https://www.nature.com/articles/s43587-025-00864-8
you can get it via ion panel urine sample [though this isn’t as reliable as blood]
Do phenylacetate-family metabolites “spike” after you eat polyphenols?
Short version:
Yes—many (but not all) polyphenol-rich foods trigger a rapid, microbiota-driven rise in free phenylacetic acid (PAA) and its conjugate phenylacetyl-glutamine (PAGln) in blood and urine. The peak is usually 1.5 – 4 h after ingestion and can reach 3- to 10-fold above fasting baseline before falling back within ∼8–12 h. The size of the spike depends on the food matrix and on your gut bugs; green-tea catechins, for example, suppress PAGln formation. Below are the key numbers and mechanisms.
1. Where does the phenylacetate come from?
| Step | Process | Notes |
|---|---|---|
| Polyphenol arrival in colon (flavan-3-ols, anthocyanins, chlorogenic acid, etc.) |
 Ring-cleavage and dehydroxylation by anaerobic gut bacteria |
Produces smaller aromatics such as phenylacetic, phenylpropionic, benzoic and hydroxybenzoic acids . |
| Absorption + phase II | Colonocytes & liver form glucuronides/sulfates; liver also ligates PAA to glutamine → PAGln | |
| Appearance in plasma | Free PAA and conjugates reach low-µM (0.1–1 µM) Cmax in human and animal studies | |
| Renal excretion | 24-h urine recovers 5–15 % of ingested (poly)phenols as PAA class; PAGln is a major nitrogen-waste carrier |
2. Typical kinetics & magnitude
| Study / matrix | Polyphenol dose | PAA / PAGln response | Timing |
|---|---|---|---|
| Wild blueberry drink, humans | 300 mg anthocyanins | Plasma PAA ↑3.1-fold; top 5 metabolite at 2 h | Tmax ≈ 2 h, back to BL by 8 h |
| Calafate berry, gerbil model | 300 mg kg⁻¹ extract | PAA family peaked 0.1–1 µM; main rise 2–8 h | Half-life ≈ 3 h |
| Apple purée, humans | 500 g apples | 24-h urinary PAGln ↑ ≈ 2.5× vs control | Integrated over day |
| Green-tea catechins, mice | 0.6 % diet GTP | PAGln in caecal contents ↓ 35 % vs control | Polyphenols can also inhibit the pathway |
Rules of thumb
- Plasma free PAA Cmax: 50–300 ng mL⁻¹ (0.3–2 µM) per single “berry-equivalent” serving.
- Urinary 24-h AUC: roughly proportional to dose; 4–10 µmol extra PAA+PAGln after a 300 mg anthocyanin load.
- Intra-individual CV: ~40 % for plasma, ~50 % for spot urine; microbiota composition dominates the variance.
3. Why do spikes vary so much?
- Microbiota guilds – Clostridium/Xenorhabdus clusters with fldB and paaK genes dictate conversion efficiency.
- Transit time – slower motility → delayed, broader peak.
- Co-substrates – abundant dietary phenylalanine can mask the polyphenol-derived signal.
- Polyphenol class – large procyanidins reach the colon intact and give bigger PAA bursts than catechins; gallated catechins (green tea) can directly inhibit aromatic amino-acid fermenters, blunting the spike.
4. Practical implications for testing
| If you want to measure… | Best sample | How to minimise noise |
|---|---|---|
| Acute post-meal kinetics | Serial plasma (0, 1, 2, 4, 6 h) | Standardise meal polyphenol dose; fast overnight; keep activity constant |
| Habitual exposure / epidemiology | 24-h urine or ≥2 first-morning spots, creatinine-normalised | Avoid extreme hydration; record recent flavonoid intakes |
| Microbiota modulation by supplements | Fasting plasma PAGln (steady-state) | Sample same clock-time after ≥3-day wash-in |
Bottom line
Most colourful plant foods deliver a short-lived phenylacetate surge in blood and urine once colonic bacteria have chopped the parent polyphenols into smaller aromatic acids. Peaks appear within a couple of hours, are gone by lunchtime, and scale with both the polyphenol load and your gut-bug toolkit. Thus, phenylacetate can serve as a fast, though highly individual, biomarker of polyphenol exposure—unless you’re guzzling green tea catechins, which seem to damp the pathway instead of feeding it.
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Thank you.
But your AI interaction went right into increase/decrease of a substance. One must first lay the predicate. Why are we even considering this substance? The article’s abstract explains why.
Abstract
Endothelial cell senescence is a key driver of cardiovascular aging, yet little is known about the mechanisms by which it is induced in vivo. Here we show that the gut bacterial metabolite phenylacetic acid (PAA) and its byproduct, phenylacetylglutamine (PAGln), are elevated in aged humans and mice. Metagenomic analyses reveal an age-related increase in PAA-producing microbial pathways, positively linked to the bacterium Clostridium sp. ASF356 (Clos). We demonstrate that colonization of young mice with Clos increases blood PAA levels and induces endothelial senescence and angiogenic incompetence. Mechanistically, we find that PAA triggers senescence through mitochondrial H2O2 production, exacerbating the senescence-associated secretory phenotype. By contrast, we demonstrate that fecal acetate levels are reduced with age, compromising its function as a Sirt1-dependent senomorphic, regulating proinflammatory secretion and redox homeostasis.
These findings define PAA as a mediator of gut–vascular crosstalk in aging and identify sodium acetate as a potential microbiome-based senotherapy to promote healthy aging.
Beyond the metabolites, gut microbiota produces a myriad of other metabolites like short-chain fatty acids (SCFAs), mainly including acetate, propionate and butyrate, which circumvent atherosclerosis and other CVD risk factors9. It is well characterized that >70% of colonic acetate, but only small amounts of propionate and butyrate, reach circulation after hepatic metabolism14. We have previously reported that aging markedly reduces fecal acetate levels by up to 80% due to the depletion of acetate-producing bacteria, such as Prevotella and Rikenellaceae _RC9_gut_group15.
Notably, the depletion of these bacteria in the microbiome has been ubiquitously observed in CVD and is associated with disease severity
“These findings define PAA as a mediator of gut–vascular crosstalk in aging and identify sodium acetate as a potential microbiome-based **senotherapy to promote healthy aging.”
Sodium acetate can be produced by vinegar and baking soda. One can also just have a go at salt and vinegar potato chips. Watch the blood glucose though, or have olive oil or cheese before the chips.
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Funny they don’t sell pills. You can buy sodium acetate anhydrous or trihydrate. 30 bucks for 500 grams. How much to take for how much polyphenol? How to figure it out? Tough problems.
Chris Masterjohn had me drinking cider vinegar with baking soda for a while for keto reasons. I forget all the chemistry and was never convinced it was doing anything. Here they’re saying it could help heart disease if you get a lot of polyphenols. I get a lot.
