2523 replies to this topic

[JamesPaul]

That product did sound unrealistically inexpensive for something that Sigma Aldrich charges $70/kg for.  Thanks for listing alternatives.  Sorry to make you go over old ground

A comment on the use of cocoa.  It looks like cocoa has the additional benefit of promoting mitochondrial fusion:

“Cocoa beans improve mitochondrial biogenesis via PPARγ/PGC1α dependent signalling pathway in MPP + intoxicated human neuroblastoma cells (SH-SY5Y),” S. Chidambaram et al., Nutr Neurosci

. 2020 Jun;23(6):471-480.

https://pubmed.ncbi....h.gov/30207204/

excerpt from abstract: “Further, the cocoa extract down-regulated the expression of mitochondria fission 1 (Fis1) and up-regulated the expression of mitochondria fusion 2 (Mfn2) proteins...”

 

This paper says EGCg also promotes fusion:

“Epigallocatechin-3-gallate ameliorates hypoxia-induced pulmonary vascular remodeling by promoting mitofusin-2-mediated mitochondrial fusion,” Tian-Tian Zhu et al., Eur J Pharmacol. 2017 Aug 15;809:42-51.

https://pubmed.ncbi....h.gov/28478070/

 

But I believe you discouraged the use of EGCg in connection with the stem cell renewal protocol on the grounds that EGCg accelerates the differentiation of satellite cells to muscle cells.  Dark chocolate is said to contain a little catechin and epicatechin, though I've not seen any mention of cocoa containing EGCg.

 

I have a question.  How soon after consuming the C60 and amino acids it is OK to eat a normal meal?  I believe you wrote "I don't eat during the protocol, and considering it is a period of only 3-4 hours..."  Does that mean it is OK to eat shortly after consuming the C60?  Or three hours after consuming the C60?  Sorry if I should know this, and thanks again for taking the time to provide so much valuable information.

 

 

 

 

[userCK]

Guys, 

 

So, Stem Cell fusion would result in de-novo cells with no methylation/no epigenetic markers. However, most brain-cells are not programmed to die every 7 years. So, is it accurate to say that this Stem Cell protocol won't demethylate brain cells?

 

If so, would taking supplements that induce neurogenesis by increasing BDNF (such as Lion's Mane Mushrooms, peptides like Dihexa, Semas etc) result in NEW brain cells that do not have any methylation?

 

[Turnbuckle]

Guys, 

 

So, Stem Cell fusion would result in de-novo cells with no methylation/no epigenetic markers. However, most brain-cells are not programmed to die every 7 years. So, is it accurate to say that this Stem Cell protocol won't demethylate brain cells?

 

If so, would taking supplements that induce neurogenesis by increasing BDNF (such as Lion's Mane Mushrooms, peptides like Dihexa, Semas etc) result in NEW brain cells that do not have any methylation?

 

 

It's mitochondrial fusion, not stem cell fusion. Think of this protocol as hijacking the two switches in mitochondria that are normally used by the body to control stem cells. One is mito fusion, the second is UCP2 blocking (though how cells naturally do the latter is presently unknown). Flipping those switches will set SCs onto the path to proliferation rather than differentiation. SC pools are then increased. Later, in the normal course of events or when senolytics are used, somatic cells undergo apoptosis (programed suicide) signaling SCs with paracrine factors to replace them via differentiation. The replacement cells with mostly de novo methylation have low epigenetic age, while the replaced cells generally have high epigenetic age. Thus average epigenetic age is reduced for most tissues. The brain is a different matter. Most neurons are not replaced, with the exception of more active regions such as the hippocampus. The general decline in memory with age is likely associated with depletion of SC pools in those active regions. When the goal is to increase neural SC pools, stearic acid won't be very useful as it doesn't penetrate the BBB. Other supplements must be used. 

 

Sulforaphane [SFN] does penetrate the BBB and is known to drive mito fusion. So I include it in the protocol*. Supplements that induce neurogenesis will certainly be helpful in utilizing those SCs.

 

Sulforaphane Protects against Brain Diseases: Roles of Cytoprotective Enzymes

 

Blood-brain barrier (BBB) is a highly selective semi-permeable membranes barrier that separates the circulating blood from the brain extracelluar fluid in the CNS. The ability to go through the BBB is essential to exert neuroprotective effects for any phytochemicals. Several researches have demonstrated that SFN can traverse the BBB and accumulate in the CNS. After SFN gavage to mice, Jazwa, et al. found that SFN was able to cross the BBB and accumulate in cerebral tissues such as the ventral midbrain and striatum. It reached the peak in 15minutes and disappeared after 2hours.

https://www.ncbi.nlm...les/PMC5880051/

 

 

Thus SFN should be timed appropriated with C60.

 

*I update this from time to time, and the latest version can be found on my profile page.

Edited by Turnbuckle, 06 November 2020 - 09:54 AM.

[Iporuru]

I have found something interesting and potentially useful: Lapatinib and other inhibitors of the EGFR-Erbb or aurora kinase (Aurk) pathways increase symmetric division of stem cells

 

„Here, through a small-molecule screen, we identified epidermal growth factor receptor (EGFR) and Aurora kinase A (Aurka) as regulators of asymmetric satellite cell divisions. Inhibiting EGFR causes a substantial shift from asymmetric to symmetric division modes, whereas EGF treatment increases asymmetric divisions. EGFR activation acts through Aurka to orient mitotic centrosomes, and inhibiting Aurka blocks EGF stimulation induced asymmetric division.”

 

Another paper by the same author: Inhibition of JAK-STAT signaling stimulates adult satellite cell function:

 

“Knockdown of Jak2 or Stat3 significantly stimulated symmetric satellite stem cell divisions on cultured myofibers. Genetic knockdown of Jak2 or Stat3 expression in prospectively isolated satellite cells markedly enhanced their ability to repopulate the satellite cell niche after transplantation into regenerating tibialis anterior muscle. Pharmacological inhibition of Jak2 and Stat3 activity similarly stimulated symmetric expansion of satellite cells in vitro and their engraftment in vivo”

 

The first paper mentions the following EGFR inhibitors: lapatinib and ZM449829 (a potent, selective inhibitor of Janus tyrosine kinase 3 (JAK3)), and its prodrug, ZM 39923 hydrochloride (a JAK1/3 inhibitor, almost no activity to JAK2 and modestly potent to EGFR). Berberine chloride is as an inhibitor of JAK3  as well as lots of other natural molecules and Chinese herbal compounds

And more

There are also lots of natural STAT3 inhibitors

Aurk inhibitors: ZM 447439, JNJ-7706621, TC-A2317, VX-680. Quercetin is an Aurora B inhibitor.

 

 

 

Edited by Iporuru, 08 November 2020 - 01:40 PM.

[userCK]

I've purchased everything for Stem Cell protocol and also for Mito Fusion/Fission protocol. My goal is to try and reverse epigenetic markers/damage caused by hair and acne drugs. In what order should I do these protocols?

 

Start with Mito and alternate each week for say next 12 weeks?

Week 1: Mito

Week 2: Stem Cell

Week 3: Mito

Week 4: Stem Cell

.....

^ My reason for selecting Mito first was that if I clear mito issues first and then perhaps stem cells can replace them later?

 

 

Thanks in advance for helping

 

 

For sake of completeness here are the two protocols I plan to take:

Mito Fission/Fusion:
Day 1-2: Fission/mitophagy

Morning
Nicotinamide (NAD+) — 2g 
Ribose (NAD+) — 2g
Jiaogulan leaf (AMPK activator) — 1g
Apigenin (fission) — 100mg
Fisetin (Sirt1 activator) — 100mg

Evening
Jiaogulan leaf — 500mg
Fisetin — 100 mg

Day 3: Fission/mitophagy

Morning & Evening
Jiaogulan leaf  — 500mg
Fisetin — 100 mg

Day 4: Fusion/biogenesis

Morning
Stearic acid (fusion) — 10 g (cook into brownies and take 3 hours before other ingredients, see notes below)
MANGO BUTTER - food grade - mixed in tea/hot water (instead of Stearic Acid cooked in brownies)

Leucine (biogenesis) — 5g
PQQ (biogenesis) — 20mg
Hydroxytyrosol (biogenesis & antioxidant) — 25mg
Vitamin B complex (commercial mix)

Evening
Leucine — 5g (cook into 
PQQ — 20mg
Hydroxytyrosol — 25mg

Day 5: Fusion/biogenesis

Morning & evening
Leucine  — 5g
PQQ  — 20mg
Hydroxytyrosol  — 25mg

And for Stem Cell:

Part 1: Stem cell self-renewal


Time 0 —
Stearic acid — 5-10 g (food grade, in brownie)
MANGO BUTTER (please let me know if this will hamper the protocol)

  
Time 3:00 —
Sulforaphane — 100 mg
Liposomal glutathione — 1 g
SAM-e — 500 mg


Time 3:30 —
C60 — 3 mg (in oil)
Amino acids: Threonine — 2-3 g, Lysine — 2 g, Methionine — 1 g, Leucine — 1 g

These amino acids should be repeated as necessary every couple of hours, and perhaps days.

Part 2: Senescent cell replacement (24 hours later)

Nicotinamide — 2g, Ribose — 2g
Curcumin (liposomal or phytosomal) — 2g
Lysine — 2 g, Methionine — 1 g, Leucine — 1 g

These amino acids should be repeated as necessary every couple of hours, and the entirety of Part 2 may be repeated the next day as well.

Also,

I'm unclear on the ATOMIC Protocol, where does that fit? Should I do it when I'm half way through (say week 6)?

The atomic protocol—

T zero — 2g nicotinamide, 5g ribose
T zero + 30 minutes — 1g TMG, 4g lysine
T zero + 60 minutes — gym weight machines 

Edited by userCK, 13 November 2020 - 01:31 AM.

[userCK]

Won't let me edit the message again. But here is what I wanted to add:

 

Mito Fission/Fusion:

1. Mango Butter instead of Stearic Acid cooked in brownie - please let me know if that will hamper the protocol?

2. Should I also use Sulforaphane in Mito Fusion (in addition to Mango Butter) so it crosses Brain Blood Barrier? If so, what dosage?

 

 

[Turnbuckle]

 

I've purchased everything for Stem Cell protocol and also for Mito Fusion/Fission protocol. My goal is to try and reverse epigenetic markers/damage caused by hair and acne drugs. 

 

 

 

Improving mitochondria should have no direct impact on epigenetics. The SC protocol is intended to restore replacement of aged-out somatic cells at a more youthful rate. Don't expect it to target any specific epigenetic changes.

 

Thus if you are young, this is the wrong approach. You will probably see improvement over time simply by discontinuing these drugs, though it may be slow. There might be supplements or protocols that will reverse these drug-induced epigenetic effects, but I don't know what they are. 

[userCK]

Improving mitochondria should have no direct impact on epigenetics. The SC protocol is intended to restore replacement of aged-out somatic cells at a more youthful rate. Don't expect it to target any specific epigenetic changes.

 

Thus if you are young, this is the wrong approach. You will probably see improvement over time simply by discontinuing these drugs, though it may be slow. There might be supplements or protocols that will reverse these drug-induced epigenetic effects, but I don't know what they are. 

Thanks! I'm 37 years old. I stopped those drugs over 2 years ago and have had zero improvement :(

[eighthman]

Perhaps someone could comment on the negative outcome of recent C60 tests.  I am unable to find any defense/apologia on this.  I still think c60 has effects against toxins and is related to an outcome showing lifespan gains using activated charcoal.

[Turnbuckle]

Perhaps someone could comment on the negative outcome of recent C60 tests.  I am unable to find any defense/apologia on this.  I still think c60 has effects against toxins and is related to an outcome showing lifespan gains using activated charcoal.

 

 

It's my hypothesis that stem cell pools are replenished by forcing SCs to proliferate rather than differentiate, resulting in longer life. For proliferation, two switches must be thrown. First, mito morphology must be driven to fusion, and second, mito quiescence must be banished. The first is done by a fusion agent such as stearic acid, or by fasting, and the second by a (hypothetical) UCP2 blocker such as C60. The first C60 longevity paper mentioned fasting for the acute, toxicology phase, but didn't say what they did for the long term study. The second paper didn't mention the feeding protocol at all. So that uncontrolledly variable could make all the difference.

Edited by Turnbuckle, 13 November 2020 - 04:52 PM.

[nadaepeu]

It's my hypothesis that stem cell pools are replenished by forcing SCs to proliferate rather than differentiate, resulting in longer life. For proliferation, two switches must be thrown. First, mito morphology must be driven to fusion, and second, mito quiescence must be banished. The first is done by a fusion agent such as stearic acid, or by fasting, and the second by a (hypothetical) UCP2 blocker such as C60. The first C60 longevity paper mentioned fasting for the acute, toxicology phase, but didn't say what they did for the long term study. The second paper didn't mention the feeding protocol at all. So that uncontrolledly variable could make all the difference.

 

Turnbuckle are you aware of any other UCP2 blocker that could be used instead of C60? For example could genipin be an alternative?

https://www.hindawi....ri/2015/323246/

Edited by panais, 15 November 2020 - 11:05 AM.

[Turnbuckle]

Turnbuckle are you aware of any other UCP2 blocker that could be used instead of C60? For example could genipin be an alternative?

https://www.hindawi....ri/2015/323246/

 

 

 

Other blockers might work, however, the fullerene C60 has some unique characteristics. It's an excellent anti-oxidant, seems to have a predilection for mitochondria, and doesn't crosslink with anything. Other fullerenes might work, but that is not a given. C70, for instance, has been shown to prefer the endoplasmic reticulum at times, and in my own experience can produce some very unpleasant symptoms when used for a few days, even at sub milligram doses. This, I suspect, is due to interference with protein folding. Other nanoparticles might work, such as gold or iridium, though I'd expect the efficiency to be low due to the spectrum of sizes. And genipin might work. But keep in mind that it is a crosslinker and has shown DNA damage in at least one study --

 

Consumer demand for healthier food products is on the rise, including the replacement of artificial food colors with natural color derived from fruits and botanicals. In preparation for the worldwide marketing of gardenia blue as a natural food colorant, gardenia blue and its natural precursor, genipin, were evaluated in a comprehensive battery of GLP-compliant genetic toxicity tests (results summarized in Table 9). The results of our in vitro testing clearly demonstrated the genotoxic potential of genipin and a lack of genotoxicity associated with gardenia blue. The positive result for genipin tested in the in vitro micronucleus assay differs from a negative result using CHO cells reported previously (Tsai et al., 2000). However, our positive results are consistent with a previous report of genipin-induced DNA damaging activity...

https://focusontoxpa...-FCT-2018-2.pdf

 

 

[Fafner55]

Possible additions to the Turnbuckle stem cell protocol?

Many readers of this forum are familiar with Harold Katcher’s paper from earlier this year demonstrating remarkable reduction in epigenetic age of rats through plasma treatment. Biomarkers such as IL-6, lipids, glucose and cognitive function reverted to youthful levels. The plasma treatment used a fraction extracted from younger rats that included undisclosed additional factors.

1. “Reversing age: dual species measurement of epigenetic age with a single clock” (2020) https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1.full.pdf
2. “Age Reduction Breakthrough” (2020) https://joshmitteldorf.scienceblog.com/2020/05/11/age-reduction-breakthrough/

 

Katcher’s experiment built on parabiosis experiments, notably from the Conboy lab. Since the Conboy research has highlighted benefits from inhibiting TGF-β1 and restoring the age-associated decline in oxytocin, it is a reasonable guess that Katcher’s undisclosed factors modulated those pathways.

1. “Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin” (2020) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288913/
2. “Rejuvenation of brain, liver and muscle by simultaneous pharmacological modulation of two signaling determinants, that change in opposite directions with age” (2019) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710051/
3. “Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches” (2012) 
4. “Relative roles of TGF-β1 and Wnt in the systemic regulation and aging of satellite cell responses” (2009) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783265/ 
5. “Rejuvenation of aged progenitor cells by exposure to a young systemic environment” (2005) 
6. “Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal” (2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494916/ 
7. “Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity” (2013) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072458/ 

 

The Turnbuckle stem cell protocol might also benefit from inhibiting TGF-β1 and restoring oxytocin. What are the thoughts of this community?

 

Oxytocin levels are readily raised by over-the-counter nasal spray.

 

TGF-β1 might be inhibited by supplementation of icariin, naringenin and gotu kola if treatment of mice translates to humans. I calculated the following human equivalent doses for a 70 kg individual.

 

Icariin

(100 mg/kg by daily gavage)(3/37)(70 kg human) = 567 mg

“Icariin Ameliorates Neuropathological Changes, TGF-β1 Accumulation and Behavioral Deficits in a Mouse Model of Cerebral Amyloidosis” (2014) https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104616 

 

Naringenin

(200 mg/kg/day)(3/37(70 kg) = 1135 mg

“Naringenin prevents TGF-β1 secretion from breast cancer and suppresses pulmonary metastasis by inhibiting PKC activation” (2016) https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-016-0698-0 

 

Gotu Kola

(16 mg/kg)(3/37)(70 kg) = 91 mg

“Treatment of renal fibrosis by rebalancing TGF-β/Smad signaling with the combination of asiatic acid and naringenin” (2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741910/

 

Narigenin and Gotu Kola are synergistic in inhibiting TGF-β1.

“Treatment of renal fibrosis by rebalancing TGF-β/Smad signaling with the combination of asiatic acid and naringenin” (2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741910/

 

[Turnbuckle]

Possible additions to the Turnbuckle stem cell protocol?

 

 

 

See also post #11 on this thread. Some things you have to be careful with. For instance, I had TUDCA in the protocol for a while, but then took it out after one person forgot that one should not drink with it, and ended up with the worst hangover in his life.

Edited by Turnbuckle, 15 November 2020 - 10:27 PM.

[QuestforLife]

Possible additions to the Turnbuckle stem cell protocol?

Many readers of this forum are familiar with Harold Katcher’s paper from earlier this year demonstrating remarkable reduction in epigenetic age of rats through plasma treatment. Biomarkers such as IL-6, lipids, glucose and cognitive function reverted to youthful levels. The plasma treatment used a fraction extracted from younger rats that included undisclosed additional factors.

1. “Reversing age: dual species measurement of epigenetic age with a single clock” (2020) https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1.full.pdf
2. “Age Reduction Breakthrough” (2020) https://joshmitteldorf.scienceblog.com/2020/05/11/age-reduction-breakthrough/

 

Katcher’s experiment built on parabiosis experiments, notably from the Conboy lab. Since the Conboy research has highlighted benefits from inhibiting TGF-β1 and restoring the age-associated decline in oxytocin, it is a reasonable guess that Katcher’s undisclosed factors modulated those pathways.

1. “Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin” (2020) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288913/
2. “Rejuvenation of brain, liver and muscle by simultaneous pharmacological modulation of two signaling determinants, that change in opposite directions with age” (2019) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710051/
3. “Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches” (2012) 
4. “Relative roles of TGF-β1 and Wnt in the systemic regulation and aging of satellite cell responses” (2009) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783265/ 
5. “Rejuvenation of aged progenitor cells by exposure to a young systemic environment” (2005) 
6. “Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal” (2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494916/ 
7. “Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity” (2013) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072458/ 

 

The Turnbuckle stem cell protocol might also benefit from inhibiting TGF-β1 and restoring oxytocin. What are the thoughts of this community?

 

Oxytocin levels are readily raised by over-the-counter nasal spray.

 

TGF-β1 might be inhibited by supplementation of icariin, naringenin and gotu kola if treatment of mice translates to humans. I calculated the following human equivalent doses for a 70 kg individual.

 

Icariin

(100 mg/kg by daily gavage)(3/37)(70 kg human) = 567 mg

“Icariin Ameliorates Neuropathological Changes, TGF-β1 Accumulation and Behavioral Deficits in a Mouse Model of Cerebral Amyloidosis” (2014) https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104616 

 

Naringenin

(200 mg/kg/day)(3/37(70 kg) = 1135 mg

“Naringenin prevents TGF-β1 secretion from breast cancer and suppresses pulmonary metastasis by inhibiting PKC activation” (2016) https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-016-0698-0 

 

Gotu Kola

(16 mg/kg)(3/37)(70 kg) = 91 mg

“Treatment of renal fibrosis by rebalancing TGF-β/Smad signaling with the combination of asiatic acid and naringenin” (2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741910/

 

Narigenin and Gotu Kola are synergistic in inhibiting TGF-β1.

“Treatment of renal fibrosis by rebalancing TGF-β/Smad signaling with the combination of asiatic acid and naringenin” (2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741910/

 

I would council caution when knocking down inflammation.

 

There are supplements available now that really can suppress inflammation below normal healthy levels.

 

For example: the powerful boswellic acid extract AKBA has been shown to help with arthritis pain (See: https://www.ncbi.nlm...s/PMC2974165/).

It also helped me to recover super-quick from workouts. But when I doubled up the dose from 1 to 2 tabs/day and used it for ~6 days I came down with a nasty bug. I originally though it was the combination with a ROCK inhibitor that did it. But it happened again with AKBA alone (I am a sucker for punishment). 

 

No doubt tgf-b is central to aging, but it is going to take some experimentation to find the correct protocol to turn it down without harmful effects. 

[JamesPaul]

I would council caution when knocking down inflammation.

 

There are supplements available now that really can suppress inflammation below normal healthy levels.

 

For example: the powerful boswellic acid extract AKBA has been shown to help with arthritis pain (See: https://www.ncbi.nlm...s/PMC2974165/).

It also helped me to recover super-quick from workouts. But when I doubled up the dose from 1 to 2 tabs/day and used it for ~6 days I came down with a nasty bug. I originally though it was the combination with a ROCK inhibitor that did it. But it happened again with AKBA alone (I am a sucker for punishment). 

 

No doubt tgf-b is central to aging, but it is going to take some experimentation to find the correct protocol to turn it down without harmful effects. 

The following article seconds the motion, so to speak.

 

http://karenkurtak.com/what-matters/

 

Scroll down to where it says "An Anti-Aging Regimen Gone Awry" and read the paragraph immediately following that phrase.  The bottom line is that subject of her story was taking too many anti-inflammatories, which suppressed his immune response, with ill effects.

[Nate-2004]

I didn't see this posted here so just FYI here's a breakdown of a recent study:

 

[userCK]

Can Niagen NAD+ be used instead of using niacinmide and ribose separately?

[Turnbuckle]

Can Niagen NAD+ be used instead of using niacinmide and ribose separately?

 

 

Sure. But keep in mind that one gram each of nicotinamide and ribose is equal to 2 grams of NR. You can also use niacin instead of nicotinamide, but only if you are used to it. The flush has caused novices to panic.

[JamesPaul]

I know someone who took a long cold shower after taking a large dose of niacin.  She thought cold showers were healthy and was in the habit of taking them.  After the niacin, she experienced hypothermia, felt dreadful, and was shivering while inside a warm blanket for a while.  Dangerous to take a long cold shower after ingesting niacin.

[Turnbuckle]

I know someone who took a long cold shower after taking a large dose of niacin.  She thought cold showers were healthy and was in the habit of taking them.  After the niacin, she experienced hypothermia, felt dreadful, and was shivering while inside a warm blanket for a while.  Dangerous to take a long cold shower after ingesting niacin.

 

Cold showers are bad, but a hot shower feels great. If you want to reduce the niacin flush faster, drink a lot of water.

[eighthman]

Life Extension is advertising a new fisetin formulation they claim is much more bio-effective. Might be handy in clearing out senescent cells in connection with this regimen.

[aribadabar]

Life Extension is advertising a new fisetin formulation they claim is much more bio-effective. Might be handy in clearing out senescent cells in connection with this regimen.

 

It is a marketing gimmick - there is no 25x better bioavailability. Stick to regular fisetin in 2-3 gram doses and ignore that nonsense.

[eighthman]

They have their marketing interests, clearly.  However, if you wish to say 'it's false', then references or facts to the contrary would be appreciated. I think LEF has reasonable credibility.

[Hebbeh]

According to their marketing data, each serving or capsule contains a paltry 8 mg of fisetin.  And then they make marketing claims of "up to 25 times better than unformulated fisetin" whatever "up to" means since they provide no study data of this claim.  It is Life Extension that needs to back up wild and vague marketing claims with hard data.  These type of marketing claims are classic.

 

Even if their "up to" claims have any validity, up to 25x of practically nothing is still practically nothing.  And I seriously doubt their vague and unsubstantiated claims.  Life Extension has a long history of hype and unsubstantiated claims.

 

 

They have their marketing interests, clearly.  However, if you wish to say 'it's false', then references or facts to the contrary would be appreciated. I think LEF has reasonable credibility.

 

Edited by Hebbeh, 26 November 2020 - 01:22 AM.

[eigenber]

I wonder what 'unformulated' even means in this context. If they're saying it's 25x more bioavailable (however they are measuring that) then it would seem you're getting 200mg of fisetin in your blood. How does that compare to letting 200mg of fisetin dissolve under your tongue where much of it is absorbed directly - or for that matter, taking a gram of it sublingually? Yes, it really does sound 'scammy'. And who knows, LEF may be changing its marketing management team. 

Edited by eigenber, 26 November 2020 - 04:32 AM.

[eighthman]

OK, are we saying that sublingual is the only way to go at present?  Is there no other way to effectively absorb fisetin?  Unless someone comes up with an alternative we can get, fisetin looks like the only game in town as far as senolytics go. And senolytics appear to be half the battle here as regards this regimen.

[Hebbeh]

Sublingual can help but oral does absorb also.  If it didn't, then we would have no data on fisetin as a senolytic.  Polyphenols are typically lipophilic or fat soluble rather than hydrophilic so taking with a source of fat and some lecithin or PC can help immensely but the bigger issue, as with all polyphenols, is surviving the CYP enzymes in the liver (which is where sublingual helps).  Any method that works with any other polyphenol (curcumin, resveratrol, catchin, and all those other phytochemicals that make fruits and veggies good form us) should work with fisetin with the 2 most common methods being CYP inhibitors like piperine or simply overwhelming the CYP enzymes with larger (gram magnitude) doses.  Hence the term, the poison is in the dose.

[mister_blue]

Re: Life extension and « 25x more absorbable fisetin ». It’s covered in the latest edition of their magazine. Too bad I can’t add pictures here I’d have photographed the article. But the study they refer to for their product is « Akay. A cross over pilot pharmacokinetic study of fisetin 1000mg and formulated fisetin 200mg administered in a single dose to healthy volunteers. Manufacturer’s study (in press for future publication. 2020

So not published, not peer reviewed at this point.

I have no opinion I just wanted to share

[OlderThanThou2]

They use fenugreek like for their new curcumin, I posted the study about fenugreek they referred to in another topic.  Concerning their new pilot study, it was done on 12 subjects:

Bio-Fisetin, a x25 Boost in Bioavailability? - Self-Experimentation - Age Reversal Forum (age-reversal.net)

 

12 subjects might be enough if the increase is 25 fold. If the increase was much less statistically it would take a much larger number of participants to prove significance.