It seems that higher cholesterol is actually good for seniors.
The association could prevailingly be described as ‘a reverse J-shaped’ association, where low TC was associated with the highest total mortality in the population of 80±year olds. Most of the observational studies found this trend of association, whereas a few found a U-shaped association, where high TC was associated with increasing mortality as well.
“No clear optimal level of TC was identified”
Many of the markers that Michael Lustgarten Ph.D. has researched seem to have a U shaped curve for all cause mortality.
I don’t currently take any statins, instead, I replaced mine with niacin.
The plan is to just to keep my TC and LDL-C in the “healthy” range.
There is a Linus Pauling protocol to lower cholesterol, involving megadose vit C and lysine. A Dr. Matthias Rath added proline to the protocol. Some vitamin adherents (Owen Fonorow) even wrote a book about the protocol, entitled “Practicing Medicine Without a License?”
Here is a summary from Jeffrey Dach, MD.
My brother did the protocol, without the proline. He took 3G vit C, 2G lysine and 300 mg niacin daily. He also did long walks. Don’t know how long, because he had no pedometer. He was already on statins when the following lipid panel was taken on 06/04/2008
TC 409
HDL 35
LDL 262
Triglycerides 6.35
almost two months after (07/31/2008), it was the following"
TC 245
HDL 50
LDL 138
Triglycerides 3.17
That is anecdotal evidence of one. There is more anecdotal evidence in the book. I bought the book many years ago. It is just a book of testimonials.
Well! I had a triple bypass 5 years ago. Cardiologists said this was my only option. He was just going to put one stent, but he said “the problem would just continue and I would have to have the operation at some point so it was in my interest to do it while I was overall health”. He has sense retired so I cannot bring this article to him and say “why the hell you did not tell me about this?”
It doesn’t vindicate NMN and other NAD precursors… There was no mention of NMN or NR in the paper cited. Lifespan increase was produced by a CD38 inhibitor, a substance they call 78c.
https://onlinelibrary.wiley.com/doi/10.1111/acel.13589
Maximum lifespan of both male and female mice was 1000 + days. At 50% survival, males were at about 850 days, versus females at about 750. See pic in study (figure c). I do not know where Matt Kaeberlein got his 300 days. No such chart in the study.
So, speaking of CD38 inhibition, Michael Lustgarten says the best substances are Kuromanin (found in Black Elderberries and Blueberries), and Luteolin (found in radicchio, Mexican Orgegano, and celery seeds. Lustgarten says they are even better CD38 inhibitors than his earlier reviewed apigenin and quercetin.
I tried NMN, from some vendor in Amazon, then later Alive by Science. Nyet. Will try this other approach - CD38 inhibition.
I like Mike Lustgarten, but I have to say I wouldn’t listen to what him or anyone else says about something being a good inhibitor of CD38 (or of other things) unless they support it with evidence indicating that it works in vivo. In case of Lustgarten and these CD38 inhibitors, he fails to look into whether there is any reasonable chance that they would work in vivo. Most plant compounds are heavily metabolized in the digestive tract and by the liver and have very poor bioavailability and you can’t just look at in vitro studies and expect something to work when ingested.
Mike Lustgarten is currently taking apigenin in an effort to inhibit CD38 to raise his NAD+ levels. While in theory that’s a good idea, practically I think it’s a long stretch to think that would have even a slightest effect.
Apigenin has indeed been shown to inhibit CD38, but this only occurs to a significant degree with concentrations of apigenin well into the micromolar range. Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome - PubMed Unfortunately that’s simply a concentration that is unreasonable to obtain by eating parsley.
.
The bioavailability of apigenin is poor in mice due to extensive metabolism in the digestive tract and also additional metabolism by the liver of whatever amount is absorbed. The bioavailability is even worse in humans. In fact, in a study where healthy adults ingested massive doses of parsley (150 g daily) the maximum apigenin concentration in plasma only reached the high nanomolar range. At such concentrations you would be lucky to get even 1% inhibition of CD38, which means that ingestion of parsley is very unlikely to have any effects on NAD+ levels downstream of CD38 inhibition in humans. Bioavailability of apigenin from apiin-rich parsley in humans - PubMed I think even high dose apigenin supplements are unlikely to make a dent in CD38 levels in humans.
Personally I wouldn’t waste money on trying to ingest apigenin (or any other plant compounds) to raise NAD+ levels.
Lustgarten experience confirms your opinion.
$250 for the jinfinity at home NAD test kit.
nope. Still thinking about Bristle though.
I am taking Apigenin already for sleep benefits (35mg of Lipo Agigenin from Renue, supposed to be as good as 100mg due to 90% bioavailability), but I am intrigued with the CD38 inhibition : Your linked paper estimates it will takes 0.9g - 4.5g / day of pure Apigenin (based on 30% bioavailability) to achieve the required plasma concentration for CD38 inhibition. 1g/day of Apigenin from DoNotAge comes to around $2/day, not cheap but worth it if it inhibits CD38 and raises NAD+ levels without all the risks that come with NMN/NR raising NAD+ levels too high. Of course if it takes 5g/day ($10/day) that would be unaffordable for most folks as a way to raise NAD+.
I am thinking of getting 2 Jinfinity NAD test kits and doing a test before starting 1g/day of Apigenin and retesting NAD after 2 months.
Update : I misread the original article : It requires the 0.9g -4.5g dosage every 8 hours, 3x/day, since the half life of Apigenin is only 4 hours.
I personally wouldn’t take apigenin on the basis of thinking it will inhibit CD38 but if you do a NAD test before and after that would be very interesting and would help give some evidence as to whether it is having any effect at all. Please post the results here if you try that. Good luck.
I think Micheal Lustgarten, who have the conquer aging or die trying youtube chanel has basically pretty much proven that Apigenin does not inhibit CD38. That episode was a month or so ago. And the cosept that CD38 inhibition will increase NAD is a theory that is yet to be proven true.
This wikipaedia article CD38 claims that the ultimate cause of age related CD38 elevation (and hence NAD depletion) are believed to be senescent immune cells that accumulate in visceral fat:
Macrophages are believed to be primarily responsible for the age-related increase in CD38 expression and NAD+ decline.[56] Cellular senescence of macrophages increases CD38 expression.[56] Macrophages accumulate in visceral fat and other tissues with age, leading to chronic inflammation.[57] The inflammatory transcription factor NF-κB and CD38 are mutually activating.[56] Secretions from senescent cells induce high levels of expression of CD38 on macrophages, which becomes the major cause of NAD+ depletion with age.[58]
Based on that using a senolytic like Fisetin might also be effective in suppressing CD38 and raising NAD. So I plan to order the 4-pack of NAD tests from Jinfinity (they offer a 10% discount of you order 4 tests) and test the effectiveness of Fisetin and Apigenin sequentially (along with ruling out any effect of alpha17-estradiol):
Mar 10: First NAD test : 24.3 uM
Mar 10 : Start 3 days of Fisetin 1.5g/day (Renue 150mg Liposomal Fisetin x 10 + LEF Senolytic Activator 3 capsules), around 20mg/kg of body weight of bioavailable Fisetin per day, equivalent to around 4g/day of regular Fisetin with 40% bioavailability. Split in 2 equal doses at 6am and 6pm.
Mar 13: Second NAD test (to see if Fisetin had any effect on NAD) + LEF blood test panel with estradiol (regular and sensitive), T, DHT, IGF1, LH+FSH (to monitor status before starting 17alpha-E2) : NAD= 28.1 uM, IGF1= 138 ng/ml, Total T= 579 ng/dL, Free T= 6.7 pg/ml, DHT = 18 ng/dL (ref=30-85), Estradiol(ECLIA)= 26.9 pg/ml, Estradiol (LC/MS/MS)= 26 pg/ml, LH= 16.4 mIU/ml (ref=1.7-8.6), FSH= 51.5 mIU/ml (ref= 1.5-12.4).
Mar 13: Start dermal 17alpha-E2 0.25mg, 2x/day (10am, 10pm) expected to absorb around 50ug/day. Also 1g DoNotAge Apigenin + 70mg Renue Lipo Apigenin, 3x/day (6am, 2pm, 10pm).
Apr 7-10 : 3 days of Lipo Fisetin 1.5g/day.
Apr 10 : Third NAD test to see if Apigenin (+ 17alpha-E2) had any effect on NAD over and above Fisetin. Will also take a panel of LEF blood tests including T+E2(sens)+DHT+FSH+LH+IGF1 to monitor effect of 17alpha-E2.
After getting results of 3rd NAD test, if NAD level is adequate (40-50 uM) see if Apigenin can be dialed back to reduce cost (or discontinued if it had no effect). If NAD is still low will consider adding Lipo NMN 250mg/day.
May 5-7 : 3 days of Fisetin 1.5g/day
May 8 : Fourth NAD test
Update 3/14/2023 : Raised my dosage of Apigenin to 1g every 8 hours and changed my schedule a bit so Fisetin is used half way between my every other week Rapamycin (20mg) to minimize interference.
Update 3/22/2023 : Added blood test results from 3/10/2023. Summary: 3 days of 1.5g/day of Lipo Fisetin raised NAD+ from 24.3uM to 28.1uM. Normal NAD+ for 20-40 year olds are 40-50uM.
No changes, but I am very interested to hear the results though!
Added my first 2 NAD+ test results :
A. DHT was low: expected due to taking Dutasteride for enlarged prostate.
B. Testosterone is back from being at the low end of normal on Oct 20, 2022 (around 280 ng/dL, same as for the last several years) to youthful levels of 579 ng/dL on Mar 13, 2023 : I suspect my use of 20mg Rapamycin every other week for the last 2 months may be responsible.
C. FSH and LH are both very high : I have never measured these before and was wondering if anyone has any idea what that means. Theory says my Pituitary is trying to stimulate production of Testosterone : Could this be how Rapamycin raises Testosterone (and Estrogen in women) to more youthful levels ?
My 3rd NAD+ test result from April 10 : 22.7 uM
So taking 1g of Apigenin (+ 70mg of Lipo Apigenin) 3x per day for 28 days actually lowered my NAD+ level from 28.1uM to 22.7 uM. I conclude that even at this relatively high dosage level Apigenin is not able to block CD38.
I have lowered my dosage of Apigenin back to just 35mg of Lipo Apigenin + 250mg of DNA Apigenin 3x per day, but added Renue Lipo NMN (250mg) + Renue Lipo NR (300mg) + Renue Lipo Quercetine (150mg) + Renue Lipo Trans-Resveratrol (125mg) per day and will retest NAD+ on May 10.
Based on your n=1 experiment, it appears Apigenin may be snake oil. Or at least not effective in humans. That’s one supplement I will hold off on. That helps.
N=1 verdict on effect of NMN.
None.
Still another reason not to waste your money on NMN
Personally, I have been taking the expensive brand of NMN sublingually at a dose of ~1 ½ to 2 grams daily for ~ 8 weeks. No change was noticed either subjectively or in the results of my latest blood work.
My suspicion for a while now, all the scientific papers on NMN the last couple of years has been grasping at straws to put it mildly. supplement companies and YouTubers love it though, NMN and Resveratrol, two things that does nothing for anti aging…is pumped to be the best anti aging strategy, go figure.
Low dose nicotine?
https://www.nature.com/articles/s41467-023-36543-8
Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity
Previous studies showed that supplementing NAD+ precursors, such as nicotinamide mononucleotide (β-NMN), nicotinamide riboside (NR), nicotinamide (NAM), or Niacin (NA), were efficient for anti-aging8,9,10. In mammalian cells, most NAD+ precursors were “reclaimed” to NAD+ via the rate-limiting enzyme nicotinamide phosphoribosyl transferase (NAMPT) of the salvage pathway. As NAMPT activity decreases with age, it results in NAD+ depletion and cognitive impairment11. Consequently, the NAMPT enhancers can effectively increase NAD+ levels and prevent neuronal degeneration12,13,14. Moreover, supplementing the high active extracellular NAMPT (eNAMPT) also increases NAD+ biogenesis and aging-related symptoms15,16,17. Therefore, the enhancement of NAMPT activity could be a potential strategy for preventing aging and age-associated diseases arising from NAD+ decline11,18,19.
Interestingly, nicotine is a secondary metabolite of the NAD+ biosynthesis and the NAD+ pathway is also coordinately regulated with nicotine biosynthesis20,21. Furthermore, the NAD+ salvage pathway is conserved across a variety of species, including bacteria, plants, yeasts, and mammals20. Consequently, we hypothesized that nicotine may play a role in the NAD+ salvage pathway. It has been discovered that minuscule amounts of nicotine, as an activator of NAD+ biogenesis, can markedly improve NAMPT activity and NAD+ synthesis, leading to improved glucose metabolism and cognitive function, as well as aging symptoms, in male mice.
Vape liquid provides nicotine.