A new AI-driven website that helps identify interactions between the drugs and supplements you are taking:
Try it out and report your findings!
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Well this is something interesting:
So, a competitive inhibition of the binding to plasma protein by metformin HCI increases the plasma concentration of caffeine.
More of a buzz from your coffee on metformin?
There is growing evidence that other B vitamins, vitamin D and magnesium may also be impacted by metformin use in addition to alterations to the composition of the microbiome, depending on the dose and duration of therapy.
This could be why my vitamin D levels are low.
“ Resveratrol is sensitizing the anti-tumor effects of rapamycin and the PI3K/AKT/mTOR signaling is involved.”
“In addition, combination treatment with rapamycin and resveratrol induced cell death specifically in TSC1−/− MEF cells, and not in wild‐type MEFs.” (Bladder Cancer)
So Resveratrol enhances the anti-tumor effects of Rapamycin?
“Furthermore, resveratrol potently inhibited inflammatory factors–mediated protein kinase B/mammalian target of rapamycin signaling in neurons.”
So Resveratrol + Rapamycin reduces brain inflammation?
“The combined use of rapamycin and resveratrol enhanced AMPK, thereby restoring downstream signaling and reducing IL1β secretion.”
What? Isn’t that brilliant?
“Addition of resveratrol , which alone did not affect insulin levels, potentiated the effect of rapamycin , so that the combination decreased obesity and prevented hyperinsulinemia.”
“Given distinct mechanisms of action of rapamycin and resveratrol at clinically relevant doses, their combination warrants further investigation as a potential antiaging, antiobesity and antidiabetic modality.”
If Rapamycin is raising your blood glucose, just add resveratrol.
Wow. You can really go down a lot of rabbit holes here. I feel like I’m in Watership Down.
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Remember the post you had about dumping your reveratrol? 
luteolin is another weak Mtor inhibitor that works synergistically with Rapamycin.
I will start taking these together with my Rapamycin.
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Most useful!
The interaction between two mTOR inhibitors show attenuation by the stronger of the weaker inhibitor’s effect on mTOR, in line with what Brian Kennedy is seeing in his mice studies.
Rapamycin (50 nM; an inhibitor of mTOR) attenuated (P < 0.05) the stimulatory effect of AKG on mTOR signaling and syntheses of milk protein and lactose, while relieving (P < 0.05) an inhibitory effect of AKG on expression of proteins related to ERS.
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I think this is a really interesting and potentially valuable resource for determining possible supplement and drug combinations. Thanks @RapAdmin
DrugBank looks like a possibly useful drug interaction site.
Easy interface and one can enter several medications at a time.
I ran Rosuvastatin and Sirolimus, which raises concerns:
The metabolism of Sirolimus can be decreased when combined with Rosuvastatin.
Any thoughts on how to navigate such a concern appreciated.
REFERENCES
- Shirasaka Y, Chang SY, Grubb MF, Peng CC, Thummel KE, Isoherranen N, Rodrigues AD: Effect of CYP3A5 expression on the inhibition of CYP3A-catalyzed drug metabolism: impact on modeling CYP3A-mediated drug-drug interactions. Drug Metab Dispos. 2013 Aug;41(8):1566-74. doi: 10.1124/dmd.112.049940. Epub 2013 May 30. [Article]
- Williams JA, Cook J, Hurst SI: A significant drug-metabolizing role for CYP3A5? Drug Metab Dispos. 2003 Dec;31(12):1526-30. doi: 10.1124/dmd.31.12.1526. [Article]
- Emoto C, Iwasaki K: Enzymatic characteristics of CYP3A5 and CYP3A4: a comparison of in vitro kinetic and drug-drug interaction patterns. Xenobiotica. 2006 Feb-Mar;36(2-3):219-33. doi: 10.1080/00498250500489968 . [Article]
- Bhagavan N. and Ha C. (2011). Essentials of Medical Biochemistry. Elsevier.
- FDA Narrow therapeutic index drugs reports [Link]
- FDA Workshops (narrow therapeutic index) [File]
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How do you search for interactions? How is it different from Drug Interaction Checker ← Quickly Check Your Meds?
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@A_User - They look like they use the same code.
Both appear to differ from Supp.ai in that one can enter a set of drugs and then get the interactions between the elements of the set.
Supp.ai, seems to only let you enter one medication then it shows everything it can access that interacts with that drug.
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The synergistic effects of Rapamycin and Resveratrol are quite interesting. Especially in it’s effects against cancer.
Resveratrol may be useful in combination with Rapamycin if you trust this AI.
Also it appears Sirolimus decreases D3 levels as well. This could explain my D3 deficiency.
The key words… Does anyone trust AI right now?
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Interesting. Do you have any thoughts on how much one should/can supplement D3 to offset the decrease in D3 from taking Sirolimus?
5000 IU of D3 was not enough. I’m trying 10,000 IUs.
I moved to the same amount. let’s keep each other posted on how it works.
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Berberine and NAD boosters cancel each other out. If you wish to take both, take an NAD booster in the morning and Berberine at night to allow the Berberine to clear your system.
AI Summary:
Introduction to Bourberine and NAD Boosters
- The discussion begins by addressing the common practice of taking bourberine supplements along with NAD boosters like NMN or NR.
- The speaker suggests that individuals may be wasting their money on these supplements due to a conflict between their effects on cellular processes.
- Bourberine is widely used for blood sugar control and other metabolic health benefits, which is supported by scientific evidence.
- Simultaneously, NMN and NR are recognized for their role in boosting NAD+ levels, which is associated with anti-aging benefits.
Bourberine’s Dual Effects on NAD+
- The speaker introduces a significant finding from a 2021 study published in the journal Aging, which indicates that bourberine enhances NAD+ production by activating specific enzymes.
- The enzymes identified include ID1, QPRT, and MPT, which contribute to the increased levels of NAD+ in cells.
- However, a 2022 study in Toxicology Letters reveals a concerning second effect of bourberine, which is its impact on the NADH to NAD+ ratio.
- NAD+ is likened to a charged battery necessary for cellular function, while NADH represents a depleted battery that requires recharging.
- Healthy cells maintain a favorable NAD+ to NADH ratio, ideally around 700 to 1, but bourberine can disrupt this balance by blocking mitochondrial complex one, leading to inefficient cellular energy use.
The Supplement Conflict Explained
- The speaker illustrates the conflict created by bourberine’s dual effects, comparing it to pressing both the gas and brake pedals in a car simultaneously.
- While bourberine does increase NAD+ production, it simultaneously disrupts the NAD+ to NADH ratio, leading to confusion about its effectiveness.
- Taking NMN or NR alongside bourberine may result in wasted effort and resources, as the benefits of NAD+ supplementation are undermined.
Strategic Timing for Supplementation
- The speaker offers a solution to maximize the benefits of both bourberine and NAD boosters through strategic timing of their intake.
- It is recommended to take NMN or NR in the morning, aligning with the body’s natural inclination for higher NAD+ levels.
- Bourberine should be taken in the evening with dinner, which is when blood sugar control is most crucial.
- This timing strategy aims to minimize the overlap where bourberine disrupts the cellular energy balance.
- The rationale behind this approach is that bourberine has a short half-life of approximately three hours, allowing it to clear from the system by morning.
Considerations for Older Adults
- The speaker raises a critical question regarding whether older adults should avoid bourberine without concurrently using a NAD booster.
- While definitive study data is lacking, it is suggested that older adults, particularly those aged 50 and above, may not achieve optimal health benefits from bourberine alone due to age-related declines in NAD+ levels.
- The implication is that promoting peak health may necessitate the combined use of both supplements for this demographic.
Conclusion and Additional Resources
- The speaker acknowledges the novelty of the information presented, emphasizing their extensive research experience in human longevity topics.
- Viewers are encouraged to consider this information as part of their health strategy, particularly in relation to supplement timing.
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I’ve done as the video suggests and switched my Berberine intake to after dinner.