Xylitol is prothrombotic and associated with cardiovascular risk

[helvella]

I just included a list of ingredients of a Calcichew product and then saw this research on one of the ingredients.

Xylitol is prothrombotic and associated with cardiovascular risk

Marco Witkowski 1 , Ina Nemet 1 , Xinmin S Li 1 , Jennifer Wilcox 1 , Marc Ferrell 1 , Hassan Alamri 1 , Nilaksh Gupta 1 , Zeneng Wang 1 , Wai Hong Wilson Tang 1 2 , Stanley L Hazen 1 2

Affiliations

PMID: 38842092 PMCID: PMC11492277 (available on 2025-06-06) DOI: 10.1093/eurheartj/ehae244

Abstract

Background and aims: The pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute.

Methods: Untargeted metabolomics studies were performed on overnight fasting plasma samples in a discovery cohort (n = 1157) of sequential stable subjects undergoing elective diagnostic cardiac evaluations; subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent, non-overlapping validation cohort (n = 2149). Complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies examined the effect of xylitol on platelet responsiveness and thrombus formation in vivo. Finally, an intervention study was performed to assess the effects of xylitol consumption on platelet function in healthy volunteers (n = 10).

Results: In initial untargeted metabolomics studies (discovery cohort), circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) major adverse cardiovascular event (MACE) risk. Subsequent stable isotope dilution LC-MS/MS analyses (validation cohort) specific for xylitol (and not its structural isomers) confirmed its association with incident MACE risk [third vs. first tertile adjusted hazard ratio (95% confidence interval), 1.57 (1.12-2.21), P < .01]. Complementary mechanistic studies showed xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. In interventional studies, consumption of a xylitol-sweetened drink markedly raised plasma levels and enhanced multiple functional measures of platelet responsiveness in all subjects.

Conclusions: Xylitol is associated with incident MACE risk. Moreover, xylitol both enhanced platelet reactivity and thrombosis potential in vivo. Further studies examining the cardiovascular safety of xylitol are warranted.

Keywords: Artificial sweetener; Cardiovascular disease; Heart attack; Low-calorie sweetener; Nutrition; Platelet; Polyol; Stroke; Sugar alcohol; Thrombosis.

Full paper accessible here:

academic.oup.com/eurheartj/...

Will be in PubMed Central sometime in 2025.

Abstract:

pubmed.ncbi.nlm.nih.gov/388...

[Thyroid17]

I currently have a dental abscess so mind pre-occupied with that discomfort but, also in a dental theme, a dentist previously advised the hygienist will be using ?Xylitol in preference to water during cleaning. I declined saying I’d rather proceed with traditional water method. I do remember the hygienist said it was only a harmless sweetener.

[Thyroid17 in reply to Thyroid17]

I still declined.

[Thyroid17 in reply to Thyroid17]

Where I was trying to go with this, through discomfort, is there will be a sizeable amount of patients receiving ?Xylitol without being fully aware. Highlighted especially due to the close link between gum and heart health.

[Tina_Maria]

Well, saccharine was banned in 1981 as a potential carcinogen and then 'unbanned' in 2000, and the WHO and FDA allowed its use in food products (no doubt through pressure by the industry). Saccharin has been extensively used by people on reduced calorie diets and diabetics as a sugar substitute. However, recent studies have shown that saccharin can increase glucose levels in some people including fasting blood glucose, although the mechanism is not yet clear.

Phenylalanine, another sweetener, has recently been shown to impair insulin signalling and delay glucose uptake - also not a desirable effect when you have it on a regular basis or if you are diabetic. A study of 5,181 Finnish men found that phenylalanine was associated with an increased risk of type 2 diabetes (although association does not necessarily mean causation, but still worrying).

Even these 'naturally derived' sweeteners are substances that are not easily recognised by our bodies and their long term effects are still unknown.

My take is, if you want to avoid sugar, just avoid sugar, but do not replace it with something that could potentially be worse than having a small bit of sugar now and then, which our metabolism can utilise and process properly.

[helvella Administrator in reply to Tina_Maria]

I've generally tried to avoid all sweeteners for many years. Remember the ban on cyclamates?

It also doesn't help that brand name sweetener products (such as Hermesetas) can vary in actual sweeteners used depending on the market.

[Tina_Maria in reply to helvella]

Oh dear, don't get me started on cyclamates...😂

Indeed, it is a minefield out there and the closer you look at all the labels, the more sh*t you find. But then if you can concoct something that is cheap to make and you can put into foods, big profits ... just not for your health 😡.

[Bertwills]

it’s very poisonous to dogs so I wouldn’t have it in my house. I used to eat bread freshening mints with it in as they were supposed to clean your teeth then I read about the effect on dogs & decided against them. Amazing how dental health is often promoted above general health eg alcohol in mouth washes, fluoride in toothpaste.

[Lynneypin]

I use Xlear nasal spray (containing xylitol) and it’s a game changer for my sinus issues….

[Zephyrbear]

I’ll stick to sugar…

[helvella Administrator in reply to Zephyrbear]

Most of us do - when it gets damp or is dissolved in water...