells unable to use oxygen to produce energy. Forced exposure to high levels of oxygen under these circumstances, when the cells cannot use oxygen, can result in large increases in oxygen free radical production, tissue oxidative damage, and no neurologic or metabolic benefit… The Scientific Advisory Board of the United Mitochondrial Disease Foundation (UMDF) addressed this issue in 2007, and this expert opinion was published in Mitochondrial News 12: 1 and 20, 2007."4) 原发性线粒体疾病:少数自闭症儿童也患有原发性线粒体疾病。线粒体疾病专家Robert Naviaux,MD,PhD表示:“原发性线粒体疾病的儿童禁用高压氧治疗,这会导致部分患者严重受伤甚至死亡。原发性线粒体疾病的特征是基因缺陷,使细胞不能利用氧产生能量。在这种情况下,当细胞不能使用氧气时,强制暴露于高水平的氧气中会导致氧自由基产生大量增加,组织氧化损伤,并且没有神经或代谢方面的益处……联合线粒体疾病基金会(UMDF)的科学咨询委员会于2007年解决了这个问题,该专家意见发表在《线粒体新闻》12: 1和20,2007上。” 5) Seizures: There have been some anecdotal reports of seizure onset following HBOT, but this has not been confirmed in a published study. A published parent survey of the effect of different treatments on individuals with autism and seizures included a small sample of 36 people who had tried HBOT. The survey found that HBOT possibly had a small beneficial effect on reducing seizures, a very low rate of adverse effects, and possible improvements in several areas, primarily communication.6) 癫痫发作:曾有一些HBOT之后癫痫发作的轶事报道,但在一项已发表的研究中尚未得到证实。一项已公布的关于不同治疗方法对自闭症和癫痫患者的影响的父母调查包括了36名尝试过HBOT疗法的人的小样本。调查发现,HBOT可能对减少缉获量有一点好处,副作用发生率很低,在几个领域可能有所改善,主要是通信。Frye RE, et al., Traditional and non-traditional treatments for autism spectrum disorder with seizures: an on-line survey, BMC Pediatrics 2011, 11:37.Frye RE,等,“伴有癫痫发作的自闭症谱系障碍的传统和非传统治疗:一项在线调查”,BMC Pediatrics 2011,11:37。
Research on Treatment:治疗研究: There are several open-label studies of HBOT therapy for children, and most suggest that HBOT therapy might be helpful, but one open-label study with rigorous pre/post assessment showed no benefit. There are also two randomized, double-blind, placebo-controlled studies, with one study showing statistically significant benefit in one of the measures but not the others, and the other study showing no benefit. Two recent reviews of these studies are Rossignol, et al 2012 and Ghanizadeh 2012.有几项针对儿童的HBOT疗法的开放标签研究,大多数研究认为HBOT疗法可能有所帮助,但一项具有严格前/后评估的开放标签研究显示无益处。还有两项随机、双盲、安慰剂对照研究,一项研究显示其中一项措施有统计学意义的获益,但其他措施无,另一项研究显示无获益。最近对这些研究的两项综述是Rossignol等人,2012年和Ghanizadeh,2012年。Rossignol DA, et al, Hyperbaric oxygen treatment in autism spectrum disorders, Med Gas Res. 2012 Jun 15;2(1):16.Rossignol DA, 等,高压氧治疗自闭症谱系障碍,Med Gas Res. 2012年6月15日;2(1):16.Ghanizadeh A Hyperbaric oxygen therapy for treatment of children with autism: a systematic review of randomizedGhanizadeh 高压氧治疗儿童孤独症的系统评价trials Med Gas Res. 2012; 2: 13试验Med Gas Res. 20122: 13 Open-label studies:开放标签病历报告:Three small open-label studies involved 6-10 children with autism, and they generally reported some improvements in autistic symptoms and therapy was well tolerated.三项小型开放标签研究涉及6-10名自闭症儿童,他们通常报告自闭症症状有所改善,治疗耐受良好。Rossignol DA, Rossignol LW: Hyperbaric oxygen therapy may improve symptoms in autistic children.Rossignol DA,Rossignol LW:高压氧治疗可能改善自闭症儿童的症状。Med Hypotheses 2006, 67(2):216-228.Med假说2006,67(2):216-228。Chungpaibulpatana J, et al., Hyperbaric oxygen therapy in Thai autistic children. J Med Assoc Thai 2008, 91(8):1232–1238.Chungpaibulpatana J,等,高压氧治疗在泰国自闭症儿童。J Med Assoc Thai 2008,91(8):1232-1238。Bent S, et al., Brief report: Hyperbaric oxygen therapy (HBOT) in children withBent S,等人,Brief report: Hyperbaric oxygen therapy (HBOT) in children withautism spectrum disorder: a clinical trial. J Autism Dev Disord. 2012 Jun;42(6):1127-32.autism spectrum disorder: a clinical trial. j自闭症发展障碍。2012年6月;42(6):1127-32. One open-label study involved eighteen children with autism, ages 3-16 years, who received 40 hyperbaric sessions (45 minutes each) over 9 weeks. Six children received 1.5 atmospheres (atm) and 100% oxygen, and 12 children received 1.3 atm and 24% oxygen. Both groups had modest improvement in social responsiveness (communication, motivation, and mannerisms) and overall autism severity (language, sensory/cognitive, and health/physical behavior). Pre and post blood tests revealed a large improvement in CRP (C-Reactive Protein, a general marker of inflammation), primarily in the 3 children who had very high levels. Measurements of oxidized glutathione (GSSG) did not change, but measurements of total and free glutathione decreased, which is unfavorable. This suggests that glutathione therapy should be done prior to HBOT. HBOT therapy was generally well tolerated.一项开放标签研究涉及18名3-16岁的自闭症儿童,他们在9周内接受了40次高压氧治疗(每次45分钟)。6名儿童接受1.5个大气压(atm)和100%氧气,12名儿童接受1.3个atm和24%氧气。两组在社会反应(沟通、动机和习惯)和整体自闭症严重程度(语言、感觉/认知和健康/身体行为)方面均有适度改善。血液检查前后显示CRP (C反应蛋白,炎症的一般标志物)有很大改善,主要是在3名水平非常高的儿童中。氧化型谷胱甘肽(GSSG)的测量值没有变化,但总谷胱甘肽和游离谷胱甘肽的测量值下降,这是不利的。这提示谷胱甘肽治疗应在HBOT之前进行。HBOT疗法通常耐受良好。Rossignol DA, et al., The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study. BMC Pediatr 2007, 7:36.Rossignol DA,等,高压氧治疗对自闭症儿童氧化应激、炎症和症状的影响:一项开放标签试点研究。BMC Pediatr 2007,7:36。 One open-label study used a multiple baseline design, in which symptoms are assessed several times before and after treatment (this is more rigorous than typical open-label designs). The study involved 16 children with ASD who received 40 HBOT sessions (1.3 atm, 24% oxygen) over approximately 56 days. There was no improvement in any symptoms, as measured by behavioral analysts directly observing the children.一项开放标签研究采用多基线设计,在治疗前后多次评估症状(这比典型的开放标签设计更为严格)。该研究涉及16名ASD儿童,他们在约56天内接受了40次HBOT治疗(1.3 atm,24%氧)。根据直接观察这些儿童的行为分析师的测量,任何症状都没有改善。Jepson B, et al., Controlled evaluation of the effects of hyperbaric oxygen therapy on the behavior of 16 children with autism spectrum disorders. J Autism Dev Disord 2011, 41(5):575-588.Jepson B,等,高压氧治疗对16例自闭症谱系障碍儿童行为影响的对照评估。j自闭症发展研究2011,41(5):575-588。 Randomized, Double-blind, placebo-controlled treatment studies:随机、双盲、安慰剂对照治疗研究:One randomized, double-blind, placebo-controlled study followed 62 children undergoing 40 treatment sessions (1.3 atm, 24% oxygen, 10 sessions/week). 55 participants completed the study, which was conducted at multiple sites.Compared to the placebo group, the treatment group had significantly greater improvements on the Clinical Global Impressions (CGI) scale rated by the clinicians. For the parent evaluations, the treatment group had slightly more improvements on the一项随机、双盲、安慰剂对照研究随访了62名接受40个疗程(1.3 atm,24%氧,10个疗程/周)的儿童。55名参与者完成了在多个地点进行的研究。与安慰剂组相比,治疗组在临床医生评定的临床总体印象(CGI)量表方面有明显更大的改善。对于母体评估,治疗组在以下方面略有改善
CGI, ABC, and ATEC scales, but the differences between treatment and placebo groups were not statistically significant.CGI、ABC和ATEC量表,但治疗组和安慰剂组之间的差异无统计学意义。Rossignol DA, et al: Hyperbaric treatment for children with autism: a multicenter, randomized, double- blind, controlled trial. BMC Pediatr 2009, 9:21.Rossignol DA,等:高压氧治疗儿童孤独症:一项多中心、随机、双盲、对照试验。BMC Pediatr 2009,9:21。 Another randomized, double-blind, placebo-controlled study involved 46 children with autism undergoing 80 sessions (1.3 atm, 24% oxygen, 6-10 sessions/week). 34 participants completed the study (most of the withdrawals were due to travel time to the clinic, not adverse effects). In this study both groups were also receiving intensive ABA therapy (109 hours/month). This study involved extensive pre and post assessment of autistic symptoms, including both direct observations of behavior and standardized questionnaires. Overall, there was no difference in improvement in any of the behavioral assessments, suggesting that HBOT therapy was not significantly beneficial.另一项随机、双盲、安慰剂对照研究涉及46名自闭症儿童,共接受80次治疗(1.3 atm,24%氧,6-10次/周)。34名参与者完成了研究(大部分退出是由于去诊所的行程时间,而非不良反应)。在本研究中,两组还接受了强化ABA治疗(109小时/月)。本研究涉及广泛的自闭症症状前后评估,包括直接观察行为和标准化问卷。总体而言,所有行为评估的改善均无差异,表明HBOT治疗无明显益处。Granpeesheh D, et al., Randomized trial of hyperbaric oxygen therapy for children with autism.Granpeesheh D,等,高压氧治疗儿童孤独症的随机试验。Research in Autism Spectrum Disorders 2010, 4:268-275.《自闭症谱系障碍研究》,2010年,4:268-275。 Research on decreased blood flow in brains of children with autism:自闭症儿童脑血流量减少的研究;Many studies have investigated blood flow in the brains of individuals with autism with brain scans (PET, SPECT, and fMRI), and they have generally found decreased blood flow (hypoperfusion) in several parts of the brain. Only one study (Zilbovicius et al 1992) was negative, possibly due to lower quality of the imaging available at that time. Most of these studies involved small numbers of participants and even fewer controls, but in total they provide substantial evidence for hypoperfusion existing in most individuals with autism. One small study included children and adults with autism, and found that the older individuals had worse hypoperfusion than the younger ones. One study of 45 children with autism found that the degree of decreased blood flow in one part of the brain (left superior temporal gyrus) correlated modestly with more severe autism scores (primarily with restricted/repetitive behaviors). One study (Ohnishi et al 2000) found that impairments in communication and social interactions correlated with decreased blood flow in one许多研究通过脑扫描(PET、SPECT和fMRI)对自闭症个体的脑血流量进行了研究,发现脑的几个部分血流量减少(灌注不足)。只有一项研究(Zilbovicius等人,1992年)呈阴性,可能是因为当时可用的成像质量较低。这些研究大多涉及少数参与者和更少的对照,但总体而言,它们为大多数自闭症个体存在灌注不足提供了实质性证据。一项针对自闭症儿童和成人的小型研究发现,老年人的灌注不足情况比年轻人更严重。一项针对45名自闭症儿童的研究发现,大脑一部分(左侧颞上回)血流量减少的程度与更严重的自闭症评分(主要是限制性/重复性行为)中度相关。一项研究(Ohnishi等人,2000年)发现,在一项研究中,沟通和社会互动的损伤与血流减少相关part of the brain, and that “obsessive desire for sameness” correlated with decreased blood flow in another part of the brain. Overall, hypoperfusion seems to be a very common problem in children and adults with autism, and likely has a large effect on their symptoms and cognitive function. The cause of the hypoperfusion is unknown, but may relate to inflammation of blood vessels leading to restricted blood flow. Effective treatments for this problem are sorely needed.大脑的一部分,这种“对相同的强迫性渴望”与大脑另一部分的血流量减少有关。总体而言,灌注不足似乎是自闭症儿童和成人的一个非常常见的问题,可能对他们的症状和认知功能有很大影响。灌注不足的原因不明,但可能与血管炎症导致血流受限有关。迫切需要对这个问题进行有效的治疗。Zilbovicius M, et al., Regional cerebral blood flow in childhood autism: a SPECT study. Am J Psychiatry 1992, 149(7):924–930. (21 children with autism and 14 controls)Zilbovicius M,等,儿童孤独症的局部脑血流:SPECT研究。Am J精神病学1992,149(7):924-930。(21名自闭症儿童和14名对照)Zilbovicius M et al., Temporal lobe dysfunction in childhood autism: a PET study. Positron emission tomography. Am J Psychiatry 2000, 157(12):1988–1993. (21 children with autism compared to 10 children with mental retardation)Zilbovicius M .等,儿童期自闭症的颞叶功能障碍:一项PET研究。正电子发射断层扫描。Am J精神病学2000,157(12):1988-1993。(自闭症儿童21名,智力低常儿童10名)Ohnishi T, et al., Abnormal regional cerebral blood flow in childhood autism. Brain 2000, 123(Pt 9):1838–1844. (23 children with autism compared to 26 non-autistic controls matched for age and IQ)Ohnishi T,等,儿童孤独症局部脑血流异常。Brain 2000,123(Pt 9):1838–1844。(23名自闭症儿童与26名年龄和智商匹配的非自闭症对照)Starkstein SE, et al., SPECT findings in mentally retarded autistic individuals, J Neuropsychiatry ClinStarkstein SE,等,弱智自闭症个体的SPECT发现,J Neuropsychiatry ClinNeurosci. 2000 Summer;12(3):370-5. (30 children with autism and mental retardation compared to 14 children with mental retardation).Neurosci. 2000年夏天;12(3):370-5.(自闭症和智力低常儿童30例,智力低常儿童14例)。Wilcox J, et al., Brain perfusion in autism varies with age. Neuropsychobiology. 2002;46(1):13-6. (14 individuals with autism age 3-37 years and 14 age-matched controls)Wilcox J, 等,自闭症的脑灌注随年龄变化。Neuropsychobiology. 2002;46(1):13-6.(14名3-37岁自闭症患者和14名年龄匹配的对照者)Meresse G, et al., Autism severity and temporal lobe functional abnormalities. Ann Neurol. 2005 Sep;58(3):466-9. (45 children with autism)Meresse g,等,自闭症严重程度与颞叶功能异常。Ann Neurol. 2005年9月;58(3):466-9.(45名自闭症儿童)
Ito H et al., Findings of brain 99mTc-ECD SPECT in high-functioning autism--3-dimensional stereotactic ROI template analysis of brain SPECT. J Med Invest. 2005 Feb;52(1-2):49-56. (15 children with autism, 5 children with epilepsy)Ito H等,高功能自闭症的脑99mTc-ECD SPECT发现-脑SPECT三维立体定向ROI模板分析。J Med Invest. 2005年2月;52(1-2):49-56.(孤独症患儿15例,癫痫患儿5例)Gupta SK, Ratnam BV. Cerebral perfusion abnormalities in children with autism and mental retardation: a segmental quantitative SPECT study. Indian Pediatr. 2009 Feb;46(2):161-4. (10 children with autism, 5 typical children)Gupta SK, Ratnam BV。自闭症和智力低下儿童的脑灌注异常:一项节段性定量SPECT研究。Indian Pediatr. 2009年2月;46(2):161-4.(10名自闭症儿童,5名典型儿童)Sasaki M, et al Brain perfusion SPECT and EEG findings in children with autism spectrum disorders and medically intractable epilepsy. Brain Dev. 2010 Oct;32(9):776-82. Epub 2010 Jul 1. (15 children with autism)Sasaki M, 自闭症谱系障碍和药物难治性癫痫儿童的脑灌注SPECT和EEG结果。Brain Dev. 2010年10月;32(9):776-82.Epub 2010年7月1日。(15名自闭症儿童)Yang WH et al., Regional cerebral blood flow in children with autism spectrum disorders: a quantitativeYang WH 等,自闭症谱系障碍儿童局部脑血流:一项定量⁹⁹mTc-ECD brain SPECT study with statistical parametric mapping evaluation. Chin Med J (Engl). 2011 May;124(9):1362-6. (23 children with autism, 8 controls)具有统计参数映射评估的⁹⁹mTc-ECD脑SPECT研究。Chin Med J(Engl). 2011年5月;124(9):1362-6.(23名自闭症儿童,8名对照)Duchesnay E, et al., Feature selection and classification of imbalanced datasets: application to PET images of children with autistic spectrum disorders. Neuroimage. 2011 Aug 1;57(3):1003-14. Epub 2011 May 10. (45 children with autism, 13 control children)Duchesnay E不平衡数据集的特征选择和分类:应用于自闭症谱系障碍儿童的PET图像。Neuroimage. 2011年8月1日;57(3):1003-14.Epub 2011年5月10日。(45名自闭症儿童,13名对照儿童) Research on effect of HBOT on brain hypoperfusionHBOT对脑低灌注影响的研究HBOT has been reported to at least temporarily improve brain hypoperfusion in two open-label studies of other conditions (veterans with post-concussion syndrome and patients with various chronic brain injuries).据报告,在两项针对其他疾病(有脑震荡后综合征的退伍军人和患有各种慢性脑损伤的患者)的开放标签研究中,HBOT至少暂时改善了脑灌注不足。Harch P, et al. A Phase I Study of Low Pressure Hyperbaric Oxygen Therapy for Blast-Induced Post Concussion Syndrome and Post Traumatic Stress Disorder. J Neurotrauma 2012, 29(1):168-185.Harch P,等。低压高压氧治疗爆震所致脑震荡后综合征和创伤后应激障碍的I期研究。j神经创伤2012,29(1):168-185。Golden ZL et al., A: Improvement in cerebral metabolism in chronic brain injury after hyperbaric oxygen therapy. Int J Neurosci 2002, 112(2):119–131.Golden ZL等,A:高压氧治疗后慢性脑损伤患者脑代谢的改善。国际神经病学杂志2002,112(2):119-131。 Formal research studies of the possible effect of HBOT on brain hypoperfusion in individuals with autism are needed to determine if it is helpful. Investigation of the effect on inflammation, such as elevations of CRP, would also be very useful.需要对HBOT对自闭症个体脑灌注不足的可能影响进行正式研究,以确定其是否有帮助。研究对炎症的影响,如CRP升高,也非常有用。
Summary摘要 Autism is a very complex disorder, and involves many genetic and environmental factors that are not well-understood. However, there are many biomedical abnormalities that have been identified, and most can be treated to some degree. By following the testing and treatments outlined above, many individuals will improve to some degree, usually slowly and steadily over months and years. Sometimes one treatment shows great benefit, but it is more common that each treatment helps a small amount. However, the cumulative effect of multiple treatments can be substantial.自闭症是一种非常复杂的疾病,涉及许多尚未完全了解的遗传和环境因素。然而,已发现许多生物医学异常,其中大多数可在一定程度上得到治疗。通过遵循上述检测和治疗,许多个体将在一定程度上得到改善,通常是在数月或数年内缓慢而稳定地改善。有时一种治疗方法获益良多,但更常见的是每种治疗方法只能提供少量帮助。然而,多种治疗的累积效应可能是显著的。 Much of the research on biomedical interventions has focused on children. Research is needed to understand their effectiveness on teenagers and adults on the autism spectrum, but it seems likely that many of the treatments listed here will also be helpful to teens and adults.许多关于生物医学干预的研究都集中在儿童身上。需要进行研究以了解其对自闭症谱系障碍青少年和成人的有效性,但这里列出的许多治疗方法似乎也可能对青少年和成人有所帮助。 Much more research is needed to improve on these treatments and to determine which individuals are most likely to benefit from a given treatment, and to discover new treatments.需要进行更多的研究来改进这些治疗,确定哪些个体最有可能从给定的治疗中受益,并发现新的治疗方法。 For more information, I encourage you to go to the website of the Autism Research Institute (www.autism.com) and attend their conferences.如需了解更多信息,我鼓励您访问自闭症研究所的网站(www.autism.com)并参加他们的会议。 Please consider filling out the ARI Treatment Effectiveness Survey at www.autism.com, to share your experiences with other families.请考虑填写ARI治疗效果调查,网址为www.autism.com,与其他家庭分享您的经历。 To read case studies of children who have greatly improved from biomedical approaches, see “Recovering Autistic Children” by Stephen Edelson, Ph.D., and Bernard Rimland, Ph.D., available from www.autism.com.要阅读有关通过生物医学方法得到极大改善的儿童的案例研究,请参阅斯蒂芬·埃德尔森(Ph.D .)和伯纳德·里姆兰(Bernard Rimland,Ph.D .)撰写的《自闭症儿童的康复》,可从以下网站获取www.autism.com。 I encourage you to support research on new treatments for autism by donating to the Autism Research Institute at www.autism.com – your donations can make a difference.我鼓励你们通过向自闭症研究所捐款来支持自闭症新疗法的研究www.autism.com –您的捐赠会有所作为。 Good luck in your journey.祝你旅途好运。 James B. Adams, Ph.D. http://autism.asu.edu詹姆斯·亚当斯,博士http://autism.asu.edu
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