Update 2018: No significant increase of Glutathione (GSH) in Brain after oral administration with 6000mg NAC /day

[Greenday]

Repeated-Dose Oral N-Acetylcysteine in Parkinson's Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress.

ncbi.nlm.nih.gov/pubmed/289...

To characterize the pharmacokinetics of repeated high oral doses of NAC and their effect on brain and blood oxidative stress measures, we conducted a 4-week open-label prospective study of oral NAC in individuals with PD (n = 5) and in healthy controls (n = 3).

Brain GSH was measured in the occipital cortex using 1 H-MRS at 3 and 7 tesla before and after 28 days of 6000 mg NAC/day.

Blood was collected prior to dosing and at predetermined collection times before and after the last dose to assess NAC, cysteine, GSH, catalase, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) concentrations and the reduced-to-oxidized GSH ratio (GSH/ glutathione disulfide [GSSG]).

Symptomatic adverse events were reported by 3 of the 5 subjects with PD. NAC plasma concentration-time profiles were described by a first-order absorption, 1-compartment pharmacokinetic model.

Although peripheral antioxidant measures (catalase and GSH/GSSG) increased significantly relative to baseline, indicators of oxidative damage, that is, measures of lipid peroxidation (4-HNE and MDA) were unchanged.

There were no significant increases in brain GSH, which may be related to low oral NAC bioavailability and small fractional GSH/GSSG blood responses.

Additional studies are needed to further characterize side effects and explore the differential effects of NAC on measures of antioxidant defense and oxidative damage.

[aspergerian]

Important stdy!

[MBAnderson]

Boo-hoo. Well, this certainly burst a lot of bubbles.

[Xenos]

FOR SALE ! BARGAIN !

6 big brand new bottles of the purest N-AC capsules

Guaranteed origin

May possibly help cure everything.

[stevie3 in reply to Xenos]

Or not. Me too.

[MBAnderson in reply to Xenos]

ha

[John112233]

B5 increases glutathione, protects against lipid peroxidation, and more

sci-hub.tw/10.1016/j.febsle...

sci-hub.tw/10.1002/biof.552...

ncbi.nlm.nih.gov/pubmed/858...

[MBAnderson in reply to John112233]

The first two links brought up this website "для просмотра статьи разгадайте капчу" and the last link is too far above my pay grade to understand how it relates to Parkinson's. Can you explain?

[John112233 in reply to MBAnderson]

Hmm the first two articles are not on NCBI anymore. Here is one of them sciencedirect.com/science/a...

The original post was about NAC not working to raise glutathione. B5 increases glutathione, and prevents damage from oxidants, and damage from oxidants can lead to tumors. B5 genetic diseases cause Parkinson symptoms, and cause iron to accumulate in the brain, which is observed in Parkinsons also so B5 supplement might be helpful for Parkinsons.

[MBAnderson in reply to John112233]

Thanks. Helpful.

[Bolero]

My understanding is that Glutathione needs a direct pathway into the bloodstream, so suppositories are recommended as the best way to administer a dose. But they didn't work with me!

[Xenos in reply to Bolero]

Do you mean that I should put my NAC capsules in my...

That's an idea...

[jeeves19]

Well I can’t say many if any of these supplements which I’ve spend hundreds of £££ On have really achieved much. I’m not surprised by this study but then again neither will I be very surprised when a contradictory article appears on Pubmed saying they found the opposite. That’s the trouble with Science: it’s rarely science!

[aspergerian13 in reply to jeeves19]

Jeeves19: good point.

Here is a functional Google search.

nac gsh brain pmc.

The pmc tends to find whole text articles free online via PubMed.

Eg:

ncbi.nlm.nih.gov/pmc/articl...

ncbi.nlm.nih.gov/pmc/articl...

[Greenday in reply to aspergerian13]

The first article links to study with IV administration of NAC which as opposed to oral NAC offers superior bioavailability and able to increase GHS in brain.

[aspergerian in reply to Greenday]

Clarification: I was not suggesting that I had found the best NAC/brain citations. Instead, I was pointing out a search strategy that is often helpful.

[AmyLindy in reply to aspergerian13]

Pmc- nice tip

[Jmwg45]

This was already proven I thought. Intravenous NAC does raise it though.

I will continue taking it though as I started taking as I had thick, stringy saliva. This stopped 2 days in and has not returned.

It is also an anti inflammatory and within 4 weeks of taking a knot in my Achilles released after 3 years. Also the pain in my left arm is now tolerable (caused by compression on c8 nerve).

Many other proven benefits to boot just curing PD when taken orally is not one of them.

All told NAC is amazing and I’ll stick with it.

[Greenday in reply to Jmwg45]

NAC is a powerful drug and may benefit the peripheral system. I've similar pain in my arm. How much NAC do you take? Do you add any other supplements? I've been taking 900mg pharmaceutical NAC but the pain insist.

[Jmwg45 in reply to Greenday]

700mg twice daily (I use the granular variety off Amazon as it’s much cheaper). The pain persists but it was unbearable, now not. I am meant to see a spine surgeon at some point.

I also take vitamin B complex 100mg and 4000mg vitamin B1 HCL (2000mg twice daily) and magnesium citrate (800mg).

The NAC is the one I took first and is definitely responsible for the saliva, possibly responsible for the Achilles (years of physio did nothing)!-“and definitely helped with the arm pain a bit (I ran out and stopped for 4 weeks and it became unbearable again). I also no longer get pins and needles in my thumbs and fingers of both hands when sat.

I hope this gives some insight

[Greenday in reply to Jmwg45]

Thank you for sharing. I noticed you take a therapeutic dose of Thiamine B1, did you experience any positives with B1 alone?

[Jmwg45 in reply to Greenday]

I’m a bit worried to get over excited by the results. After seeing stuff on here about b1 I looked up symptoms of deficiency and identified several that I thought were just PD.

I have been on 5 weeks total, 3 weeks at 4g/day.

In the last 10 days I have felt better than for 5 years (dx June 2015).

I went on a 3.5 mile hilly dog walk and took 12 minutes off my time 4 weeks ago. My normal 40 minute walk (flat) now takes 35 minutes. I am now full of energy at the end instead of depleted.

I do PD warrior which normally takes a couple of days to recover from. Felt great next day and ready to go again.

I am better able to focus at work and get more done. According to my wife I am far easier to live with, do more to help and deal better with our young children.

All told, I might be just having a really good couple of weeks so trying to not get carried away. But so far I feel transformed

[Greenday in reply to Jmwg45]

It seems to produce measurable results. Please keep us update here or the thiamine related threads. Your genuine account is well appreciated.

[parkie13 in reply to Jmwg45]

That is very good to know.

[aspergerian in reply to Jmwg45]

Gsh taken orally may benefit intestinal tissue:

ncbi.nlm.nih.gov/m/pubmed/9...

ncbi.nlm.nih.gov/m/pubmed/2...

ncbi.nlm.nih.gov/pmc/articl...

ncbi.nlm.nih.gov/pmc/articl...

ncbi.nlm.nih.gov/m/pubmed/2...

[AmyLindy in reply to Jmwg45]

Good feedback,specifics count!

[sunvox]

NAC was on my short list for research, but I stopped when I found the same paper and posted it on my Who is taking NAC thread, but I have to admit after reading more and more positive comments I'm back to thinking I will add it to my list. My main reason is this:

-

" peripheral antioxidant measures (catalase and GSH/GSSG) increased significantly relative to baseline . . "

-

What that says to me is that although it is not impacting indicators of oxidative damage at right away who is to say that taking it daily for a lifetime isn't simply boosting your bodies anti-oxidant ability ever so slightly. Certainly the evidence is clear for IV administration that the molecule is capable. It really is the same thing I am doing by taking trehalose. BioBlast showed that IV administered trehalose worked so I tried oral trehalose and against all scientific odds it appears to have helped.

[Greenday]

Possibly; additional studies will clarify NAC antioxidant activity in PD Patients as authors suggest.

My concern is the following statement:

"Symptomatic adverse events were reported by 3 of the 5 subjects with PD"

A daily dose of 6,000mg oral NAC is not tolerable by most people for long term use.

[Greenday in reply to Greenday]

Liposomal Glutathione is possibly a safer and efficient alternative to the high daily dose of NAC.

Liposomal Glutathione elevates stores of GSH just after a week at a much lower dose of 500mg /day.

"Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function (2018)."

ncbi.nlm.nih.gov/pubmed/288...

BACKGROUND/OBJECTIVES:

Glutathione (GSH) is the most abundant endogenous antioxidant and a critical regulator of oxidative stress. Maintenance of optimal tissues for GSH levels may be an important strategy for the prevention of oxidative stress-related diseases. We investigated if oral administration of liposomal GSH is effective at enhancing GSH levels in vivo.

SUBJECTS/METHODS:

A 1-month pilot clinical study of oral liposomal GSH administration at two doses (500 and 1000 mg of GSH per day) was conducted in healthy adults. GSH levels in whole blood, erythrocytes, plasma and peripheral blood mononuclear cells (PBMCs) were assessed in 12 subjects at the baseline and after 1, 2 and 4 weeks of GSH administration.

RESULTS:

GSH levels were elevated after 1 week with maximum increases of 40% in whole blood, 25% in erythrocytes, 28% in plasma and 100% in PBMCs occurring after 2 weeks (P<0.05).

GSH increases were accompanied by reductions in oxidative stress biomarkers, including decreases of 35% in plasma 8-isoprostane and 20% in oxidized:reduced GSH ratios (P<0.05).

Enhancements in immune function markers were observed with liposomal GSH administration including Natural killer (NK) cell cytotoxicity, which was elevated by up to 400% by 2 weeks (P<0.05), and lymphocyte proliferation, which was elevated by up to 60% after 2 weeks (P<0.05).

Overall, there were no differences observed between dose groups, but statistical power was limited due to the small sample size in this study.

CONCLUSIONS:

Collectively, these preliminary findings support the effectiveness of daily liposomal GSH administration at elevating stores of GSH and impacting the immune function and levels of oxidative stress.

[aspergerian]

Ecological Formulas makes a product called "IGA+" Intracellular Glutathione Enhancers.

The "IGA+" is not to be confused with IgA or sIgA.

[Greenday in reply to aspergerian]

25mg Reduced Glutathione, 300mg NAC, and certain aminoacids and precursors in miniscule quantities... I'm not sure whether those synergistically or alone can do anything for PD.

You may check the following liposomal glutathione compositions:

LypriCel, Liposomal Glutathione, 30 Packets, 450mg

Lypo-Spheric Glutathione 30 Packets, 450mg

They both use Setria Glutathione in liposomal form.

There are many other brands of course but the fact that their liposomes come in single-use individual packets lessens the degree of degradation.

Glutathione is heat sensitive though; a useful rule of thumb is to buy in volume during the colder months and store in the fridge throughout the year to prolong shelf-life and efficacy.

[AmyLindy]

How about injection GSH? Some Dr.s will Rx. Then absorption is bypassed.

[bassofspades]

healthline.com/nutrition/ho...

Not very scientific but a good simple guide to glutathione production. I personally use whey protein isolate and it has been wonderful. Also of note, my NAC has added selenium and molybdenum which i think helps accomplish the gsh production.

I once attended a seminar on glutathione presented by a couple of MD PhD's and they recommended Immunocal platinum, which is basically low temperature pasturized whey protein isolate with bonded cysteine. The tripeptide bonded cysteine is clinically proven to survive the digestion process and create more brain glutathione. Stuffs expensive though, but i tried it for a few months and, by golly, the stuff works well! I honestly felt a huge difference. Now i just use a good quality undenatured grass fed cold processed whey protein isolate you can get at Amazon in 5 lb jars.

[bassofspades]

And all joking aside, someone mentioned shoving it up your arse, thats actually a thing! The simplest way to try it is a coffee enema. There was an anecdote about how a nurse in a war, i forget which one, gave some wounded soldiers coffee enemas and they recovered way faster than the rest. The reason was the glutathione it made. No joke. Hold the cream and sugar.

[junipertree in reply to bassofspades]

Thanks for the unexpected post. Definitely outside the box. Not versed in Glutathione vs enzymes but saw this study sited? I test very deficient in glutathione.

"Along with clearing out the bile duct, coffee enemas boost key antioxidants in your body. Glutathione S-transferase, an enzyme produced by the liver, has been shown to increase by 600-700% after just one coffee enema, according to research from the University of Minnesota."

Grain of salt: Don't know anything about Dr. Jay Davidson, but he's very pro-coffee enema!

drjaydavidson.com/coffee-en...

Increased glutathione S-transferase activity rescues dopaminergic neuron loss in a Drosophila model of Parkinson's disease.

ncbi.nlm.nih.gov/pubmed/159...

[bassofspades in reply to junipertree]

Out of the box is my specialty! Cures dont come from inside the box. Just Google coffee enema glutathione and youll get a sh*tload of links. Lol.