14 replies to this topic

[JBForrester]

Hi Everyone, 

 

I wanted to see if we could compile a list of supplements that could potentially cause any sort of down-regulation of some kind within the body - basically supplements that you shouldn't take long-term and that should only be taken intermittently. I've tried to look online to see if there is a list anywhere, but I couldn't find anything of the sort, so I thought I'd reach out to you guys! It's the first thing I look for before taking any new supplements, but sometimes there's no information available. So far here is a list of supplements that I've read can cause down-regulation: 

 

- melatonin

- rhodiola rosea

- NAC

 

A pretty short list, but I'm super curious to hear what you guys know, experienced, or have researched. 

 

Thanks so much!

[Benko]

Not what you had in mind, but the only supp I've run across that you have to "cycle" on/off because the body develops tolerance was pramacetam which I took ages ago. 

 

 

I do not believe there is any feedback inhibition for melatonin.  Also, I personally have not experienced any lessening of effects from the 1 mg I've taken on and off, mostly on for years.

 

What evidence do you have that NAC induces tolerance?

 

PS You are lucking living in NZ.    Great place. Hope the volcanoes stay quiet.  

Edited by Benko, 30 June 2017 - 02:11 AM.

[joelcairo]

I'm also skeptical of this effect in melatonin. It sounds like a caution that turned into conventional wisdom and eventually into an accepted fact, simply by repetition. I take 10mg nightly, but if I skip it occasionally my sleep quality goes back to the previous normal, not worse.

 

BTW I take this dose for cancer prevention; a good night's sleep is just a pleasant side effect.

Edited by joelcairo, 01 July 2017 - 04:34 PM.

[normalizing]

what a stupid thread. all things in the world you consume or somehow welcome to your organism WOULD eventually naturally cause downregulation/dependency.

what, you think eating peanuts regularly would not cause your body to crave them when you dont have them anymore?

[JBForrester]

Not what you had in mind, but the only supp I've run across that you have to "cycle" on/off because the body develops tolerance was pramacetam which I took ages ago. 

 

 

I do not believe there is any feedback inhibition for melatonin.  Also, I personally have not experienced any lessening of effects from the 1 mg I've taken on and off, mostly on for years.

 

What evidence do you have that NAC induces tolerance?

 

PS You are lucking living in NZ.    Great place. Hope the volcanoes stay quiet.  

From what I've experienced and understand, with any hormone with which we supplement, this can down-regulate the body's natural production of it. I worry about taking any supplement of something that your body produces naturally. Regarding melatonin, what I've experienced is that upon taking it (mind you, I do not suffer from insomnia), the following night, I would be awake until 4 in the morning without any ability to go to sleep. There is something called "Rebound Insomnia", which, from what I understand, is something that is frequent upon the cessation of sleeping pills. 

https://en.wikipedia.../Rebound_effect

 

I couldn't find many studies to reference this, but perhaps melatonin has a similar effect? 

 

I'm also skeptical of this effect in melatonin. It sounds like a caution that turned into conventional wisdom and eventually into an accepted fact, simply by repetition. I take 10mg nightly, but if I skip it occasionally my sleep quality goes back to the previous normal, not worse.

 

BTW I take this dose for cancer prevention; a good night's sleep is just a pleasant side effect.

If we are speaking empirically, my experience is that my sleep got worse after trying out melatonin. Eventually it went back to normal, but for a while without it, I would experience insomnia, something that I never experienced previous to supplementing with it. 

 

 

Another question - there have been a lot of health gurus discussing the advantages of glutathione, but like I mentioned previously, I worry about taking anything that might negatively affect my body's natural production of it. Does anyone have any thoughts on this? 

[Benko]

 

Not what you had in mind, but the only supp I've run across that you have to "cycle" on/off because the body develops tolerance was pramacetam which I took ages ago. 

 

 

I do not believe there is any feedback inhibition for melatonin.  Also, I personally have not experienced any lessening of effects from the 1 mg I've taken on and off, mostly on for years.

 

What evidence do you have that NAC induces tolerance?

 

PS You are lucking living in NZ.    Great place. Hope the volcanoes stay quiet.  

From what I've experienced and understand, with any hormone with which we supplement, this can down-regulate the body's natural production of it.

 

 

1. What you read is based on the fact that there are feedback loops so that e.g. if you take certain hormones the body senses that and makes less. As far as I know these feedback loops do not exist for melatonin.  Don't believe me, research it for yourself.

 

NB: melatonin is a hormone, not a man made sleeping pill.  Having said that, if it doesn't work for you, don't take it.  

 

2. Re: glutathione:

 

A. You'll need someone with more biochemistry than I to address feedback and glutathione.   

 

B.  From Josh Mitteldorf (Cracking the Aging Code):

 

https://joshmitteldo...og.com/2017/07/  [scroll down]

 

 title of this blog entry is 

Mitochondria in Aging, II: Remedies

Gutathione / NAC

I’ve never heard anyone say a bad word about glutathione.  It’s the antioxidant with no downside.  Genetic modifications that upregulate glutathione have increased lifespan in worms, flies and mice.  

For a long while, it has been assumed that you can’t eat glutathione, because it doesn’t survive digestion.  Some researchers at Penn State disagree, finding impressive increases in tissue and blood levels when people were supplemented with up to 1 g per day raw glutathione.  Liposomal glutathione is an oral delivery form that gets around the digestion problem, especially when taken with methyl donors like SAMe....

For the future, we might hope to do better.  Less than 20% of the cell’s glutathione actually makes its way to the mitochondria, where it is most needed. 

Edited by Benko, 01 September 2017 - 11:00 PM.

[aconita]

Exogenous melatonin doesn't cause any down regulation, dependency or affects in any ways endogenous production.

 

https://examine.com/...ents/melatonin/

[normalizing]

im still skeptical of this as many people report insomnia after stopping melatonin including me. why would that be? perhaps its not related and we already have insomnia problems to begin with and melatonin only helps temporary

[Benko]

im still skeptical of this as many people report insomnia after stopping melatonin including me. why would that be? perhaps its not related and we already have insomnia problems to begin with and melatonin only helps temporary

 

 

If you believe stopping melatonin will cause insomnia (and it sounds like you do), it will. 

Edited by Benko, 02 September 2017 - 03:29 AM.

[aconita]

You have insomnia, you take melatonin, insomnia is solved, you stop taking melatonin, insomnia is back.

 

Does that mean exogenous melatonin leads to down regulation or affects in any way endogenous production?

 

I don't think so. 

[normalizing]

that is what im trying to figure out though. as all hormones, natural downregulation can occur over prolong use of them. im just not very convenienced melatonin is that special and never causes downregulation. for one, it hasnt been studied enough and paid attention to and good trials are done so i will stay negative about it as far it goes

[aconita]

No comment.

 

 

[JBForrester]

im still skeptical of this as many people report insomnia after stopping melatonin including me. why would that be? perhaps its not related and we already have insomnia problems to begin with and melatonin only helps temporary

Three years ago when I took melatonin for the first time, I had always had a normal, healthy sleeping pattern, and would soundly sleep 7.5-8 hours every night. I only took melatonin because it was given to me by a friend - it was one of those "dream water" supplement bottles (opposite of those 5-hour energy bottles). I slept soundly as usual that night, along with a bit of a deeper sleep and feeling a little more refreshed. The next night was the first time I had ever experienced insomnia. I was up until 4am (after going to bed at 10pm)! So, to answer most of the comments here, I don't think everyone experiencing these rebound insomnia had prior insomnia problems.

 

 

im still skeptical of this as many people report insomnia after stopping melatonin including me. why would that be? perhaps its not related and we already have insomnia problems to begin with and melatonin only helps temporary

 

 

If you believe stopping melatonin will cause insomnia (and it sounds like you do), it will. 

 

In response to this, I was too ignorant about melatonin to even hypothesize that it would cause insomnia, so I don't believe any pre-existing belief would cause insomnia. 

 

You have insomnia, you take melatonin, insomnia is solved, you stop taking melatonin, insomnia is back.

 

Does that mean exogenous melatonin leads to down regulation or affects in any way endogenous production?

 

I don't think so. 

And again, I did not have or had ever experienced insomnia prior to taking melatonin, and once I stopped taking the supplement (I took only one day of it), I was back to normal after two days. Chissa'!

[aconita]

If you read the a few post ago link I provided you'll see there is no research finding disruption of sleep patterns due to melotonin, not even at very high dosage, it just doesn't make a dent to endogenous production, and research about melatonin is quite extensive, we aren't talking about some obscure substance here.

 

Not even any remarkable influence on sleep patterns while on it have been found apart for a tendency to shorter lag time to fall asleep.

 

That said it is what the vast majority of people would be likely to experience but it doesn't necessarily mean there will be no exceptions.

 

Since melatonin does a bit more than just signaling time to fall asleep but starts an hormonal cascade which involves complex mechanisms it might be possible that what you did experience isn't related to the melatonin sleep signals themselves but to its effect on the hormonal balance in its whole, which might, and I underline MIGHT, mean something there isn't as it should. 

 

After years of continuous melatonin supplementation I don't find any difference in my sleep when on or off it.

[joelcairo]

How does one single use of melatonin cause downregulation of the hormone or dependency in the body? It doesn't.