Ha, YES!
“I won’t mention any particular company, COUGH , PENDULUM, COUGH COUGH”
I did enjoy the episode!
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I’ve been taking the Pendulum metabolic daily for about a year. It consistently lowers my fasting BG to the high 80’s low 90’s. Without it I am typically 104 even with Jardiance or metformin.
When I ran out because wife was taking it without letting me know, BS jumped back over 100 so it does not have a lasting effect on me
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Akkermansia muciniphila modulates intestinal mucus composition to counteract high-fat diet-induced obesity in mice
Open Access Paper: https://www.tandfonline.com/doi/full/10.1080/19490976.2025.2612580
In a new study from the laboratory that originally identified Akkermansia muciniphila as a metabolic regulator, researchers have decoded the specific chemical “software” this bacterium uses to repair the aging gut. While previous research established Akkermansia as a correlation to longevity (abundant in centenarians), this paper moves from correlation to mechanistic causation.
The “Big Idea” here is Mucus Architecture Remodeling. The study reveals that Akkermansia (specifically the live MucT strain) does not merely inhabit the gut; it actively re-engineers the glycosylation profile (sugar coating) of the mucus layer. In mice fed a High-Fat Diet (HFD), the protective mucus layer typically collapses, leading to “leaky gut” and systemic inflammation—a hallmark of aging (inflammaging). Supplementation with live Akkermansia completely restored the expression of Muc3 (a specific mucin protein) and upregulated antimicrobial peptides (defensins) in the colon.
Crucially, this intervention decoupled obesity from diet: treated mice ate the same high-fat “junk food” as controls but gained significantly less fat mass. By reinforcing the gut barrier’s chemical integrity, Akkermansia prevented the metabolic toxicity usually associated with poor diet. For the longevity enthusiast, this suggests a protocol for “gut barrier resilience,” potentially mitigating the inflammatory cost of caloric surplus or aging-related gut permeability.
Novelty vs. Yesterday’s Science
- Yesterday: We knew Akkermansia reduces obesity and strengthens the gut barrier.
- Today: We know how. It restores Muc3 specifically (which is usually deleted by HFD) and alters the glycan profile (the specific sugar codes on the mucus) to prevent pathogen intrusion. It proves that live bacteria can remodel the physical structure of the host tissue without changing the overall microbiome composition.
Critical Limitations
- Short Duration: 6 weeks is insufficient to assess long-term safety or true anti-aging effects.
- Strain Specificity: The study used the MucT (ATCC BAA-835) strain. Commercial probiotics often use different strains (e.g., WB-STR-0001). Efficacy may not transfer 1:1.
- Translational Gap: Mice were gavaged daily. In humans, Akkermansia colonization is notoriously difficult; once supplementation stops, levels often crash.
| Claim | Hierarchy | Verdict & Context |
|---|---|---|
| “Counteracts diet-induced obesity (Body Weight/Fat Mass reduction).” | Level B | Verified. Human RCTs (Depommier et al., Nat Med 2019) confirm metabolic improvements (insulin sensitivity, slight weight loss) in humans, though effect size is smaller than in mice. |
| “Modulates intestinal mucus composition (restores Muc3).” | Level D | Translational Gap. Mechanism proven in mice. Human mucus biopsy data confirms Akkermansia abundance correlates with barrier health, but direct “Muc3 restoration” in humans is inferred, not proven. |
| “Increases Antimicrobial Peptides (Reg3g, Lyz1).” | Level D | Mechanistic Speculation. Murine data only. Human relevance is high (Reg3g has human homologs), but direct causation in humans via oral supplementation is not yet established. |
| “Live bacteria required for specific effects.” | Level D | Contested. This paper uses live bacteria. However, Depommier (2019) and Plovier (2017) showed that Pasteurized Akkermansia (specifically the Amuc-1100 protein) is equally or more effective for metabolic parameters in humans. |
| “Safe for consumption.” | Level A | Verified. Multiple human trials and EFSA/FDA evaluations confirm safety of both live and pasteurized A. muciniphila (up to 10 billion bacteria/day). |
Biomarker Verification Panel
-
Efficacy Markers:
- Fasting Insulin & HOMA-IR: Expect improvement within 3 months.
- hs-CRP: Should decrease as “leaky gut” resolves.
- LPS (Lipopolysaccharide): If available, measuring serum Endotoxin is the “Gold Standard” for barrier function.
-
Safety Monitoring:
- Standard CMP (Liver enzymes ALT/AST) to rule out rare dysbiosis-induced issues (though safety profile is excellent).
Feasibility & ROI
-
Commercial Availability:
- Live: Available via Pendulum Therapeutics (Strain WB-STR-0001).
- Pasteurized: Available via The Akkermansia Company (Weight Management formulations).
- Cost: High. ~$65–$90 USD/month.
- ROI: Medium-High for those with Metabolic Syndrome or elevated HbA1c. Low ROI for healthy, lean individuals (diminishing returns).
Part 5: The Strategic FAQ
Q1: You used Live Akkermansia (MucT). Human trials and recent FDA/EFSA approvals often favor Pasteurized. Which is better?
- Answer: The data is conflicted. This paper proves Live works for mucus remodeling. However, human RCTs (Depommier 2019) showed Pasteurized was slightly superior for insulin sensitivity, likely because pasteurization exposes the Amuc-1100 membrane protein to the host immune system.
- Unknown: Whether Pasteurized induces the same “Muc3 restoration” and glycan shifting as Live.
Q2: The study duration was only 6 weeks. Does this effect last?
- Answer: Likely not without continuous use. Akkermansia is a “transient tourist” in many supplement protocols. If you stop taking it (and don’t feed it polyphenols/fibers), levels drop.
- Clinical Conflict: None. Consistent daily dosing is required.
Q3: Can I take this with Rapamycin?
- Answer: Yes, potentially synergistic. Rapamycin inhibits mTOR, which mimics a fasting state. Akkermansiathrives during fasting (mucin foraging) and is naturally upregulated during Caloric Restriction. Both interventions aim to lower systemic inflammation.
- Caution: Monitor immune markers (WBC) as both modulate immunity.
Q4: Is “MucT” available to consumers?
- Answer: “MucT” is the ATCC BAA-835 research strain. Consumer products (Pendulum) use proprietary strains (e.g., WB-STR-0001). While genomically similar (>98%), their mucin-degrading efficiency could theoretically differ.
- Action: Look for “Genomic equivalence” data from manufacturers.
Q5: Does this replace Metformin?
- Answer: No. Metformin changes the microbiome (increasing Akkermansia is actually one of Metformin’s mechanisms!). They can be stacked, but Akkermansia is a “barrier reinforcer” while Metformin is a systemic metabolic drug.
Q6: This paper focuses on obesity. I’m skinny. Should I take it?
- Answer: Maybe. The value here isn’t weight loss; it’s Barrier Integrity. If you have high systemic inflammation (hsCRP) or digestive issues despite being lean, the “Muc3 restoration” mechanism is relevant to you.
Q7: How do I measure if it’s working? Gut microbiome test?
- Answer: Yes. A PCR-based stool test (e.g., GI-MAP or Ombre) can quantify Akkermansia abundance. Test at Day 0 and Day 90. If levels don’t rise, you are a “non-responder” or your prebiotic fuel is missing.
Q8: Any side effects?
- Answer: Bloating/Gas is common in the first 1-2 weeks as the mucin layer shifts and fermentation changes. Safety data is otherwise robust (NOAEL in rats is massive).
Q9: What is the “Glycan Profile” modulation, really?
- Answer: It’s a change in the sugar structures on the mucus surface. Think of it as changing the “locks” on the door so pathogens can’t pick them, while inviting beneficial immune cells to stand guard.
Q10: Does 2’-Fucosyllactose (2’-FL) achieve the same thing?
- Answer: Partially. 2’-FL feeds Akkermansia. The paper cites that prebiotics can increase Akkermansia, but this study shows that adding the bacteria directly repairs the machinery (Muc3) faster/more specifically than just adding the fuel.
I have had great results with Pendulum’s Metabolic Daily. Perhaps you are not aware, but it contains five strains (not one):
- Akkermansia muciniphila — a keystone gut strain associated with strengthening the gut lining and supporting metabolic function.
- Clostridium butyricum — a butyrate-producing species that supports digestive health and metabolism.
- Anaerobutyricum hallii — another butyrate producer involved in metabolic and gut health.
- Clostridium beijerinckii — butyrate-producing strain that helps promote a balanced microbiome.
- Bifidobacterium infantis — aids digestion of complex carbohydrates and supports immune function and overall microbiome balance.
Total probiotic blend: ~300 million AFU per capsule (combined).
These strains are chosen for their roles in metabolizing fiber into beneficial short-chain fatty acids (like butyrate), enhancing metabolic pathways, and supporting gut barrier integrity.
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The problem with Metabolic Daily is that it contains so little Akkermansia, which is why I personally chose Pendulum Akkermansia. Unfortunately, Pendulum’s best products are not shipped to my home country. However, I did find one supplier that carries both Pendulum Akkermansia and Metabolic Daily.
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When I first learned about this brand, perhaps a couple years ago, for the very reason you mentioned, I took their glucose control for a while because it had a lot of Akkermansia, plus the other things. I just didn’t continue because it’s pretty expensive, most people don’t seem to take it, and I also didn’t notice anything different, but I admit I was taking a half dose to reduce costs while getting some benefit.
The people at the company even told me most people start with GC and then switch to their akkermansia product.
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When you say great results, you mean biomarkers or just subjectively feeling great. If biomarkers, which ones are you tracking?
I have much better regularity, with well formed soft normal brown colored stools. Formerly I had occasional loose or watery stools. I do not mean any specific biomarkers in terms of lab results. My A1C has never been high, running 5.2-5.3 before and after.