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Sensitivity to NAD+ precursors and inflammation?

nad+ sensitivity inflammation side effects nam niacinamid

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#1 Biotochandron

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Posted 01 July 2020 - 12:09 PM


Hello

 

As I do have mitochondrial damage due to fluoroquinolone toxicity I read Turnbuckles thread on manipulating mitochondria with great interest.

 

About one year ago I started to take NAM + R cyclically. I always felt euphoric and energetic on the day of taking it. And in the days that followed I got muscle and tendon pain which I attributed to the reduced mitochondrial mass (mitophagy due to increased fission).

 

However then I observed that I could tolerate less and less NAM + R and the pain reactions became stronger and stronger and lasted for weeks after taking NAM + R for just one day.

 

Last year I could tolerate two days of 1,7g NAM + R in the beginning and had only slight muscle pain for some days - and this year doses of 1x 400mg NAM + R almost crushed me and set my achilles tendons and muscles all over my body on fire for over two weeks.

 

Three months ago I switched to NR and get the exact same reactions. I never take NR more often than one day per week.

 

I took 1x 175mg NR 10 days ago. As always I felt euphoric and good on the day of taking it, but now it feels like my whole body is inflamed and I can hardly walk more then 300 meters because of the knee pain and burning achilles tendons.

 

At the beginning I welcomed these symptoms and hoped that my defective mitochondria were cleared up.

 

But now I have the feeling that I have developed a sensitivity to the smallest doses of NR?

 

I know some of you have this issue with resveratrol but are there others who have it also with NAD + precursors?

 

Any ideas on that? Will stop taking NR now and hope that I return to baseline over weeks and months.

 

In the weeks after such a "NR flareup" I noticed that my body reacts with extra pain and tendon burning after every meal (whether carbs are included or not) and I'm already on an anti-inflammatory diet. So I suspect NR is somehow messing with my mitochondria and my immune system.

 

 



#2 Michael

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Posted 01 July 2020 - 04:25 PM

You should first be aware that Turnbuckle's protocol is based almost entirely on in vitro studies on single components of the protocol: there is nothing to show that a human or even a mouse following his protocol derives the sequential effects on mito fission and fusion that he postulates, let alone the health benefits.

 

In any case, there are many, many reports of joint pain linked to higher-dose resveratrol supplementation, possibly resulting from inhibition of aromatase (inhibition of estrogen production has been associated with joint pain in all forms of estrogen production inhibitors):

https://www.longecit...rol-and-joints/

https://mindblog.der...iment-with.html

https://web.archive....-of-resveratrol

https://www.livestro...ts-resveratrol/

https://www.longecit...-and-bad/page-8

https://www.google.c...trol joint pain

 

 

 

 

 


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#3 Biotochandron

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Posted 01 July 2020 - 05:46 PM

You should first be aware that Turnbuckle's protocol is based almost entirely on in vitro studies on single components of the protocol: there is nothing to show that a human or even a mouse following his protocol derives the sequential effects on mito fission and fusion that he postulates, let alone the health benefits.

 

In any case, there are many, many reports of joint pain linked to higher-dose resveratrol supplementation, possibly resulting from inhibition of aromatase (inhibition of estrogen production has been associated with joint pain in all forms of estrogen production inhibitors):

https://www.longecit...rol-and-joints/

https://mindblog.der...iment-with.html

https://web.archive....-of-resveratrol

https://www.livestro...ts-resveratrol/

https://www.longecit...-and-bad/page-8

https://www.google.c...trol joint pain

 

Thanks for your post and provided links.

 

I understand that Turnbuckles protocol is experimental. I don't even use the whole protocol but just use a low dose of NR (much less than what is normally taken every day) less than once a week.

 

What is interesting is that the pain symptoms build up over many days after NR usage and often reach a peak after 10 days and then it slowly gets better. I can't make sense of it.

 

Turnbuckl has considered that if I am getting increasing side effects day by day after only one dose of N+R (or NR), then I may be experiencing a build up of glycogen and waste materials that lysosomes are tasked with dealing with - as the lysosomal system might be overwhelmed due to heavy load of defective mitochondria.

 

Furthermore the reduction in the mitochondrial mass could lead to an upregulation of glycolysis, which could explain my symptoms. However it does not explain why I get more sensitive to these side effects. It feels like my physiology has a memory of this stress stimulus.

 

 

One possibility to explain these observations would be that the absence of mitochondria significantly impairs the cell‘s energy production capacity, thereby precluding the execution of the senescence programme. In order to test this hypothesis, we analysed the bioenergetics status of mitochondria‐depleted cells. Analysis of the extracellular acidification rate (ECAR) (Fig EV2A) confirms that mitochondria‐depleted senescent cells have a substantially increased glycolytic rate when compared to controls; the addition of the glucose uptake inhibitor 2‐deoxyglucose (2DG) has a considerably stronger effect in ECAR of mitochondria‐depleted cells than in controls (Fig EV2A). Furthermore, glycolysis‐dependent ATP production rate is greater in mitochondria‐depleted senescent cells than the ATP production rate driven collectively by both glycolysis and OXPHOS in controls (Fig EV2B). Subsequent measurements of steady‐state cellular ATP levels confirmed that these were elevated in mitochondria‐depleted cells when compared to senescent controls (Fig EV2C). Consistent with a reliance on glycolysis, glycolysis‐associated genes were generally up‐regulated in mitochondrial‐depleted senescent cells (Fig EV2D). Together, these data suggest that the failure to execute the senescence programme is not dependent on ATP levels.

 

www.embopress.org/doi/10.15252/embj.201592862

 

 

 

To say something about Turnbuckl's protocol I want to share the experiences from some severely fluoruqouinolone damaged people of our FQAD forum. Especially when people applied the protocol in the first few months of their "floxxing/poisoning" they were able reverse much damage in a few cycles. At first they could not tolerate more than one day 500mg NAM + R without severe symptoms but after >10 cycles they could do two days of 2g NAM + R with only minor symptoms until their pain and limitations in life have almost completely disappeared. So the protocol of cycling NAD+ precursors might a game changer in the early stages of FQAD. In the later stages it seems more difficult to tolerate even the smallest doses of NAM, NR or NMN.


Edited by Biotochandron, 01 July 2020 - 05:48 PM.

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#4 Harkijn

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Posted 04 July 2020 - 04:14 PM

Hi Bio,

 

You're in a bad predicament and I sympathize. Therefore I urgently advise you to look elsewhere for possible cures and care. Some of the 'protocols' vented on this site cannot even be called experimental but at best hypothetical or experimental.

And if you want to read up on the downsides of taking NAM Longecity has a number of informative topics such as this one:

ttps://www.longecity.org/forum/topic/107181-nicotinamide-worse-than-nicotinic-acid-for-homocysteine/



#5 MikeDC

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Posted 05 July 2020 - 06:57 PM

I always said people on the manipulating mitochandria dynamics are drug addicts. High dose NAM may have done some long term damage.
You know most NR turns to NAM. So you are really allergic to NAM.

#6 Biotochandron

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Posted 08 July 2020 - 02:01 PM

I always said people on the manipulating mitochandria dynamics are drug addicts. High dose NAM may have done some long term damage.
You know most NR turns to NAM. So you are really allergic to NAM.

 

I don't know why but I have found that I need at least twice the amount of NAM to get the same effects of NR. This applies to the positive effects as well as the negative effects.

 

So I need 300mg NAM to get the effects of 150mg NR (euphoria and energy on the day of taking it and muscle pain all over the body a few days later).

 

But 150mg NR contains only 75mg NAM. So 300mg NAM has 4x more NAM than 150mg NR. If the allergy is to NAM it does not make sense to me that I tolerate more NAM than NR?

 

Another thing is that there are some people in our forum who started with NR and never tried NAM and still have this phenomenon of getting those nasty flare ups. And we alle have in common that we have mtDNA damage due to fluoroquinolones. However, the phenomenon of increasing sensitivity is strange to me - yes it's just like an allergy.

 



#7 joesixpack

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Posted 09 July 2020 - 02:34 AM

I don't know why but I have found that I need at least twice the amount of NAM to get the same effects of NR. This applies to the positive effects as well as the negative effects.

 

So I need 300mg NAM to get the effects of 150mg NR (euphoria and energy on the day of taking it and muscle pain all over the body a few days later).

 

But 150mg NR contains only 75mg NAM. So 300mg NAM has 4x more NAM than 150mg NR. If the allergy is to NAM it does not make sense to me that I tolerate more NAM than NR?

 

Another thing is that there are some people in our forum who started with NR and never tried NAM and still have this phenomenon of getting those nasty flare ups. And we alle have in common that we have mtDNA damage due to fluoroquinolones. However, the phenomenon of increasing sensitivity is strange to me - yes it's just like an allergy.

I think your problem is taking too much. I had trouble taking NR for the first 18 months. I could not take more than 125 mg without getting some unpleasant side affects, despite getting good results, like no pain from osteoarthritis. I stuck with it for that result. I can now take 300 mg without a problem. My goal was to experience no side affects, like the drug like rush, etc. I have achieved that, and feel good. By adding mass quantities of NAM +R you are probably over dosing. I would drop it and then gradually try to get to 300mg Nr and forget about the euphoria side affect. 


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