5 mg rosuvastatin is very potent, so I don’t think there is a large difference in side effects from other statins at similar intensity. It is hydrophilic so it might not get into certain tissues.
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I had terrible muscle soreness on Rosuvastatin 5 mg every other day. My body just couldn’t tolerate it. Bempedoic acid works just fine though. Some people just can’t tolerate some medicines, and that’s OK. If it works for you, go for it.
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These are all interesting findings but we need to remind ourselves about the significant limitations in play when attempting to generalize research on mice to humans.
In a 2004 study of basic biomedical research discoveries (101 studies) described as highly promising for new diagnostic tests and therapies:
• 33% were found to translate (well) to human experimentation
• 20% were found to be relevant only to basic research
• 47% were found to have deficiencies that made translation impossible
Other studies and observations support this picture, although the percentages vary. Overall, I have concluded it is safer to assume that research on mice will not turn out to generalize well.
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Well, it comes in 5, 10, 20 and 40 mg. So, potent in the sense that 5mg while small, does show an effect?
It would be interesting to see if 15-20 mg of Rosuvastatin weekly generates the same amount of side effects as say, 150 mg weekly . One would think that 8x of a drug would generate more, but we are speculating. An interesting aspect of statin side effects is that the rate of reported myalgia is much higher than the rates in clinical trials. And my polling of friends puts it at maybe 50%!
Personally I have chronic Lymes with a peripheral nerve focus that comes and goes and so it’s not easy to sort out which things hurt for what reason! And with chronic diseases (like ageing!) you get jaded to ongoing pains. I may be getting light side effects and attributing it elsewhere.[quote=“AnUser, post:79, topic:11127, full:true”]
5 mg rosuvastatin is very potent, so I don’t think there is a large difference in side effects from other statins at similar intensity. It is hydrophilic so it might not get into certain tissues.
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The reason canines are a good model of aging is that they are prone to some of the same diseases as humans including CVD, T2D, cancer, hypothyroidism, arthritis, epilepsy and so on. For example, check out the Dog Aging Project at the University of Washington: https://dogagingproject.org.
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See the Acarbose thread. Here is why I work to lower blood sugar spikes:
What is Rich Miller ’s hypothesis on why acarbose extends lifespan?
Rich Miller’s current interpretation of the life extension benefits of acarbose is that it is blocking the very highest levels of glucose. He suggests that in humans, we often look at hemoglobin A1C, which gives you a measure of avg. blood glucose over the last few weeks, and if a person with diabetes takes acarbose, that hemoglobin A1C goes down — signifying that it’s working in a person, but in mice it turns out that HbA1c does not go down. Therefore, he suggests it’s probably not an overall change in the amount of glucose that gets in, but a change in how quickly the glucose enters the blood stream.
In summary :
Rich Miller’s guess is that acarbose was working by blocking the peak glucose. Acarbose (and canagliflozin) are working by eliminating the huge peak of glucose you get after you eat a meal with a lot of starch in it.
More reading in this thread: Acarbose - Details On Another Top Anti-Aging Drug
and this thread: Canagliflozin - Another Top Anti-aging Drug
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Yes, that’s it. It appars to be mostly assumptions by Miller. But what is the actual evidence that high blood sugar after meals, corrected for insulin resistance and poor beta cell function, impairs health? Now, I don’t have any references for the contrary, because it appears to never have been tested. There are studies on low glycemic index diets, but these studies are in all cases I have seen confounded by the fact that the high glycemic index comparison is more processed than the low glycemic intervention. In any case, the low glycemic index diet interventions have rather modest, or no effects, on markers of health (aging not measured as far as I know) IMO.
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I have been wondering about this as well. It is a popular sentiment on the internet l, I think driven by the CGM marketers (Levels). I believe it is understood that higher spikes and longer lasting elevations in blood glucose post meal are symptoms of disfunction (insulin resistance, impending T2D). But if HbA1c is good, and fasting blood glucose is good, do periodic spikes cause some accumulation of damage somewhere? That’s the question.
Possible answers involve: damage to endothelium, AGEs, ? Another issue that I experienced a lot before I figured it out was rebound hypoglycemia. If I ate a high glycemic index food to “top off my glycogen” an hour or so before a hard workout or race, I would experience low blood sugar during my exercise (tired legs). I learned to eat during my warmup not before. I think this was a sign of future blood sugar issues.
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Do you ever workout in a fasted state? I eat my calories in the latter part of the day in a 10 hour window. Seems to leave plenty of fuel for my workouts the next day until I eat again. When using a CGM,I noted blood sugar rising during exercise.
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I don’t workout fasted as a part of a program. I do workout in the morning before I eat breakfast so that is “fasted” for about 12 hours. But I wouldn’t want to stress my body with a fasted state during a hard cardio workout (>1 hour of higher intensity). A lot of people do, but that’s my preference.
I also see a rise in blood sugar during exercise (when I used a CGM). I cannot reconcile that with the rebound hypoglycemia. I did not try to simulate that condition when I had the CGM. I should have.
One of the key learnings for me that didn’t happen until recently (and might be involved here) was that a long warmup was the most important part of a good race (or high intensity workout). I now warmup for 1 hour before an important event. And at least 30 minutes before a hard workout. The warmup includes hitting a max HR for a few seconds.
There goes the idea that HIIT training is time efficient.
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I definitely feel the need to be warmed up 30 minutes or much more. Oddly, my body feels more primed and ready for a hard cardio workout when having expended calories for a long period of time (versus when younger). My conjecture is that my mitochondria aren’t ready until they have been exposed to some sort of zone 2 training for a period of time. With strength training, I seem to transition pretty smoothly into my reps without extensive warming up.
I agree HIIT is time consuming 
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It could actually be that it is not “corrected for insulin” resistance but that regular spikes does lead to increased risk of insulin resistance.
Or that even in a non insulin resistant person (or mouse) it is still not good for longevity to increase insulin secretions and that is what happens each time blood glucose goes up.
That insulin could be bad in many ways for longevity could be part of how other growth pathways (mTOR, IGF-1, high T / Free T, etc) are massively bad for longevity.
Btw, absence of evidence if not evidence of absence.
So when you state “I can see no clear evidence that spikes after meals can be harmful” that does not mean that a longevity optimizing person should feel that they can or should ignore spikes.
Rather without black and white evidence we still need to do the best we can and still weight
all the reasons why it “could” be bad even if we don’t “know” and then trade that off agains all the reasons it might be bad (whether there are risks, costs, effort) to avoiding the thing (in this case spikes). (And of course weigh the strength of support for each type of information, data, mechanistic rationale, etc)
For me personally, is seems that this is a very asymmetric trade off that clearly lines up that it’s worth the trade-off to seek to generally avoid blood spikes as it may be (or in my view likely) is a more pro longevity behavior.
For instance I’d need evidence that the glucose spikes *are not”
- increasing AGEs in my body and that could risk even a small increase in cardiovascular risks over the next decades and stroke or heart attacks
- that the extra insulin I’m washing my cells in is not up-regulating growth pathways that are anti-longevity - or taking my cells out of a state of pro-longevity,
- that the sugar spikes are not impacting my blood vessels in other ways, and
- importantly that it over decades to come in not increasing the risk of feeding cancers
While Levels does have an incentive and you should review what they say with skepticism, the underlying sources they cite/link to might be helpful for you (see further below)
Also looking at the logic in how Peter Attia feels that spike and variability is negative might be helpful:
Levels
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What glucose reading after a meal is considered a glucose spike?
@LaraPo, I’ve personally been aiming for an increase in blood glucose of less than 30 mg/dL at 1-2 hours post meal compared to the premeal reading. I’m not a doctor so you may get better input from someone else of course. I took a course this year called data driven fasting and that was the recommendation we followed to determine how to eat to avoid large glucose spikes. As I understand things it’s somewhat individual with different amounts of food, types of food and macro splits having varying impacts depending on the person. I was not in a good place diet wise when I started rapa due to numerous food sensitivities/intolerances. Rapa seems to have resolved most of that (Thank God) but in the process I had to learn how to strategically manage reincorporating foods I hadn’t consumed for years without becoming diabetic! I’m looking forward to learning and improving more but in the meantime I’m continuing to regularly check my glucose.
I read that if Acarbose is started at 16 months in mice, it seemed less effective than Rapamycin alone. Is that correct?
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Hi, and welcome to the forums. yes - acarbose is less effective the older you get (at least in mice). Details here: Acarbose - Details On Another Top Anti-Aging Drug
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Thank you, I appreciate that you sent the links, and sharing your line of thinking about this . Originally I asked about evidence/references for postprandial blood sugar spikes per se being harmful in healthy people, in this thread. And I agree: Nobody needs high blood sugar peaks in their day to day life. In other words: There is no clear advantage to having these blood sugar peaks, so why not try to minimize the spikes?
If one has a crappy diet and then decides to change the diet according to one parameter only: lower postprandial blood glucose, then sure, that will undoubtedly lead to better health outcomes since a lot of the food that has a high glycemic index is of low quality in many other respects. But lets say you have a diet that includes a decent level of vegetables, fruits, berries, animal foods and very little ultraprocessed foods, and little processed foods. Will a change from a fair amount of potatoes, rice and other high glycemic foods in that diet to for instance low glycemic beans and lentils change anything?
The links you sent do not address that question, as far as I can see.
Insulin is related to glucose spikes, but consuming low glycemic index meals do not appear to give lower IGF-1 than high glycemic index meals, postprandially: Glycemic load effect on fasting and post-prandial serum glucose, insulin, IGF-1 and IGFBP-3 in a randomized, controlled feeding study The fasting IGF-1 was reduced after the low-GI-diet, but this, again, can be related to a range of other diet quality factors.
Non UPF high carbohydrate foods are typically lower in AGEs than foods that contain more protein and fat, so even though you might get lower amounts of endogenous AGEs with a diet that aimes at reducing PPG, what is the total sum of the preformed diet AGEs and the endogenous AGEs in any given diet? And there are many more questions such as these. And we can get sidetracked with the details, and bends and turns here, but my main point was that I am looking for mechanistic or clinical studies that elucidate better the effect of postprandial glucose peaks in its own right, and not as a proxy for diabetes, insulin resistance, a low quality diet or other aspects.
An asymmetric trade off for me and my patients would be to advice people against potatoes for dinner in exchange for more meat or legumes for instance. The upside of not limiting potatoes appears larger than the possible downsides given the evidence. Especially if you really like potatoes, and don’t get that much vitamin C from other foods for instance. So this is not about not erring on the side of caution or that one should wait with doing something in spite of there not being clear evidence.
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This is an area of interest for me given my genetic predisposition toward t2d. I am not certain that blood sugar “spikes” are damaging but I try to avoid adding to the problem by:
(1) eat a lot of fiber at every meal, in part to slow digestion of carbs
(2) eat some fats and protein before eating carbs, to slow digestion of carbs
(3) exercise immediately after eating high carb foods, such as apples
(4) almost never eat added sugar or highly processed starches (bread, pasta)
(5) new: exercise zone 1 (easy) to start the day and end the day to lower cortisol (lower adrenaline—> lower blood sugar)
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It’s an important course to take! I also would love to understand more about food intake and glucose changes. The normal fasting (10-12 h) range is from 70 mg/dL to 100 per Google 
. Hyperglycemia is when it spikes higher than 180 mg/dL after a meal. Mine is never higher than 130 mg/dL after a meal. My fasting glucose when on Rapa is 90-94 mg/dL, when off Rapa it’s below 90.
30 mg/dL seems abnormally low. Are you sure it’s the right number?
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FWIW
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