Key Takeaways
They might have mixed up the results.
"The placebo group exhibited significant reductions in total cholesterol, LDL-C, non-HDL-C, total LDL-P, large LDL-P, and ApoB, while the blueberry group exhibited significant reductions in total HDL-P and ApoA-I after 12 weeks compared to baseline."
Blueberry supplementation (equivalent to 1.5 human servings) reduced circulating TMAO in CB vs C mice (~48%) without changing choline or TMA. This effect was not mediated through alterations in metabolic parameters. Dietary strawberries did not reduce choline, TMA or TMAO. Depleting gut microbes with antibiotics in these cohorts drastically reduced TMA and TMAO to not-quantified levels. Further, dietary blueberries increased the abundance of bacterial taxa that are negatively associated with circulating TMA/TMAO suggesting the role of gut microbes. Our phenolic profiling indicates that this effect could be due to chlorogenic acid and increased phenolic contents in blueberries. Our study provides evidence for considering dietary blueberries to reduce TMAO and prevent TMAO-induced complications.
Unlikely. See:
Dietary phenolics and their microbial metabolites are poor inhibitors of trimethylamine oxidation to trimethylamine N-oxide by hepatic flavin monooxygenase 3
Quote:
“However, bioavailable chlorogenic acid metabolites did not generally inhibit FMO3 at physiological (1 µM) nor supra-physiological (50 µM) doses. Thus, the effects of chlorogenic acid in regulating TMAO levels in vivo are unlikely to occur through direct FMO3 enzyme inhibition. Potential effects on FMO3 expression remain unknown. Intestinal inhibition of TMA production and/or absorption are thus likely their primary mechanisms of action.”
FWIW.
TMAO Is Bad For Health, But Can Be Reduced (21-Test Analysis) - via Conquer Aging Or Die Trying! Mike Lustgarten, PhD
It’s interesting that those two papers have two coauthors in common, and both papers were published near to the same time.
The authors in common were: Lisard Iglesias-Carres, and Andrew P Neilson.
Here is the high-resolution summary and analysis of the provided transcript.
This video provides a deep dive into Trimethylamine N-oxide (TMAO), a gut-microbiome-derived metabolite associated with increased risk of heart failure, kidney disease, atherosclerosis, and all-cause mortality. The core thesis argues that while TMAO is dangerous, the dietary solution is nuanced. Although fish is the highest dietary source of pre-formed TMAO, data indicates fish intake is not associated with adverse outcomes (like Alzheimer’s), creating a “fish paradox.” Instead, the speaker identifies the primary driver of harmful TMAO levels as gut dysbiosis—specifically, an age-related increase in gut pH (alkalinity) that allows TMA-producing pathogenic bacteria to thrive.
The speaker presents rigorous n=1 data (21 blood tests over 3 years) showing that his TMAO levels correlate inversely with garlic intake. He proposes a protocol to keep TMAO levels below the optimal target of <2 µM by acidifying the gut lumen through high fiber intake and exercise (which produce short-chain fatty acids) and consuming garlic (specifically allicin) to inhibit bacterial TMA production.
| Claim from Video | Speaker’s Evidence | Scientific Reality (Best Available Data) | Evidence Grade | Verdict |
|---|---|---|---|---|
| “TMAO causes heart failure & atherosclerosis” | Cites general associations/studies. | Supported by Meta-analyses. High TMAO is linked to >60% higher risk of mortality/MACE. Causality is strongly suggested by animal models, though human reverse causality (kidney function) is debated. | A (Meta-analysis) | Strong Support |
| “Fish raises TMAO but isn’t harmful” | Cites 11-study meta-analysis on Alzheimer’s risk. | The “Fish Paradox” is real. Fish acutely spikes TMAO >50x more than meat, yet fish intake is cardioprotective. The “harmful” TMAO likely requires the context of dysbiosis or meat-based precursors (choline/carnitine). | A (Cohort/Meta) | Strong Support |
| “Optimal TMAO level is <2 µM” | Cites mortality hazard ratios. | Accurate. Studies show risk stratification often begins >4–6 µM. Healthy controls typically range 2–3 µM. Heart failure patients often >5–10 µM. | B (Clinical Data) | Strong Support |
| “Garlic reduces TMAO levels” | Cites n=1 data; mentions correlations. | Plausible. Allicin (in garlic) acts as a non-lethal inhibitor of the bacterial enzyme (CutC/D) that produces TMA. Human trials are limited but animal data is robust. | C/D (Animal/n=1) | Plausible |
| “Aging causes gut alkalinity (high pH) which drives TMAO” | Cites comparison of young vs. centenarians. | Supported. Aging is linked to lower SCFA production and higher colonic pH, favoring proteolytic/TMA-producing bacteria (e.g., Proteobacteria). | C (Observational) | Plausible |
| “Salt intake raises TMAO” | Cites n=1 correlation. | Unclear/Speculative. High salt can alter gut microbiome composition (reducing Lactobacillus), potentially increasing inflammation, but direct TMAO link is not well-established in humans. | E (Anecdote) | Speculative |
Top Tier (High Confidence & Safety)
Experimental (Risk/Reward)
Garlic Supplementation (The “Allicin Protocol”):
Based on the speaker’s data and mechanistic studies, consume 2–5 grams of raw garlic daily (approx. 1–2 cloves) or a high-allicin aged garlic extract.
Note: Allicin is the active compound. If cooking, crush the garlic and let it sit for 10 minutes before heating to maximize allicin production.
Foods to Prioritize: Avocado, Olive Oil, and Zinc-rich foods (Oysters, Pumpkin seeds) correlated with lower TMAO in the speaker’s dataset.
Foods to Moderate: If TMAO remains stubbornly high, consider reducing Salt, Bananas, and Dates (based on speaker’s negative correlations), though this is less validated than the garlic intervention.
This relates to a new study: The Berry Defense: Meta-Analysis Confirms Anthocyanins Reverse Cognitive Decline Domains
in which the summary states:
2. Can I just eat blueberries, or do I need an extract?
Answer: [Confidence: High] You can eat blueberries, but you need Wild Blueberries (smaller, darker) to reach the 200 mg+ therapeutic threshold without consuming excessive fructose. Extracts (Cyanidin-3-Glucoside) are superior for ketogenic/low-carb protocols.