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BobM
Hi Bob!
I start this thread to avoid polluting the fisetin thread with posts about information about green tea (alone or in combination with other substances). There is plenty of research supporting that combination of green tea and quercetin. I throw in some links to research that I find convincing.
https://www.ncbi.nlm.nih.gov/pubmed/22438067
Quercetin increased bioavailability and decreased methylation of green tea polyphenols in vitro and in vivo.
https://www.ncbi.nlm.nih.gov/pubmed/22452782
Quercetin increased the antiproliferative activity of green tea polyphenol (-)-epigallocatechin gallate in prostate cancer cells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384709/
Primary Cancer Prevention by Green Tea, and Tertiary Cancer Prevention by the Combination of Green Tea Catechins and Anticancer Compounds. (Table 1)
There are also a body of research that support the use of of Sulforaphane and 3,3′-Diindolylmethane alone or in a combination with green tea.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086787
Effects of Sulforaphane and 3,3′-Diindolylmethane on Genome-Wide Promoter Methylation in Normal Prostate Epithelial Cells and Prostate Cancer Cells. - Wong et al. aimed to evaluate the genome-wide effects of sulforaphane (SFN) and 3,3′-diindolylmethane (DIM) on DNMT1, DNMT3A, and DNMT3B activity and promoter methylation status in normal prostate epithelial cells and LnCAP and PC3 prostate cancer cell lines. For all three prostate cell lines, the authors revealed widespread changes in promoter methylation patterns in response to SFN or DIM interventions. Importantly, SFN and DIM reversed many of the cancer-associated methylation alterations, including aberrantly methylated genes that are dysregulated or are highly involved in cancer progression, such as C–C chemokine receptor type 4 (CCR4), transforming growth factor-β1 receptor type I (TGFBR1), cysteine-rich angiogenic inducer 61 (CYR61), and C-X-C chemokine receptor type 4 (CXCR4).
I have previously used life extensions Triple Action Cruciferous Vegetable Extract but will change to their new optimized cruciferious blend. The combination Green tea, quercetin and sulforaphanee+DIM is a very promising combination for health promotion and disease prevention.
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Staffan Olsson
Staffan, this is an excellent study and summary!!
I am taking the optimized quercetin with the green tea both from Life Extension.
Also fresh broccoli sprouts which are VERY rich in sulphoraphane. These are so easy to grow. I’m having some with every meal now.
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BobM
I don’t grow broccoli sprouts so I have to buy them dried. And then I take a teaspoon or two with meals. I take the capsules as a complement to the real thing. To make sure I get a meaningful amount into my system.
Same things with green tea. Now I drink green tea but take capsules to make sure I get a physiological meaningful amount catechins into my body. I saw a research paper from japan where they hade people drink 1 liter of green tea but also had them eat green tea capsules. (it was about preventing coloncancer) I think this indicate that serious research has an idea that we have to ingest a fair amount of green tea to reach a disease preventing amount.
In the fisetin thread I linked to another study that showed that an amount of 1 Liter green tea had a significant preventive effective. (Measured by delayed onset of cancer). And then we have to face the variability of EGCG content. Today I read that the catechin content can be between 20 – 100 mg of per 100 ml tea. In other papers I read different amounts, usually less than 100 mg per 100 ML tea. The conclusion from this is that we never really know how much catechins we get from drinking green tea.
I drink green tea that is harvested in the fall. They say that those kind of late harvest tea has more catechins than the spring harvest (Which has more theanin). And I only drink Japanese green tea. Some chinese green tea have a history of being polluted by lead.
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Staffan Olsson Thanks for sharing that! Really helpful
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I started drinking green tea decades ago after living in Japan. Better than coffee for me, it does wake me up and calm me down. And yes we've since come to find out the tremendous health benefits.
Tea is the second most drunk liquid on the planet, after water. I wouldn't touch pills, straight from the source gives more benefits, health is body body and spirit.
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Dan
I would not trade the pleasure of tea for capsules. But I use capsules to make sure I get a enough of catechins.
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I'm not sure why this study isn't getting more attention but I think it's very important. It's from the Conboys at UC Berkley:
Recalibrating old blood to be young again
The new study suggests that the majority of aging is driven by changes to a limited number of regulatory signals present in blood. This is a reasonable hypothesis given that the bloodstream is the uniting communication network in the body and that the signals traveling through it do indeed have the potential to influence every cell within the body.
The study focuses on two of the key molecules that influence the ability of stem cells to function and regenerate tissues: TGF-β1, which increases during aging, and oxytocin, which falls during aging. Using a pharmacological approach, they were able to reduce TGF-β1 levels and increase oxytocin, spurring rejuvenation and leading to significantly increased neurogenesis, a reduction of neuro-inflammation, increased cognitive performance, and rejuvenation of the liver and muscle in aged mice.
https://www.leafscience.org/brain-liver-and-muscle-rejuvenated-by-calibrating-aged-blood/
How do you reduce TGF-b1 levels? How about EGCG and myricetin? See this study:
I'm not sure how you would increase oxytocin. Nasal spray?
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Larry
Hi Larry!
Thank you for bringing my attention to this study. It is very interesting. The first thing that come to my mind when I read the other link (about myrcetin and EGCG) is the product from lifeextension that is called ageless cell.
https://www.lifeextension.com/vitamins-supplements/item02119/geroprotect-ageless-cell
It has EGCG and Myricetin (+ NAC, Gamma tocotrienol). I have been thinking about what kind of information they have based their formula on. But your link indicate the possibility of a potential rejuvenating effect from EGCG and Myricetin.
In the conboys study they used a TGF-β1 Type I Receptor Kinase Alk5 inhibitor called “2-(3-(6-Methylpyridin-2-yl)- 407 1H-pyrazol-4-yl)-1,5-naphthyridine”. The question is to find the best available alternative to the above mentioned substance. I wonder if there are any other alternatives than myrcetin and EGCG? But EGCG and Myricetin I should be an easy self-experiment to do. And oxytocin can be taken as nasal spray or tablet dissolved under the tongue.
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Staffan Olsson https://selfhacked.com/blog/tgf/
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Larry Thank you.
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Larry BobM Dan
I have made one observation that I don’t know how to make good sense of. In the now famous Fisetin study they screened several substances for an improved senolytic effect (compared to the relative week effect that we get from quercetin).
In that screening process they used EGCG as one of the substances. Kindly look at figure 1 in section 3: results.
https://www.ebiomedicine.com/article/S2352-3964(18)30373-6/fulltext
There they show that EGCG has the opposite effect as fisetin. Can this be an indication that EGCG is prosenescense? Being prosenescense is not a bad thing since. Increased senescense can be a result from EGCG stopping dysfunctional cells and “throwing” them into senescent state where they no longer will replicate themselves or progress the evolution into full-blown diseases.
This might be one of the ways that EGCG initiate to block or to delay the progression of diseases (Cancers). But EGCG is not senolytic and although arresting dysfunctional cell cycles are a good thing it becomes vital for the body to add senolytic treatments to get rid of the senescent burden.
This is my own speculative thinking based of nothing else than the above-mentioned figure 1 in the fisetin study. The consequence of this speculation is not to stop drinking green tea. On the contrary. We know EGCG has a very favorable effect on many cells in the human body and arresting dysfunctional cell cycles is good. But we need to stop dysfunctional cells from accumulating in the body.
So to maximize the disease preventing effect from EGCG we have to get rid of the senescent cells. This thinking makes it rational to use EGCG in a combination with senolytic therapy. So green tea lovers should really keep doing senolytic therapy on a regular basis.
I am very interested in hearing other interpretations of the above mentions figure 1 in the Fisetin study.
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Staffan Olsson and Larry:
Great thoughts here!
I’m sure other researchers are quietly following along. It’s this kind of outside the box brainstorming that leads to big breakthroughs. Keep it going!
The body has a lot of “tear it down” “build it up” processes. With multiple mechanisms at play.
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Larry
Hi Larry!
You got me started on the Myrcetin -EGCG combination. Myrcetin is a MRP2 inhibitor and the combination EGCG and quercetin have shown synergies in quite many research papers. Myrcetin but also curcumin might be added to design a cocktail that acts synergistically on many cells in the human body.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820202/
Down below I have taken some of the thoughts from a paper called "Improving the oral bioavailability of beneficial polyphenols through designed synergies."
"the beneficial green tea component EGCG and its methyl metabolites have low oral bioavailability, which is thought to be partly due to the actions of the MRP efflux pumps [29, 79]. Co-consumption with a polyphenol MRP2 inhibitor (my note - myrcetin and curcumin are MRP2 inhibitors) may greatly increase the oral bioavailability of EGCG, and putatively, its beneficial activity on human health. Furthermore, if the efflux pump inhibitors themselves have reasonable oral bioavailability, they may also facilitate the increased penetration through the BBB [90]. For example, quercetin is a weak ligand of the benzodiazepine site of the GABA-A receptor [70] and thus might have anxiolytic activity if it were able to reach its site of action in the brain. The co-consumption of a product rich in quercetin, with a bioavailable BCRP inhibitor may increase quercetin’s entry into the brain and hence unleash novel bioactivity from a very commonly consumed polyphenol."
"For example, quercetin bioavailability may be greatly increased when co-consumed with a polyphenol BCRP inhibitor-like apigenin, hesperetin or naringenin [6]. ( my note - naringinin is a grapefruit flavonoid and curcumin is also a BCRP inhibitor) Furthermore, polyphenols which can increase the function or expression of MRP3 activity, thus increasing substrate movement into plasma, may further add to this synergistic interaction. This approach is likely to be more successful when used acutely and short term, as chronic exposure to some polyphenol efflux pump inhibitors may actually increase transporter expression over time [14, 27]."
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Staffan Olsson Thanks for the info Staffan. It's interesting to note that Hesperetin is also a TGF-b1 signal inhibitor. I started a Myrcetin -EGCG combination too. I also started drinking more green tea. Good luck and cheers!
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Staffan Olsson Please read this blog from Josh Mittledorf. He has talked to Dr Harold Katcher who claims to have reversed aging in mice using small molecules:
"Our first pass was to try a combination of known herbal supplements that are known to bind with the targets we’d identified. We gave them to rats, and at first nothing seemed to be happening. But after two months (about 4 years in human terms) the rats showed signs of rejuvenation. We were encouraged. Rather than continue with the herbs, though, we formulated the elixir that we report on here. This is our first iteration, with dosage and timing determined theoretically, yet to be optimized in the lab"
https://joshmitteldorf.scienceblog.com/2019/02/05/rumors-of-age-reversal-the-plasma-fraction-cure/
I "think" that they used some herbal supplements to clean out TGF-b1 from the blood. If the Conboys and Dr. Katcher are right then it must be some of the supplements we are looking at but perhaps they have something better.
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Larry Thank you for bring my attention to this. And now I will try to find a good source of myricetin.
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Larry Hesperitin looks interesting as TGF-b1 inhibitor. But should be careful not to take hepseridin for being equal to hesperitin. "hesperetin interacts with membranes stronger than hesperidin"
https://www.ncbi.nlm.nih.gov/pubmed/20447374
I am looking for a good source for M;yricetin. Have you found one? I have not tried myricetin yet. They also promote dihydromyricetin as a cure for hang overs.
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Staffan Olsson Amazon
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Larry I must have missed it. I use Amazon in the UK.
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Larry
This might be interesting. Lactobacillus reuteri upp-regulates oxytocin.
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Staffan Olsson Staffan Olsson I bought a yogurt maker and some Biogaia so I'll be trying it out in a few days. More info here: https://selfhacked.com/blog/l-reuteri/
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Larry
Reuteri is a probiotic I use from time to time. One thing I did not know about reuteri until a few days ago is that the Reuteri probiotics can increase the level of oxytycin. I have experienced a wellbeing effect when I previously have used reuteri, and now I can guess that it might have to do with increased oxytocin (or decreased inflammation).
PS reuteri can also be used to manage and treat chronic periodontitis (gum disease). With that purpose in kind it is important to keep the probiotics in in the mouth for some time.
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Larry Hi Larry! I read this report from MIT and I think that maybe it also can be interesting to you. The report is about TGF signalling and how it can effect senescense and aging.
"TGF-β Signaling in Cellular Senescence and Aging-Related Pathology"
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Staffan Olsson Thanks!
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Larry Hi! I read this interview with the prof Conboys'. I find their work on blood factors and aging fascinating.
https://www.leafscience.org/apheresis-with-profs-irina-michael-conboy/
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