My view is that canker sores etc come from more ROS in the cytosol and fewer WBC.
Do you have any research papers that suggest this?
Not in a direct sense. As you know I have my own theories about cellular metabolism and the reasons why autophagy has the broader effects it has. Although I do have a science degree from Oxford University (Physics, specialising in Atomic, Nuclear and Theoretical - I had a scholarship in Natural Science in 1978) because I am not strictly an “academic” I find journals really sniffy about considering publishing anything from me. Hence I tend to publish things on my blog and do videos.
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Hello, everyone! I haven’t posted for a while, because–and I’m not complaining here–I haven’t really had anything of interest to post! (Yes, I’m very boring as a rapa user, although I’m a very interesting cat burglar. Just kidding.)
However, I think it’s time to report in…as of yesterday, I took my 8th dose of rapa at the dosage/dosing schedule I was aiming for when I began my rapa journey back in September: 5mg/once per week. I worked my way up to this dosage, increasing the dose by 1mg per week. I skipped one week when I got my Covid booster, but otherwise, it’s been a steady climb to my current 5mg dose, with no reportable side effects.
Just so you don’t have to go back and look at my original post, I’ll paste in my personal description here:
I’m a healthy 67-year-old female clinical psychologist, 5’10", 140 pounds. I exercise regularly, drink alcohol occasionally. I just had my annual wellness exam, and my blood panel (plus everything else) looks great. I’m a healthful, knowledgable vegan eater, and along with the usual vitamin supplements, I take NMN and metformin in what would be considered “typical” doses for my size/age.
So, now, after 8 consistent dosages of 5mg, how am I doing? Just fine. In fact, as I mentioned, I don’t have anything to report, side effect-wise–either positive or negative. I’ve been fascinated with so many of our community’s posts, which have, on occasion, left me feeling as if I’m not very perceptive when it comes to reading my own body! I might be one of those people who just goes about her business without really noticing small changes in energy levels, muscle strength, brain fog (or lack thereof), or whatever. All in all, I simply feel great.
Here’s the one thing I can report, and I’m wondering whether anyone else has experienced this, or whether you might have an explanation for it: On the first few days after I take my dose (which is on Sunday afternoons) I MIGHT notice that I’m a bit colder than usual. (Again, I’m not entirely sure, and I may be inventing this feeling.) It’s like I can’t quite get warm for a couple days. It’s that feeling where you want to bundle up in more clothing, even though everyone around you reports feeling perfectly warm. Does anyone relate to this?
As I originally mentioned, it’s been my intention to remain at 5mg, once per week, for the time being. Next, from reading all your posts and articles on this very helpful site, I will probably take a rapa holiday for a month or so, at the one-year mark, and then resume at the former dosage/dosing schedule. Do I seem to be on the right track? If anyone has any other advice, please chime in!
One last thing: I’m thinking of D/C-ing my NMN, since I can’t find any good, verifiable evidence of its efficacy as a life-extender. Again, if anyone has any thoughts on this, I’d be grateful for your advice.
Thanks so much, my beloved Rapa Community, and I will look forward to your comments, suggestions, and–as usual–your much-appreciated support!
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I think you’re going the right way with NMN. I tried it briefly, then just went to Niacin. If you try that…tread lightly and learn about the burn. I worked up to 3-4 grams a day then tapered back down to just a couple. My lipids are less of a problem now.
If they are going to charge that much money (for the NMN) there should be less fog about whether it does anything.
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This has come up before and seems it may be an effect of rapamycin Rapamycin can lower body temperature - Anyone Measure This?
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Thanks so much for replying, Bicep! I appreciate your opinion, which seems to validate what I’m thinking. And thanks for the reminder about the niacin burn! I haven’t taken niacin in quite a while, so I will slowly work my way up to an appropriate dose. I’m too old to pretend I’m blushing! Best wishes.
Thanks for validating my Monday/Tuesday cold hands and feet, mike666! I thought I might be making it up. It’s very interesting that other people have had the same side effect. Best wishes to you and your wife!
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Thanks so much for responding, RapAdmin! As usual, you’re really excellent at pointing me in the right direction with the link you provided. Just read up on it, and I guess I might actually be experiencing a somewhat common side effect. Feeling cold for a couple days doesn’t really bother me–I simply thought it was interesting and that I should report it to our community.
How in the world you keep track of all us chickens and our queries is truly beyond me. You seem to always have the answer at your fingertips. (Perhaps it’s the rapamycin…) Best wishes, and thanks for being our leader.
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There isn’t an official dose as others have mentioned. The typical dose used is 6 mg per week and your doc may reference Dr. Green’s protocol since he appears to have the most clinical experience regarding rapamycin and what labs to consider monitoring, although I’m still scratching my head on a few things he uses.
I avoid grapefruit juice out of an abundance of caution but everyone has different tradeoffs and risk tolerance. The main question has been what dose rapamycin crosses the blood-brain barrier significantly or not - which I’m assuming you already have a very good idea why that matters.
As you may know, if you are vegan, taking metformin, in the long run, puts you at even higher risk of vitamin B12 deficiency - not to mention, older adults generally may require more. Ultimately, if veganism is not a hard value for you, I would consider switching to adding some fatty fish to diet for pragmatic purposes (hard to get available protein where older adults should consider higher amounts). The AHA scientific committee has an official recommendation of >=2 servings of fish (preferably fatty) per week. Creatine, taurine, EPA/DHA, choline, and potentially collagen peptides and beta-alanine (carnosine levels might have some “anti aging”) are just some of the substances in fish/meat/animal derivatives that have significant potential benefits and are incredibly unlikely to cause harm when under the maximum amount of what can be obtained from diet. Highly targeted correction of nutritional deficiencies preferably with USP grade (my definition of a drug is what is beyond what can be obtained from a diet in a subpopulation that show from diet alone has no clear side effects) is what I prefer if eating food directly is not practical. There are instances where vitamin D supplements were tested 2-10x the labeled amount and I do not want to have excessive levels of Vitamin D
I avoid multivitamins personally, as they are not quite the same as food - check out the Cochrane reviews on increased mortality vs vitamin E/multivitamins/beta-carotene, as well as calcium supplement/fortification potentially increasing the risk of CAD as opposed to dietary calcium in a typical food matrix. This is more than enough to be concerned.
NMN may also exacerbate issues with the availability of methyl donors and it may be worse in certain individuals - NMN/NR may have very preliminary risks of increasing the risk of tumor growth in those who have tumors. Not enough data to say for sure, but there are some high-quality anecdotes. Not to mention, NMN storage and manufacturing could be an issue compared to NR.
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Up to 7mg now and still no side effects at all! Planning on increasing to 10mg per week now, instead of stopping at 7mg.
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Could you expand on your aversion to Vitamin D3 supplementation? It seems that since around 50% of the population is deficient, supplementing would be advisable. I’m interested in your opinions.
Bryan Johnson, who is optimizing supplements and behaviors to a next-level, tweeted today:
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I assume that’s without GFJ?
DMD, I suggest a CBC blood panel during the time you’re feeling cold. Rapamycin lowers my red blood cell count to below normal, and it may affect yours, too. As for NMN, I took it for several years and thought it helped, but now I’m not so sure. I continue experimenting with the supply I have in different ways (amount, time of day, etc.) to see if I can find any discernible improvement in energy or strength levels, but have not found any evidence yet. So, I’m on the fence, too.
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Anything that supplements NAD levels will depend on how low your levels are in the first instance.
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Most of the observational studies are weak and I’ve seen pretty over-exaggerated claims on higher end of Vitamin D from scientists like Dr. Rhonda Patrick (she is sensational and overhypes some things, but not to the point of a quack) to the random typical quacks claiming ultra mega-dosing vitamins are good for you when there is no “gold standard” trial proving this and a few trials against this.
The current “official” recommendation is 600-800 IU depending on adult vs older adult. Generally, Vitamin D levels are not tested unless there is a good reason to due to cost effectiveness and issues with assays commonly used in commercial labs. (For reference, I use LC-MS/MS based on NIST standard to be as confident as possible on the accuracy since I’m trying to go for a fairly tight window to minimize any potential harms)
I’m going a bit against the official rec by taking Vitamin D 2,000 IU USP grade with cold water fish/roe & quality fish oil (which adds a labeled tiny amount of mixed tocopherols - with frequent independent third party testing and my own tests to avoid rancidity) based on the VITAL trial on NEJM.
Keep in mind - I’ve been really careful with genetics before and tested baseline as well as ongoing levels which is not generally cost-effective. I also avoid sunlight exposure from all angles as much as possible for skin cancer prevention (only have a tiny amount in the early morning indirectly). So individual supplementation will vary with a lot of caveats.
https://www.nejm.org/doi/full/10.1056/NEJMoa2202106
In this vitamin D and omega 3 (VITAL) trial, 25,871 participants (mean age 67 years and mean baseline of approximately 30 ng/mL) were randomly assigned to vitamin D 2000 IU or placebo. After a median follow-up of 5.7 years, the cumulative incidence of autoimmune disease was lower in the treatment group (0.95 versus 1.2 percent, HR 0.78, 95% 0.61-0.99). I have family that has autoimmune disorders so I’ve been following many options for things like “pre-RA” and other proposed pre-disease states based on known genetics associated with HLA (which can vary by reference population and ethnicity) and other issues. I’m quite familiar with the immune system in general. If I’m right, then I might make a big gain on life expectancy, since autoimmune disorders like RA add 3x CV risk. Other people might not find that potential gain compelling enough in their circumstance.
There are no prospective studies to define optimal Vitamin D levels for extraskeletal health with widespread definitive conclusions though but I suspect >=80 ng/mL is very likely “bad” because there isn’t enough of a feedback mechanism for this hormone and <80 is what one would get if from all-day constant direct sun exposure. We also saw decreases in bone mineral density at >=40 ng/mL or around 4,000 IU, so may be potential harmful dose if it gets you to >40. >50 is a common agreed upon upper limit, where >60 is where more associations of potential negative effects occur.
We also have an official recommended upper limit of 4,000 IU (assuming no malabsorption etc). So I aim for 30-40 personally with 2,000 IU per day. Preferably closer to 35-40 based on some small association with tiny additional cancer prevention. That’s my personal interpretation of the literature where benefit and harm is balanced towards possibly insignificant likelihood of harm for me personally. Some experts previously claimed around 25-30 is best for maximum PTH suppression - a fair position to take.
Vitamin D levels have a genetic basis for variations with a high degree of heritability in twin studies. Some may have malabsorption but it’s much less likely if you are “healthy”. So when you talk to your doc, must take that and a lot of other things into account. Not as simple as it’s made out as there are actually still knowledge gaps on this hormone. Don’t let the “vitamin” name make it seem like it must be innocuous - it’s always about getting close to the “right” amount at the “right” time often with limited imperfect data anytime you take anything. The deepest experts in the field for new therapies often get it wrong statistically and the likelihood of a non-expert getting it wrong is probably even more likely on average, especially if they are an influencer trying to sell you something with an affiliate link or they are tied to some ideology.
The thing is contrarianism is usually wrong and if one is trading one potential small benefit for a small likely known harm, one is probably bad at math, risk management, and recognizing cognitive biases. So if you are going contrarian against official guidelines like myself, you better be pretty darn familiar with the potential tradeoff and evidence.
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Why is that? Most capsules contain liquid vitamin D. Do you have any supporting data that the capsules prevent the proper absorption of vitamin D?
I am not necessarily disputing you, but suppliers of competing products such as raw fish oil, etc., are course touting their own products.
Thank you for your detailed response! The last time I had my vitamin D measured, I was deficient as I too avoid sunlight due to a family history of skin cancer (both parents). Also, I have heard the many negatives about a deficiency. I had my parents taking 5000 IU daily as well, but they tested too high. Therefore I switched them to 1000 IU.
I need to get a new blood test done to see if 5000 IU is too much for me as well. I had tried 1000 IU, but then I read about the Mexican Vitamin D COVID study, and they used 4000 IU to prevent COVID, so I switched back to 5000 IU. I am now concerned that 5000 IU may be too much. My youngest son, 10 yo is very concerned about COVID, so I give him some as well. What do you think? I really want to give everyone in my family an optimal amount. Thank you for your time and consideration .
DeStrider
Review the following;
“Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study)”
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