Updated x2: NAC May Mitigate Coronavirus Severity, also Potential Risks

[park_bear]

I wrote about a study indicating that NAC is beneficial in Parkinson's here: healthunlocked.com/parkinso... That benefit may have been due to NAC administered by the IV route.

The idea that NAC may mitigate coronavirus severity is based upon the effect of NAC upon influenza. From an article entitled: "Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus": sciencedirect.com/science/a...

"Glutathione production can also be promoted by administration of N-acetylcysteine (NAC), which has been shown to be protective in rodents infected with influenza.16., 17., 18. In a little-noticed 6-month controlled clinical study enrolling 262 primarily elderly subjects, those receiving 600 mg NAC twice daily, as opposed to those receiving placebo, experienced significantly fewer influenza-like episodes and days of bed confinement.19 Although the rate of seroconversion to influenza A was comparable in the two groups – indicating that they were exposed at the same frequency – only 25% of the virus-infected subjects in the NAC group developed symptoms, as contrasted to 79% of those of placebo. (Given the carnage that influenza wreaks among the elderly, it is most regrettable that no effort has been made to replicate this study, conducted over 20 years ago.) The particular utility of NAC in the elderly might reflect the fact that plasma cysteine levels and cellular glutathione levels tend to decline with advancing age.20" [Emphasis added]

Beneficial Effects Of NAC For Other Respiratory Conditions

COPD [Chronic obstructive pulmonary disease] patients treated with NAC had fewer exacerbations:

sciencedirect.com/science/a...

"we noted 497 acute exacerbations in 482 patients in the N-acetylcysteine group who received at least one dose and had at least one assessment visit ...and 641 acute exacerbations in 482 patients in the placebo group (... risk ratio 0·78, ... p=0·0011)."

Meta-analysis of use of NAC in COPD:

sciencedirect.com/topics/me...

" A meta-analysis of randomized controlled trials retrieved from PubMed and Medline databases (12 trials; 2691 patients). High-dose [relative ratio (RR) = 0.90...P = 0.041] and low-dose (RR = 0.83... P = 0.043) NAC reduced COPD exacerbation prevalence. Long-term (≥6 months), but not short-term, NAC reduced exacerbation prevalence (RR = 0.85...P = 0.024)."

NAC has been reported to be useful in studies of cystic fibrosis patients:

cysticfibrosisjournal.com/a...

" Results: Lung function (FEV1and FEF25–75%) remained stable or increased slightly in the NAC group but decreased in the placebo group"

High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis:

pnas.org/content/103/12/462...

" N-acetylcysteine, given orally in high doses (0.6 to 1.0 g three times daily, for 4 weeks). ... Consistently, neutrophil burden in CF airways was decreased upon treatment (P = 0.003), as was the number of airway neutrophils actively releasing elastase-rich granules (P = 0.005)...positive treatment effects ... included decreased sputum IL-8 levels (P = 0.032). "

Please be aware that some animal studies have found potential adverse effects: Here is a study showing NAC caused pulmonary arterial hypertension (PAH) in an animal model:

jci.org/articles/view/29444...

jci.org/articles/view/33136

PAH is a serious and relatively unusual condition. When there was a rash of cases of PAH caused by a diet pill combination it was rapidly tracked down to the source. NAC is a common supplement. If it were causing PAH in humans it seems likely it would have been noticed. Poor exercise tolerance is a symptom of PAH. I personally have been taking NAC for years and have excellent exercise tolerance. That said, I am in no position to make any guarantee to others regarding NAC and PAH.

Another study found NAC accelerated development of cancer in an animal model:stm.sciencemag.org/content/...

insight.jci.org/articles/vi...

blogs.sciencemag.org/pipeli...

Apparently this was a result of NAC being an antioxidant, preventing DNA damage, and down regulating the p53 gene as a result. This concern applies to any antioxidant, such as vitamin E which was also found to have the same effect. For what is worth, folate supplementation is even worse - has been demonstrated to increase cancer incidence in humans. I wrote about that here - Folate Supplementation Carcinogenic tinyurl.com/ycdrz5lj

For important additional perspective on this see comment by rescuema here:

healthunlocked.com/parkinso...

Although I do take NAC myself, in view of the foregoing I cannot say whether anyone else should take it or not. Each person must decide for him or herself whether the benefits sufficiently outweigh the risks to make NAC supplementation appropriate.

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

Update - Dr. Seheult with additional information:

youtu.be/Dr_6w-WPr0w(Not working as expected?)

[rescuema]

Add glycine to the NAC and it'll be even more potent in the benefit

academic.oup.com/biomedgero...

[park_bear in reply to rescuema]

This is very interesting because there is research indicating that the abnormal Alpha synuclein of Parkinson's degrades mitochondria:

"Several mitochondrial genes reduced with aging were upregulated in hearts by NAC+Gly diet supplementation. These Krebs cycle and oxidative phosphorylation enzymes, suggesting improved mitochondrial function, and permeabilized cardiac fibers from NAC+Gly-fed mice produced ATP from carbohydrate and fatty acid sources, whereas fibers from control old mice were less able to utilize fatty acids"

[rescuema in reply to park_bear]

Yup, but also supporting methylation with enough methyl donors such as SAM is the key to improving the transsulfuration pathway rate for the glutathione synthesis, so that excess homocysteine can be redirected by the CBS enzyme that also requires serine, B6, and iron.

When oxidative stress is present, your body wants to make glutathione through a feed-forward mechanism, but this will take a backseat to the priority of creating SAM for the main methylation pathway to convert methionine, and you need SAM to produce glutathione. So low SAM, a high risk of low glutathione and compromised detox.

In the very least, to help fight the oxidative stress, you need adequate Zinc, Magnesium, and B6 for glutathione. If you get deficient in B6 (via C/L), you can see the negative implication.

To help spare SAM (depending on where the jam is) in the state of methyl donors shortage, you may possibly supplement with TMG/Betaine (to improve choline pathway) and/or Creatine as needed to indirectly boost the detoxification through NAC+Gly.

[beaglefan1 in reply to rescuema]

My neurologist tested my B6. The normal range is 5-50ug/L, mine was 3ug/L. As B6 had never been tested before I have no idea how long it was this low.

I'm taking 50mg in the P-5-P form. It should be daily but it has been 3-4x/week, because of the need to take it away from c/l (Rytary in my case). I'm due for labs but haven't figured out how to do that safely here in Washington state. (Covid-19)

My neurologist ordered the B6 levels because I was having numb tingly feelings in both feet. That has improved 60-70% since starting the P-5-P.

[rescuema in reply to beaglefan1]

Look into sublingual P5P to enhance absorption. If your blood level was that low, it's probable that the level was even lower in the brain compared to the periphery. Also look into supplementing Allithaimine (TTFD B1), so that you gain synergistic benefit past the blood brain barrier along with B6.

[beaglefan1 in reply to rescuema]

Thank you for your reply. What dose of allithiamine? Also I try to take the P-5-P two hours before or after Rytary. Do you have any resources regarding timing?

Also I started taking NAC since then my sense of smell has improved. Of course I can't say it is the NAC, too many variables.

[rescuema in reply to beaglefan1]

Start with 50mg per day, which is 1 pill for a few weeks. You may increase the dosage as needed but probably unnecessary for a long-term strategy, but if you want to titrate up as you notice improvement of symptoms, go up slowly to adjust as needed. Unless your diet is pristine, you'll need to supplement with a good multi vitamins or b complex, since all Bs must work in concert to allow the cogwheel to turn. Adding a sublingual b12 is also a good idea.

As for P5P, at least a few hours before C/L is ok as you're doing now, but best if furthest away from the meds as possible to avoid interfering with the drug mechanism. It would be a good idea to continually monitor your B6 status with your neurologist.

[beaglefan1 in reply to rescuema]

Thanks, I do take a B complex at the same time. I will get levels checked soon.

[healthabc in reply to beaglefan1]

NAC is definitely & directly beneficial to my sense of smell too! I have tested it out....

[glenandgerry in reply to rescuema]

Thanks for this - very helpful. You're such a mine of information. I seem to be supplementing the right things for my husband eg B6, Zinc, Magnesium, Vitamin B1, B12, NAC, plus lots of other things but it's all a bit 'trial and error' as I'm not as scientific as you.

[rescuema in reply to glenandgerry]

Thanks. I keep my mind open and learn down to the nitty-gritty to try seeing the big picture. I posted the below movie link on another recent post, but since we're all under a lock-down, it might be a good entertainment and a case for upping the l-serine mentioned above.

amazon.com/TOXIC-PUZZLE-Hun...

sciencedaily.com/releases/2...

academic.oup.com/jnen/advan...

[ParlePark in reply to rescuema]

Rented toxic puzzle. Excellent film. Thanks!

[rescuema in reply to ParlePark]

Another piece of puzzle under our belt.

[zawy]

20,000 IU vitamin D 3x a day stops any flu I get from being anything more than being tired and with sniffles. This raises blood levels of D3 dangerously high, so it shouldn't be done more than a few days. I've hit friends and family with it as I keep the vit D3 handy and they are universally impressed. 15 to 30 minutes later, we feel a lot better. Zinc lozenges and only hot water to drink are also important. I also do massive amounts of A but I don't know if it helps and I don't do it nearly as regularly as the D3. I could never see more than a small benefit to vitamin C at 1 gram every hour. I had an odd "flu" that lasted 1.5 days. It was odd because besides being very tired and initially starting with minor scratchy throat, I had a headache the whole time and ringing in the ears. The ringing in the ears is the only thing distinctive from a flu that happens in COVID patients and I don't hardly ever get a headache like it was.

[park_bear in reply to zawy]

Indeed there is good evidence showing vitamin D mitigates respiratory infections. However, I not been aware of the idea of attacking it so aggressively. Thanks for your report!

[GymBag in reply to zawy]

"This raises blood levels of D3 dangerously high," what are the indicators that one has taken enough or too much. What is the side effect that you are concerned about .

Zinc lozenges , I have never herd of them is ingesting zinc safe or just doable if the end is near?

I understand that this treatment would be an emergency only but at what stage do you start it.

[park_bear in reply to GymBag]

Zinc lozenges are readily available over the counter. No safety issues that I am aware of but have not researched the matter. The issue with zinc is to get protection against coronavirus it needs to get inside the cell. It seems the antimalarial drug chloroquine does that. This video explains the details:

youtube.com/watch?v=U7F1cnW...(Not working as expected?)

[parkie13 in reply to park_bear]

I really enjoy his presentations.

[park_bear in reply to zawy]

Overdose:

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

"The skin produces 10,000 units of vitamin D after total body exposure to UV light. The current tolerable upper intake level in both Europe and North America is 50 ug/day (2000 iu/day) but overwhelming bulk of clinical trial evidence indicates that prolonged intake of 10,000 units of vitamin D3 likely poses no risk. Because of this wide therapeutic index, vitamin D toxicity is extremely rare, but does occur at excessively high doses. Doses more than 50,000 IU/day raise levels of 25(OH) vit D to more than 150 ng/ml and are associated with hypercalcemia and hyperphosphatemia.4 Vitamin D intoxication can be iatrogenic, due to self medication...

Ten patients with various features of hypercalcemia due to vitamin D overdose were seen over a decade from 2000, and included 6 male and 4 female patients with ages ranging from 48 to 75 years (median: 61 years). The patients presented with clinical features of lassitude (n=3), vomiting (n=4), polyuria (n=5)[excessive urination], polydispsia (n=5)[thirst], altered sensorium (n=4) [inability to think clearly or concentrate], anorexia (n=3) and oliguria (n=5) [the production of abnormally small amounts of urine.]...

The dose of vitamin D ingested ranged from 3.6 million units to 210 million units over periods ranging from 1-4 months (median: 2). "

3.6 million units over 2 months would amount to 60,000 units per day. I am also aware of a supplementation trial that gave patients 100,000 units every four months. It would seem that 20,000 units daily for a few days is unlikely to cause toxicity.

[zawy in reply to park_bear]

Yeah, I looked at it later and fuond out my dosing was safer than I thought. If I get anything like the COVID I'll be taking 25,000 IU 4 times a day for a week. But I don't know how vitamin D3 works because I would have thought it assists the immune system in some way instead of immediately killing viruses. But from my experience in colds/flu, it acts so quickly it must kill them more directly.

Here's a review of vit D in treating viruses as it relates to COVID. Judging from the data, it looks like there would be less than 1/2 the current ER visits and deaths from COVID if people took 10,000 IU a day now and did my dosing if they got it. But judging from my experience with flu, I would not be surprised if it was 1/8 as many ER visits

preprints.org/manuscript/20...

[Sapeye2020 in reply to zawy]

MED CRAM # 50 is on the news stand and it covers more about the Natural Killer cells and how to boost them earlier in the cycle... Very interesting.

[zawy in reply to park_bear]

I noticed a small study showing a simple 60,000 IU once per month had a 40% increase in falls in those > 70 yrs old that have already had a fall. 200 people divided into 3 groups. 24,000 IU once per month had fewer falls than 60,000 IU. They were studying this because higher blood levels of vit D were associated with fewer falls so it's a confusing situation that will take them forever to figure out.

[Gioc in reply to zawy]

I notice a correlation between the lack of vitamin D, the pollution from fine particles, the areas affected by the virus and the elderly age of the people. This correlation proves nothing but is curious..

scholar.google.it/scholar?q...

scholar.google.it/scholar?q...

This recent paper entitled: Position Paper Report on the effect of pollution of atmospheric particles and the spread of viruses in the population. (you have to copy / paste it in the address bar of the browser, only in this way it works). brings us to subsequent videos.

‘simaonlus.it/wpsima/wp-cont...

Pollution in Italy (lombardy) Skorea , Wuhan 2020

youtu.be/YECpQhR9cAA(Not working as expected?)

youtu.be/UwlQkgLKPtQ(Not working as expected?)

This video relates the spread of the virus with the climate, except Turkey which has no pollution !!!!

Remember that at the end of winter we have the lowest point of vitamin D in the body.

youtu.be/9w58SYc7JYY(Not working as expected?)

In my opinion there are many indications that vitamin D3 deficiency favors the spread of the virus.maybe.

[MBAnderson]

Thanks much.

[Gioc]

Contro la mia ultima influenza di metà febbraio il NAC mi ha fatto molto bene.

Lo ha usato anche mia zia di 83 anni con lo stesso problema con buoni risultati.

Io ho preso 600mg di NAC 2 volte al giorno per 10 giorni e ho risolto la fase acuta della forza tosse che avevo.

Io vivo in Provincia di Como, Lombardia, Italia. lo trovi scritto nei miei post.

Ho l'impressione che il prodotto vecchio possa perdere di efficacia.

Io prendo il tipo granulare effervescente.

[park_bear in reply to Gioc]

Translation:

The NAC did me a lot of good against my last flu in mid-February.

My 83 year old aunt also used it with the same problem with good results.

I took 600mg of NAC 2 times a day for 10 days and resolved the acute cough strength phase I had.

I live in the Province of Como, Lombardy, Italy. you find it written in my posts.

I have the impression that the old product may lose effectiveness.

I take the effervescent granular type.

------

Thanks Gio!

Good to have this report!

[Gioc]

hi Park Bear, thank you for traslation and the post.

[rescuema]

I agree that people should be aware of the potential for "existing cancer" growth when taking antioxidants such as NAC. However, you should be aware that this warning applies to pretty much any antioxidant that fight the damaging reactive oxygen species (ROS) and reactive nitrogen species(RNS) that are byproducts of the normal mitochondrial metabolism and immune function that over time could actually trigger the DNA/protein/membranes damage that could give rise to cancer and neurodegeneration if not mitigated.

Once/if you have cancer cells, the malignant cells are vulnerable (as the normal cells) to the damaging ROS/RNS that could cause apoptosis (kill cancer), but the tumors actually benefit from the excess antioxidants such as NAC, glutathione, vitamin E, vitamin C, resveratrol, beta-carotene, etc. more than the normal cells leading to faster growth, the same as in certain nutrients and B vitamins. However, you must put this into a proper context since your normal cells NEED antioxidants to combat the damaging ROS/RNS to start with, and your body does not simply depend on p53 tumor suppressor genes activated by ROS/RNS attempting DNA damage inside your cells, but through multiple mechanisms to kill precancerous cells including the immune system not dependent on p53. In mice that didn't have cancer, the same dose of antioxidants did not cause cancer, but in fact prevented DNA/protein damage that engender cancer.

So the bottom line is that we depend and require antioxidants to survive the daily assault of oxidation that could give rise to cell mutations over time. If you're already deficient in glutathione to counter oxidative stress, you (especially PWP) would benefit more from supplementing with antioxidants such as NAC than worrying about the potential for fueling new tumor, especially to combat/clear the protein aggregates that contribute to neurodegenerative diseases and to prevent cell membrane rigidity that affect neurotransmitter transporter/receptor functions. If you already have metabolic syndrome/disease and your mitochondria are working inefficiently and producing even more of ROS, the need for antioxidants naturally go up as long as you're not already diagnosed with cancer. Avoid going overboard with antioxidant supplements but do seek to have enough so that your body can combat the assault of the oxidants. Antioxidant therapy is controversial but mostly found to be beneficial even with chemotherapy which kills cancer cells by increasing free radicals and oxidative stress.

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

For what it's worth, there's an inverse relationship of PD and overall cancer risk - and you tend to be in shortage of antioxidants such as glutathione.

"there have been many epidemiological studies over past decades that have shown that patients who have had cancer have a lower risk of developing PD than the general population. Other studies have shown that people with PD have lower overall cancer risks than people without PD."

apdaparkinson.org/article/c...

"In people with PD, glutathione levels are lower in the brain, specifically in the substantia nigra (the area in which dopamine cells are lost). Also, the level of reduction in glutathione has been associated with Parkinson's disease severity (less glutathione, more advanced PD)."

michaeljfox.org/news/ask-md...

[parkie13 in reply to rescuema]

What kind of glutathione should we be using? Also what is a good dosage? Should we be using every single day or make up a different schedule?

[Despe in reply to parkie13]

Mary,

rescuema is more qualified to answer your question. However, Dr. Mischley did recommend to my husband to stop NAC and start Glutathione. He was getting intranasal glutathione (her prescription) for about 1 1/2 months. Then she recommended QuickSilver Liposomal 5 pumps X 2 day.

[parkie13 in reply to Despe]

Thank you

[rescuema in reply to parkie13]

As mentioned by Despe, look into liposomal or S-acetyl glutathione - cross the BBB.

Dr. Mischley is actively working with the MJF foundation and "attempting to determine whether (in)GSH boosts brain glutathione and improves health" and as far as I'm aware there's no definitive data on the magnitude of benefits.

Also as discussed above, NAC + glycine (and l-serine) are good inexpensive precursors to increase glutathione + other benefits. You must ensure not be deficient in B6, Zinc (needed to convert homocysteine to glutathione), etc., while not going low on methyl donors through good nutrition - thus glutathione supplementation is a quicker measurable shortcut. The below are decent articles with more detail on NAC and glutathione for you to check out.

scienceofparkinsons.com/201...

selfhacked.com/blog/glutath...

healthline.com/nutrition/ho...

[parkie13 in reply to rescuema]

Thank you

[park_bear in reply to rescuema]

Thanks for adding this perspective.