Other NAD+ BoostersInfo on recent reports on increasing nad.

Alxd
Posts: 4
Joined: Wed Sep 11, 2019 3:52 pm

Info on recent reports on increasing nad.

Post by Alxd » Wed Sep 11, 2019 4:01 pm

I do not know if this would add to the effects of nad precursor benefits. But you can peruse. https://www.ncbi.nlm.nih.gov/pmc/articl ... IzOIakXpQU


zisos
Posts: 4
Joined: Thu Apr 09, 2020 3:52 pm

Re: Info on recent reports on increasing nad.

Post by zisos » Thu Apr 09, 2020 4:03 pm

Supplementation with apigenin (inhibitor of CD38) might be a more cost-effective and more appropriate way of keeping NAD+ level high.
Most likely, a lower level of NAD+ as we age is due to higher CD38 as we age. Treating the problem (high CD38) is probably more appropriate than treating the symptom (low NAD+ level) using precursors such as NMN and NR. Apigenin is also much cheaper than NMN and NR.
In fact, you could easily get enough apigenin by eating plenty of parsley, thus avoiding any supplementation altogether.
User avatar
jocko6889
Posts: 232
Joined: Tue Jul 23, 2019 11:35 pm
Location: Tulsa, OK
Contact:

Re: Info on recent reports on increasing nad.

Post by jocko6889 » Fri Apr 10, 2020 4:49 am

zisos wrote:
Thu Apr 09, 2020 4:03 pm
Supplementation with apigenin (inhibitor of CD38) might be a more cost-effective and more appropriate way of keeping NAD+ level high.
Most likely, a lower level of NAD+ as we age is due to higher CD38 as we age. Treating the problem (high CD38) is probably more appropriate than treating the symptom (low NAD+ level) using precursors such as NMN and NR. Apigenin is also much cheaper than NMN and NR.
In fact, you could easily get enough apigenin by eating plenty of parsley, thus avoiding any supplementation altogether.
Thanks for your post. I had done some research on apigenin awhile back but can't remember why I didn't end up ordering some. I have repeated the Mayo Clinic human trial using fisetin, another flavonoid a couple of times now. It goes after the source, senescent cells which secrete SASP that is responsible for the buildup of CD38. Probably would be good to add apigenin as well. What daily dose are you on?
Taking:
NMN - 1 gram
LSG Resveratrol/Curcumin
Methyl Folate - 1,000mcg
Methyl B12 - 5,000mcg
PQQ - 20mg
Vitamin D3 & K2 - (D3 25mcg, K2 45mcg)
Creatine Monohydrate - 800mg
NAC - 600mg
Glycine - 1,000mg
Acetyl L-Carnitine - 500mg
CoQ10 - 100mg
RobSmith
Posts: 66
Joined: Mon Feb 24, 2020 10:34 am
Location: UK

Re: Info on recent reports on increasing nad.

Post by RobSmith » Fri Apr 10, 2020 4:55 am

zisos wrote:
Thu Apr 09, 2020 4:03 pm
Supplementation with apigenin (inhibitor of CD38) might be a more cost-effective and more appropriate way of keeping NAD+ level high.
Most likely, a lower level of NAD+ as we age is due to higher CD38 as we age. Treating the problem (high CD38) is probably more appropriate than treating the symptom (low NAD+ level) using precursors such as NMN and NR. Apigenin is also much cheaper than NMN and NR.
In fact, you could easily get enough apigenin by eating plenty of parsley, thus avoiding any supplementation altogether.
Not sure you want to inhibit too much CD38 as that would make you more susceptible to infection... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017097/
2. CD38 Deficiency Results in Increased Susceptibility to Several Pathogens
Pathogenic bacteria are causative agents for a wide spectrum of infectious diseases. Bacterial infection causes tissue damage through different mechanisms, including the killing of infected host cells, the secretion of toxins and the induction of an exacerbated inflammatory response [21]. In vivo studies demonstrated that CD38 deficiency in mice conferred increased susceptibility to infection by several bacteria, namely Listeria monocytogenes (L. monocytogenes) [22], Mycobacterium avium (M. avium) [23] and Streptococcus pneumoniae (S. pneumoniae) [24,25], and the parasite Entamoeba histolytica (E. histolytica) [26].

though a bit of inhibition is probably not a bad thing as more CD38 appears as one ages - it's all about maintaining a good balance.
zisos
Posts: 4
Joined: Thu Apr 09, 2020 3:52 pm

Re: Info on recent reports on increasing nad.

Post by zisos » Fri Apr 10, 2020 5:29 am

jocko6889 wrote:
Fri Apr 10, 2020 4:49 am
zisos wrote:
Thu Apr 09, 2020 4:03 pm
Supplementation with apigenin (inhibitor of CD38) might be a more cost-effective and more appropriate way of keeping NAD+ level high.
Most likely, a lower level of NAD+ as we age is due to higher CD38 as we age. Treating the problem (high CD38) is probably more appropriate than treating the symptom (low NAD+ level) using precursors such as NMN and NR. Apigenin is also much cheaper than NMN and NR.
In fact, you could easily get enough apigenin by eating plenty of parsley, thus avoiding any supplementation altogether.
Thanks for your post. I had done some research on apigenin awhile back but can't remember why I didn't end up ordering some. I have repeated the Mayo Clinic human trial using fisetin, another flavonoid a couple of times now. It goes after the source, senescent cells which secrete SASP that is responsible for the buildup of CD38. Probably would be good to add apigenin as well. What daily dose are you on?
Currently taking 50mg daily. But I donot know if this is optimum
zisos
Posts: 4
Joined: Thu Apr 09, 2020 3:52 pm

Re: Info on recent reports on increasing nad.

Post by zisos » Fri Apr 10, 2020 5:39 am

Alxd wrote:
Wed Sep 11, 2019 4:01 pm
I do not know if this would add to the effects of nad precursor benefits. But you can peruse. https://www.ncbi.nlm.nih.gov/pmc/articl ... IzOIakXpQU
It certainly will add to the effect of nad precursors.
apigenin will inhibit cd38, which will allow you to "conserve" NAD+, whereas precursors will help produce.
In other words "conservation" vs "production"

An analogy with energy would be: "use electricity more efficiently" vs "produce more energy by building more power plants
The former is analogous to CD38 inhibition
User avatar
jocko6889
Posts: 232
Joined: Tue Jul 23, 2019 11:35 pm
Location: Tulsa, OK
Contact:

Re: Info on recent reports on increasing nad.

Post by jocko6889 » Fri Apr 10, 2020 5:25 pm

Before supplementing with a senolytic like fisetin or a CD38 inhibitor like apigenin, it would be nice to know whether you even have a problem with excessive levels of senescent cells due to aging. Unfortunately, there is currently no commercial test to check for levels of cellular senescence.
However, there may be an indirect way to measure this.

A company called InsideTracker (insidetracker.com) has a bioage test called the InnerAge test that checks for various biomarkers of aging (blood sugar, inflammation, liver function and toxicity, bone health/vitamin D, testosterone, and iron). Inflammation is checked by looking at levels of high-sensitivity C-reactive protein (hs-CRP). There is some research showing that levels of hs-CRP are correlated with levels of cellular senescence.

It's important to note that an hs-CRP test checks for OVERALL levels of inflammation in the body. The test doesn't indicate the CAUSE of inflammation, so it's possible that a high hs-CRP level could mean there's inflammation caused by something besides cellular senescence, such as an infection or a chronic inflammatory disease, such as rheumatoid arthritis or lupus, as well as coronary artery disease. But given that these factors could be ruled out, levels of hs-CRP can be a good indicator of how far along your body is on the aging scale and the buildup of senescent cells. In as far as taking senolytics, this is important to know because as mentioned above some senescent cells actually serve a useful purpose, such as in the healing of wounds.

I have taken the InsideTracker InnerAge test annually for the past 2 years and in both instances my hs-CRP level was in the optimal range. This means I probably don't have any of the diseases of inflammation mentioned above and in all likelihood have youthful, normal levels of cellular senescence. So in my case, even though I've experimented with fisetin in the past, taking it might run the risk of destroying perfectly normal, beneficial senescent cells. Even some CD38 is normal and beneficial for fighting inflammation. It only gets to be a problem when levels of inflammation go up from an over-abundance of senescent cells, producing more CD38 and using up excessive levels of NAD+, disturbing the balance of the three NAD+-consuming pathways - sirtuins, PARPs, and CD38 which all compete for the same finite pool of NAD+.
Taking:
NMN - 1 gram
LSG Resveratrol/Curcumin
Methyl Folate - 1,000mcg
Methyl B12 - 5,000mcg
PQQ - 20mg
Vitamin D3 & K2 - (D3 25mcg, K2 45mcg)
Creatine Monohydrate - 800mg
NAC - 600mg
Glycine - 1,000mg
Acetyl L-Carnitine - 500mg
CoQ10 - 100mg
zisos
Posts: 4
Joined: Thu Apr 09, 2020 3:52 pm

Re: Info on recent reports on increasing nad.

Post by zisos » Sat Apr 11, 2020 6:00 am

jocko6889 wrote:
Fri Apr 10, 2020 5:25 pm
Before supplementing with a senolytic like fisetin or a CD38 inhibitor like apigenin, it would be nice to know whether you even have a problem with excessive levels of senescent cells due to aging. Unfortunately, there is currently no commercial test to check for levels of cellular senescence.
However, there may be an indirect way to measure this.

A company called InsideTracker (insidetracker.com) has a bioage test called the InnerAge test that checks for various biomarkers of aging (blood sugar, inflammation, liver function and toxicity, bone health/vitamin D, testosterone, and iron). Inflammation is checked by looking at levels of high-sensitivity C-reactive protein (hs-CRP). There is some research showing that levels of hs-CRP are correlated with levels of cellular senescence.

It's important to note that an hs-CRP test checks for OVERALL levels of inflammation in the body. The test doesn't indicate the CAUSE of inflammation, so it's possible that a high hs-CRP level could mean there's inflammation caused by something besides cellular senescence, such as an infection or a chronic inflammatory disease, such as rheumatoid arthritis or lupus, as well as coronary artery disease. But given that these factors could be ruled out, levels of hs-CRP can be a good indicator of how far along your body is on the aging scale and the buildup of senescent cells. In as far as taking senolytics, this is important to know because as mentioned above some senescent cells actually serve a useful purpose, such as in the healing of wounds.

I have taken the InsideTracker InnerAge test annually for the past 2 years and in both instances my hs-CRP level was in the optimal range. This means I probably don't have any of the diseases of inflammation mentioned above and in all likelihood have youthful, normal levels of cellular senescence. So in my case, even though I've experimented with fisetin in the past, taking it might run the risk of destroying perfectly normal, beneficial senescent cells. Even some CD38 is normal and beneficial for fighting inflammation. It only gets to be a problem when levels of inflammation go up from an over-abundance of senescent cells, producing more CD38 and using up excessive levels of NAD+, disturbing the balance of the three NAD+-consuming pathways - sirtuins, PARPs, and CD38 which all compete for the same finite pool of NAD+.
I agree with you that we must be careful. However, in the end someone has to consider the risks of interventions vs the risk of non-intervensions. Personal goals, age, risk evaluation, risk appetite, available information etc play a role in decision making.
Here are some parameters to take into account:
a) Age:
In one of Sinclair's presentation, he mentioned that NAD+ at age 50 is about half than at age 20. At age 90, there is almost no NAD+ left.
So, at age 50 I might not take the risk of reducing CD38, because most likely it is low. At age 70, my decision might be different (I am now 69). I tend to think that CD38 is much higher than the optimum.
b) Personal Goals:
I personally believe Kurzweil's prediction that "Longevity Escape Velocity" (LEV) might be achievable for most people in about 15 years. So my thinking is as follows:
At age 69, if I do nothing, I expect to live about another 10 years. By making risky (Not reckless) interventions, there is a chance that if I am wrong, I might lose 3 years of life, whereas if I am right, I might gain 5 years of life. This might bring me close to the time of LEV. Even though the probability of that happening is relatively small, the potential gain is so huge, that it allows me to take bigger risks (I.e. potential loss of 3 years vs a potential gain of eternity)
My thinking would be very different if I did not believe that Kurzweil's prediction is plausible. I would certainly be more conservative.
My goal is to live indefinitely. So I am willing to take a higher risk for this very ambitious goal.
c) Risk evaluation:
Blagosklonny said that Not taking rapamycin when over 70 is riskier than driving at excessive speed, drunk, without wearing a seatbelt. Of course, not everyone evaluates risk the same way. In fact, very few people think so. In other words, people that evaluate risk in a different way will come up with different decisions.

To ensure that interventions are not "reckless" we must stay informed. So I appreciate the information that you provided regarding too much inhibition of CD38. I was not aware of it. More good information results in better evaluation of risks.
Drdavid
Posts: 721
Joined: Thu Aug 15, 2019 9:59 am

Re: Info on recent reports on increasing nad.

Post by Drdavid » Mon Apr 13, 2020 12:00 pm

zisos wrote:
Sat Apr 11, 2020 6:00 am
jocko6889 wrote:
Fri Apr 10, 2020 5:25 pm
Before supplementing with a senolytic like fisetin or a CD38 inhibitor like apigenin, it would be nice to know whether you even have a problem with excessive levels of senescent cells due to aging. Unfortunately, there is currently no commercial test to check for levels of cellular senescence.
However, there may be an indirect way to measure this.

A company called InsideTracker (insidetracker.com) has a bioage test called the InnerAge test that checks for various biomarkers of aging (blood sugar, inflammation, liver function and toxicity, bone health/vitamin D, testosterone, and iron). Inflammation is checked by looking at levels of high-sensitivity C-reactive protein (hs-CRP). There is some research showing that levels of hs-CRP are correlated with levels of cellular senescence.

It's important to note that an hs-CRP test checks for OVERALL levels of inflammation in the body. The test doesn't indicate the CAUSE of inflammation, so it's possible that a high hs-CRP level could mean there's inflammation caused by something besides cellular senescence, such as an infection or a chronic inflammatory disease, such as rheumatoid arthritis or lupus, as well as coronary artery disease. But given that these factors could be ruled out, levels of hs-CRP can be a good indicator of how far along your body is on the aging scale and the buildup of senescent cells. In as far as taking senolytics, this is important to know because as mentioned above some senescent cells actually serve a useful purpose, such as in the healing of wounds.

I have taken the InsideTracker InnerAge test annually for the past 2 years and in both instances my hs-CRP level was in the optimal range. This means I probably don't have any of the diseases of inflammation mentioned above and in all likelihood have youthful, normal levels of cellular senescence. So in my case, even though I've experimented with fisetin in the past, taking it might run the risk of destroying perfectly normal, beneficial senescent cells. Even some CD38 is normal and beneficial for fighting inflammation. It only gets to be a problem when levels of inflammation go up from an over-abundance of senescent cells, producing more CD38 and using up excessive levels of NAD+, disturbing the balance of the three NAD+-consuming pathways - sirtuins, PARPs, and CD38 which all compete for the same finite pool of NAD+.
Thank you for your post. I appears that you are moving toward what you believe will the best strategy for your goal acquisition. Kudos to you!

I agree with you that we must be careful. However, in the end someone has to consider the risks of interventions vs the risk of non-intervensions. Personal goals, age, risk evaluation, risk appetite, available information etc play a role in decision making.
Here are some parameters to take into account:
a) Age:
In one of Sinclair's presentation, he mentioned that NAD+ at age 50 is about half than at age 20. At age 90, there is almost no NAD+ left.
So, at age 50 I might not take the risk of reducing CD38, because most likely it is low. At age 70, my decision might be different (I am now 69). I tend to think that CD38 is much higher than the optimum.
b) Personal Goals:
I personally believe Kurzweil's prediction that "Longevity Escape Velocity" (LEV) might be achievable for most people in about 15 years. So my thinking is as follows:
At age 69, if I do nothing, I expect to live about another 10 years. By making risky (Not reckless) interventions, there is a chance that if I am wrong, I might lose 3 years of life, whereas if I am right, I might gain 5 years of life. This might bring me close to the time of LEV. Even though the probability of that happening is relatively small, the potential gain is so huge, that it allows me to take bigger risks (I.e. potential loss of 3 years vs a potential gain of eternity)
My thinking would be very different if I did not believe that Kurzweil's prediction is plausible. I would certainly be more conservative.
My goal is to live indefinitely. So I am willing to take a higher risk for this very ambitious goal.
c) Risk evaluation:
Blagosklonny said that Not taking rapamycin when over 70 is riskier than driving at excessive speed, drunk, without wearing a seatbelt. Of course, not everyone evaluates risk the same way. In fact, very few people think so. In other words, people that evaluate risk in a different way will come up with different decisions.

To ensure that interventions are not "reckless" we must stay informed. So I appreciate the information that you provided regarding too much inhibition of CD38. I was not aware of it. More good information results in better evaluation of risks.
drkris69
Posts: 620
Joined: Tue Aug 20, 2019 2:41 pm

Re: Info on recent reports on increasing nad.

Post by drkris69 » Mon Apr 13, 2020 3:12 pm

Great thread guys I need to look into this apigenin. I havent heard of this before.
Post Reply Previous topicNext topic