Hydrogen sulfide, garlic, alpha lipoic acid, theabrownin, PTP1B

[silvestrov]

Quite a while ago I looked into the HU posting,

Can Garlic Treat Parkinson’s Disease?

healthunlocked.com/parkinso...

137378476/can-garlic-treat-parkinson%E2%80%99s-disease

After reading the imbedded article,

realnatural.org/can-garlic-...

The authors noted 2 specific targets for possible improvement of PD symptoms by eating aged garlic: raising low thiol levels (and consequently low glutathione levels). Secondly, raising hydrogen sulfide (H2S) levels. I wrote the following in a way so the narrative can understood on the first reading.

Alpha lipoic acid has a number of different names including thioctic acid

From Wikipedia:

"Lipoic acid....α-lipoic acid...alpha lipoic acid...thioctic acid is an organosulfur

compound derived from octanoic acid. LA contains two sulfur atoms (at C6 and C8)

connected by a disulfide bond and is thus considered to be oxidized although either

sulfur atom can exist in higher oxidation states."

en.wikipedia.org/wiki/Lipoi...

"Diallyl disulfide....is an organosulfur compound derived from garlic and a few

other genus Allium plants."

"It is produced during the decomposition of allicin, which is released upon

crushing garlic and other plants of the Alliaceae family."

en.wikipedia.org/wiki/Diall...

"The present in vivo studies demonstrated that diallyl disulfide..., occurring

in garlic, elevated hepatic sulfane sulfur level...in healthy mice..."

sciencedirect.com/science/a...

Lipoic Acid as a Possible Pharmacological Source of Hydrogen Sulfide/Sulfane Sulfur

"The aim of the present study was to verify whether lipoic acid (LA) itself is

a source of H2S and sulfane sulfur."

"The study performed in the presence of rat liver and kidney homogenate

revealed an increase of H2S level in samples containing LA and its reduced

form dihydrolipoic acid (DHLA). It was accompanied by a decrease in sulfane

sulfur level. It seems that, in these conditions, DHLA acts as a reducing

agent that releases H2S from an endogenous pool of sulfane sulfur compounds

present in tissues."

mdpi.com/1420-3049/22/3/388...

My Summary: Allicin decomposes and forms diallyl disulfide which raises liver

sulfane levels. In the presence of the reduced form of alpha lipoic acid,

dihydrolipoic acid, H2S is produced from the reduction of sulfane by

dihydrolipoic acid.

What is allicin?

"Researchers have widely believed that the organic compound, allicin – which

gives garlic its aroma and flavour – acts as the world's most powerful antioxidant."

"Basically the allicin compound has to decompose in order to generate a potent

antioxidant," ..... "The reaction between the sulfenic acid and radicals is as

fast as it can get, limited only by the time it takes for the two molecules to

come into contact. No one has ever seen compounds, natural or synthetic, react

this quickly as antioxidants."

sciencedaily.com/releases/2...

Is allicin neuroprotective in PD models?

Allicin Protects PC12 Cells Against 6-OHDA-Induced Oxidative Stress and

Mitochondrial Dysfunction via Regulating Mitochondrial Dynamics

researchgate.net/publicatio...

PC12_Cells_Against_6-OHDA-Induced_Oxidative_Stress_and_Mitochondrial_

Dysfunction_via_Regulating_Mitochondrial_Dynamics

Is alpha lipoic acid neuroprotective in PD models?

Combined R‐α–lipoic acid and acetyl‐L‐carnitine exerts efficient preventative effects in a cellular model of Parkinson’s disease

onlinelibrary.wiley.com/doi...

-------------------------

WARNING: Allicin is a blood thinner and cannot be taken with other blood thinners

like warfarin or fish oil. In the absence of taking an allicin supplement, hydrogen sulfide/H2S can be produced non-enzymatically through the exposure of alpha lipoic acid/LA to direct sunlight.

Lipoic Acid as a Possible Pharmacological Source of Hydrogen Sulfide/Sulfane Sulfur

"The present results indicate that not only H2S but also sulfane sulfur

is formed from LA non-enzymatically under in vitro conditions in the presence

of visible light."

"....when LA samples were left for three days at room temperature and

unprotected from light, the amount of H2S strongly increased. These results

suggest that, in the presence of light, LA can be decomposed non-enzymatically

with H2S release."

"Interestingly, the results of this experiment demonstrated that H2S liberated

from seven-days LA left exposed to environmental light was nearly twice the

amount lower than three-days LA samples at both pH values."

mdpi.com/1420-3049/22/3/388...

WARNING: It has to be noted that hydrogen sulfide/H2S is poisonous at high levels so in my experiment I exposed R-alpha lipoic acid to light until I smelled rotten eggs -

the second day. So days 3-7 did not happen.. Without knowing the parts per million of Hs2 produced it is best to play it safe.

-------------

The supplementation of allicin in combination with R-alpha lipoic acid may help to

produce hydrogen sulfide levels in the body. And exposure of R-alpha lipoic acid to

sunlight produces both H2S and sulfane sulfur.

------

PTP1B

Alzheimer's/Parkinson's: Unexpected signaling role for foul-smelling hydrogen sulfide in cell response to protein misfolding

"Hydrogen sulfide is produced 'as part of the cell's response to endoplasmic reticulum

(ER) stress."

My article synopsis:

In ER stress, H2S is released and induces modification to an enzyme called PTP1B, (protein tyrosine phosphatase), thus preventing the inactivation of an enzyme called PERK, "which is a sensor of the presense of unfolded proteins and a critical regulator of the cell's response to ER stress."

sciencedaily.com/releases/2...

Theabrownin May Be the Main Bioactive Molecule in Pu-erh Tea

"This rust-brown colored pigment is also found in black tea but at lower concentrations (4% to 9% in black tea as compared to 10% to 14% in pu-erh tea)."

life-enhancement.com/magazi...

Application of theabrownin in pharmacy

4. theabrownin their formulations in the manufacture of proteins by tyrosine phosphatase inhibiting drug.

"Tea is a natural plant, drug side effects, theabrownin is one of the main active ingredient in tea, but tea has not yet found a clear structure theabrownin reported inhibition of PTP1B."

patents.google.com/patent/C...

[GymBag]

How does the body absorb the H2S gas? Through the nasal system ?

Why do you think that being able to smell strong hydrogen sulfide is a cut off point. What is the PPM that is a toxic level and can you measure in you experiment?

Last, how do you feel after exposure. It always made me sick to my stomach.

Really last. Is there any information that might indicate that exposure could cause or aggravate PD

[silvestrov in reply to GymBag]

In writing this post I concentrated on either the production of H2S by combining allicin and alpha lipoic acid or by exposing alpha lipoic acid to direct sunlight. What I left out was an excellent article entitled 'Rotten eggs, Rotorua and Parkinson’s disease' on the Science of Parkinson's Disease website: scienceofparkinsons.com/tag...

Rotorua ('sulfur city') is a New Zealand town who has continuous low level exposure to H2S and were shown to have finer movement/motor control than the the general population and H2S has been shown to degrade both alpha synuclein and beta amyloid (in the article).

I stopped the light exposure process when I first smelled H2S because of the following paragraph (Science of PD):

"The gas is both corrosive and flammable. More importantly, at high concentrations, hydrogen sulfide gas can be fatal almost immediately (>1000 parts per milllion – source: OSHA). And the gas only exhibits the “rotten eggs” smell at low concentrations. At higher concentrations it becomes undetectable due to olfactory paralysis (luckily for the folks in Rotorua, the levels of hydrogen sulfide gas there are between 20-25 parts per billion)."

So basically I stopped the process at 20-25 parts per billion (within the safety level).

I believe I exerted more control over the process of generating H2S by direct sunlight because I only allowed lipoic acid to be exposed to room temperature during the daylight hours and was refrigerated prior to and after exposure. In the following monogram of lipoic acid, 'ALPHA LIPOIC ACID Ingredient for weight loss, beauty and anti-oxidative products ORYZA OIL & FAT CHEMICAL CO., LTD.', they note that alpha lipoic acid is heat sensitive.

"6.

Stabilities of ALPHA LIPOIC ACID (1) Thermal Stability

Thermal stability of α-lipoic acid was examined.

"α-lipoic acid easily destroyed at temperature as low as 60ºC (as illustrated in Fig. 17). In general, there is a 25% loss of α-lipoic acid upon heating at temperature >60ºC."

oryza.co.jp/html/english/pd...

I keep alpha lipoic acid in the refrigerator for the obvious reason. If the researchers did not keep the alpha lipoic acid refrigerated prior to the generation of H2S by sunlight, the true potential of H2S generation may have been skewed downwards due to initial 25% loss of potency.

In the Science of PD H2S article the healthy population absorbed the H2S through their olfactory function and this raises a question about using H2S for therapy to PD patients. People with Parkinson's have impaired olfactory function and will this limit the absorption of H2S? And would an activated (sun exposed alpha lipoic acid swallowed) be a better source of H2S? So many questions, so little time.....

In the following article entitled "Luminal sulfide and large intestine mucosa: friend or foe?"....

link.springer.com/article/1...

......H2S appears to be either good or bad for the health. Does colonic microbiome diversity affect the production of H2S? PwP have a microbiome imbalance as compared to healthy individuals: time.com/4587498/parkinsons...

Normal Human Levels

"No information was located regarding normal levels of hydrogen sulfide in humans."

atsdr.cdc.gov/toxguides/tox...

So taking allicin and (non-sun exposed) alpha lipoic acid is best but I am trying this experiment since I cannot take both fish oil and allicin.

How do I feel after taking sun exposed alpha lipoic acid after 4 days? Fine. The only difference I feel after swallowing 300 mg R-alpha lipoic acid with 500 mg acetyl l carnitine is a slight uptick in my mood after ingesting the combined supplement. ALA and ALCAR is a nootropic and I could feel its effects in my head previously and it seems that its mental effect is slightly altered to effect mood and cognition versus only effecting cognition. Then again, everyone with some form of parkinsonism seems to react differently to therapy and this may be my own personal reaction (and this experiment may effect others differently).

[JANVAN in reply to silvestrov]

Interesting and same time difficult.....

How can I that "translate" by taking tablets of R-alpha-liponsäure. My doctor said I've have to take that, but now the box is already empty......which branch do you recommend ??

And what do you think about selenium drops ??

[silvestrov]

First of all I take 200 mcg of selenomethionine (divided doses of 100 mcg) everyday and it has been tested in PD models.

Selenomethionine Prevents Degeneration Induced by Overexpression of Wild-Type Human [alpha]-Synuclein during Differentiation of Neuroblastoma Cells [2005]

agris.fao.org/agris-search/...

The best forms of selenium are selenomethionine and selenium as derived from yeast cells. Sodium selenite is the inorganic form of selenium and is most commonly added to multi vitamins, etc....but it is not as well absorbed as either selenomethionine or selenium derived from yeast. Plus, in the full text of the above selenium study) they note that only selenomethionine and neither sodium selenite or methionine prevented alpha synuclein misfolding.

Taking selenium with alpha lipoic acid is a good idea because the following article noted.

In a rat model:

"Apparently in keeping with its metal chelating abilities (see below), this group noted that LA lowered selenium levels in the serum, heart, brain, and muscle;"

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

The article noted that alpha lipoic acid does not deplete metals, it modulates them - big difference. So though it may lower selenium levels it will not totally deplete them.

As for which brand to purchase? The ONLY brands I would consider buying are the ones which specifically note on the label, R-alpha lipoic acid. Every other brand which does not place an 'R' is part R and part S (synthetic) lipoic acid.

The following brand is R and it is either a 60 day or 30 day supply depending on which dose you take. (Unfortunately it is out of stock.)

geronova.com/store/products...

This product is more expensive than most but it is a combination of R-Lipoic Acid 75 mg, R-Dihydro-lipoic acid 75 mg. I do not take this brand but in the future I am going to try it (when it is back in stock). R-Dihydro-lipoic acid is the reduced (and most potent) form and it helps recycle vitamin C & E.

"DHLA appears to regenerate other endogenous antioxidants (e.g. vitamins C and E)." - (The above article.)

After taking a R-alpha lipoic acid supplement (which also has DHLA), the second best form of R-alpha lipoic acid is the sodium salt form:

"Carlson et al. followed appearance of R-LA in plasma following administration of its sodium salt to human subjects, and observed that both peak plasma appearance (Cmax) and total LA absorbed (area under the curve) were higher than that of the free acid [18]." (the above article)

This company has the sodium salt of alpha lipoic acid:

R-Lipoic Acid (from Sodium R-Lipoic Acid)* 100 mg.

geronova.com/store/products...

I am glad you asked to recommend a brand because I just finished reading the article about alpha lipoic acid and immediately looked for either the DHLA or sodium salt forms and I found the above brand. Many thanks....

The form I would have recommended (prior to reading the article) is this brand:

amazon.com/R-Alpha-Lipoic-R...

The 'beauty' of using a alpha lipoic acid supplement with DHLA or the sodium salt form(s) is you can use a smaller dose. More bang for the buck.

Finally, supplementing (which ever form) of ALA you use I also add acetyl l carnitine because it has synergy with ALA:

Combined R‐α–lipoic acid and acetyl‐L‐carnitine exerts efficient preventative effects in a cellular model of Parkinson’s disease

"Most notably, we found that when combined, LA and ALC worked at 100–1000‐fold lower concentrations than they did individually."

onlinelibrary.wiley.com/doi...

A bonus from reading the featured ALA article was one of its references:

?-Lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3-L1 adipocytes (PTP1B)

researchgate.net/publicatio...

Given the quality of either DHLA or the sodium salt form of ALA, I would forego any air exposure to generate hydrogen sulfide. Considering ALA can do this in the body, with help from garlic/sulfane sulfur/allicin, I would take the supplements in their original (unaltered form).

I hope this helps.

Rich

PS. a few more quotes from the article.

"The efficiency of LA uptake was also lowered by its administration in food,.."

It needs to be taken on an empty stomach.

"LA transport was also inhibitable by benzoic acid and medium-chain fatty acids,"

So if you are taking coconut oil, which is 60% medium chain fatty acids,

The coconut oil has to be taken at a different time than the lipoic acid.