Tag /

Autism

Episodes

Posted on November 19th 2024 (7 months)

Dr. Rhonda Patrick discusses silicone safety, grounding, pentadecanoic acid, and the potential benefits of olive leaf extract and peptides.

Posted on April 9th 2022 (about 3 years)

In this clip, Dr. Jed Fahey describes the beneficial effects of sulforaphane in modulating the symptoms of autism and other brain disorders.

Posted on February 6th 2021 (over 4 years)

Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.

Topic Pages

  • Sulforaphane

    Sulforaphane modulates Nrf2-dependent antioxidant and heat-shock responses, a proposed mechanism for reducing oxidative stress linked to autism.

News & Publications

  • Estrogen may protect the brain against autism.

    Children with autism have fewer estrogen receptors in their brains than children without the disorder, a 2014 study found. The children had low brain levels of proteins involved in estrogen signaling, as well.

    Researchers analyzed brain tissue from healthy children and children with autism who had died from non-natural causes. Specifically, they quantified the expression of the estrogen receptor-beta and related proteins in tissue from the prefrontal cortex, an area of the brain involved in social behavior and cognition.

    They found that children with autism had 35 percent lower estrogen receptor-beta expression in their brains compared to healthy children. Children with autism also had 38 percent less aromatase, a protein that converts testosterone to estrogen. Levels of other proteins involved in estrogen metabolism were also low.

    Estrogen receptor-beta plays important roles in the human brain, where it participates in aspects of movement, behavior, and learning. Evidence suggests estrogen is neuroprotective, and low levels of estrogen contribute to cognitive dysfunction.

    Autism is a developmental disorder characterized by impaired social interaction, behavioral problems, and poor communication. It typically manifests in early childhood and is more common among boys than girls.

    These findings demonstrate that low brain levels of the estrogen receptor-beta and its related proteins are associated with a greater risk of autism, likely due to impaired neuroprotection from estrogen. In clinical trials, sulforaphane, a compound derived from broccoli and broccoli sprouts, reduces the characteristic behaviors associated with autism. Learn more in this clip featuring sulforaphane expert Dr. Jed Fahey.

  • The gut microbiome influences the development of social skills later in life, a recent study in fish has found. Fish that have delayed microbiome development show distinct differences in their brain structure and behavior compared to those with appropriately timed development.

    Researchers studied zebrafish, which are naturally social, to see how the microbiome affected the animals' behavior. Using a special type of zebrafish that lacked a microbiome, they inoculated one group of fish with bacteria immediately after birth to promote microbiome development. They delayed the inoculation of another group of fish by one week.

    They found that the fish that had delayed microbiome development exhibited more neural circuits in their brains and fewer microglia – a type of immune cell that “prunes” the brain and is necessary for normal development. These fish were also less social than the fish that had appropriately timed microbiome development.

    This study suggests that the microbiome influences the social behavior of zebrafish by reducing microglial pruning. Although the study was conducted using fish, other research suggests that these findings could translate to mammals, including humans. Learn more about the role of the gut microbiome in this episode featuring Dr. Eran Elinav.

  • From the article:

    The new study has several important implications. First, that current levels of testosterone directly affect the ability to read someone else’s mind. This may help explain why on average women perform better on such tests than men, since men on average produce more testosterone than women.

    Second, that the digit ratio (2D:4D), a marker of fetal testosterone, predicts the extent to which later testosterone has this effect. This suggests testosterone levels in the womb have an ‘organizing’ or long-range effect on later brain function. Finally, given that people with autism have difficulties in mind reading, and that autism affects males more often than females, the study provides further support for the androgen theory of autism.

    From the publication:

    Fetal testosterone is associated with a fixed somatic marker that can be indexed after birth: the length ratio of the right hand’s second (i.e., index) to fourth (i.e., ring) finger (2D:4D ratio). Males on average have a significantly lower 2D:4D ratio on their right hand and fetal testosterone is thought to underlie this sex difference, including its variability within the sexes. The reliability of 2D:4D ratio as a marker of fetal testosterone is substantiated by a large amount of correlational evidence in animals and humans. Moreover, meta-analytic data show that 2D:4D ratio is unaffected by later testosterone fluctuations or circulating levels of testosterone in adulthood. The ratio is therefore considered a useful, noninvasive marker of fetal testosterone.

    View full publication

  • From the article:

    Garcia and Atzori hypothesized that the protein IL-6 acutely and directly induces hyper-excitability by altering the balance between excitation and inhibition within synaptic communication. In other words, IL-6 is not just present when hyper-excitability occurs in the nervous system. It may actually cause it in some circumstances, Garcia said.

    The UT Dallas research team administered IL-6 to rat brain tissue and monitored its synaptic excitability. The brain tissue exhibited higher than normal excitability in their synapses, a symptom that may lead to misfiring of signals in epilepsy and other conditions.

    The researchers then injected sgp130 -a novel drug that acts as an IL-6 blocker- into the laboratory animals' brains. The substance limited excitability and appeared to prevent the conditions that lead to related neurological and psychiatric disorders, Garcia said.

    View full publication

  • From the article:

    It has been known for some time that schizophrenia is more common among people born in the winter and spring months, as well as in people born following influenza epidemics. Recent studies suggest that if a woman suffers even one respiratory infection during her second trimester, her offspring’s risk of schizophrenia rises by three to seven times.

    […]

    To prove this, they triggered an artificial immune response in pregnant mice–giving them a faux case of the flu. The trigger they used was a snippet of double-stranded RNA called poly(I:C), which fools the immune system into thinking there has been an infection by an RNA virus.

    A single, mid-gestation injection of poly(I:C) creates a strong immune response in a pregnant mouse. When her offspring reach adulthood, they display behavioral and tissue abnormalities similar to those seen in schizophrenia in humans.

    Though there might be some disagreement over what it means for a mouse to be schizophrenic, these abnormalities are generally marked by inappropriateness of response and difficulty in coping.

    […]

    The team tried injecting the pregnant mice with individual cytokines, rather than with poly(I:C). It turned out that after a single dose of a specific cytokine known as interleukin-6 (or IL-6), a mouse would give birth to offspring who, at maturity, exhibited the familiar schizophrenia- and autism-like behaviors.

    To confirm the role of IL-6, Steve Smith, the lead researcher, gave fake colds (poly(I:C)) to two groups of pregnant, IL-6-free mice. One group had received anti-IL-6 antibodies which blocked IL-6; the other consisted of so-called IL-6 knockout mice (mice whose genetic makeup prevents them from synthesizing IL-6). In both groups, offspring grew up normal, showing that IL-6 is necessary for the maternal poly(I:C) treatment to alter fetal brain development and subsequent behavior in the offspring.

    View full publication

  • From the article:

    Blood drawn from mothers during their third trimester was tested for levels of IL-6 and CRP – two proteins that are found at higher levels when the immune system is activated. Peterson’s team also monitored fetal heart rate as an indicator for nervous system development. The team found that CRP did correlate with variability of the fetal heart rate, which is influenced heavily by the nervous system, indicating that maternal inflammation was already beginning to shape brain development.

    When the babies were born, they were given MRI scans in their first few weeks of life, providing researchers a unique view of early neural development and the influence of prenatal factors. Brain imaging revealed a striking finding – significant changes in the communication between specific brain regions correlated with elevated maternal IL-6 and CRP levels. These brain regions are known collectively as the salience network, whose job is to filter stimuli coming into the brain and determine which deserve attention.

    […]

    “The salience network sifts through that information and decides what is important and warrants action.” Disturbances in the functioning of this network, as well as various kind of infection and other triggers of a pregnant woman’s immune response, have been linked to development of psychiatric illnesses, such as schizophrenia and autism spectrum disorders.

    […]

    The correlations of elevated maternal inflammatory markers were not limited to the newborn period, but continued to persist into toddlerhood. When the babies turned 14 months of age, researchers assessed them for motor skills, language development, and behavior. Following the established Bayley Scales of Infant and Toddler Development-Third Edition, Peterson found significant changes in the scores of toddlers born to mothers with elevated levels of both IL-6 and CRP.

    View full publication

  • From the article:

    “We discovered that higher levels of interleukin-6, an inflammatory marker, were associated with changes in the neonatal amygdala in terms of its anatomy and connectivity. Furthermore, our subsequent findings showed that these changes were also associated with lower impulse control at 2 years of age,” explains Prof. Buß. “We therefore conclude that a link exists between higher levels of maternal inflammatory markers and an increased risk of psychiatric disorders that are commonly associated with impaired impulse control.” Animal models have shown that infections and inflammation in the pregnant animal lead to both changes in offspring brain development and behavior. Epidemiological studies also support the findings of this study, suggesting that maternal infections and other clinical phenotypes associated with increased interleukin-6 concentrations (such as obesity) during pregnancy increase the risk of psychiatric disorders such as schizophrenia and autism.

    View full publication

  • From the article:

    The group analyzed postmortem cerebral cortex and cerebellum tissues from 33 individuals – 8 with ASD, 10 with schizophrenia and 15 healthy controls. Altered expression of genes associated with blood-brain-barrier integrity and function and with inflammation was detected in ASD tissue samples, supporting the hypothesis that an impaired blood-brain barrier associated with neuroinflammation contributes to ASD.

    In keeping with the hypothesis that the interplay within the gut-brain axis is a crucial component in the development of neurodevelopmental disorders, the group also analyzed intestinal epithelial tissue from 12 individuals with ASD and 9 without such disorders. That analysis revealed that 75 percent of the individuals affected by ASD had reduced expression of barrier-forming cellular components, compared with controls, and 66 percent showed a higher expression of molecules that increase intestinal permeability.

  • Sulforaphane improves behavioral symptoms of autism. molecularautism.biomedcentral.com

    Autism – often referred to as autism spectrum disorder, or ASD – is a neurodevelopmental disorder characterized by impaired social interaction and communication, as well as restrictive, repetitive patterns of behavior. The disorder typically manifests in early childhood and is slightly more common among boys than girls. Roughly one in 54 people living in the United States has ASD. Findings from a recent clinical trial suggest that sulforaphane improves behavioral symptoms associated with autism.

    Sulforaphane is a bioactive compound derived from precursors (glucoraphanin and myrosinase) in broccoli and broccoli sprouts. It exhibits antioxidant and anti-inflammatory properties and may be beneficial against a wide range of chronic and acute diseases, including cardiovascular disease, neurological disease, cancer, and others. Previous research has demonstrated that sulforaphane reduces behavioral symptoms of autism in young men. Sulforaphane exerts its therapeutic effects through a variety of mechanisms, the most notable of which is the activation of Nrf2, a cellular protein that regulates the expression of antioxidant and stress response proteins that provide protection against oxidative stress due to injury and inflammation. Sulforaphane is the most potent naturally occurring inducer of Nrf2.

    The randomized, placebo-controlled trial, which involved 45 children (ages 3 to 12 years) with autism, occurred in three distinct phases. During the first phase, half of the children received a commercially available dietary supplement containing glucoraphanin and myrosinase (yielding approximately 15 micromoles of sulforaphane) every day for 15 weeks, while the other half received a placebo. During the second phase, which also lasted 15 weeks, all the children received the supplement. During the third phase, which lasted six weeks, none of the children received the supplement. Before and after the intervention, caregivers and investigators evaluated the participants' symptoms using standardized behavioral assessments. Investigators collected blood and urine samples from the participants to assess metabolic and biochemical changes.

    They found that behavioral symptoms among the children who received the sulforaphane supplement improved during the first phase (compared to those on the placebo), but the differences between the two groups were not statistically significant. However, both groups' behavioral symptoms improved during the second phase, as did markers of oxidative stress, mitochondrial respiration, inflammation, and heat shock proteins. The supplement elicited no adverse effects and was well tolerated.

    These findings suggest that sulforaphane improves behavioral symptoms associated with autism. However, the study investigators caution that further study is needed to fully elucidate the clinical effects and mechanisms of action associated with the compound’s effects on autism.

  • The pain relieving drug acetaminophen (commonly known as Tylenol or paracetamol) is considered safe for use during pregnancy by the Food and Drug Administration and European Medicines Authority; however, recent evidence suggests that acetaminophen may increase the risk of fetal neurodevelopmental, reproductive, and urogenital disorders.. A group of expert scientists, clinicians, and public health professionals recently issued a statement calling for greater caution in recommending acetaminophen use during pregnancy.

    Acetaminophen is the most common medication used during pregnancy. Most often, pregnant women use the medication to reduce headache, muscle pain, and back pain; however 8 percent of pregnant women use acetaminophen to reduce fever, which is a risk factor for fetal neural tube defects and later life cardiovascular disorders. There are very few alternative medications for reducing pain and fever, so acetaminophen use in pregnancy may be difficult to eliminate.

    The authors conducted a systematic review of studies conducted over a 25-year period involving acetaminophen use during pregnancy. Then they used a set of criteria to select only relevant studies with appropriate study design. The 13 authors discussed the results of their systematic review and issued a statement that was later signed by 78 scientists, clinicians, and epidemiologists.

    Acetaminophen use in pregnant rats and mice directly interfered with the fetal production of sex hormones and other steroids; perturbed immune function by excessive dampening of inflammation; and increased oxidative stress. All of these changes increased the risk of neurodevelopmental and urogenital and reproductive disorders in offspring. This preclinical evidence in animals may provide a mechanistic understanding of the effects of acetaminophen use in humans.

    Epidemiological evidence from a sample of 130,000 mother-child pairs demonstrated increased risk of male urogenital abnormalities, including undescended testicles and reduced anogenital distance (i.e., the distance between the anus and penis), both markers of male sexual immaturity, in children born to mothers who used acetaminophen. Further epidemiological evidence from a sample of over 220,000 mother-child pairs demonstrated an increased risk of attention deficit hyperactivity disorder, autism spectrum disorder, and other neurodevelopmental abnormalities with acetaminophen use during pregnancy. One important observational study published in 2021 found an association between acetaminophen metabolites in umbilical cord blood collected at birth and the incidence of physician-diagnosed neurodevelopmental disorders in childhood. However, it is important to note that there are many factors that interfere with these statistical relationships, such as the incidence of maternal infection, other health conditions, and use of other medications.

    Given this evidence and more presented in the literature, the experts recommended that pregnant women should be cautioned at the beginning of pregnancy to reduce or stop use of acetaminophen unless it is medically necessary and should consult with a physician or pharmacist before using acetaminophen long-term. The authors recognize the need for rigorous meta-analyses to understand the hormonal, epigenetic, and metabolic mechanisms by which acetaminophen affects development in humans.

  • Autism spectrum disorder is a developmental condition characterized by impaired social interaction, behavioral problems, and poor communication. It typically manifests in early childhood and is slightly more common among boys than girls. Roughly one in 54 people living in the United States has ASD. A team of researchers has developed an assay that predicts the risk of having a child with maternal autoantibody-related autism.

    Maternal autoantibody-related autism spectrum disorder is a developmental condition that occurs when proteins (called autoantibodies) that are produced by a pregnant woman’s immune system react with proteins in the developing fetus’s brain. It accounts for approximately 18 percent of all autism cases.

    The study involved nearly 800 women enrolled in the Childhood Autism Risks from Genetics and Environment study, which includes mothers of children diagnosed with autism spectrum disorder as well those with normal development. The researchers collected blood from the women and assessed the children’s health and social and cognitive development. They developed an assay to detect and quantify maternal autoantibody reactivity to eight proteins that are highly expressed in the developing brain.

    The assay identified four common patterns of reactivity to some of the proteins, and these patterns correlated with having autism spectrum disorder with 100 percent accuracy. The researchers found that reactivity to a protein called CRMP1 increased the odds that a child would have autism spectrum disorder more than twofold.

    These findings have relevance for women at high risk of having a child with autism spectrum disorder, such as those with a child previously diagnosed with the disorder or who have health conditions that have been linked with the disorder, such as metabolic syndrome during pregnancy.

  • Autism spectrum disorder, or ASD, is a neurodevelopment disorder characterized by impaired social interaction and communication, as well as restrictive, repetitive patterns of behavior. ASD affects roughly one in 68 people and is more common among males than females. A 2014 study showed that sulforaphane reduces communication impairments and behavioral symptoms in young men with autism.

    Sulforaphane demonstrates low toxicity. It has been shown to reverse physiological anomalies commonly associated with ASD, including increased oxidative stress, mitochondrial dysfunction, and neuroinflammation.

    The placebo-controlled, double-blind, randomized trial involved 44 young men between the ages of 13 and 27 years who had been diagnosed with moderate to severe ASD. The authors of the study gave 29 of the participants sulforaphane derived from broccoli sprout extracts and gave the remaining 15 participants a placebo. They received their respective treatments for 18 weeks, followed by four weeks without treatment. Sulforaphane doses ranged between 50 and 150 micromoles (~9 milligrams and 26 milligrams, respectively). The participants' parents, caregivers, and physicians provided assessments of the young men’s behavior using the Aberrant Behavior Checklist, Social Responsiveness Scale, and Clinical Global Impression Improvement Scale (CGI-I).

    After 18 weeks on the treatment, the participants who took the placebo experienced little change, but those who took the sulforaphane showed marked improvements in their behaviors. In particular, the CGI-I scores reflected improvements in social interaction, behavior, and verbal communication. After the sulforaphane treatment ended, the participants' scores rose toward pretreatment levels on all assessments.

    These findings suggest that sulforaphane ameliorates many of the behavioral symptoms associated with ASD. A follow-up study reflected similar effects.

  • Autism spectrum disorder (ASD) is a developmental condition characterized by impaired social interaction, behavioral problems, and poor communication. The disorder typically manifests in early childhood and is slightly more common among boys than girls. Roughly one in 54 people living in the United States has ASD. Findings from a new study suggest that maternal immune activation during pregnancy increases the severity of ASD in offspring.

    Maternal immune activation due to autoimmune disorders, asthma, or allergies switches on the activity of inflammatory pathways and proinflammatory molecules. Many of these molecules can cross the blood–brain barrier and the placenta, potentially disrupting fetal development. Elevated levels of these proinflammatory molecules have been found at birth or during development in some people with ASD – a finding that has been linked with increased severity of symptoms.

    The study involved 363 children who were enrolled in the Autism Phenome Project or the Girls with Autism Imaging of Neurodevelopment studies, along with their mothers. The authors of the study assessed children’s behavioral and emotional problems and reviewed the mothers' pregnancy histories.

    They found that asthma was the most common immune condition among the mothers, but other conditions, including Hashimoto’s thyroiditis, rheumatoid arthritis, and psoriasis were reported as well. Roughly 20 percent of the mothers of male children with ASD had asthma. Maternal immune conditions were associated with increased behavioral and emotional problems but not cognitive function in both sexes.

    These findings indicate that maternal immune conditions may influence the severity of ASD symptoms in offspring and the severity of these symptoms may vary between males and females. Although there is no cure for ASD, robust data demonstrate that sulforaphane, a bioactive compound derived from cruciferous vegetables, especially broccoli sprouts, may be beneficial in reducing many of the behavioral and emotions symptoms associated with the condition.

  • Autism is a developmental disorder characterized by impaired social interaction, behavioral problems, and poor communication. Autism typically manifests in early childhood and is slightly more common among boys than girls. Findings from a new study indicate that oxytocin may improve social interactions among men with autism.

    Oxytocin is a hormone produced in the hypothalamus and released by the posterior pituitary gland of the brain. It is an important chemical messenger that influences certain human behaviors as well as social interaction. Previous research has shown that an oxytocin nasal spray can improve some autistic behaviors in people with autism.

    This double-blind, randomized, placebo-controlled clinical trial involved 40 adult men with autism who took 24 IU of intranasal oxytocin or a placebo once daily for four weeks. The participants (or their caregivers) completed questionnaires about their autistic behaviors at the beginning and end of the treatment and at four weeks and one year post-treatment.

    Participants who took the oxytocin reported decreased repetitive behaviors and feelings of avoidance toward others, even at four weeks and one year post-treatment. Those who took the oxytocin also reported feeling more energetic, active, or lively than those who took the placebo.

    Other studies have shown that levels of oxytocin vary significantly in children with and without autism and that children with low oxytocin levels have difficulties functioning socially. Children with the lowest levels of oxytocin at baseline were found to benefit the most from the treatment.

    This was a pilot study, so more research is needed to determine the safety and therapeutic value of oxytocin administered via nasal spray for people with autism.

  • Prenatal exposure to organophosphate pesticides has been associated with reduced IQs, mental and motor delays among preschoolers, memory and attention deficits, and autism (review of 27 studies).

    A higher likelihood of an autism diagnosis was observed for children born to women residing within (versus beyond) 1.5 km of organophosphate pesticide applications on agricultural fields. Another recent study showed that higher organophosphate pesticide metabolite concentrations in maternal urine during pregnancy were associated with autism traits identified in adolescence. Risks for impaired neurodevelopment were greater among children of farmworkers, who experience higher exposures, and children with genetic susceptibility factors that reduce capacity to detoxify organophosphate pesticides.

    Still, these are associations and it is difficult to establish causality. Animal studies have shown effects on cognition, motor activity, and social behaviors when dosed in early life with concentrations of organophosphates.

  • A new study found sulforaphane (found in broccoli sprouts) improved behavior and social responsiveness in children with autism spectrum disorder. It also found that clinical improvements were correlated with two urinary metabolites known to be involved in redox metabolism, which sulforaphane is known to affect.

    This study builds upon findings from a prior randomized, placebo-controlled trial which showed sulforaphane improved symptoms of autism in young adults.

    I did a podcast with one of the scientists involved in both of these clinical studies, Dr. Jed Fahey. We discuss the effects of sulforaphane on the brain and specifically how it helps treat autism spectrum disorder.

    You can find the episode on sulforaphane with Dr. Fahey along with show notes and a transcript on the foundmyfitness episodes page: https://www.foundmyfitness.com/episodes/jed-w-fahey Link to the previous RCT: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217462/

  • A supplement containing the active form of vitamin D was shown to prevent autistic-like behaviors in mice that are predisposed to them. The active vitamin D was given to pregnant mice during the first trimester and this prevented deficits in social interaction, basic learning, and stereotyped behaviors. While this study did not find a mechanism, I published a study in 2014 suggesting that low maternal vitamin D may increase the risk of autism because vitamin D controls the production of serotonin. Serotonin acts as a brain morphogen during early brain development and it shapes the structure and wiring of the developing brain. Low brain serotonin during development has also been linked to autism. It is unclear what maternal vitamin D levels are optimal but I like to shoot for levels between 40-60 ng/ml based on all-cause mortality studies. Levels above 30 ng/ml are considered sufficient. I like to measure vitamin D levels even after supplementation to make sure that I am getting the right amount (not too low or high). I take between 2,000 IU to 4,000 IU of vitamin D3 per day, depending on the season.