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NAM works like a brake on SIRT1 at even very low dosages

nicotinamide

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33 replies to this topic

#31 pamojja

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Posted 02 December 2023 - 08:32 PM

When people talk about extending lifespan, they mean for an average healthy person without serious diseases. Two studies have show that NAM and NR don’t extend mice lifespan.

 

Ever considered that lab-rats are living like human prisoners? The average healthy?



#32 osris

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Posted 03 December 2023 - 12:39 AM

When people talk about extending lifespan, they mean for an average healthy person without serious diseases. Two studies have show that NAM and NR don’t extend mice lifespan.

 

Yes, this sound right. NAM is quite a weak longevity substance. It has benefits of course but not the most effective longevity supplement.


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#33 Heisok

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Posted 09 December 2023 - 06:28 AM

It looks like only partial information came through your chat. I do not have access to the complete Journal article 

 

Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells

 

"Nicotinamide (NAM), a form of vitamin B3, plays essential roles in cell physiology through facilitating NAD+ redox homeostasis and providing NAD+ as a substrate to a class of enzymes that catalyze non-redox reactions. These non-redox enzymes include the sirtuin family proteins which deacetylate target proteins while cleaving NAD+ to yield NAM. Since the finding that NAM exerts feedback inhibition to the sirtuin reactions, NAM has been widely used as an inhibitor in the studies where SIRT1, a key member of sirtuins, may have a role in certain cell physiology.

 

     However, once administered to cells, NAM is rapidly converted to NAD+ and, therefore, the cellular concentration of NAM decreases rapidly while that of NAD+ increases. The result would be an inhibition of SIRT1 for a limited duration, followed by an increase in the activity. This possibility raises a concern on the validity of the interpretation of the results in the studies that use NAM as a SIRT1 inhibitor. To understand better the effects of cellular administration of NAM, we reviewed published literature in which treatment with NAM was used to inhibit SIRT1 and found that the expected inhibitory effect of NAM was either unreliable or muted in many cases. In addition, studies demonstrated NAM administration stimulates SIRT1 activity and improves the functions of cells and organs. To determine if NAM administration can generate conditions in cells and tissues that are stimulatory to SIRT1, the changes in the cellular levels of NAM and NAD+ reported in the literature were examined and the factors that are involved in the availability of NAD+ to SIRT1 were evaluated.

 

We conclude that NAM treatment can hypothetically be stimulatory to SIRT1."

 

https://pubmed.ncbi....h.gov/28417163/

 

 

Oral Nicotinamide Prevents Common Skin Cancers in High-Risk Patients, Reduces Costs

The prevention of common skin cancers and precancers is possible by taking an inexpensive, widely available, oral pill twice daily. The pill—the vitamin B3 supplement called nicotinamide—cut the rate of new squamous-cell and basal-cell skin cancers by 23% compared with placebo after 1 year among patients at high risk for skin cancer. Nicotinamide also reduced the risk for developing actinic keratosis, a common precancer of the skin. (The participants already had 2 or more non melanoma cancers.

 

 

https://www.ncbi.nlm...les/PMC4570055/

 

I take a 500mg dose twice a day. After 2 years, somebody that I know who started this protocol after his second Squamous Cell Carcinoma, has just gotten an SCC, and BCC removed. He is very high risk due to lifestyle and work environments. I am also with one SCC so far. Just an anecdote.

 

 

 

 


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#34 osris

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Posted 28 December 2023 - 01:37 AM

It looks like only partial information came through your chat. I do not have access to the complete Journal article 

 

Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells

 

"Nicotinamide (NAM), a form of vitamin B3, plays essential roles in cell physiology through facilitating NAD+ redox homeostasis and providing NAD+ as a substrate to a class of enzymes that catalyze non-redox reactions. These non-redox enzymes include the sirtuin family proteins which deacetylate target proteins while cleaving NAD+ to yield NAM. Since the finding that NAM exerts feedback inhibition to the sirtuin reactions, NAM has been widely used as an inhibitor in the studies where SIRT1, a key member of sirtuins, may have a role in certain cell physiology.

 

     However, once administered to cells, NAM is rapidly converted to NAD+ and, therefore, the cellular concentration of NAM decreases rapidly while that of NAD+ increases. The result would be an inhibition of SIRT1 for a limited duration, followed by an increase in the activity. This possibility raises a concern on the validity of the interpretation of the results in the studies that use NAM as a SIRT1 inhibitor. To understand better the effects of cellular administration of NAM, we reviewed published literature in which treatment with NAM was used to inhibit SIRT1 and found that the expected inhibitory effect of NAM was either unreliable or muted in many cases. In addition, studies demonstrated NAM administration stimulates SIRT1 activity and improves the functions of cells and organs. To determine if NAM administration can generate conditions in cells and tissues that are stimulatory to SIRT1, the changes in the cellular levels of NAM and NAD+ reported in the literature were examined and the factors that are involved in the availability of NAD+ to SIRT1 were evaluated.

 

We conclude that NAM treatment can hypothetically be stimulatory to SIRT1."

 

https://pubmed.ncbi....h.gov/28417163/

 

 

 

 

I agree that hypothetically it can stimulate Sirt1.

 

 

 


Edited by osris, 28 December 2023 - 01:44 AM.

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