About the increase in blood lipids and blood sugar caused by Rapamycin

Hello everyone, I would like to discuss with you what measures you have taken when experiencing abnormal blood sugar or lipid levels caused by Rapamycin. Did you observe after discontinuing the medication or did you continue to use aggressive methods such as adding metformin or statins to counteract this process? I am a bit concerned about this issue and wonder if this counteracting approach is scientifically reasonable. I look forward to your extensive discussion.

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I don’t think statins are aggressive, they seem pretty benign. I am very pro statins. I think they are longevity drugs.
In fact most people have too high lipids which indicates statin treatment (along with lifestyle changes).

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Before i did this i was of the view that i should take rapa less frequently than most do. It supported the thesis that the effect on glucose is probably temporary.

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From our survey of our forum members, at the typical dosing used for longevity (between 3mg and 8mg once per week dosing) we are not getting a lot of these issues reported - you can see our survey here: Rapamycin User Poll / Survey - Please Respond

The higher the dose, and the more frequent the dosing, the more you tend to run into these issues. We really don’t know the best approach here. In all the mouse studies, they dose daily at very high levels, they do have these issues, but they still live 15% to 30% longer.

Of course, if the mice also take Acarbose they live even longer - so there seems to be some benefits to maintaining lower blood glucose levels.

The issue you face pretty quickly is that of the complications of polypharmacy (taking multiple drugs simultaneously). Biology is complex, and there have not been many long-term human clinical trials on how these drugs interact and affect longterm outcomes. As a general rule of thumb, I think most doctors would say you want to take as few drugs as possible. The research in mice on rapamycin + acarbose seems to suggest synergistic positive effects. New Paper: Lifespan Benefits for the Combination of Rapamycin plus Acarbose in mice

But we really don’t know for sure in any other drug combinations, and of course it gets even more complex as you add supplements to the mix. We’ve discussed this in this thread: Combine them all! (Longevity Drugs and Supplements)

What many of us do here, since we don’t want to wait 50 years for all the clinical studies to be done, is do frequent blood testing to track how our bodies are responding to these drugs or combinations of drugs over time.

And - as this Buck Institute PHD candidate suggests, track how you feel:

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Dear administrator, thank you for your detailed response, it was very helpful. I am 42 years old and I plan to start taking Rapa. I intend to slowly transition from 1mg to 5mg per week, without increasing the dosage any further. I am wondering if there is a high risk of increased blood sugar and blood lipid levels at this dosage, thank you.

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I think the response is dose dependent and justifies larger doses less frequently. That, however, is a minority view.

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I think this is indisputable

" larger doses less frequently"

Based on my blood markers, if I were to take Rapamune again, this is the approach I would take. Once per month perhaps like long infrequent fasting… but without the muscle loss.

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“So, if taken once a month, how many milligrams per dose? Does this dosing regimen have anti-aging effects?”

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These are the key questions to which there is not a definitive answer.

People have varied views as to the causes of aging. However, there is a limited consensus that efficient mitochondria mitigate against age based deterioration.

My view is that is because the cell produces more ATP and Acetyl-CoA.

Inhibiting mTor leads to increased mitophagy/autophagy. That results in more efficient cells.

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As MK would say, ‘we don’t know’ but as MB says, ‘increase the dosage until you get side effects’.

Which is why @John_Hemming 's regular blood testing is to be applauded.

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We’re around the same age. I’ve tracked my bio markers pre and post rapa and I have seen a mild increase in blood sugar and lipids.

The lipids can be controlled - I added 10mg Zetia daily and that brought my Apo B from 98 to 64. Once an oral PCSK9 inhibitor is available (ie MK-0616) I will look to add that and reduce even further.

In terms of rising blood sugar, I belive Blagosklonny is on point with the term “benelovent pseudo-diabetes”. If you haven’t read his paper, here is a quote “rapamycin can induce insulin sensitivity, but may also induce insulin resistance or glucose intolerance without insulin resistance. This mirrors the effect of fasting and very low calorie diets, which improve insulin sensitivity and reverse type 2 diabetes, but also can cause a form of glucose intolerance known as benevolent pseudo-diabetes. There is no indication that starvation (benevolent) pseudo-diabetes is detrimental. By contrast, it is associated with better health and life extension.”

That being said I did add blood sugar meds to my regimen because the evidence supports it with rapa for longevity. I alternate between Metformin, Acarbose, and Canagliflozin.

Anecdotally, I look and feel great, better than I have in several years.

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Thank you for your reply, it was very helpful. By the way, how long have you been taking rapa, and what is your current dosage? Also, what is your daily dosage of Acarbose? Thank you.

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I’ve been taking rapa for 4 months so I don’t have years of history with it, but the mild lipid and blood sugar rise became noticeable in the last couple of months (I blood test regularly). I take 5mg rapa weekly with avocado oil.

Acarbose I use intermittently. It does cause GI issues, it’s just not comfortable to take everyday, although some people say the discomfort goes away in time. I built up to 200mg twice a day, the same dose Bryan Johnson uses.

Metformin and Canagliflozin are both easier for me to take though.

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I wear a CGM. I have not had any increase in my A1c scores since I started taking rapamycin (actually a slight decrease). This is with 6-8 MG weekly dosing.

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sml491010, My approach was to reduce sugars, simple carbohydrates and saturated fats. So far, this works for me.

But you are also taking metformin and acarbose…

Thank you for your responses. What I really wanted to ask was whether the long-term use of metformin and acarbose to control blood sugar and blood lipids could cause damage and negative effects on the body. For example, if the fact that rapa causes false blood sugar elevation is true, would it be better not to intervene? If we use metformin to intervene, could it have a counterproductive effect? Although some studies have shown that using both drugs together can synergize, these studies are based on experiments in mice. As humans have a longer lifespan, we are more prone to cardiovascular and cerebrovascular problems. Therefore, how do you view the issue of long-term use?

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All great questions which few here are truly facing into. If CHD is the leading cause of death; and ApoB is the best marker for CHD risk… then why would we take a drug that increases ApoB?! Perhaps we should only take it in conjunction with a statin?

RE: Metformin
There are several threads that debate the pros and cons. I don’t believe the current research supports its use in non diabetics. I think acarbose has much more potential as a longevity agent and now take it rather than rapamycin.

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I agree. We need more focus on the main killer of mankind. Cardiovascular diseases/metabolic dysfunctions.

I take rapamune and my question is also. How to do more than lifestyle interventions like, exercise and sleep and diet, to reduce risk for death due to CVD?

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There is some good evidence that rapamycin protects against ASCVD, there are several studies that confirm that in animal models and dyslipidemia does not produce the same result as without rapamycin. I understand that is really counterintuitive to take something that raises causative agent as we understand it now. I think ASCVD is complex disease that is not yet fully understood especially the inflammation factor.
You can always add statins, but I would prefer to add something like ezetimibe that is similar to acarbose in the fact that it is not a systemic and has minimal absorption and yet a really good effect on lowering apoBs.
IR and “benevolent” diabetes caused by rapamycin as I understand is easily controlled with diet, some moderate caloric restriction and avoidance of refined carbohydrates, but you can always add acarbose to reduce glucose spikes and at the same time feed your microbiome which is favorable on its own.