Sulforaphane, NAC, H2O2, and the Circadian Rhythm

[Bolt_Upright]

I have no answers. Just questions. Questions about Sulforaphane, NAC, and their effects on the Circadian Rhythm.I recently stopped taking my Broccoli Sprout Tea as it boosts NRF2, and boosting NRF2 may amplify the Circadian Rhythm, but if you want to amplify the Circadian Rhythm you probably want to boost it at the correct time (you don't want to boost it on the down-stroke). I don't know when the natural peak in NRF2 is supposed to be, and I don't know how long from ingesting Broccoli Sprout Tea before the NRF2 gets boosted. I know, in mice, there is a 12 hour lag between boosting H2O2 and the NRF2 boosting. Also, the Sulforaphane boost of NRF2 may last days, so what is the effect of 36-48 hours of elevated NRF2? See "NRF2 regulates core and stabilizing circadian clock loops, coupling redox and timekeeping in Mus musculus" ncbi.nlm.nih.gov/labs/pmc/a...

So... while researching this NRF2 issue (in the same article) tonight I found this gem: "Reinforcement of circadian amplitude, following the addition of H2O2, could be blocked in the presence of an antioxidant (N-acetylcysteine; NAC) (Figure 4D), suggesting that oxidation was indeed the relevant signal responsible for the reinforcement of circadian amplitude. Interestingly, treatment with NAC alone resulted in significantly decreased rhythm amplitude and period length, suggesting that endogenous oxidative signals (Sies, 2017) may play a role in the maintenance of circadian timekeeping."

What I am reading (with my High School education) is: H2O2. Peroxide. Oxidation. May be part of the natural control of the Circadian Rhythm. And if you tamp down H2O2 with NAC, you "significantly decreased rhythm amplitude and period length". This does not sound good. I take NAC. I just ordered 10 more bottles.

- Maybe I should not take NAC? Or maybe I need to time my NAC? When is the best time to dampen H2O2 and how long from NAC ingestion to H2O2 dampening?

I apologize. If you take away only one thing from this, it is: I only have a High School degree. There is a good chance I am way off base here.

[park_bear]

This was a cell culture study where they could control the concentrations of H202 and NAC at will. This is not the case in the intact animal:

jasn.asnjournals.org/conten...

"[NAC] pharmacokinetics are remarkable for almost complete first pass metabolism after oral administration, resulting in no free drug reaching the circulation."

Internal H2O2 is completely regulated by the body.

The study you have cited is interesting theoretical work but it should not be taken as applicable to the whole human.

[Bolt_Upright in reply to park_bear]

Thank you so much park_bear! Especially since I just got my 10 bottles of NAC!

[park_bear in reply to Bolt_Upright]

It appears that the reference I cited in my prior comment was not entirely accurate:

pubmed.ncbi.nlm.nih.gov/202...

"After an oral dose of N-acetylcysteine 200 to 400 mg the peak plasma concentration of 0.35 to 4 mg/L is achieved within 1 to 2 hours."

I do take NAC personally and it does have many beneficial qualities. It has been shown to improve Parkinson's although that was likely due to high concentrations from IV administration. I would not worry about the cell culture study.

If you are just starting to take it you could track its effect upon sleep which could be affected by a modification of biological clocks.

[Bolt_Upright in reply to park_bear]

I've been taking it for months and months. Looks like more digging is needed.

If we are attempting to save mitochondria by reducing H2O2 and H2O2 controls the circadian rhythm, well... that could be a problem. Or I could be way wrong.

[Smittybear7]

Some of the alternative supplements for Parkinson's include NAC. Restore gold and life extension .I take it twice a day as directed by the nutritionist/pharmacist I am working with. Thanks for sharing

[Bolt_Upright]

I have been studying the circadian rhythm: Light and diet affect the circadian rhythm. I have learned that light affects the SCN circadian rhythm and diet affects the circadian rhythm of the cells in the body. I have started eating only during the sunlight hours, as I read that eating outside of daylight hours can put your cellular circadian rhythm out of sync with the SCN. I am also getting up at dawn, walking outside in the morning, and wearing blue blocker glasses after sundown.

I have decided to take the Sulforaphane in the morning as the circadian rhythm is on the rise (A) and go back to taking my NAC (plus Taurine) at night as the circadian rhythm is on the decline (B).

circadian rhythm