Why would a healthy 40-year-old man with good body composition (5% body fat), an HbA1c of 5%, fasting insulin of 16 pmol/L, and triglycerides of 43 mg/dL consider Acarbose?

I’m curious about the benefits you all are seeking by avoiding the peaks. I’ve never found reliable data showing that occasional glucose spikes are detrimental to healthy individuals. In fact, considering glycogen storage after a workout, allowing some glucose spikes might even be a beneficial strategy.

Thank you everyone!

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Those of us who take Acarbose are doing it based upon the ITP trial results that showed the maximal increase in mouse lifespan when Rapamycin is paired with Acarbose.

Since there is a large synergy in mice, we have extrapolated that synergy to humans.

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Thank you @DeStrider, I do understand, but every time I read here, people are focusing on glucose peaks. In this matter, I don’t see any rationality. Maybe I am wrong, that’s why I opened this one

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We don’t know for sure it’s the blood glucose spikes that provide the large healthy lifespan increase shown in the itp studies, but that is what is hypothesized as the method of action since they saw the same with canagliflozin. Did you read this thread? Acarbose - Details On Another Top Anti-Aging Drug

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Recurrent large glucose excursions, such as those that occur in PPHG, lead to insulin resistance and hyperinsulinemia. In turn, these lead to changes in glucose and lipid metabolism [40]. Post-prandial glucose excursions have been shown to induce endothelial dysfunction, inflammatory reactions and oxidative stress, unlike high fasting-glucose levels alone, and have been linked to the development of atherosclerosis and the occurrence of cardiovascular events [3].

https://www.metabolismjournal.com/article/S0026-0495(23)00244-5/fulltext

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Thank you! I understand this.
But let’s put my case (so no science).
I eat a predominantly plant-based diet, probably 70% carbs. I have some peaks here and there, but my insulin is lower than the average minimum levels, my hba1c is also 5, and triglycerides are low… Am I being naive, and should I try to find other biomarkers?

Thank you

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What are your postprandial blood glucose levels like? Do they stay under 140 mg/dl? If so, I wouldn’t be concerned at all. And IMHO a slight rise above 140 mg/dl every now and then after a large carb meal is unlikely to be an issue.

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Yes, normally below. But I already saw higher, like after hours of cycling I arrived and drank rice milk + protein and went up to 200ish. I tried again and similar results. In conclusion, I stopped rice milk, except if I am in a multi-stage race :grin:

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Prolonged exercise reduces glucose tolerance and increases insulin resistance in endurance athletes the following day. These findings are associated with an increased lipid load, a high capacity to oxidize lipids, and increased fat oxidation.

See also: https://www.researchgate.net/publication/373631382_Continuous_Glucose_Monitoring_in_Endurance_Athletes_Interpretation_and_Relevance_of_Measurements_for_Improving_Performance_and_Health

Of course they are not real elites.

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I tend to agree that the 140mg/8 mmol threshold is the one it is best to stay below.

I have tracked my changes until recently through various protocols and I think it evidences that improvements are possible although the last few I think are an overreaction to rapamycin that will fade upwards in a couple of weeks.

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I think that’s a maybe.

Absolute median lifespan (rather than relative increase) for rapa + acarbose comes in at 1100, 1000 days for females and males respectively.
Just rapamycin comes in at 1150, 1000 days for females and males respectively. So basically the same.

On the other hand in the rapa+acarbose study, controls were slightly shorter lived than pure rapa study. If they weren’t, would rapa+acarbose win? Probably (since acarbose alone extends lifespan) but we really can’t be sure until a study emerges directly comparing rapa Vs rapa+acarbose.


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And it’s a study in mice. I wouldn’t bet my life on that translating cleanly to me. But…if it’s cheap, no serious side effects…why not? Add it to 50 other drugs / supplements taken every day…no.

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Funny you mention milk. I’ve been monitoring my glucose for a while now and for the most part it stays under 140 post meals. However, if I drink milk (I only use organic milk) I get the highest reading which at times as high as 180. I even tried eating couple pieces of pecan pie and glucose level still at around 145, yet milk never fails to send it much higher (170-189). I would have never thought milk would make a bigger impact than say sugar? Anyone in here has an explanation for this? and also wouldn’t it be a good idea (in my case) to totally avoid milk?

That’s probably the bottom line here, and with most of the supplements.

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A fasting insulin of 16 is a bit high, and I’d encourage you to enter in your values into an online HOMA-IR calculator like on MDCalc. If your HOMA-IR is >2.0 then you are insulin resistant - and my experience is most of the time someone who has a fasting insulin of 16 will be getting some insulin resistance - it’s an early warning that you are headed toward Type 2 Diabetes. So calculate that – I’ll be interested.

I take Acarbose to blunt rises and minimize my HbA1C and am insulin sensitive, but fasting insulin is 4-5.

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Would also look into these reasons

mTORC2 and gut microbiome:

the lifespan of male mice is extended ***by acarbose *** and 17α estradiol, and these compounds increased hepatic mTORC2 activity Is there a way to selectively upregulate Mtor2 while on Rapamycin? - #6 by Neo

(And some posts above and below)

Acarbose’s longevity capabilities is not only from preventing blood sugar spikes after meals I think. Probably more important is its gut microbe effect. The increase of butyric acid is noticeable after very short usage, and other SCFA’s for that matter. There is a reason why almost all centenarians has very healthy guts, it makes you live longer and healthier. Acarbose - Details On Another Top Anti-Aging Drug - #51 by Goran

(Other posts on the forum about that)

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‘Noticeable’ how? And at what dose?

Who has data to back this up?

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Per Vera-Health.ai
Acarbose, an alpha-glucosidase inhibitor, is primarily used to manage type 2 diabetes by delaying the digestion and absorption of carbohydrates in the small intestine. This mechanism results in more carbohydrates reaching the colon, where they are fermented by gut bacteria, potentially increasing the production of short-chain fatty acids (SCFAs) such as butyrate.

Butyrate is a SCFA produced through the microbial fermentation of indigestible carbohydrates and plays a crucial role in maintaining gut health by regulating luminal pH, supporting mucus production, and providing energy to colonic epithelial cells. It is known for its beneficial effects on gut health, including maintaining intestinal barrier integrity and exerting anti-inflammatory properties.

Several studies suggest that acarbose can increase gut butyrate levels. For instance, research has shown that acarbose treatment leads to increased fecal SCFA concentrations, including butyrate, in both healthy volunteers and diabetic patients. This is attributed to the increased delivery of fermentable substrates to the colon, enhancing butyrate production by gut bacteria.

However, while there is a theoretical basis and some evidence supporting the potential of acarbose to increase gut butyrate production, the evidence from human studies is limited. More well-controlled studies are needed to confirm this effect and to better understand the implications for metabolic health and disease prevention.

In summary, acarbose likely increases gut butyrate levels due to its effect on carbohydrate fermentation in the colon, but further research is necessary to establish a definitive link and understand the broader health implications.

References

  1. Gut Microbiota and Short Chain Fatty Acids: Implications in Glucose Homeostasis
    International Journal of Molecular Sciences
    Portincasa et al.
    Diet might influence gut microbiota composition and activity, SCFAs production, and metabolic effects, as well as modulate several metabolic pathways and are involved in obesity, insulin resistance, and type 2 diabetes.

  2. Short chain fatty acids in human gut and metabolic health.
    Beneficial Microbes
    Blaak et al.
    Overall, the available mechanistic data and limited human data on the metabolic consequences of elevated gut-derived SCFA production strongly suggest that increasingSCFA production could be a valuable strategy in the preventing gastro-intestinal dysfunction, obesity and type 2 diabetes mellitus.

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The less sugar enters the blood, the less the TCA cycle works, meaning the less free oxygen radicals are formed, which is actually very important for long life. A second benefit is that it provides a stable blood sugar level, and the third is that it regulates the intestinal flora. For a healthy individual, I think 50 mg of acarbose per day before a meal is enough, which is what I do personally.

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And here is summary by one of the providers (so you should verify anything you might rely on yourself)

The Longevity Mechanisms of Acarbose

1. Regulating Glucose Spikes—Reducing ROS

Acarbose works by blocking an enzyme called alpha-glucosidase, which helps digest and absorb carbohydrates in the small intestine. By inhibiting this enzyme, acarbose slows down the digestion and absorption of carbs, which can help regulate blood sugar levels and prevent spikes in blood glucose.

In studies of diabetes patients taking acarbose, we have observed an absolute decrease of 0.7% in HbA1c levels, which translates to approximately a 10% reduction in typical HbA1c values for diabetes patients. This reduction in blood glucose levels has a profound impact on longevity.

As we age, our bodies become less able to regulate glucose and insulin levels. High levels of glucose in the body can increase the risk of cardiovascular and metabolic problems and can also damage the endothelial cells that line our blood vessels.

The toxic effects of elevated glucose levels may be due to the increased production of mitochondrial reactive oxygen species (ROS). These molecules, which contain oxygen and can be either free radicals or non-radicals, are highly reactive and can cause damage to cells and tissues. This can lead to the development of diseases such as cancer, heart disease, and neurodegenerative disorders.

In addition, hyperglycemia-induced production of ROS can cause systemic damage to the cardiovascular system, contributing to complications associated with diabetes.

Acarbose lowers the risk of cardiovascular disease through its reduction of these glucose peaks and lowering the vascular damage incurred by elevated concentrations of glucose in the bloodstream.

2. Regulating Glucose Spikes—Lowering IGF-1

By dampening the postprandial peaks in glucose, acarbose also indirectly increases insulin sensitivity—lower concentrations in glucose levels require less insulin to transport the glucose into the cell for energy. This is critically important for longevity.

Elevation in insulin corresponds to an elevation of a growth hormone called insulin-like growth factor-1 (IGF-1). Both insulin and IGF-1 play a role in promoting cellular growth. These hormones are often used by bodybuilders for their anabolic effects, which can help to increase muscle tissue. However, it is also known that bodybuilders have higher rates of early onset of age-related chronic diseases such as cancer and cardiovascular disease. This may be due to the fact that excessive growth signals can lead to the proliferation of unhealthy cells, including senescent and cancerous cells, in addition to healthy cells.

Through the understanding of Mikhail Blagosklonny’s hyperfunctionality theory of aging, we know that most disease states occur when cells excessively grow, overexpress, and secrete certain molecules and proteins, and stimulate growth and replication of adjacent cells.

Excessive growth signals from elevated glucose, causing increasing amounts of insulin needed to metabolize that glucose, lead to the acceleration of disease states.

It is known that individuals with defective IGF-1 receptors, which do not recognize the IGF-1 hormone, have a lower incidence of cancer. This is because when these cells are exposed to IGF-1 hormone, they do not have the necessary receptors to recognize the hormone and trigger cellular hyperfunction and growth—ultimately increasing the individual’s healthspan.

This mechanism may contribute to the observed longevity benefits of acarbose, which has been shown to have a dampening effect on glucose and insulin signaling.

3. Microbiome Remodeling and Optimization

It is well established that the blunting of glucose levels can promote healthspan and longevity. However, metformin also delivers some of the same benefits. The ITP, however, did not show that metformin increased lifespan. There have to be other mechanisms outside of glucose regulation to explain the divergence in results in metformin and acarbose.

There is a growing body of evidence suggesting that imbalances in the microbiome, known as dysbiosis, drive aging.

The gut microbiota is the community of microorganisms that live in the digestive tract. It is known to play a role in many aspects of human health, including digestion, immune function, and metabolism.

Research has shown that the diversity of the gut microbiota tends to decrease with age, which can lead to a condition known as dysbiosis. Dysbiosis is an imbalance in the gut microbiota that can trigger low-grade inflammation and has been linked to the development of certain diseases, including cancer.

One potential mechanism by which dysbiosis may contribute to cancer development is through the presence of abnormal cells in the intestine (intestinal dysplasia). These abnormal cells may be a precancerous condition and may eventually progress to cancer.

Acarbose increases the amount of resistant starch that cannot be broken down by intestinal enzymes. Resistant starch enters the colon, where it is fermented by the gut microbiota, leading to an increase in the production of short-chain fatty acids (SCFAs). SCFAs may play a critical role in extending longevity and may also produce other signaling molecules that have been associated with longevity benefits.

The balance of gut microbiota has been shown to have numerous benefits, including the reduction of inflammation. There is increasing evidence that suggests a link between inflammation and the gut microbiota, and that modifying the gut microbiota can help reduce age-related chronic inflammation and promote healthspan. One way to do this is by using a medication like acarbose, which has been shown to help remodel the gut microbiota to optimal levels. In summary, maintaining a healthy gut microbiota balance through the administration of acarbose may help reduce inflammation and improve overall health and lifespan.

4. Reduction of Systemic Inflammation

The downstream effects of inflammation reduction have significant implications for longevity. For example:

  • Increased inflammatory activity has been linked to brain aging, but acarbose, a medication that inhibits the activation of the hypothalamic nuclear factor kappa B (NF-κB) inflammatory pathway, has been shown to delay aging in mice. Acarbose has been found to inhibit the activation of interferon-γ inducible protein-10, monocyte chemoattractant protein-1, macrophage-derived chemokine, and TNF-α, and to downregulate NF-κB-P65 activity in human monocytic THP-1 cells.
  • Furthermore, the levels of IL-6 in patients with diabetes treated with acarbose are also significantly reduced.
  • Adipose tissue is a significant source of inflammation. There is evidence that acarbose has the ability to curb adipose tissue inflammation.

Acarbose reduces the expression levels of inflammatory factors by increasing the abundance of beneficial bacteria. Many species of these anti-inflammatory bacteria are recognized as short-chain fatty acid-producing bacteria that exert anti-inflammatory effects. These findings provide strong evidence for the anti-inflammatory potential of acarbose.

5. GLP-1 Derived Cardiovascular Health Benefits

Acarbose also increases concentrations of circulating glucagon-like peptide 1 (GLP-1). GLP-1 is a hormone that is produced in the gut in response to food intake. It helps regulate glucose metabolism, and has been shown to improve insulin sensitivity and reduce blood sugar levels in people with diabetes.

GLP-1 also seems to act directly on the vasculature, liver, myocardium, β cells, and brain to safeguard the structural and functional integrity of these organs in a way likely to slow aging and promote longevity.

Mechanistically, we now have multiple pathways that acarbose seems to be working on, which comports with our understanding of aging as dysfunction in multiple interconnected biological pathways.

From

Healthspan Research Review | Exploring the Anti-aging Potential of Acarbose and Rapamycin: Insights from the NIA Interventions Testing Program?

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