RE: Rapamycin - 3

David M. Sabatini, einer der bgenadesten Forscher über das Thema Rapamycin, gesteht in diesem wahrhaftig epischen Podcast mit Peter Attia und Tim Ferriss ebenfalls 3 mg Rapamycin je Woche als seine persönliche Dosis:

http://tim.blog/2016/10/20/my-life-exten...o-easter-island

Wie schwer ist es eigentlich in D Rapamycin für Off-label-use via Privatrezept zu erhalten?

Zitat

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Der Arzt müsste bereit sein, seine Verschreibung vor Gericht zu verteidigen wenn etwas schief läuft und würde dabei seine Approbation riskieren.

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danke- ich seh schon, dafür müsste ich mal wieder Urlaub in Thailand oder Ägypten planen...

Ein neues interessantes Paper von Blagoskonny. Seine aktuellste cutting-edge NEM-Empfehlung (eigentlich alles Arzneimittel) für Anti-Aging-Zwecke:

Zitat

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Rapamycin-based mixtures:

A. Rapamycin plus metformin (especially in insulin-resistant and obese people, metformin is indicated).

B. Rapamycin plus Lisinopril (or other angiotensin II-inhibitor) plus propranolol. Like in Polypill, these prescription drugs may be used at ½ doses in normotensive individuals. Hypertensive patients may require full doses.

C. Rapamycin plus Statin (such as lovastatin, simvastatin and atorvastatin)

D. Rapamycin plus Statin plus metformin. This combination with rapamycin may be the most attractive for people with metabolic alterations: hyperlipidemia, obesity, insulin resistance.

E. Rapamycin plus polypill-like combination (Lisinopril, propranolol, aspirin, statin). This is especially attractive in people with atherosclerosis given that rapamycin prevents atherosclerosis too.

F. Rapamycin plus Lisinopril (or other Angiotensin II-inhibitor) + propranolol + aspirin + statin + metformin + PDE5inhibitor. This is a comprehensive 7-drug combination.
Doses and schedules

In the 7-drug anti-aging combination, rapamycin, metformin, lisinopril (or its equivalent), a statin, a PDE5 inhibitor and propranolol are prescription drugs (in the USA). So I will not discuss doses and schedules here. They should be determined for each individual individually. Polypill composition provides the hint on doses of 4 drugs in healthy individuals. The doses of rapamycin are beyond the scope of this article. Mixtures of anti-aging drugs should be further complemented with physical exercise and low-calorie diet or intermittent diet. Additional drugs such as melatonin may be considered. The 7-drug combination can be tested in mice, especially in mice on high fat diet and in cancer-prone mice. If started late in life, the experiments will take just several months to evaluate the effect on lifespan and cancer incidence as well as weight, blood pressure, glucose, insulin, triglycerides and leptin. In humans, the treatment program can be initiated regardless of any pre-clinical studies, because all 7 drugs are approved for human use and some of them such as aspirin and statin are widely used for disease prevention anyway. The only what is needed is to watch for side effects. Especially, heart rate, blood pressure and glucose levels should be monitored.

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http://www.impactjournals.com/oncotarget...ath%5B%5D=57761

Allantoin, glaub ich sofort!

Bisher nicht über innere Gabe von Allantoin nachgedacht. Vlt. ein Fehler. Danke für den Hinweis.

https://www.ncbi.nlm.nih.gov/pubmed/22147657

https://www.ncbi.nlm.nih.gov/pubmed/24296131

Olivenblattextrakt, genauer gesagt: Oleuropein: der kleine Bruder von Rapamycin! Rezeptfrei erhältlich in der Naturapotheke.

Zitat

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Oleuropein potently inhibits mammalian target of rapamycin: possible involvement of tandem anomeric hyperconjugation–Michael reaction



The reported anti-cancer properties of oleuropein combined with the recently elucidated role of mammalian target of rapamycin (mTOR) in various cancers, suggested the possibility that oleuropein inhibits mTOR. To validate this hypothesis, we docked oleuropein into the ATP-binding pocket of a close mTOR protein homolog, namely PI3K-γ. Apparently, oleuropein shared at least six critical binding interactions with the potent dual PIK3-γ/mTOR natural inhibitor quercetin. Subsequent experimental validation indicated that oleuropein indeed inhibited the enzymatic activity of mTOR with an IC50 value of 0.905 µM. Lineweaver–Burk plot showed that oleuropein inhibits mTOR via mixed competitive/noncompetitive mechanism suggesting that inhibition is mediated, at least partially, by covalent bonding to mTOR binding pocket. Our findings strongly suggest that mTOR inhibition is at least one of the reasons for the reported anti-cancer properties of oleuropein.

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http://link.springer.com/article/10.1007/s00044-014-1168-9

Zitat von Prometheus im Beitrag #63

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Ja! Wer mag, kann auch Oleuropein auch gerne als Tee genießen:

Olivenblättertee

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Nicht unbedingt. Olivenblätter weisen einen Oleuropeingehalt zwischen 10 und 100 mg/kg auf. Ein Aufguß mit einem pulverisierter EL wären also im Idealfall bereits 100 bis 1000 mg des wasserlöslichen Oleuropein.

Na gut, das klingt machbar.

Zitat von Scout im Beitrag #65

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Nicht unbedingt. Olivenblätter weisen einen Oleuropeingehalt zwischen 10 und 100 mg/kg auf. Ein Aufguß mit einem pulverisierter EL wären also im Idealfall bereits 100 bis 1000 mg des wasserlöslichen Oleuropein.

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Sorry, gemeint waren pro GRAMM.Also 10 bis 100 Promille.

Quelle: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674619/

Die Konzentration von Oleuropein in vitro um mTOR um 50% zu hemmen lag übrigens bei 22 mg/L. Also sollte ein EL schon recht potent wirken wenn die Absorbtionsrate im Darm hoch genug ist- letzere dürfte der entscheidende Faktor werden.

#69 #70
Das finde ich echt interessant! Es ist ja vermutlich eine Art Autoimmunkrankheit, wenn bei manchen Menschen die Knorpel sehr schlecht sind. Gibt es schon Ärzte die es anwenden bei Kreuzschmerzen oder Knieschmerzen?

Studie über Creatin als Ketamin-Alternative bei schweren Deperessionen - hier bei Mäusen künstlich durch Glucocorticoid-Gabe induziert. Creatin und Ketamin wirken beide effektiv gegen diese Form von "affektiver Störung". Gleichzeitige Rapamycin-Gabe verhindert diesen kurativen Effekt!




https://www.ncbi.nlm.nih.gov/pubmed/26660117

Creatine, Similar to Ketamine, Counteracts Depressive-Like Behavior Induced by Corticosterone via PI3K/Akt/mTOR Pathway.

Ketamine has emerged as a novel strategy to treat refractory depression, producing rapid remission, but elicits some side effects that limit its use. In an attempt to investigate a safer compound that may afford an antidepressant effect similar to ketamine, this study examined the effects of the ergogenic compound creatine in a model of depression, and the involvement of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in its effect. In order to induce a depressive-like behavior, mice were administered with corticosterone (20 mg/kg, per os (p.o.)) for 21 days. This treatment increased immobility time in the tail suspension test (TST), an effect abolished by a single administration of creatine (10 mg/kg, p.o.) or ketamine (1 mg/kg, i.p.), but not by fluoxetine (10 mg/kg, p.o., conventional antidepressant). Treatment of mice with wortmannin (PI3K inhibitor, 0.1 μg/site, intracerebroventricular (i.c.v.)) or rapamycin (mTOR inhibitor, 0.2 nmol/site, i.c.v.) abolished the anti-immobility effect of creatine and ketamine. None of the treatments affected locomotor activity of mice. The immunocontents of p-mTOR, p-p70S6 kinase (p70S6K), and postsynaptic density-95 protein (PSD95) were increased by creatine and ketamine in corticosterone or vehicle-treated mice. Moreover, corticosterone-treated mice presented a decreased hippocampal brain-derived neurotrophic factor (BDNF) level, an effect abolished by creatine or ketamine. Altogether, the results indicate that creatine shares with ketamine the ability to acutely reverse the corticosterone-induced depressive-like behavior by a mechanism dependent on PI3K/AKT/mTOR pathway, and modulation of the synaptic protein PSD95 as well as BDNF in the hippocampus, indicating the relevance of targeting these proteins for the management of depressive disorders. Moreover, we suggest that creatine should be further investigated as a possible fast-acting antidepressant.

Anmerkung:
Glucocorticoide sind meines Wissens nach bei praktisch jeder depressiven Störung chronisch erhöht (HPA-Axis/chronische Neuroinflammatio). Rapamycin ist, wie hier mehrfach beschrieben, wirklich nichts zum drauflos-probieren!