There have been three major acarbose lifespan studies that all showed significant life extension results, with up to 17% seen in males at the highest dose. Life extension effects were slightly lower for females (see details below).
Acarbose is a low cost, widely available, medication that is typically used in treatment of diabetes because it slows the digestion of carbohydrates / starches in the body, which helps lower peak blood sugar levels. Acarbose works best (in terms of life extension) when started earlier in life (vs. middle age).
The key problem with acarbose is its’ high rate of unfortunate side effects:
- abdominal pain (19%)
- diarrhea (31%)
- flatulence (74%)
There are reports that the side-effects may be highly diet related - specifically “Wheat” seems to cause a lot of the GI issues - people who largely avoid wheat are apparently spared the worst side effects. Rich Miller discussed this in the recent LiveLonger World Podcast:
Though, on the positive side, the flatulance/gas you create while on acarbose doesn’t smell very bad it seems:
Mice were fed ACA from 4 months of age (youth), Maximum lifespan (90th percentile) increased 11% in males and 9% in females.
Beginning at 16 months of age (middle age), mice were fed chow containing ACA. Pooling the data across sites, there was a significant increase in survival for male mice treated with ACA, with a 6% increase in median lifespan and a significant 12% increase in maximal lifespan. ACA started at this late age had only a small effect on median lifespan in females (2%), but led to a significant (6%) increase in maximal lifespan.
we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneous mice at three sites. Mice were fed ACA from 8 months of age (teen/young adult in human terms).
The two higher doses produced 16% or 17% increases in median longevity of males, but only 4% or 5% increases in females. Age at the 90th percentile was increased significantly (8%–11%) in males at each dose, but was significantly increased (3%) in females only at 1,000 ppm.
What is acarbose?
Acarbose belongs to a class of drugs called alpha-glucosidase inhibitors. It works by slowing the action of certain enzymes that break food down into sugars. This slows down digestion of carbohydrates to keep your blood sugar from rising very high after you eat
Why did the National Institute on Aging ITP program do these studies?
The following information is sourced from the Peter Attia / Richard Miller podcast. The rationale for testing acarbose on impact on lifespan was that “Caloric restriction is good for you” and acarbose is sort of like caloric restriction (CR) in that it blocks the digestion of starches to sugars. Peter Attia has pointed out that there are really two different hypotheses that you could be testing:
- One is that you will functionally consume or absorb fewer calories, and therefore it’s like CR
- Another could be that the animal will continue to eat the same calories, but they will have lower glucose (which is a good thing for long-term health)
The three studies showed results from using various doses and starting at 4, 8 and 16 months. Both sexes has significant improvement in lifespan but the improvement was higher in the males; From the abstract:
“The acarbose results confirm and extend our original report, prompt further attention to the effects of transient periods of high blood glucose on aging and the diseases of aging, including cancer, and should motivate studies of acarbose and other glucose‐control drugs in humans .”
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.
Was there any gastro-intestinal (GI) / stomach/bowel distress in the mice?
Richard Miller says that the mice didn’t stop eating or show obvious signs of distress, but their GI tract is very different from that of humans, so a direct one-to-one comparisons for what our GI tract can handle and theirs is difficult. Most people experience some sort of gastro-intestinal distress from acarbose, especially at the higher dosages (e.g. 100mg, typically taken with a meal).
Where there changes in weight in the mice?
Rich Miller states that acarbose led to weight loss (or a lack of weight gain) in the original ITP paper. That is seen in some populations, but not all. For example, in Rich Miller’s lab, he made a batch of acarbose-treated mice for another purpose and they didn’t see a dramatic change in weight — “We really don’t know why. So it’s a little bit frustrating .”
In human studies with acarbose, there is a weight loss typically seen in acarbose as this study shows:
Acarbose, especially in combination with the low calorie diet and exercise, seems to lose weight effectively in obese and overweight patients in communities that have a high carbohydrate intake (like Persian diet).
Acarbose as a candidate for human trials
Since acarbose is FDA-approved and has a long safety history—hundreds of thousands of people take it, particularly in Asia and in some parts of Europe—it’s an obvious candidate for human clinical trial in terms of anti-aging. Therefore, Rich Miller suggests, if one was thinking about what drug that works pretty well in mice would be safe for human clinical trial, acarbose has to be on that list. Rich has said that he is urging Matt Kaeberlein—who is studying rapamycin in dogs—to study acarbose in dogs as well. We have heard that Matt Kaeberlein has said his concerns with Acarbose are that it can cause diarrhea and gas, and if in a clinical trial with companion dogs the animals make a mess in the house, the trial might not go well - so it is not high on his priority list of anti-aging medications.
Personal Observations from Acarbose Use:
I have found that using acarbose (while taking rapamycin) for anti-aging is very effective in moderating glucose spikes. I use a continuous glucose monitor and while I was using acarbose my blood sugar levels seem to be well-moderated and mostly kept within the range of 80 to 110 mg/dL (approx. 3.9 and 6.0 mmol/L). However, the high level of gas / flatulence makes the drug for me far from the ideal drug for daily use. Because of this problem I investigated using canagliflozin - which I’ve reported on here:
Canagliflozin for Anti-aging - One Month and 4 Month Updates
Acarbose in Anti-Aging (mice);
acel.12898.pdf (893.2 KB)