This information comes from an Autism study. You will see that Autism and Parkinson's have many things in common (I [Dave] am on the spectrum).
This 2014 study, “Sulforaphane treatment of autism spectrum disorder (ASD)” 2014 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217462/, explains “a placebo-controlled, randomized, double-blind clinical trial, daily oral administration for 18 wk of the phytochemical sulforaphane (derived from broccoli sprouts) to 29 young men with ASD substantially (and reversibly) improved behavior compared with 15 placebo recipients. Behavior was quantified by both parents/caregivers and physicians by three widely accepted measures. Sulforaphane, which showed negligible toxicity, was selected because it upregulates genes that protect aerobic cells against oxidative stress, inflammation, and DNA-damage, all of which are prominent and possibly mechanistic characteristics of ASD.”
Placebo-controlled, double-blind, randomized trial, young men (aged 13–27) with moderate to severe ASD received the phytochemical sulforaphane.
• The sulforaphane was derived from broccoli sprout extracts.
• Dose was daily oral doses of sulforaphane (50–150 µmol) for 18 wk, followed by 4 wk without treatment
• After 18 wk, participants receiving placebo experienced minimal change (<3.3%), whereas those receiving sulforaphane showed substantial declines (improvement of behavior):
• 34% for ABC (P < 0.001, comparing treatments) and 17% for SRS scores (P = 0.017).
• On CGI-I, a significantly greater number of participants receiving sulforaphane had improvement in social interaction, abnormal behavior, and verbal communication.
• Upon discontinuation of sulforaphane, total scores on all scales rose toward pretreatment levels.
• Dietary sulforaphane, of recognized low toxicity, was selected for its capacity to reverse abnormalities that have been associated with ASD, including oxidative stress and lower antioxidant capacity, depressed glutathione synthesis, reduced mitochondrial function and oxidative phosphorylation, increased lipid peroxidation, and neuroinflammmation.
“The decision to test sulforaphane to treat ASD was based on four premises.
• First, extensive evidence shows that sulforaphane counteracts many of the same biochemical and molecular abnormalities associated with ASD, including oxidative stress and reduced antioxidant capacity, defects in glutathione synthesis, mitochondrial dysfunction and low oxidative phosphorylation, increased lipid peroxidation, and neuroinflammation. Although it is unclear whether these anomalies are etiological or secondary manifestations, their correction often improves ASD behavior.
• Second, a variety of small molecules including sulforaphane can ameliorate a number of unrelated genetic disorders by activating the “stress proteome,” which regulates many of the aforementioned damaging processes. Sulforaphane, as well as hydroxyurea, phenylbutyrate, and trichostatin A, have been shown in vitro to have therapeutic potential to reestablish cellular homeostasis in a number of unrelated genetic disorders.
• Third, sulforaphane is a dietary phytochemical, derived from its precursor glucosinolate glucoraphanin, that is widely consumed in cruciferous plant-rich diets, and qualifies for consideration as a food, a dietary supplement, or a drug, depending on its intended use. Sulforaphane is therefore justifiably considered to be of low toxicity, and its administration to humans is well tolerated.
• Fourth, widespread anecdotal reports have suggested that fever can dramatically but temporarily ameliorate the disturbed behavior of many autistic patients. Notably, the degree of improvement (mostly in stereotypic behavior and inappropriate speech) was unrelated to the severity of fever or of autism. This study explicitly suggested that elucidation of the fever response might provide insight into the mechanisms of ASD and point to new therapeutic approaches. Fever up-regulates heat-shock proteins and related mechanisms central to multiple cellular processes in the CNS, including synaptic transmission, and may improve long-range cerebral cortical connectivity that is depressed in ASD. Sulforaphane also up-regulates expression of the heat-shock response."
"We hypothesized that daily treatment with sulforaphane at levels achieved by diet might reduce the severity of socially impaired behavior in ASD."
"Significantly greater improvement was observed among participants randomized to sulforaphane at 4, 10, and 18 wk for irritability, lethargy, stereotypy, and hyperactivity subscales of the ABC, and in awareness, communication, motivation, and mannerism subscales of SRS. After stopping sulforaphane treatment, both ABC and SRS subscores tended to revert toward baseline."
My key takeaways are (my [Dave the high school graduate] takeaways):
• Sulforaphane counteracts many of the same biochemical and molecular abnormalities associated with ASD, including oxidative stress and reduced antioxidant capacity, defects in glutathione synthesis, mitochondrial dysfunction and low oxidative phosphorylation, increased lipid peroxidation, and neuroinflammation.
• Sulforaphane can ameliorate a number of unrelated genetic disorders by activating the “stress proteome".
• Sulforaphane has been shown in vitro to have therapeutic potential to reestablish cellular homeostasis in a number of unrelated genetic disorders.
• Sulforaphane is considered to be of low toxicity, and its administration to humans is well tolerated.
• Fever up-regulates heat-shock proteins and related mechanisms central to multiple cellular processes in the CNS, including synaptic transmission, and may improve long-range cerebral cortical connectivity that is depressed in ASD. Sulforaphane also up-regulates expression of the heat-shock response.
• The participants in the trial generally improved with daily sulforaphane treatment up to week 18. At week 18 they discontinued the treatment and the participants scores returned to baseline. This tells me this sulforaphane treatment needs to be continued to be effective. Maybe instead of trying to slay the dragon, we need to work at taming the dragon?
• I have a high school degree. Caveat Emptor.
Additional Reading:
• 7+ Sulforaphane Benefits (Broccoli Sprouts or Supplements) Biljana Novkovic, PhD 2021 https://supplements.selfdecode.com/blog/panacea-benefits-broccoli-sprouts-sulforaphane/
• Sulforaphane treatment of autism spectrum disorder (ASD) 2014 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217462/
• Activation of the stress proteome as a mechanism for small molecule therapeutics 2012 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441123/
• Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism 2004 https://sci-hub.se/10.1093/ajcn/80.6.1611
• Neuroglial Activation and Neuroinflammation in the Brain of Patients with Autism 2004 https://sci-hub.se/10.1002/ana.20315
• Treatments for Biomedical Abnormalities Associated with Autism Spectrum Disorder 2014 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073259/
• Keap1-Nrf2 Signaling: A Target for Cancer Prevention by Sulforaphane 2013 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553557/
• Notes from the Field: “Green” Chemoprevention as Frugal Medicine 2012 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273844/
• Health Span Extension through Green Chemoprevention 2013 https://journalofethics.ama-assn.org/article/health-span-extension-through-green-chemoprevention/2013-04
• Behaviors Associated With Fever in Children With Autism Spectrum Disorders 2007 https://sci-hub.se/10.1542/peds.2007-0360
• Autism, fever, epigenetics and the locus coeruleus 2008 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668953/
• Heat Shock Proteins: Cellular and molecular mechanisms in the CNS 2010 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939168/
• Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27 2010 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975177/
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