New Rapamycin paper in humans: my main takeaways

Adam Bataineh

A new study published in the New England Journal of Medicine has convinced me to start taking microplastics way more seriously (Study title: Microplastics and Nanoplastics in Atheromas and Cardiovascular Events).

The study was a first of its kind to analyze plaque samples obtained from the carotid arteries of 304 participants for the presence of microplastics and nanoplastics. They followed the participants for 34 months and compared those with microplastics and nanoplastics in their samples to those without. The results were quite alarming.

Here are my main takeaways:

1- Polyethylene— a common type of plastic—was detected in the carotid artery plaque of nearly 58.4% of the patients, with some also showing traces of polyvinyl chloride. 

2- The presence of microplastics and nanoplastics in arterial plaque was associated with a significant increase in the risk of severe cardiovascular events such as heart attacks, stroke and death from any cause. These people were over 4 times more likely to have a cardiovascular event happen compared to those without plastic particles in their arteries. 

- This is one of the best designed studies I have seen on this topic. It clearly demonstrates that microplastics accumulate in our bodies and more importantly, increase risk of severe health issues and death. 

4- The main behavior changes I now implement personally and recommend to avoid microplastics: 
• Stop using plastic containers or bottles for food or fluids (especially if heated)
• Limit single use plastics in general unless necessary (I always remove plastic coffee cup lids for example).
• Don’t use tea bags (replace with loose leaf tea)

Let me know if you have any questions about this topic or other topics you’d like me to cover.

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Adam Bataineh MD
Medical Director, Numenor

A new review paper (study title: targeting ageing with rapamycin and its derivatives in humans: a systematic review) was published recently in The Lancet Healthy Longevity summarizing the effects of Rapamycin age-related diseases in humans. I found it very interesting albeit slightly disappointing.

Here are my main takeaways and criticisms:

While the paper does a good job of collating the evidence for safety of Rapamycin and shows possible targets for future trials, I found some of the conclusions the authors make exaggerated and in some cases incorrect.

The main figure summarizing the effects of Rapamycin on different organs is shown below (red arrows are mine). The figure and the paper’s conclusion claims that Rapamycin improved the cardiovascular system in healthy individuals. They specifically cite two papers as evidence for this which are pointed out by the red arrows I added to the image.

This unfortunately is not true from the papers included in the review. The two papers that were cited to show cardiovascular benefit were:

  • The first paper (Boni et al. 2012) studied the effects of one single dose of IV Temsirolimus (a rapamycin analogue) on a measure of the electrical activity of the heart called QTc. In this study there was no positive (or negative) effect. This study does not show any kind of long term benefit from use of Rapamycin yet is cited as such. 

Note: my feedback that this data point is in the wrong place was shared with one of the authors, Prof Andrea B Maier. The paper has already been through peer-review and yet this error was not picked up.

  • The second paper (Seyfarth et al. 2013) did show some improvements in cardiac output with people taking Everolimus (Rapamycin analogue). But this was a pilot study on 8 patients who had a condition called pulmonary hypertension. You could argue that pulmonary hypertension can be considered an age-related disease, I find it difficult to extrapolate this finding to healthy individuals.

While the data in humans is lacking, this doesn’t mean the benefit does not exist. We do have promising data from nonhuman studies showing interesting effects on the cardiovascular system. A canine trial by Matt Kaeberlein showed some improvements in age-related measures of heart function in the Rapamycin treated dogs for example.

I found other parts of the paper more compelling especially the effects of Rapamycin on the immune system which I think is a very interesting effectiveness marker although difficult to measure in a non research setting. The cognitive and brain-related benefits of Rapamycin were not very convincing in this review. The Skin benefits of topical Rapamycin were compelling and worth pursuing.

Perhaps my main takeaway from this paper is that we haven’t studied Rapamycin as a geroprotector well enough yet. The evidence is still very scarce in humans compared to vertebrate (especially rodent) data which makes a more compelling case for the potential of Rapamycin. 

Adam Bataineh MD
Medical Director, Numenor

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