Upping My Niacin to 1000 mg

Update 01/22/2023:

I just learned there is an increased risk of diabetes on niacin therapy: https://heart.bmj.com/content/102/3/198
This study was based on people taking Niacin for cardiovascular reasons, which I think would be dosed at 500 to 6000 mg a day: https://www.mayoclinic.org/drugs-supplements/niacin-oral-route/proper-use/drg-20065086
According to this video you should be able to eliminate the diabetes risk by not having carbs 3 to 6 hours after your niacin, therefore I will start taking my 1000 mg of niacin after my last meal of the day: How to Take Niacin Without Getting Diabetes https://youtu.be/76mrnovnGQ4

EVERYBODY: FEAR THE FLUSH. DON'T TRY TO START AT 1000 MG. DO YOUR RESEARCH.

I have a high school degree. Caveat Emptor. 

I hope everybody is taking Nicotinic Acid.

I've been taking 250 mg of Niacin (Nicotinic Acid) every day ever since this study came out in June of 2021: Niacin Enhancement for Parkinson’s Disease: An Effectiveness Trial - https://www.researchgate.net/publication/352486597_Niacin_Enhancement_for_Parkinson's_Disease_An_Effectiveness_Trial

In this study 47 people took 250 mg of slow release (no flush) Nicotinic Acid for 12 months and all of their UPDRS scores improved (except executive function). Pretty dramatic success.

So... I started on 250 mg time released (could not find slow release) and then switched to fast release (flushing) as I heard time released is not good for the liver (allegedly).  I am no worse than I was 18 months ago.  Probably a little better.  

I should add: I have not been diagnosed with PD. I have RBD, a sore left shoulder and left leg, face dandruff, get dizzy when I stand, and have random involuntary movements. I can say "had" to most of those conditions: My RBD is now very mild and rare. Random involuntary movements are rare. I don't get dizzy when I stand. My face dandruff is better but still there. My sore shoulder is still sore, but not as bad. I have gone back to using a mouse left handed after a year of going right handed.  I should also add: I do a lot of things besides Niacin.

So why am I taking this dose up to 1000 mg? Because I've been looking at papers that show Nicotinic Acid may be able to:

• Cure Systemic NAD+ Deficiency.
• (PwP have low NAD+).
• Treat mitochondrial myopathy.
• Boost Mitochondrial Biogenesis.
• Restore the BBB integrity. 
• This is pretty cool. I had not seen anything capable of maybe fixing the blood brain barrier.
  

These all look like good things to me.

 

So here are the papers:

Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy 2020
https://www.sciencedirect.com/science/article/pii/S155041312030190X

• "NAD+ is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD+ depletion occurs in patients with degenerative disorders and whether NAD+ repletion improves their symptoms has remained open. Here, we report systemic NAD+ deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD+-booster niacin, a vitamin B3 form (to 750–1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively. Blood NAD+ increased in all subjects, up to 8-fold, and muscle NAD+ of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%. Our evidence indicates that blood analysis is useful in identifying NAD+ deficiency and points niacin to be an efficient NAD+ booster for treating mitochondrial myopathy."
• This is an article about the same paper: Vitamin B3 Boosts Muscle Health in Mitochondrial Myopathy, Study Suggests 2020
  https://mitochondrialdiseasenews.com/2020/05/15/vitamin-b3-niacin-aids-muscle-metabolism-in-mitochondrial-myopathy-pilot-study-suggests/

 

Niacin mitigates blood–brain barrier tight junctional proteins dysregulation and cerebral inflammation in ketamine rat model of psychosis: Role of GPR109A receptor 2022
https://www.sciencedirect.com/science/article/abs/pii/S0278584622000756

• Male Wistar rats Niacin 40 mg/kg/day. Divide by 8 for Humans and you get 5 mg per kg. For 70 kg human dose would be 350 mg.
• "Niacin also augmented the hippocampal expression of ZO-1, occludin, and claudin-5 proteins, indicating the ability of niacin to restore the BBB integrity."

 

Niacin improved rigidity and bradykinesia in a Parkinson's disease patient but also caused unacceptable nightmares and skin rash--a case report 2005
https://sci-hub.se/10.1080/10284150500484638

• "At a routine primary care visit, niacin was increased to 500 mg twice a day for triglyceride reduction. At a three-month follow-up, his family reported he was now initiating many routine activities of daily living that previously required their prompting. At this office visit, on exam he could rise from a chair independently and start walking with minimal latency. Previously, he needed the examiner to lend him a hand to get up, and he took a few seconds to start walking. Rigidity was noticeably diminished."

Progresses in both basic research and clinical trials of NAD+ in Parkinson’s disease 2021
https://sci-hub.se/10.1016/j.mad.2021.111499

• "These studies indicate disturbances in NAD+ metabolism as a common feature in cellular and animal models of PD and point toward NAD+ supplementation as a valuable therapeutic approach to boost mitochondrial function and halt DA neurodegeneration. However, additional studies are needed to further substantiate the relationship between NAD+ levels and PD onset and progression".

 

These 3 studies and the case study all used Nicotinic Acid, not NR and not NMN. Plain old cheap Niacin.

 

Why am I going with 1000 mg a day?

• My lack of education makes me think more is better.
• The "Niacin Cures Systemic NAD+ Deficiency..." study used 750 to 1000 mg.
• The case report from 2005 used 500 mg twice a day.
• And I will throw in the NADPARK study (ClinicalTrials.gov: NCT03816020) where they went with 1000 mg of NR a day.
• I know this is not niacin, but it is close to niacin.
  

Dave

Vinpocetine

Vinpocetine regulates levels of circulating TLRs in Parkinson's disease patients 2018 https://sci-hub.se/10.1007/s10072-018-3592-y
I get 30 mg capsules from Swanson and take one a day with food.
Per this article: https://nootropicsexpert.com/vinpocetine/
Vinpocetine helps:
• Cerebral Circulation. Vinpocetine helps boost blood flow to and within the brain. Improving the flow of oxygen and glucose that feed ATP to power brain cells. Improving alertness, cognition, concentration, memory and mood.
• Neuroprotectant. Vinpocetine blocks the accumulation of sodium in neurons, reduces the toxic effects of oxidative stress, inhibits the enzyme PDE1 and boosting blood flow, scavenges free radicals, and protects neurons from glutamate and NMDA toxicity.
• Neuroplasticity. Vinpocetine inhibits the enzyme PDE1 which can increase cAMP and cGMP. These cyclic nucleotides in turn activate a series of kinases that phosphorylate the transcription factors cAMP response element binding protein (CREB) and serum response factor (SRF), leading to the expression of plasticity-related genes.[iii] Boosting neuroplasticity enhances cognition and memory.

Special Precautions and Warnings: https://www.webmd.com/vitamins/ai/ingredientmono-175/vinpocetine
• Pregnancy: Vinpocetine is possibly unsafe when used during pregnancy or by those who may become pregnant. Vinpocetine might increase the risk of miscarriage and might cause harm to the fetus. Avoid using.
• Breast-feeding: There isn't enough reliable information to know if vinpocetine is safe to use when breast-feeding. Stay on the safe side and avoid use.
• Bleeding disorders: Vinpocetine might increase the risk of bleeding. Use cautiously if you have a bleeding disorder.
• Weakened immune system: Vinpocetine might weaken the immune system in some people. This might reduce the body's ability to fight infections. If you already have a weakened immune system, check with your healthcare provider before using vinpocetine.
• Surgery: Vinpocetine might slow blood clotting. This might increase the risk of bleeding during and after surgery. Stop using vinpocetine at least 2 weeks before you are scheduled for surgery.

New Binaural Beats Files: Immortality and the Unseen World (W. O. E. Oesterley)

I really need to write up why I think Binaural Beats should help with PD.   Something about improving brain plasticity and Binaural Beats being the poor man's Caloric Vestibular Stimulation. I will get this written up (in the mean time, everybody is welcome to look at my notes: https://rbd-pd-protocols.blogspot.com/p/binaural-beats-research.html)

But this post is to let people know I added some new Binaural Beats files to my blog site and I also cleaned the page up really well. I got rid of some of my early efforts at Binaural Beats, added a pure one hour Binaural Beats file with no audio book content, and added details of just which frequencies you are shoving in your ears when you listen to these files :)

The new Binaural Beats files are: Immortality and the Unseen World (W. O. E. Oesterley): The full title of this book is Immortality and the Unseen World - A Study in Old Testament Religion. Oesterley describes the beliefs that pre-Christian Hebrews and Semites held regarding the afterlife and the immortal nature of humans. The nature, form and evolution of these beliefs are derived from the Tanakh (Old Testament), comparisons with the beliefs and mythologies of neighboring cultures, and archeological finds. To develop a full study, additional beliefs of these people are also considered, including the beliefs of the constituent parts of humans; demonology, angelology, shades and the Satan; the home of the dead, ancestor worship, necromancy, and burial customs. Oesterley also hypothesizes on how primitive beliefs in immortality may have developed in pre-Christian times.

You can download these, and other, Binaural Beats files here: https://rbd-pd-protocols.blogspot.com/p/binaural-beats-files.html

High Dose Thiamine vs Low Dose

This is interesting: Somebody on HU shared a study showing a good benefit from high dose thiamine to treat fatigue in patients with IBD (spoiler alert: It worked!): https://sci-hub.se/10.1111/apt.16166

 

This is the more interesting point:

The doctors had the participants go 12 weeks longer with just 300 mg a day. The results showed that 300 mg a day did not maintain the benefit:

Long-term maintenance treatment with 300 mg thiamine for fatigue in patients with inflammatory bowel disease: results from an open-label extension of the TARIF study https://pubmed.ncbi.nlm.nih.gov/34592862/

 

Objective and aims: Fatigue is common in inflammatory bowel disease (IBD). In a RCT we demonstrated reductions in fatigue after 4 weeks' treatment with high-dose oral thiamine. We aimed to investigate whether 300 mg thiamine daily for 12 weeks could maintain the achieved levels of fatigue in patients with IBD after a 4-week intervention with high-dose thiamine; and evaluate the effect of a 6-month period where patients were free to take oral thiamine.

 

Methods: A randomised, open-label, controlled trial, performed as a long-term extension (LTE) study of an initial randomised, high-dose thiamine trial. Patients were allocated 1:1 to 300 mg oral thiamine or no thiamine for 12 weeks. Subsequently, the patients were allowed to self-treat with over-the-counter (OTC) oral thiamine 6-month.

 

Results: Regardless of allocation in the LTE study fatigue severity increased in the study period. No significant effect of 300 mg oral thiamine were found, when stratifying for initial allocation in the high-dose study or fatigue level at entry in the LTE study. Patients who took OTC thiamine had lower level of fatigue 6 month later (7.8; 95% CI: 5.5-10.1) when compared to the remains (11.0; 95% CI: 9.2-12.8) (p = .02). After the 6-months follow-up without restrictions, 66% of patients had reached normal fatigue levels.

 

Conclusions: We found no beneficial effect on fatigue from thiamine taken in doses of 300 mg per day for 12 weeks following high-dose treatment. After a 6-months follow-up without restrictions 66% had reached a normal level of fatigue.

 

Dave's uneducated thoughts: Sometimes I think "I won't do high dose thiamine, but maybe I should just take 500 mg a day and that might do the trick". This extension of the HDT trial for IBD fatigue seems to indicate that you actually need the high dose to get the benefit.

Here is the thread on HU: https://healthunlocked.com/cure-parkinsons/posts/148900950/randomised-clinical-trial-high-dose-oral-thiamine-versus-placebo-for-chronic-fatigue-in-patients-with-quiescent-inflammatory-bowel-disease

Rhonda Patrick Sprouting Guide + Q&A with Dr. Jed Fahey

Dr. Rhonda Patrick is a prolific evangelist for sulforaphane and Dr. Jed Fahey is like the Godfather of sulforaphane and you can get her 15 page sprouting guide along with his Q&A at Rhonda Patrick's Found My Fitness web site: https://www.foundmyfitness.com/sprouting

Dr. Fahey also answers a bunch of questions about broccoli sprouting and sulforaphane in the document.

Some points of interest:
 - Most broccoli sprouting guidance suggests 2 tablespoons of seeds for a quart jar, but Rhonda recommends between 3 and 7 tablespoons. I am guessing the reason she suggests more seeds is because, to get maximum sulforaphane, "It’s best to harvest them in the first two to five days, when their cotyledons – the seed leaves – pop out of the seed".  I'm thinking if you harvest earlier, that mean you can get more seeds into the jar and it will not fill up before you harvest. Put another way: If you use 2 tablespoons of seeds and don't harvest until the jar fills up, then you are probably harvesting too lat for maximum sulforaphane content.  I use 4 tablespoons.
 - Both doctors make a big deal about disinfecting your seeds.
 - Here is an interesting quote from Dr. Fahey: "Many people talk about sprouting all sorts of cruciferous vegetables and assume that they will have
sulforaphane or its precursor glucoraphanin in them. It ain’t so! Unfortunately, it’s pretty much only
broccoli seeds and their sprouts that contain glucoraphanin."
 - This guide has a LOT of great information and lists of resources.

Please check out the PDF.  It is well worth having in your library.

Sulforaphane may activate certain genes that protect cells against oxidative stress, inflammation, and DNA-damage

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/

Chris Lacey Story: Mindfulness and Wood Carving

Chris Lacey story. He allegedly recovered from PD through mindfulness and wood carving: https://www.themercury.com.au/news/tasmania/how-i-unfroze-my-tin-man-body/news-story/0e8a6a73a75598c1f39fd37c4d041baf 

Health Unlocked has a post from somebody who knows Chris and has some video clips 2 clips of Chris walking from his wood shed, both without medication, about 18 months apart: https://healthunlocked.com/cure-parkinsons/posts/148078793/chris-lacey-before-and-after 

There is a lady in a FB PD group who has had similar success, but creating jewelry instead of carving wood.

Here is a video that also purports the benefits of exercising fine motor skills: Hands and Fingers in Parkinson's Disease https://youtu.be/V7gSvUbUdkE

Seems worth keeping in mind. 

Glycine Post 12/08/2022

Somebody on HU asked people to weigh in on whether or not taking Glycine was a good idea. I don't have a good answer, but this was my response:

So I was taking Glycine (and Taurine and NAC) together up until a year ago, when I made this post (you should read through it): Time to Cut Glycine from my Stack? (this would include GlyNAC) https://healthunlocked.com/cure-parkinsons/posts/146726012/time-to-cut-glycine-from-my-stack-this-would-include-glynac

Without re-reading all the documents in my first post, the mayor points seemed to be
A) The ability of homocisteine to do neurological harm depends on glycine levels. Without the glycine the homocisteine can only do a fraction of the damage: The Controversial Role of Homocysteine in Neurology: From Labs to Clinical Practice 2019 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337226/
B) Glycine has also been implicated in demyelination: The Inhibitory Neurotransmitter Glycine Modulates Macrophage Activity by Activation of Neutral Amino Acid Transporters 2009 https://sci-hub.se/10.1002/jnr.22395

I stopped Glycine cold.

Then about two months ago I added Glycine back to my stack. I probably added it back because A) I have a lot of Glycine in my cupboard leftover from when I was taking it, and B) I had forgotten the bad things I read about Glycine.
This is one of the pages you linked to. This is the full article: Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, enotoxicity, muscle strength, and cognition: Results of a pilot clinical trial 2021 https://sci-hub.se/10.1002/ctm2.372

"This study found that compared to healthy young adults, older humans have severely elevated oxidative stress, glutathione deficiency, impaired mitochondrial function, increased inflammation, insulin resistance and endothelial dysfunction, and lower muscle strength and mental cognition. We tested and found that supplementing GlyNAC (combination of glycine and N-acetylcysteine) improved all these defects, and that stopping GlyNAC resulted in a loss of benefits. The results of this trial suggests that GlyNAC supplementation could be a simple, safe and effective nutritional strategy to boost cellular defenses to protect against oxidative stress, correct mitochondrial defects to improve energy availability, increase muscle strength and cognition, and thereby promote healthy aging in humans."
"CONCLUSIONS: The results of this trial suggest that GlyNAC supplementation in OA is well tolerated and could play a novel role in improving healthy aging in OA by correcting GSH deficiency, OxS, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, body fat, muscle strength, gait speed, and cognitive function. GlyNAC supplementation also appears to improve hallmark defects in aging, which could be an exciting discovery and needs to be confirmed in future studies. Dietary supplementation of GlyNAC could improve the cellular, mitochondrial, and metabolic health of OA, improve strength and cognition, and thereby promote healthy aging. No side-effects of GlyNAC supplementation were detected during 36-week duration of the study. The results of this study support the need for future trials to assess the effects of GlyNAC supplementation in a larger population of OAs receiving GlyNAC supplementation for a longer duration."

There were only 8 older people in the trial, but the results looked really good. Especially table 4 and table 6.

The thing about evaluating treatments when you have PD, or any disease, is that it is not like nothing bad is going to happen to you if you don't take the treatment. There is hopefully a reward to go along with the risk and maybe (maybe) you can avoid the status quo risk. Or maybe you will make things worse.

It is still a coin toss. To win this game I need to move the needle, so for now I am in on Glycine. Personally, I take 1200 mg NAC, 1000 mg Taurine, and 1000 mg of Glycine together about 30 minutes before bed. There are articles showing combinations of these supplements work better together than separately.

Low Sulfur Diet?

So I was reading this Martha's Quest blog post: Desulfovibrio bacteria, Parkinson's and diet https://www.marthasquest.com/post/desulfovibrio-bacteria-parkinson-s-and-diet
She was talking about Desulfovibrio Bacteria being associated with Parkinson’s Disease. In fact, she linked to a paper from 2021 “Desulfovibrio Bacteria Are Associated With Parkinson’s Disease” https://www.frontiersin.org/articles/10.3389/fcimb.2021.652617/full and offered this quote from the paper “Desulfovibrio bacteria produce hydrogen sulfide and lipopolysaccharide, and several strains synthesize magnetite, all of which likely induce the oligomerization and aggregation of α-synuclein protein”.
Martha then went on to discuss hearing Dr. Michael Ruscio and Heidi Turner speak about the low sulfur diet and the many health conditions a low sulfur diet can address.

So then I looked up the low sulfur diet. It is like the exact opposite of my diet. Here is a great web site listing various low sulfur diets: The Most Popular Low Sulfur Diets By Andrew Day, ND https://www.lowsulfurdoctor.com/popular-low-sulfur-diets/

I'm going to come out and say it is very unlikely I will ever try a low sulfur diet. I eat an onion a day. Broccoli is high in sulfur. Check out this list. I can't even have well water (I live in the country. I have a well): https://www.lowsulfurdoctor.com/low-sulfur-diet/

So why am I posting on this subject? Because, as irritating as the subject is to me, there is a lot there, and it is fresh:

Here is another paper on this topic, from Jan 2022: Hydrogen Sulfide Produced by Gut Bacteria May Induce Parkinson’s Disease https://www.mdpi.com/2073-4409/11/6/978

"Conclusions: Considerable amounts of evidence support the view that an overgrowth of H2S-producing bacteria takes place in the gut microbiome of PD patients. It is plausible that by inhibiting acetyl-CoA synthesis, H2S decreases the amount of butyrate-producing gut bacteria. Furthemore, H2S can diffuse easily to gut cells and the vascular compartment. In blood circulation, some part of the bacterially produced H2S may end up at the brain level. When the gut cells are exposed to unphysiologically high concentrations of H2S, the release of Cyt c from the mitochondria will likely begin. In addition, H2S increases the iron content in the labile iron pool of the cell cytosol and the ROS content. In case the cell expresses aSyn, in the way that EECs and enteric neurons do, a development of aSyn oligomers and fibrils may start in the presence of Cyt c and increased ROS. The toxic oligomers and fibrils may spread to the lower brainstem via the vagal nerve and some oligomers will likely end up in the blood circulation. As to H2S producers, species of the genera Desulfovibrio, Escherichia, Bilophila, Porhyromonas, Prevotella, Corynebacterium, Veillonella, Helicobacter, and Clostridium invite particular attention when identifying the role of different bacterial genera in the etiology of PD. The bacterial composition of the microbiome in duodenum require special attention in PD as it is likely that the quantities and characteristics of the small intestinal bacteria, including the H2S-producing bacteria, differ significantly from those of the colon. Notably, studies on the bacterial composition of duodenal microbiome in PD are lacking. In future, microbiological and metabolomics-based studies on duodenal aspirates combined with the corresponding analyses of fecal samples may offer key information on the pathogenesis of PD. In case H2S plays a substantial role in the pathogenesis of PD, several strategies are already available to counteract its actions. In 2003, Braak and his colleagues proposed that PD is caused by an intestinal pathogen [107]. H2S could be that ”pathogen”. "

Maybe I will circle back to this topic. I will definitely circle back if somebody else starts having success with a low sulfur diet :)

Broccoli Sprout Beverage can clear Acrolein

 

A trial showed that a Broccoli Sprout Beverage can clear Acrolein (at least exogenous acrolein). Here is the study: Rapid and Sustainable Detoxication of Airborne Pollutants by Broccoli Sprout Beverage: Results of a Randomized Clinical Trial in China 2014 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125483/


I encourage people to read the paper if you want details. The main points I see is:
1. They did a 12 week trial of people drinking this Broccoli Sprout beverage every day.
2. The beverage had both Broccoli Sprouts AND Daikon.
3. The beverage cleared both Benzine and Acrolein. The participants had been exposed to these as airborne pollutants.
4. The researchers found that among the people consuming the broccoli sprout beverage, the rate of excretion of benzene increased 61 percent throughout the 12-week period. As for the acrolein, the excretion rate went up 23 percent during the trial.

Why should we care that a a Broccoli Sprout Beverage can clear Acrolein? We should care because, according to this study, Acrolein is a “key factor” in the development of PD: 'Key factor' in development of Parkinson's disease identified 2018 https://www.purdue.edu/newsroom/releases/2018/Q2/key-factor-in-development-of-parkinsons-disease-identified.html

To be fair, it seems the article on Acrolein being a “key factor” in the development of PD seems to be talking about Endogenous (created within the body) Acrolein. The study on the Broccoli Sprout beverage is talking about exogenous (from outside the body) Acrolein.

Here is the key point from the article (they are talking about Endogenous Acrolein): “Researchers at Purdue University have identified a compound that accumulates in Parkinson's disease-affected brain tissue. The compound, acrolein, is a toxic, foul-smelling byproduct of burning fat (the brain uses fat for fuel) and is normally eliminated from the body. But the research team has found that the substance can promote the build-up of a protein called alpha-synuclein. When this protein accumulates in a region of the brain called the substantia nigra, it destroys the cell membranes and key machineries of neurons, killing these brain cells.”


So Acrolein builds up and promotes the build-up of Alpha-Synuclein. And Acrolein can be created within cells and you can also be exposed to it through pollution.


But wait, there is more: Endogenous Acrolein can also be created in your gut: Gut Microbial Glycerol Metabolism is also an Endogenous Acrolein Source, 2018 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770549/:
• “The major conclusion is that gut microbes can metabolize glycerol to reuterin and that this transformation occurs in vivo. Given the known toxicity of acrolein, the observation that acrolein is formed in the gut necessitates further investigations on functional relevance for gut microbiota and the host.”
• “Acrolein induces apoptosis, endoplasmic reticulum stress, and oxidative stresses. Acrolein can decrease mitochondrial membrane potential and active apoptotic enzymes, such as caspase 9 and caspase 7. Acrolein can trigger immune and inflammatory responses, such as the increased expression of nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), or IL-8, contributing to endoplasmic reticulum stress. Moreover, acrolein decreased barrier function and increased permeability, potentially due to the downregulation of tight junction proteins ZO-1, occludin, and claudin-1.”


So far this seems to show that Acrolein is bad, and that a Broccoli Sprout beverage can help clear Acrolein. Here is another article showing Sulforaphane can protect against the damage from Acrolein: Sulforaphane protects against acrolein-induced oxidative stress and inflammatory responses: modulation of Nrf-2 and COX-2 expression 2018: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947616/

• This article has a lot of big words in it. As close as I can tell, the message is:
• We pre-treated cells with Sulforaphane.
• We exposed the cells to Acrolein.
• The Sulforaphane protected the cells from the Acrolein.
• “The present study provides clear evidence that pre-treatment with sulforaphane completely restored the antioxidant status and prevented inflammatory responses mediated by acrolein. Thus the protection offered by sulforaphane against acrolein-induced damage in PBMC is attributed to its anti-oxidant and anti-inflammatory potential”.
• Some people might say this test is not valid as they pre-treated the cells with Sulforaphane, but in this case I think it IS valid. Acrolein seems to be something you can be exposed to every day, either exogenously or endogenously, so MAYBE we need to be pre-treating our cells EVERY day to protect against Acrolein.


Dave’s conclusions:
• Acrolein can be created endogenously within our cells and promote the build-up of a protein called alpha-synuclein in the substantia nigra.
• Some doctors believe that Acrolein is a “key factor” in the development of PD.
• Acrolein can also be created in the gut and “trigger immune and inflammatory responses, such as the increased expression of nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), or IL-8, contributing to endoplasmic reticulum stress. Moreover, acrolein decreased barrier function and increased permeability, potentially due to the downregulation of tight junction proteins ZO-1, occludin, and claudin-1.
• If all this is happening in my gut, having my 40 grams of Broccoli Sprouts every morning seems like a good idea.
• The “40 grams” number come from another report I read that 40 grams was the minimum effective dose of Broccoli Sprouts.
• We can also be exposed to Acrolein through pollution.
• Broccoli Sprouts - Sulforaphane can clear Acrolein from the body and protect cells from the damage Acrolein can do.
• It makes sense to me, David Farris, to keep eating at least 40 grams of Broccoli Sprouts every morning to clear Acrolein from my body and to protect cells from from the damage Acrolein can do.


Additional Reading:
• Acrolein (Sources, metabolism, and biomolecular interactions relevant to human health and disease) 2008: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2423340/
• Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death 2017: https://www.nature.com/articles/srep45741
• Molecule from Fat Burning Linked to Protein Clumps That Typify Parkinson’s in Study 2018: https://parkinsonsnewstoday.com/news/acrolein-molecule-created-by-burning-fat-linked-to-hallmark-parkinsons-protein-clumps-study/
• Acrolein-mediated neuronal cell death and alpha-synuclein aggregation: Implications for Parkinson's disease 2018: https://www.sciencedirect.com/science/article/abs/pii/S1044743116302780?via%3Dihub