Should We Take Rapamycin For General Health? The Story So Far

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Rapamycin is a drug that is considered, at least by some, to be the most promising lifespan-extending drug we have. In the Interventions Testing Program, the gold standard program for determining whether a drug extends lifespan in mice, rapamycin has repeatedly been shown to keep mice alive for longer. Other animal studies suggest that rapamycin delays ageing, pushing age-related diseases back and preserving health for longer. But what about the effects on humans? In this review, researchers examine those clinical trials that have been done, which unfortunately remain few in number.

What Is Rapamycin?

Rapamycin is a drug that was first identified in bacteria living on the island of Rapa Nui, more commonly known as Easter Island. Rapamycin works mainly by inhibiting a cellular pathway called the mTOR (mammalian target of rapamycin) pathway, which plays a crucial role in cell growth, metabolism, and ageing. mTOR is a ‘master regulator’ of energy handling – inhibiting it generally causes cells to restrict energy expenditure, slowing down growth and instead switching to a ‘survival and repair’ mode. A similar response involving mTOR occurs in calorie restriction and fasting, which are also very successful in extending health and lifespan in animals.

Rapamycin has a well established safety profile in humans as it is used to suppress the immune system and prevent the rejection of organ transplants. Based on this safety profile as well as the animal data showing health benefits and lifespan extension, some people choose to take low dose, off-label rapamycin or rapalogs (drugs with similar properties) in the hope that it will improve general health and delay the occurrence of age-related diseases. Is this a bad idea, or a calculated risk? Ultimately, everyone must decide (and according to many, should have a right to decide when adequately informed) whether it is worth taking a drug for an unproven benefit when there is no scientifically proven alternative. For now, the best we can do is look at the limited existing evidence in humans, which is what researchers summarise in this review.

The Studies

To address the gaps in our understanding of the effects of rapamycin in humans, the researchers summarise the important studies that have been done:

Immune Health

In 2014, a study found that giving people a rapalog followed by an influenza vaccine resulted in a stronger immune response, suggesting a more youthful immune system. Later studies also suggested that rapalogs could reduce the incidence of respiratory tract infections. These studies suggested that rapamycin doesn’t just suppress the immune system – it can also enhance it under some circumstances.
Later studies experimented with doses and suggested that rapalogs might enhance the immune system at low doses but suppress it at higher doses.
More recently, a study found that people who were taking rapalogs for longevity purposes had lower rates of COVID-19 than the general population. This should be taken with a grain of salt, as this was not a placebo-controlled trial, and people who take rapamycin or rapalogs for longevity are an unusual group likely to be far more health-conscious than most people (and therefore more likely to engage in illness-avoiding behaviours).

Cardiovascular Disease and Muscle Health

The researchers give a brief overview of the study of the effects of rapamycin on cardiovascular and muscle health, which can essentially be summarised as ‘there’s not enough data’.

Cancer

Studies suggest that kidney transplant recipients taking rapamycin get fewer kidney and non-melanoma skin cancers than those taking other immune suppressing drugs. However, these are high doses of rapamycin.
There is no data for the effects of rapamycin on cancer risk in healthy people taking low doses.

Neurodegenerative Disease

There is currently no data on the effects of rapamycin in people with neurodegenerative diseases.
There are several ongoing clinical trials investigating the effects of rapamycin in mild cognitive impairment and Alzheimer’s patients, focusing mainly on markers of Alzheimer’s disease and structural changes in the brain.

General Health

It is common for people who self-medicate with rapamycin or rapalogs to report improved general health and wellbeing, such as increased physical stamina or reduced chronic pain.
A small, 8-week randomised trial in elderly (but otherwise healthy) adults found that rapamycin significantly improved walking speed and reduced body weight, but had no significant effects on immune function or grip strength. There were also some inconclusive changes in blood markers. The authors concluded that there were no clear benefits, at least after 8 weeks.
The authors of the present study decided to re-analyse data from the aforementioned trial, using it to estimate the biological age of the participants. They found that the biological age of the participants taking rapamycin decreased by around 4 years relative to the controls.

The Implications

Even though animal studies of rapamcyin have been promising, there is still not much human data available, either for the treatment of age-related diseases, for general health, or for lifespan extension. There are a few reasons for this. It takes a long time (decades) to observe the impact of an intervention on general health, age related disease and lifespan, and it’s simply not practical to run a clinical trial for that long. Compounding this problem is the fact that rapamycin is a generic drug, so there’s no financial incentive for companies to fund big studies.

This means that studies are often small (making it harder to show a statistically significant effect even where a benefit may exist) and short (meaning that there may not be enough time to observe an effect where it exists). For individuals considering off-label rapamycin therapy, it is essential to proceed with caution, with adverse side effects monitored vigilantly. In the future, we need larger, well-designed human studies and better established dosing strategies in particular.