[esperent]

> However, this study shows that the concentration of erithritol is well above the concentration where they see negative effects in vitro when consuming a realistic dose.

Are you saying that when you eat a normal/largish amount of erithritol (say 1-10g), the concentration of erithritol in your brain is similar to what they tested on brain cells in vitro here?

Also, how can they make a link to stroke when testing in vitro?

[nerdsniper]

The study used a concentration of 6mM erythritol. This would be the mean (“bulk”) concentration found in the body after drinking 2-3 erythritol-sweetened soft drinks. I can find several with 10+ grams of it per bottle/can.

Erythritol Concentration: 6 mM (0.006 mol/L)

Molar Mass of Erythritol: 122.12 g/mol

Water in human body: 42 Liters

Calculated Total Mass: 30.77 grams (0.006 * 122.12 * 42)

[esperent]

You're assuming that:

A) all of the erithritol consumed ends up in serum (blood)

B) is equally distributed throughout all the blood in the body

C) entirely bypasses the blood brain barrier

These are huge assumptions. A) is certainly wrong.

[nerdsniper]

A) Erythritol has ~90% bioavailability. See note at bottom.

B) Is a reasonable assumption. See same note at bottom.

C) Erythritol damages the microvascular endothelial cells, which form the BBB. So it doesn't need to cross the BBB, because that's what it damages directly. The name of TFA's study is "The non-nutritive sweetener erythritol adversely affects brain microvascular endothelial cell function"[0].

N.B. Erythritol is known to pass through the BBB via diffusion, though that's somewhat limited by its partition coefficient (logP) of -2.3. It's a small molecule, so it's not blocked based on size.

Also, this study isn't "just one study". There's a large corpus of research accumulating data both in vivo and in vitro showing both that erythritol causes these problems, and demonstrating how. This was a very thoughtful and reasonable study. The main point of the study was to measure oxidative stress, nitric oxide (NO), endothelin (ET)-1, and tissue-type plasminogen activator (t-PA). Their dysregulation is already well-known to be directly linked to the health of brain blood vessels and shown to be quite relevant in the development of stroke.

Epidemiological studies involving thousands of patients first established a strong, independent link between higher blood levels of erythritol and an increased risk for events like heart attack and stroke[1]. Subsequent mechanistic studies then showed that erythritol makes blood platelets hyper-reactive and more prone to clotting, providing a direct link to thrombosis[2]

Also in response to:

> A) is certainly wrong.

A previous study gave participants 30g of erythritol orally and their serum concentration rose from 4 µM to 6,480 µM [3]. That's why this study chose 6mM - they didn't just do some napkin math and YOLO it - previous studies pointed the way after showing that "(A) is certainly right".

[0] https://journals.physiology.org/doi/full/10.1152/japplphysio...

[1] https://pubmed.ncbi.nlm.nih.gov/36849732/

[2] https://www.ahajournals.org/doi/10.1161/ATVBAHA.124.321019

[3] https://consultqd.clevelandclinic.org/evidence-mounts-that-s...