I wonder what convinced the ITP to try lactoferrin in 2023. There might be unpublished data?
Well, the CRSociety discussions centered around claims that it was good for mitochondrial longevity. Unfortunately the website is no more (a big loss), but as I recall there were some in vitro studies, which of course means just speculation.
I suppose there’s a more recent overview, again I post it because I don’t have the time atm to go hunting for old studies, so this has a bunch of citations pulled together.
The Lactoferrin Phenomenon—A Miracle Molecule
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There is a complex issue relating to Iron. On one side it inhibits mitophagy, but on the other side (beyond oxygen transfer) it is needed for dopamine production.
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I wonder if they’re using the right form, I did post this before:
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Thanks. The interesting bit:
Thus, the natural, partially iron-saturated form of lactoferrin is what should be used to try to resolve sticky inflammation.
Until recently, the only lactoferrin supplement on the market was an Italian product, Lattoglobina.
However, two brands have recently started selling such a product in the US:
Double Wood sells a natural partially iron-saturated lactoferrin that appears to be purified from dairy products using a patented process with high purity.
The Lactoferrin Co sells 95% pure partially iron-saturated lactoferrin isolated from grass-fed milk, as a powder or as enterically coated capsules.
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I bought the doublewood product right away, but couldn’t start it until I had swallowed my supply of the other kind. I have a drawer of supps that I bought on a whim then didn’t finish. I was going through the other day and deciding which I could use up, which to throw. First world problem, but still a problem. I do believe in lactoferrin.
What’s the current lactoferrin you’re using? Any effects noticed?
I think Iron levels are important. To what extent lactoferrin helps in dealing with this is unclear. I have bought some and may try it.
I used liposomal pepeior before. I think absorption is an issue with this. It can absorb or donate iron. Reduces inflammation. Helps NK cells against disease and cancer I suppose. Helps my gut mostly.
It naturally occurs in milk but is destroyed by pasteurization.
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I’m trying to find native lactoferrin supplements in the UK.
This one seems to do the job: https://osavi.com/en/lactoferrin-200-mg.html
They use a branded form of lactoferrin called Proferrin which according to another website has 9% iron saturation.
@Davin8r you mentioned a product called ProFerrin before. But yours is heme iron and not lactoferrin, right?
Yes that’s correct – it’s synthetic heme iron.
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- Serum Iron & TSAT: Interestingly, a 2025 study in Nutrients found that higher circulating serum iron and TSAT were actually associated with slower epigenetic aging, contradicting their negative impact on telomere length and genetically predicted lifespan.
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However, looking at the abstract, but not reading the paper:
Results: In adjusted models, a one standard deviation increase in serum ferritin was positively associated with higher standardized levels of DunedinPACE, GrimAgeAccel, and PhenoAgeAccel (DunedinPACE: 0.05, (0.00, 0.10); PhenoAgeAccel: 0.06 (0.00, 0.11); GrimAgeAccel: 0.06 (0.01, 0.11)). In contrast, higher serum iron and transferrin saturation were inversely associated with the biological aging metrics (serum iron, DunedinPACE: −0.02, (−0.07, 0.03); PhenoAgeAccel: −0.04 (−0.10, 0.01); GrimAgeAccel: −0.05 (−0.10, −0.01); transferrin saturation (DunedinPACE: −0.01, (−0.06, 0.05); PhenoAgeAccel: −0.01 (−0.06, 0.05); GrimAgeAccel: −0.05 (−0.10, −0.01))). Conclusions: The positive association with ferritin is consistent with the proposed role of oxidative stress in accelerated aging associated with high iron exposure. However, the observed inverse associations with serum iron and transferrin saturation are not consistent with this common explanation, and future studies are needed to examine potential explanations.
I have been a bit more focussed on ferritin as a guide to intracellular iron. I may read up on this a bit more, but until you get quite low on iron stores I don’t think that there is a lot that can be read into particularly serum iron.
Think I need to remind myself that all of my coffee and tea interferes with any Lactoferrin or iron absorption
Yes, and soy milk. At one point i was drinking coffee in the morning, tea at work, and soy milk with lunch and dinner along with testosterone replacement therapy (exogenous T can deplete iron stores) and ended up with ferritin in the 20s (i.e. anemia). Now I just take a daily heme iron supplement (Proferrin) which is not significantly affected by the above dietary factors, and my ferritin has been in the healthy range ever since.
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I’m getting a bunch of labs done tomorrow.
AI says I most likely am fine and don’t need a recheck, but the tests are cheap, so if it’s wise to check yearly or so, I guess it would be time. ?
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Is Ferroptosis the Mechanistic Bridge Connecting Iron Dysregulation to Muscle Wasting and Functional Decline in Aging?
Paper here: https://onlinelibrary.wiley.com/doi/10.1111/acel.70367
First published: 14 January 2026
Institution: Department of Physiology and Aging, University of Florida, USA; Università Cattolica del Sacro Cuore, Italy Journal: Aging Cell
This review article advances a “Ferroptosis Bridge” hypothesis, proposing that age-related muscle wasting (sarcopenia) is not merely a result of wear and tear, but a specific form of iron-dependent cell death known as ferroptosis. The authors argue that as we age, skeletal muscle—which naturally holds 10-15% of the body’s iron—loses its ability to regulate iron homeostasis. This leads to an accumulation of labile iron (free Fe2+), which interacts with hydrogen peroxide via the Fenton reaction to generate hydroxyl radicals. These radicals aggressively attack polyunsaturated fatty acids (PUFAs) in cell membranes (lipid peroxidation), causing membrane rupture and cell death.
Crucially, the paper distinguishes this process from general oxidative stress or apoptosis. It posits that the convergence of three aging hallmarks—iron dyshomeostasis, mitochondrial dysfunction, and impaired antioxidant defenses (specifically GPX4 and GSH)—creates a “pro-ferroptotic milieu”. This environment compromises muscle energetics and regenerative capacity. The authors suggest that targeting this specific pathway via iron chelation or lipid peroxidation inhibitors could offer a more precise intervention for sarcopenia than generic antioxidants, which have largely failed in clinical trials.
Impact Evaluation The impact score of this journal is ~7.8 (JIF), evaluated against a typical high-end range of 0–30+(where 30+ is elite general science like Nature), therefore this is a High impact journal within the specialized field of Geriatrics and Gerontology.
2. Mechanistic Deep Dive
The authors construct a specific “lethality pathway” for aging muscle that moves beyond generic “wear and tear.”
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The Ferroptosis Trigger (Iron + Lipids): The core pathology is the intersection of Labile Iron Pool (LIP) expansion and PUFA-containing phospholipids. Aging downregulates Ferroportin (iron exporter), trapping iron inside the myocyte.
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The Failed Guardian (GPX4): Under healthy conditions, Glutathione Peroxidase 4 (GPX4) utilizes Glutathione (GSH) to neutralize lipid hydroperoxides. In aging muscle, GPX4 expression declines, removing the “brake” on ferroptosis.
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The Senescence Loop (Hepcidin Axis): The paper identifies a systemic loop where “Inflammaging” (elevated IL-6) triggers the liver to produce Hepcidin. Hepcidin degrades Ferroportin on muscle cells, forcing iron retention. This creates a feed-forward loop: Senescent cells secrete cytokines → Hepcidin → Iron Retention → Ferroptosis →DAMP release → More Inflammation.
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Organelle Crosstalk (Ferritinophagy): The review highlights NCOA4-mediated ferritinophagy (autophagic degradation of ferritin) as a double-edged sword. While necessary for iron recycling, dysregulated ferritinophagy in aging releases excessive free iron, overwhelming mitochondrial buffers and triggering the Fenton reaction.
3. Therapeutic Interventions & Biohacks
The review categorizes interventions into three tiers based on the mechanism:
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Tier 1: Iron Chelation (Direct):
- Agents: Deferoxamine, Deferiprone.
- Mechanism: Binds excess labile iron, preventing the Fenton reaction.
- Efficacy: Reduced muscle loss in sarcopenic mice.
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Tier 2: Lipid Peroxidation Inhibitors (Specific):
- Agents: Ferrostatin-1, Liproxstatin-1, Vitamin E (limited), Vitamin K (potential).
- Mechanism: Acts as radical-trapping antioxidants (RTAs) specifically within lipid membranes.
- Note: Generic antioxidants (Vit C) fail because they do not specifically target lipid radicals.
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Tier 3: Lifestyle (Upstream):
- Action: Resistance training and Nordic walking.
- Mechanism: Reduces serum ferritin and enhances antioxidant defense (GPX4/Nrf2).
4. Novelty
- Specific Definition of Death: It reframes sarcopenia not as “atrophy” (shrinkage) but as “regulated necrosis” (ferroptosis), distinct from apoptosis (which is rare in aged muscle) and necroptosis.
- The “Double-Hit” Theory: Proposes that muscle wasting requires both iron accumulation and proteostatic collapse (ER stress), identifying why simple iron supplementation or simple antioxidants fail in isolation.
5. Critical Limitations (Ruthless Evaluation)
- Biomarker Vacuum: The authors admit a critical “Hard Fail” in current diagnostics: there are no specific biomarkers for ferroptosis in humans. Markers like Ferritin and 4-HNE are non-specific indicators of oxidative stress. Without a unique signature (like specific oxidized phospholipids), clinical diagnosis is currently impossible.
- Translational Gap: The majority of mechanistic proof comes from rodent models or cell cultures where ferroptosis is chemically induced (e.g., by erasing GPX4). Natural aging in humans is messier; the “clean” ferroptosis signal seen in mice may be drowned out by comorbidities in humans.
- Therapeutic Toxicity: Iron chelators have narrow therapeutic windows. Over-chelation risks anemia and mitochondrial failure (mitochondria need iron for ATP). The review correctly notes that using thalassemia drugs for sarcopenia is high-risk.
- Data Quality: As a review, this paper generates no new data. It relies on the validity of cited studies, some of which use “ferroptosis” loosely to describe general lipid peroxidation.
Biohacker Verdict: This is a high-confidence hypothesis with medium-confidence evidence. The pathway is biologically sound, but the tools to measure and treat it safely in humans are not yet mature.
- Hypothesis Confidence: High
- Translational Readiness: Low
Part 4: Actionable Intelligence (Deep Retrieval & Validation Mode)
The Translational Protocol (Rigorous Extrapolation)
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Primary Candidate: Deferiprone (DFP)
- Rationale: It is the only oral iron chelator with blood-brain barrier permeability and clinical precedent for neurodegeneration (PKAN) that is also cited for sarcopenia in mice.
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Human Equivalent Dose (HED) Calculation:
- Source Data: The key mouse study (Bose et al., 2025, J Cachexia Sarcopenia Muscle) used 25 mg/kg/day in Klotho mice to prevent sarcopenia.
- The Math:
HED(mg/kg)=Animal Dose(mg/kg)×(Human KmAnimal Km)
HED=25×(373)≈2.03 mg/kg
- Adult Human Dose (75 kg person): 2.03 mg/kg×75 kg≈152 mg/day.
- Standard Clinical Dose: For iron overload/Thalassemia, the standard dose is 75 mg/kg/day (approx. 5,600 mg/day).
- Biohacker Insight: The “anti-aging” HED (152 mg/day) is roughly 3% of the standard clinical dose. This suggests a “micro-dosing” strategy might be safer and sufficient for maintenance, though unproven in humans.
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Pharmacokinetics (PK/PD):
- Bioavailability: High (~78% urinary recovery). Rapid absorption.
- Half-life: Short (t1/2≈1.5−2 hours).
- Implication: Requires divided doses (b.i.d or t.i.d) to maintain chelation, though the “micro-dose” strategy might aim for pulsed “iron sweeping” rather than constant suppression.
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Safety & Toxicity Profile:
- Black Box Warning: Agranulocytosis (sudden drop in white blood cells) occurs in ~1-2% of patients. Neutropenia in ~5%.
- Monitoring Protocol: FDA mandates weekly Absolute Neutrophil Count (ANC) monitoring.
- Liver/Kidney: Gastrointestinal distress is common. Zinc deficiency can occur (chelates Zinc too).
Biomarker Verification
- Primary Target Engagement: Serum Ferritin (Goal: Reduction, but not below <30 ng/mL).
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Downstream Verification:
- Transferrin Saturation (TSAT): Should drop but stay >20%.
- Lipid Peroxidation Markers: Oxidized LDL (OxLDL) and F2-Isoprostanes (urine test) are the best available clinical proxies for ferroptosis reduction.
- Functional: Grip strength (Dynapenia) is the clinical endpoint for sarcopenia.
Feasibility & ROI
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Sourcing:
- Status: Rx Only (Ferriprox).
- Research Chemical: Available but high risk due to purity needs for chronic use.
- Supplements: None match this mechanism (IP6 is a weak chelator; Curcumin is a weak iron chelator).
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Cost:
- Retail: ~$4,000 - $6,000/month for standard clinical dose (Thalassemia).
- Micro-dose Estimate: If effective at 3% dose, cost theoretically drops to ~$150/month (if compounding/splitting were possible/legal), but shelf-availability is limited to 500mg/1000mg tabs.
Part 5: The Strategic FAQ
1. “Does the ‘Ferroptosis Bridge’ theory hold up if I don’t have iron overload (e.g., normal ferritin)?” Answer: Unclear. The paper argues that labile iron (free floating) is the culprit, not just total storage iron (Ferritin). You can have “normal” ferritin but high labile iron if your antioxidant defense (GPX4) is weak. However, chelating someone with normal/low iron carries a high risk of anemia.
2. “Can I just take Vitamin E to stop lipid peroxidation instead of risky chelators?” Answer: Likely No. Clinical trials of Vitamin E for sarcopenia are largely disappointments. Standard Vitamin E doesn’t penetrate lipid membranes efficiently enough to stop the “ferroptotic wave.” Novel “Radical Trapping Antioxidants” (RTAs) like Liproxstatin-1 are needed but are not human-approved.
3. “If I take Deferiprone, will it strip my Zinc and Copper too?” Answer: Yes. Deferiprone is not perfectly selective. It has an affinity for Zinc (Zn2+). Long-term use requires monitoring of plasma Zinc and potentially supplementation (spaced 4 hours apart).
4. “Is there a ‘Natural’ biohack to mimic Deferiprone without the agranulocytosis risk?” Answer: Pectasol (Modified Citrus Pectin)? Maybe. While not a direct iron chelator, it inhibits Galectin-3 (driver of fibrosis/inflammation). Quercetin and Curcumin have mild iron-chelating properties and are safer, though their potency is orders of magnitude lower than Deferiprone.
5. “How does Rapamycin interact with this pathway?” Answer: Synergistic. Rapamycin inhibits mTOR. High mTOR drives iron uptake (via Transferrin Receptor). By lowering mTOR, you theoretically lower iron influx, complementing the chelator’s removal of existing iron.
6. “Does Resistance Training actually ‘detox’ iron from muscle?” Answer: Yes, indirectly. Exercise upregulates antioxidant enzymes (GPX4, SOD) and improves mitochondrial turnover (mitophagy), effectively “cleaning up” the damage caused by iron, even if it doesn’t directly remove the metal atoms.
7. “I’m on TRT (Testosterone). Does this increase my ferroptosis risk?” Answer: Potentially. Testosterone stimulates erythropoiesis (red blood cell production) and can suppress Hepcidin, potentially increasing iron absorption. Monitoring Hematocrit and Ferritin is crucial for TRT users to avoid “over-juicing” the iron system.
8. “What is the specific ‘Red Flag’ value for Ferritin where I should worry about Sarcopenia?” Answer: Context-dependent. While >300 ng/mL is clinical overload, “optimum” for longevity is debated (often cited as 40-100 ng/mL). High Ferritin + High HS-CRP (inflammation) is the specific “Toxic Combination” linked to frailty.
9. “Can I measure ‘Labile Iron’ directly?” Answer: No. There is no commercial blood test for Labile Plasma Iron (LPI) or Labile Cellular Iron (LCI). We are flying blind using proxies like Ferritin and Transferrin Saturation.
10. “Is this just ‘Anemia of Chronic Disease’ rebranded?” Answer: Nuanced. Anemia of Chronic Disease locks iron away (high Ferritin, low serum iron). This paper argues that inside the muscle cell, that locked-away iron is leaking and causing rust. So, you can be “anemic” in your blood but “iron-toxic” in your muscles.
I find it interesting that GPs are thought to want Ferritin at 30 or above, but neurologists aim for 70 or over (dopamine).
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Just looking at MOA, it seems astaxanthin would fit the bill. It uniquely stabilizes the lipid membrane as a highly effective and persistent antioxidant. Additionally, other carotenoids can be synergistic in this context (zeaxanthin, lycopene, beta carotene).
Antioxidant synergism between carotenoids in membranes. Astaxanthin as a radical transfer bridge
https://www.sciencedirect.com/science/article/abs/pii/S0308814609001319
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