Two supplements can augment the concentrations and absorption of rapamycin. 1) Grapefruit can increase the levels of rapamycin or sirolimus in the blood. (Some biohackers will take rapamycin and grapefruit to get higher amounts of rapamycin in their bloodstream). 2) St. John’s wort can decrease the effectiveness of rapamycin or sirolimus
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I have been told by my medical advisor that drinking grapefruit does put more Rapa into your blood, but he disagrees that it’s a good thing. I haven’t read anything that convinces me that spiking the treatment is a better strategy. However, I have read about several people taking it that way.
I hope to start my program next week. I believe slow and low is the way to start.
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This is great news! I love grapefruits! I will continue to eat my grapefruits especially when I take Rapamycin! Thank you so much for letting us know this important fact!
I have been taking rapa for almost 2 years, and I know if I take grapefruit juice with rapamycin i get mouth sores
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Hi there, I am about to begin my 3 mg weekly dose of Sirolimus on May 1st, after all my blood panels have been documented. Liked your comment, “slow and low” is the way to start…curious how you are doing so far? Don’t know why I am a bit apprehensive, but I get over it once I begin…thanks
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Approximately 18 months ago, I commenced treatment with a dosage of 2 milligrams per week. Over time, I gradually escalated my dosage to 6 milligrams per week. This approach is considered appropriate to obtain the intended therapeutic effects while also assessing the medication’s tolerability and efficacy in one’s system.
I also take acarbose with meals and get blood testing through Healthspan every quarter to monitor my biomarkers.
I will take weeks off occasionally if I am feeling run down. Taking time off of rapamycin is perfectly fine.
Thanks Daniel…Jeff sent me a LabCorp blood test which I completed on Wednesday, and my primary care doctor sent me approval for a extensive blood panel which I took this morning, 4/13. I can share those result with you through your labs email address. Found it interesting that you begin with 2 mgs per week. I may consider that too…I look forward to the endeavor…kc
Thanks for the question. Like you, I have moved very slowly in my process. I just started my treatment this week. I picked Monday to be my once-a-week day to take the Sirolimus.
I purchased 2mg pills, and I took one pill in my low & slow strategy. Based on that minimal history, I have no negative or positive effects to report.
I am planning on ramping up to 4mg next week and then the following week I will move to my final planned full ongoing dose of 5mg. BTW it is more cost-effective to purchase 2mg over 1mg and I bought a pill cutter.
Good luck on your journey and let’s all hope we are at the forefront of a new and better way to live longer and healthier!!!
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Thank you for your insights. I may begin dosing at 2mg p/w and see how it goes. Nice to hear you’ll experienced no side effects…wish you the best…kc
Are there benefits to titrating up compared to maintaining a 2mg dose? Meaning, is 6mg somehow considered the “sweet spot” where additional benefits are seen given the person can tolerate that dose?
Are there benefits to titrating up compared to maintaining a 2mg dose? Meaning, is 6mg somehow considered the “sweet spot” where additional benefits are seen given the person can tolerate that dose?
Hello, this is Brandon from the Healthspan Clinical Team. Thank you for your question! There is a constellation of factors to consider, which our team strives to hold high while keeping patient safety and service as a core tenet. Based on the available literature (primarily animal models), 6mg per week of oral rapamycin appears to be the optimal dose for longevity purposes [1]. Like many medications, supplements, or adjuvant therapies intended to promote health, this can depend largely on an individual’s condition and health targets. Casting this net becomes even murkier without the ability to easily or non-invasively quantify mTOR activity (or lack thereof) or senescent cell concentration, and instead, having to rely on a vague statement such as “I am currently disease-free”.
For example, if a patient presents with concerns about medication sensitivity or is prone to canker sores, we would recommend titrating up at a rate of 1- 2mg weekly, allowing time for the body to adjust to a new medication. Moving forward, we can test sirolimus bioavailability in 6-week intervals. The peak level of sirolimus is the highest concentration of the drug in your bloodstream, reflecting the maximum absorption of the drug after it’s taken at your weekly dose and is crucial for determining if the dosage is at a therapeutic level that is both effective and safe. The results will show if the sirolimus concentration is within the therapeutic range prescribed for longevity purposes. High peak levels may suggest a risk of toxicity, while low levels might indicate insufficient dosage for therapeutic efficacy [2]. Toxicity could be defined as slower wound healing, getting sick more frequently than you otherwise do, canker sores, or things like hyperlipidemia and hyperglycemia (noting that mTOR is a glucose and lipid metabolism pathway). It is important note that peak levels may vary among individuals, and some individuals may require different peak levels.
Alternatively, we can weight dose for a more accurate regimen. Again, all of this can change if there is a condition you are trying to manage. An important note here is that during this 6-week interval between CMP/CBC labs, the Healthspan Clinical Team is readily accessible through the convenience of your back pocket through a HIPAA-compliant chat stream, eager to field questions about not only lab results, but also how you may be feeling subjectively or objectively. This allows us to provide physician-backed feedback in real-time and adjust a protocol specfic to your health goals.
Regarding oral rapamycin and vitamin contraindications, there really aren’t any. What is important to consider is anything that may interact with the P450 enzymes/CYP3A4 pathway of the liver - the same pathway which metabolizes rapamycin. Grapefruit juice inhibits this enzyme and as a result increases serum sirolimus. At low doses, such as 3-6mg per week, this might not necessarily indicate a bad thing. Similar to how Vitamin C enahnces iron absorption, there may potentially be a symbiotic relationship here. This would be an applicable plug for the sirolimus bioavailability lab draw. Additionaly, according to researchers, the drug ketoconazole, which is commonly used to treat infections, can raise patients’ sirolimus levels by 500%. This body of literature administered rapamycin dosage in the 16-35mg/week range (depending on the arm of the study), which could offer an opportunity to achieve desired benefits with a reduced spending on medications [3].
The impact of rapamycin on mTORC1 and mTORC2 can vary significantly depending on an individual’s unique metabolism, which is influenced by factors like genetic makeup, overall health, and lifestyle. This variability can affect how the body processes the drug and responds to its mechanism of action. Therefore, by carefully monitoring the drug’s peak and trough levels, dosages can be customized to an individual’s unique metabolic profile. This personalized approach ensures that the drug’s effects on mTORC1 are optimized while minimizing unintended effects on mTORC2, thus enhancing both the safety and efficacy of the treatment [4].
The time it takes for rapamycin to exit the bloodstream is determined by its half-life, which is the time required for the concentration of the drug in the blood to decrease by half. The half-life of rapamycin in most patients ranges from 57 to 63 hours. However, this can vary depending on individual factors such as age, liver function, and concurrent medications. It generally takes about 4 to 5 half-lives for a drug to be mostly eliminated from the body. For rapamycin this translates to approximately 10 to 14 days for the drug to exit the bloodstream fully, which is another reason Healthspan protocol doses cyclically, paralleling patient goals, labs and health history [5].
I hope this helps!
[1] Kaeberlein TL, Green AS, Haddad G, Hudson J, Isman A, Nyquist A, Rosen BS, Suh Y, Zalzala S, Zhang X, Blagosklonny MV, An JY, Kaeberlein M. Evaluation of off-label rapamycin use to promote healthspan in 333 adults. Geroscience. 2023. [Epub ahead of print]. 10.1007/s11357-023-00818-1
[2] Cohen EE. Clin Cancer Res. 2012;doi:10.1158/1078-0432.CCR-12-0110
[3] Blagosklonny M. V. (2023). Towards disease-oriented dosing of rapamycin for longevity: does aging exist or only age-related diseases? Aging, 15(14), 6632–6640. Towards disease-oriented dosing of rapamycin for longevity: does aging exist or only age-related diseases? | Aging
[4] Konopka, A.R., Lamming, D.W., RAP PAC Investigators. et al. Blazing a trail for the clinical use of rapamycin as a geroprotecTOR. GeroScience (2023). Blazing a trail for the clinical use of rapamycin as a geroprotecTOR | GeroScience
[5] Mahalati, K., Kahan, B.D. Clinical Pharmacokinetics of Sirolimus. Clin Pharmacokinet 40, 573–585 (2001). Clinical Pharmacokinetics of Sirolimus | Clinical Pharmacokinetics