Intro to rapamycin

loveyouyrlongevity .... there is a study on c. Eligans and fruit flies where the the food component allantoin found in sprouting wheat germ and allo Vera, doubles the life extension effect of rapamycin... summary...actually there were many synergistic drug combinations graphs. Odly metformin was absent.

are we there yet  ....  The study is over now.  I am waiting to see what the results of the year show, if anything.  I have read that they now think that the 5 mg a week is not enough.  We shall see when the results are tabulated what that dosage meant for participants.  I have not heard about what you bring up, but I am sure as we travel down this road we shall find more refinements to the regimine .  

loveyouyrlongevity ..... my self experimenting with sirolimus (rapamycin) has shown a clear near elimination of left knee arthritus pain. I am 70 on a 10 day interval of 2mg.

are we there yet I've just started my self-experiment with rapamycin. I'm 73 and it would be a stunning endpoint if I shared your achievement of elimination of arthritic pain. I am curious about your dosage. From prior readings, I would think 2mg would be too small a dose to show efficacy. If you don't mind, would you share your weight and how long you've been on your regiment? Also, how long did it take prior to you feeling noticeable pain relief? Thanks.

Sanford Finley 

Sanford Finley I will give what you ask. I am 280 pounds 5 ft 8 in, 71 yo normal blood work. Used to have significant arthritis in left knee and right hip. I am a physicist with intellectual seduntary lifestyle. No notable health issues. Normal blood work. I currently take 1.5 to 2 mg metformin daily with noticibly good effect, 2 mg sirolimus every 7 to 10 days unless I get a vaccination or travel on an airplane to lecture. I am told my guessed age is mid fifties. Less if I shave off my grey facial hair.

my latest health device that I am excited about is a vibration plate for mostly static exercise. It appears to work. My legs are sore the next day. 

Sirolimus seems to help regenerate cartridge and joint tissue as well as improve heart mussle myocite health in animal studies as well as improved stamina I find noticible. I started noticing arthritis pain go away if I walk less than a half mile after about 2 weeks. Note: take b12 supplements to counter metformin reduction in b12 absorption. What are you medication plans?

are we there yet Thank you for the information. RE: my medication plan, I took my 1st dosage of 4mg Rapamycin one week ago and plan to take it weekly unless I experience an adverse effect. I also take metformin 500 mg. 1 daily, fisetin 1 g. once monthly. Additionally, I take b12, fish oil, pomegranate tabs 250 mg. daily. I am 73 yrs. old, 5' 11 and 170 pounds. I am healthy except for spinal osteoporosis which presents with hip pain when walking long distances. Since the introduction of the Rapamycin into my routine, I have experienced a profound placebo  (I assume) effect. I feel considerably less hip pain and feel more energetic. As an interesting aside, I started my 13-year-old dog on 1/4 mg of Rapamycin weekly at the same time I began. He too suffers from arthritis. Concurrent with my increase in well being he now is able to jump in the back seat of my car without assistance, whereas he previously needed to be helped. Who knows? Do dogs experience placebo effects? Finally, I purchased a neutral face cream and made a compounded mixture of 20mg. of Rapamycin with the 4 oz. cream which I apply to my "turkey" neck 2x daily. I will monitor this for any change. I plan to update the forum as to future outcomes.

Sanford Finley regular feedback will be greatly appreciated.  Good luck.

Karl Thank you for your good wishes in my endeavor. Be assured I shall provide ongoing feedback barring an unexpected endpoint (fatality) is encountered. 😉

Sanford Finley 

Sanford Finley Just wanted to comment on the topical cream. The concentration of 20mg in 4 ounces will be around 1.8 micro molar (approximate). The recent study of topical rapamycin which found significant benefit for senescent clearing and improved appearance etc used a 0.1 micromolar concentration (approximate). Studies on hair (fur) growth in mice using topical found effectiveness at 0.1 - 1.7 micromolar concentrations. At concentrations above this there was mention of non-healing wounds. In tuberous sclerosis patients they use 10 micromolar to inhibit growth. Just wanted you to be aware that there may be some unwanted effects at higher concentrations. Reading through the literature I believe what you want to do is influence autophagy moreso than inhibit growth. In cell cultures they use about 0.2 micromolar concentrations to influence autophagy. I've been using this concentration (approximate) for a topical (2mg in 4 Oz) for a while and see some marked improvements and feel safe in doing so. You may be fine with the 10X higher concentration but sometimes to much may not be as good. 

Mark Thimineur Your point is well taken; more is not necessarily better. Perhaps I will add more cream to dilute my alchemy. If you could share a link to the mice study you referenced it would be greatly appreciated. Thank you.

Sanford Finley The link is

Cell Reports Volume 27, Issue 12, 18 June 2019, Pages 3413-3421.e3

A relevant paragraph below:

(G) Rapamycin (1.6 μM) induces hair regeneration. Male mice were shaved on postnatal day 43 and treated topically every other day. Photographs were taken on day 37 post-treatment. Number of animals: control, n = 18; rapamycin, n = 17. Rapamycin at 100 nM gave similar results as 1.6 μM (Figure S2). Similar effects by rapamycin were seen in female mice (Figure S2B). Rapamycin at 16 μM, however, resulted in hair loss and open wounds (data not shown), consistent with a previous vascular grafts study in rats receiving high-dose rapamycin (Walpoth et al., 2001); this may be due to more severe inhibition of mTOR, which was reported to be required for hair follicle stem cell activation (Castilho et al., 2009, Kellenberger and Tauchi, 2013, Deng et al., 2015).

Sanford Finley Just wanted to let you know that my math was off. mixing 20mg of rapamycin in 4 ounces (assume U.S.) comes out to be a concentration of 185 micro molar. If it is UK ounce it is 192 micro molar. For reference, the recent study of topical rapamycin for skin was a concentration of 10 micro molar. I've been using 27 micro molar (2mg in 4 Oz).  Should be careful with this stuff - the topical can cause skin ulceration etc. Useful tool for molarity concentration is https://www.omnicalculator.com/chemistry/Molarity

Mark Thimineur Per your previous caution, I compounded a new batch with 2mg. in 8oz. It has now been 3 weeks of oral (4mg, 1x week) and topical administration. To date, I cannot reliably attest to any significant change but will be having blood work done in February. However, I can report that the topical application has resulted in a rather amazing effect. I have male pattern baldness and there is now "peach fuzz" growing in my previously bald spot. Also, my scalp has considerably less dryness and flaking. I have yet to experience any adverse reactions. I would be most interested to read your experience.

Sanford Finley Your new batch will be about 8-9 micromolar depending on wastage. I've used topical at 16-18 micromolar (2mg/4ounces) and repeated the experiment treating the back of my right hand with active and left hand with just vehicle twice daily for 6 weeks. There is already a noticable difference in the skin of the treated side compared to the untreated. I plan to do this for at least 4 months for comparison.  At the same time I have used it on face and neck twice daily for same amount of time. I don't have a comparison but it appears to me that anti-aging effect on skin is apparent. I have mixed a new batch at 3mg/4oz which is about 25 micromolar due to a probable 10% wastage and will begin using this in the same areas. I feel that it is safe at 25 micromolar or less. I have also used a 2.2 micromolar solution (0.2mg in 100ml DMSO) on scalp for about 6 weeks. I have a pretty full head of hair but mostly gray. The gray hairs are thinner and less coarse than the remaining black hair. To early to tell but there may be proportionally more coarse black hair at 6 weeks. I keep it cut very short (2-3mm) so it is easy to see. I think this concentration is safe on the hair as the follicle bulbs need mtor activity to generate but benefit from autophagy activation. This is about the same concentration as the rodent fur studies showing anagen phase of hair(fur) stimulated at 0.1 - 1.7 micromolar. Concentration of 17 micromolar caused fur loss due to mtor inhibition overriding autophagy effect. Keep me posted on observations and I'll do same.

At the same time I have been on oral weekly doses of 0.05mg/kg cycling with 0.1mg/kg doseage (3.5-7.0mg) for about 12 months. Have experienced many positive effects which are more pronounced at the higher dose. I am going to do the same cycling with a 0.1mg/kg - 0.2mg/kg and see what the differences are. In particular I am looking for any side effects such as stomatitis developing at the higher dose vs enhancement of the positive effects. It seems to me that one reaches a relative stability after about 6 months based on my experiences with self, family members, friends, and patients.

Mark Thimineur , Sanford Finley   Dosage is critical which really emphasizes the importance of consistent quality in the product.  Having other than reliable pharmaceutical grades frankly scares me a quite a bit.  But, very much looking forward to your results and success.

Dorian Gray Agree. All persons that I have responsibility for are using Rappamune (Pfizer) or Sirolimus (Biocon) which assures pharmaceutical grade. One can assume variable amounts of impurity from non-pharmacetical suppliers.

Mark Thimineur Are you able to share how do you make the cream? My Sirolimus is in tablet form so Do you take the pill and break it down as fine as possible
and then mix it in a cream? I feel like I’m missing something possibly a way to dissolve the tablet? Thanks 

John Mcgough Mortor and pestle to reduce the pills to powder. Place the powder in a vessel for dissolving in DMSO. I use a test tube with a secure plug. Dissolve in DMSO thoroughly by shaking and letting sit for 10 minutes or so. You only need 2 ml of DMSO but you could use more if you want. There are insoluble fillers in the pills but the rapa is highly soluble so even though it appears milky it is OK. The vehicle cream (I use a 70% DMSO, 30% Aloe base) put in a small mixing vessel like a cereal bowl. Add the dissolved rapa into the base and mix thoroughly. Put base cream back in original container and label.

3mg of rapamycin in 4 ounces will provide a 25 micromolar concentration allowing 10% wastage in the whole process. This is 2.5 times stronger than the 10 micromolar concentration used in the recent study on skin. It seems to work well applied once or twice daily. Two months of daily application to back of right hand has now produced a noticable difference from the appearance of the left hand (hands have some issues from years of performing procedures under xray guidance). Two months of application to face and neck are showing quite surprising disapearance of wrinkles. The women relatives in my life are quite demanding that I keep them supplied. 

If used on scalp for hair the concentration should be much less. In this case 1/4 tablet dissolved in 100ml DMSO provides about 2.2 micromolar. In the case of hair, anagen phase (growth) is encouraged by autophagy induction and inhibited by to much mtor block. In the case of rodent fur, a 1.6 micromolar concentration was effective for anagen phase induction but a 16 micromolar concentration caused problems. So far, my hair seems thicker and has more black course hairs but it is to early to know. Hope this helps

Mark Thimineur that is very helpful and I will let you know how my skin and scalp experiment goes. I can’t express to you enough my gratitude and I’m sure others feel the same about the useful information you are providing. To have somebody in addition to Dr. Green who has experience with other patients is invaluable and I’m sure it gives others including myself more confidence to follow  your footsteps. The impact you’re having on others and the ripples it creates are beneficial for  so many which I’m sure is your intent. But I applaud your courage as many others for liability reasons might be afraid to share this information or subject themselves to such scrutiny. Thank you for being such a good and inspiring person!

Mark Thimineur 
Hi Mark...Can I use any vehicle cream for a new batch or should it specifically be the "70% DMSO/30% Aloe" you recommend? I live in Europe and can't get the application. I'd appreciate your help. tx

Ed probably OK with other vehicles. I use DMSO base because the rapamycin is highly soluble in that but it likely OK in any sort of oily base

Mark Thimineur  Hello Mark.  I was reading that rapamycin is fat soluble. I also think fisetin is good for this experiment as well so I wanted to mix these 2 together with alpha lipoic acid into Emu Oil. I heard emu oil was great at getting deep into the skin.  What do you think of this idea?  Also, I have read that DMSO is dangerous at certain amounts. 70% seems high.  The label on these bottles with dmso and aloe say that it should only be used as a solvent. What are your thoughts?