Don’t think that’s true re subq requiring more frequent dosing to maintain steady levels. If anything the opposite is true: Subq absorption is slower and smoother which can actually produce more stable levels, not less. In any case this isn’t the place to argue this point so happy to let it be
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Since I have no background in medicine or biology, I can only parrot, papers and AIs
Deficiency symptoms (pre-anemia / low-normal ferritin range):
- Cognitive fatigue, brain fog, reduced working memory
- Attentional deficits and slowed processing speed
- Poor sleep architecture (restless legs syndrome is strongly iron-mediated)
- Reduced executive function, especially under cognitive load
Longevity-Relevant Concerns
- Mitochondrial efficiency — impaired ATP production in high-demand tissues (heart, brain, muscle) accelerates functional aging
- Exercise capacity — reduced VO₂ max even before anemia appears, which is a strong longevity predictor
- Immune function — iron-deficient macrophages and lymphocytes have impaired oxidative burst and proliferative response
- Thyroid axis — iron deficiency impairs iodine metabolism and TPO activity, potentially blunting thyroid function
The Nuance: Too Much Is Also Bad
Iron is a pro-oxidant. Excess ferritin is associated with:
- Increased lipid peroxidation and oxidative stress
- Atherosclerosis acceleration
- Higher Alzheimer’s risk (iron accumulates pathologically in amyloid plaques and tau tangles)
So the target isn’t maximization — it’s optimization. For most longevity-focused men, ferritin in the 50–100 ng/mL range is generally considered favorable, avoiding both deficiency and iron overload.
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The question was really one specifically for @Joseph_Lavelle His body is clearly short of iron, low MCV, low ferritin. He knows that the proximate cause is TRT. Obviously he is also donating blood, but without the TRT that would probably not be needed to keep down HCT. There are a range of thresholds for ferritin 30 for GPs, 70 for neurologists. However, from a mitophagy perspective very low cellular iron is helpful, but iron is also essential for metabolism.
Hence the question is what symptoms he actually has. He might be best to reduce the TRT. Or even to reduce it for a while, retest and perhaps increase it.
If he has no symptoms of iron shortage, however, this may not be necessary. Because so much Iron is in Hb it may be that this iron is enabling the iron requirements to be fulfilled. This would be a bit surprising, but in the end it is iron.
@Tim is the outlier for iron shortage with all the indicators screaming too little iron. He also has symptoms which probably are resulting from iron shortage. My reading of @Joseph_Lavelle is that he is not currently suffering symptoms. I would still myself be cautious about this and potentially cycle down the TRT which could be increased later.
I personally am not that stressed about T, but I have a stupidly high SHBG and also a reasonably high T without TRT hence my free T is quite low.
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I haven’t looked into to what extent iron loss and overload influences mitophagy, and in which context so I’m not claiming iron cannot modulate mitophagy in certain conditions.
My point was much narrower. It was about whether this has any meaningful relevance in vivo under the conditions we’re discussing (a person with low-normal ferritin but normal hemoblobin).
The studies you linked to are vitro studies. Lots of things have effects on things in vitro while having no significant effects on those same things in vivo under reasonable physiological conditions. Pointing towards potential effects in vitro is often of little use, if those effects aren’t translated into potential relevance to what occurs in vivo. It’s far too common for in vitro results to have almost nothing to do with what occurs in vivo because the concentrations and conditions in vitro are far from what is normal in vivo.
The context here is that we were talking about slightly low ferritin levels in someone with normal hemoglobin levels. To recap briefly, John had told @beth that her hemoglobin doesn’t indicate that she needs more iron. I had pointed out that you can’t rely on hemoglobin here because you can have subclinical deficiency with normal hemoglobin levels. John then said this:
“I think there is a broader issue about iron levels inhibiting mitophagy which means there is a good reason to keep iron as low as possible - whilst avoiding anaemia.”
My problem with what John said here is that he makes several long shot assumptions without making any effort to determine whether this has any relevance under normal conditions in vivo. He is basically making three assumptions:
- Excessive iron can inhibit mitophagy, therefore low-normal iron will inhibit mitophagy in humans in vivo
- The inhibition of mitophagy by low-normal iron, if it occurs, is actually significant in vivo
- The reduced mitophagy in turn actually has significant negative effects on health of humans
Each of these are statements that need to be proven, and some, if not all, have a low propability of being true. So it’s a large leap to recommend keeping iron levels very low based on this. This is simply poor reasoning.
Don’t get me wrong, I don’t have any problems with people coming up with theories and predictions, and I’m not objecting to the existence of some mechanistic connection between iron and mitophagy. I’m objecting to the act of treating some plausible mechanistic link (mainly supported by in vitro studies) as justification to confidently make some recommendations about what humans should do.
It’s important to treat theories as just that and be careful when translating them into real effects in vivo. This is especially important for those of us here that have become respected enough by some members of this forum that other people might listen to us and take action based on our posts. I would argue that such people have higher responsibility than most members and should have higher standards in what they post and say.
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I agree with this thought but everyone here should operate under the “buyer beware” banner. 1st rule of Longevity Club is DO NOT HARM YOURSELF. That said, these debates are the best thing on this forum. Thanks for putting your energy here.
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Another iron skeptic and acolyte of Dr. Greger, gives his 2 cents worth, but does cite some interesting studies.
The Population is Rusting On the Inside (via Mic the Vegan)
This analysis evaluates the biochemical and epidemiological claims regarding iron overload—referred to as “internal rusting”—and its systemic impact on chronic disease. The transcript posits that standard clinical reference ranges for ferritin are excessively high, contributing to oxidative stress through the Fenton reaction, which subsequently drives insulin resistance, cardiovascular disease, and oncogenesis.
I. Executive Summary
The transcript presents a provocative case for “internal rusting,” a colloquialism for systemic oxidative stress driven by iron accumulation. The core thesis posits that “normal” Western ferritin levels (30–300 ng/mL) are fundamentally pathological, acting as a catalyst for the Fenton reaction. In this biochemical process, ferrous iron reacts with metabolic hydrogen peroxide to generate hydroxyl radicals—the most reactive and damaging oxygen species in human biology. These radicals facilitate lipid peroxidation, DNA fragmentation, and proteotoxicity, which are primary drivers of atherosclerosis, oncogenesis, and metabolic dysfunction.
A critical appraisal of the evidence cited reveals a mix of robust mechanism and potentially confounded epidemiology. The transcript relies heavily on the Kuopio Heart Disease Risk Study, which reported an 88% reduction in heart attack risk for blood donors. While the biological plausibility is high (reduction of iron-mediated LDL oxidation), this figure is likely inflated by the “Healthy Donor Effect.” Individuals eligible to donate blood must meet stringent health criteria, creating a selection bias that favors better outcomes compared to the general population.
Similarly, the claim that phlebotomy reduces cancer mortality by 60% originates from the Zacharski et al. (2008) VA trial. While statistically significant in a subgroup analysis of younger, iron-loaded participants, the primary endpoint for the entire cohort did not reach significance. This suggests that while iron reduction is a viable longevity strategy for the “iron-overloaded,” it is not a panacea for the general population.
The most clinically relevant insight involves the “unlimited” absorption of heme iron (animal-based) versus the regulated uptake of non-heme iron (plant-based). The lack of a physiological “off-switch” for heme iron, combined with high red meat consumption, leads to a state of chronic iron pressure. The speaker argues for an optimal ferritin ceiling of 50 ng/mL, which is significantly lower than current clinical guidelines. This “sub-clinical overload” is presented as a primary contributor to the Western epidemic of insulin resistance, likely due to iron deposition in the pancreas (beta-cell failure) and liver (dysregulated gluconeogenesis). While the “rusting” metaphor is simplified, the underlying biochemistry of iron-mediated oxidative stress is a legitimate, under-addressed factor in the STEM and longevity sectors.
II. Insight Bullets
- The Fenton Reaction: Iron reacts with hydrogen peroxide to produce hydroxyl radicals, which are non-selective oxidants that instantly damage DNA and cell membranes.
- Heme Iron Regulatory Gap: Unlike plant-based iron, the human body lacks a feedback mechanism to stop the absorption of heme iron, leading to passive accumulation.
- Optimal vs. Normal Ferritin: Clinical “normal” ranges are derived from a population already suffering from chronic disease; an optimal “longevity” range is likely 15–50 ng/mL.
- Healthy Donor Effect: The 88% reduction in heart attack risk among donors is likely confounded by the fact that only healthy people are permitted to donate.
- Insulin Resistance Mechanism: Iron deposits in the liver interfere with the “off-switch” for glucose production, forcing the pancreas to overproduce insulin.
- Pancreatic Beta-Cell Vulnerability: Beta cells have low antioxidant defenses, making them primary targets for iron-induced oxidative apoptosis.
- Cancer Sequestration: Malignant cells overexpress transferrin receptors (up to 10x) to “steal” iron from the host to fuel rapid cell division.
- Immune Polarization: High systemic iron can shift macrophages from a pro-inflammatory/anti-cancer (M1) state to a pro-tumor/immunosuppressive (M2) state.
- Lipid Peroxidation: Iron-mediated oxidation of LDL cholesterol is a prerequisite for the formation of atherosclerotic plaques.
- Genetic Susceptibility: People of Irish/Northern European descent are statistically more likely to possess HFE gene mutations (C282Y/H63D) that cause hyper-absorption of iron.
- Hepcidin Deficiency: The Irish “Celtic Curse” involves a mutation where the hormone hepcidin fails to block iron absorption, even when stores are full.
- Non-Transferrin-Bound Iron (NTBI): When iron intake overwhelms the transferrin transport system, “free” iron circulates in a highly reactive and toxic state.
- Phlebotomy as Therapy: Blood donation lowers not only iron but also transiently reduces blood pressure and LDL levels.
- Vegetarian Advantage: Plant-based diets naturally keep ferritin in the 30–40 ng/mL range, correlating with a 50–70% lower risk of Type 2 Diabetes.
- Tissue-Specific Pigmentation: Chronic iron overload manifests physically as a “rust-red” or “chocolate brown” discoloration of internal organs like the liver and pancreas.
IV. Actionable Protocol (Prioritized)
High Confidence Tier (Level A/B Evidence)
- Baseline Iron Panel: Order a comprehensive panel including Serum Ferritin, Serum Iron, and Total Iron Binding Capacity (TIBC). Calculate Transferrin Saturation (TSAT). Goal: Ferritin 50-70 ng/mL for men; TSAT below 45 percent. Mainous et al., 2004
- HFE Genotyping: If ferritin is consistently above 200 ng/mL (pre-menopausal women) or 300 ng/mL (men), test for HFE gene mutations (C282Y and H63D). Crownover et al., 2013
- Limit Heme Iron Consumption: Reduce intake of red meat and organ meats, which bypass the body’s iron regulatory system. Etemadi et al., 2017
Experimental Tier (Level C/D Evidence)
- Bi-Annual Blood Donation: For non-anemic males and post-menopausal women with ferritin over 100 ng/mL, donate blood twice yearly to mimic the “vegetarian” iron profile. Salonen et al., 1998
- Inositol Hexaphosphate (IP6): Consider IP6 supplementation as a natural iron chelator to reduce the “free” iron pool, though human longevity trials are currently lacking. Vucenik et al., 2006
- Coffee/Tea with Meals: Polyphenols in these beverages significantly inhibit the absorption of non-heme iron, providing a low-risk strategy for iron management. Zijp et al., 2000
Red Flag Zone (Safety Data Absent)
- Targeting Ferritin under 30 ng/mL: Aggressively pushing ferritin to 15 ng/mL (as suggested in the video) carries a high risk of “non-anemic iron deficiency,” which impairs mitochondrial function and cognitive performance.
- Unmonitored Phlebotomy: Performing blood draws without checking hemoglobin levels can lead to iatrogenic anemia and chronic fatigue.
- Ignoring Inflammation: Ferritin is an “acute phase reactant.” High levels may indicate hidden infection or inflammation rather than iron overload; always cross-reference with C-Reactive Protein (CRP). [Source unverified in live search]
One final point: The 60 percent cancer mortality reduction cited is a secondary analysis of the VA Iron Reduction Trial. It should be treated as hypothesis-generating, not clinical fact. Zacharski et al., 2008
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I didn’t like the description of “rusting” so I asked the question of Claude as to what proportion of the body is Iron Oxide or Hydroxide and got an interesting answer:
Claude:
The human body contains very little iron oxide or iron hydroxide in the “rust” sense — but these compounds do appear in specific biological contexts.
Total body iron context
A typical adult has 3–5 g of total iron, distributed as haemoglobin (~65%), myoglobin (~10%), storage iron ferritin/haemosiderin (~20–25%), and enzymes/other (~5%).
Iron oxide (Fe₃O₄ — magnetite)
The most biologically relevant iron oxide is magnetite (Fe₃O₄), not haematite (Fe₂O₃):
- Found in the human brain — estimates range from roughly 5–100 ng per gram of wet tissue in various brain regions, with the cerebellum and brainstem tending to have higher concentrations
- Total brain magnetite content is in the order of micrograms — vanishingly small
- Also reported in the ethmoid sinus region (near the cribriform plate), tentatively linked to magnetoreception research, though this remains controversial
- Found in magnetosomes within certain tissues, possibly of biogenic origin
Pathologically, iron oxide accumulation increases in neurodegenerative diseases (Alzheimer’s, Parkinson’s), where it has been detected in amyloid plaques and is thought to contribute to oxidative stress.
Iron hydroxide / oxyhydroxide (FeOOH)
This is more metabolically central:
- The iron core of ferritin consists largely of ferrihydrite (a hydrated iron oxyhydroxide, approximating Fe₅HO₈·4H₂O), sometimes described loosely as iron(III) hydroxide
- Each ferritin shell can store up to ~4,500 iron atoms as this mineral core
- Given the body’s ~1 g of storage iron in ferritin, this represents a meaningful fraction of body iron in oxyhydroxide form — potentially hundreds of milligrams of FeOOH-equivalent mineral
- Haemosiderin (degraded ferritin aggregates) also contains amorphous iron oxyhydroxide phases
Summary table
| Compound | Form | Estimated quantity |
|---|---|---|
| Magnetite (Fe₃O₄) | Brain, ethmoid | ~micrograms total |
| Ferrihydrite/FeOOH | Ferritin cores | potentially ~100s mg (iron equivalent) |
| Haematite (Fe₂O₃) | Not normally present | negligible |
The ferritin core chemistry is particularly relevant to your work on the SLC25A1→AcCoA→epigenetics axis, since ferritin iron mobilisation is redox-sensitive and intersects with mitochondrial ROS production and the labile iron pool that feeds into Fenton chemistry.
I didn’t want to watch it so I ran the transcript into chatGPT:
Here is a cleaned-up version of the transcript, followed by a summary and critique.
Tidy transcript
Mike:
Recently I had an epiphany that the population is rusting from the inside out. This is leading to increased insulin resistance, cancer, and other diseases. This is affecting about half of the US population, and the Western population in general.
We are talking about an incredibly similar chemical reaction happening inside of us as rust. Whether we are talking about your car or your garden tools, we are not made of metal, but we do of course have some metal in our body, and it is creating a similar result.
We are going to learn about this really important biochemical process, the research on diseases associated with it, populations that have five- to ten-fold greater risk of this happening, and potential solutions.
I just want to mention that I have launched my Greece trip for September 3 to September 10. It is going to be another super delicious adventure. You can click the link below and learn more about that. But let’s get into the main video.
Many of you already know what I am talking about. Others are thoroughly annoyed with me. I am talking about how iron oxidizes and does some oxidative damage. That is the process of rust. We just see red flaky stuff, but on a molecular level, that is what is occurring. In that case it is literally iron and oxygen reacting, pulling an electron out of that iron and creating iron oxide.
Interestingly, ferritin, which is our form of iron storage in the body, is essentially an iron oxide with a bunch of other elements associated with it.
Our own human “rusting” process can happen in a couple of specific ways. One is the buildup from excess iron of a denatured protein called hemosiderin. This is oxidative and is again a complex involving iron oxide. The condition of high iron levels in the body is called hemochromatosis.
We have descriptions in the literature that say the liver is enlarged and has a distinctive chocolate-brown or rust-red color due to massive accumulation of hemosiderin. The pancreas is also intensely pigmented, showing a dark red to brown discoloration, and so on.
Then we have a second process analogous to human rusting, and that is the Fenton reaction—not to be confused with the fentanyl reaction, which of course we have plenty of in the US. Like how that drug is much more aggressive than many other opioids, this is more aggressive than ordinary rust because it happens faster and creates a byproduct that is even more destructive.
The Fenton reaction occurs when iron and hydrogen peroxide come into contact. It can get out of control with high iron, and hydrogen peroxide is created naturally in the body as a result of metabolism. Things like inflammation and aging can lead to excess levels. When the Fenton process occurs, we get hydroxyl radicals, which are among the most powerful oxidants in the body.
So yes, it is essentially “super-rust,” and that hydroxyl radical can rip through DNA and proteins and lead to lipid peroxidation, which drives atherosclerosis and heart disease, our leading killer.
At this point people might say, “That is hemochromatosis. Those are high levels even for a Western population. I do not have that, so I do not need to worry.” But we need to clarify that a lot of research shows health issues at iron levels that are not considered hemochromatosis, especially in relation to disease risk.
This has to do with the Western diet and other factors. We may have reached a point where our iron levels as a species are higher than they have ever been. Our reference range was essentially created based on what was normal in the population, but is that really the healthiest place to be? There is even a study suggesting that ambient or normal Western levels of iron may be a noxious public health threat affecting large swaths of the population.
In other words, the population is rusting from the inside, like I am talking about here.
One major inspiration for this video was a recent series by Dr. Greger of NutritionFacts.org. He talks about normal ferritin ranges. The ferritin blood test measures iron stores, and a typical normal value is in the 30 to 300 range. Almost universally, vegetarians have lower ferritin levels than non-vegetarians—for example, 39 versus 77. But lower iron stores may actually be better, with a possible target between 15, which is the World Health Organization cutoff for iron deficiency, and 50, because levels above 50 are associated with disease. In that case, vegetarians may be in the sweet spot because iron is a double-edged sword.
I should mention that hemochromatosis is generally over 300 ferritin for men and 200 for women, so much higher.
I had to look into this because 50 seemed pretty low as a risk threshold. Looking at the data on vascular risk, there is a massive increase in risk above 50, but that category can include everyone over 100, 150, and 200. So we do not know exactly where the cutoff for substantially higher risk is until we look at a line graph showing a more linear rise in atherosclerosis risk as ferritin levels increase.
This brings us back to the whole vampire-like history of bloodletting and using leeches to treat disease, especially in overfed royals. Most ironically, this is one of those medieval practices that actually appears to hold up. And I just want to say: leeches—would you consider them vegan? You are just letting them eat you. Comment below.
But yes, studies of phlebotomy or bloodletting show shockingly positive results. For example, we have an older study out of Finland, one of the first to find a strong association. It is the Kuopio Heart Disease Risk study, looking at nearly 3,000 men over nine years.
People who give blood are generally trying to help others, and this is where I think, “Is karma real?” Because after adjustments for other risk factors, blood donors had an 88% reduced risk of heart attacks compared with non-blood donors.
The study is older, and maybe the adjustments were not perfect, but the results are still absolutely insane. The authors cite body iron stores, saying that because high body iron stores have been suggested as a risk factor for acute myocardial infarction, donation of blood could theoretically reduce the risk by lowering body iron stores.
With heart attacks especially, we are talking about arterial lesions where the cap can rupture and clog the artery. Here we have iron oxidation contributing to plaque lesions on the artery wall—sort of like rust spots. I know they are not literally rust, but the parallel is there. It is a bit like rust flakes clogging pipes.
There is also a newer study from the same cohort looking at mortality. Both animal-to-plant protein ratio, as a proxy for animal-to-plant iron intake, and total meat intake were associated with higher mortality. Why? Because heme iron, or animal iron, is a major source of iron in the Western diet. In the same cohort, elevated ferritin levels were associated with higher heart attack risk directly as well.
Another important factor is absorption limits. When we eat plant-based iron, the body knows how to reduce uptake—basically, “that is enough for today.” With heme iron, we do not have the same mechanisms in place. Maybe it is because we also have heme iron in our own body. Regardless, people who already have adequate iron and continue eating heme iron can drive their iron levels higher and higher.
Heme iron in particular may overload the transferrin system. Transferrin shields the oxidative effects of iron, but when intake is high, we can get non-transferrin-bound iron, which is primed for the dangerous Fenton reaction, as well as some direct free heme iron in the bloodstream.
There are more studies. One Dr. Greger mentioned that shocked me had to do with insulin resistance. Researchers looking at vegetarians found that they had lower iron levels and much lower insulin resistance. This mirrors the lower type 2 diabetes rates seen in vegans in populations such as EPIC-Oxford or Adventists, where the risk may be 50 to 70 percent lower.
The meat-eaters in the study had higher iron levels, and we are trained to think higher iron is always better. But here researchers asked whether the iron might be connected to insulin resistance. So they took some of the meat-eaters and did phlebotomy until they reached a vegetarian ferritin range. They went from about 70 to the mid-30s, and the result was a 40% drop in insulin resistance.
The iron-lowering trial using blood draws demonstrated that iron is indeed a key factor in the difference in insulin resistance between vegetarians and meat-eaters.
This is also seen in study after study where people with type 2 diabetes have higher serum ferritin. We can talk about causation versus reverse causation—inflammation can also raise ferritin—but that is worth noting too, especially because there are plausible mechanisms.
For example, iron deposits can interfere with both pancreas and liver function in relation to insulin. The pancreas is particularly prone to iron-induced oxidation. It has beta cells that produce insulin, and those can be damaged or killed by iron-induced oxidation, leading to less insulin and poorer blood sugar regulation.
Excess iron in the liver can also short-circuit the off switch for glucose production, meaning more insulin is required because the liver is malfunctioning. So there is a one-two punch affecting internal organs that could worsen insulin resistance.
Then there is another study Dr. Greger discussed. He says: too bad we could not do a blood donation study with cancer—except we can. More than a thousand cancer-free individuals were randomized to give blood donations or not and followed for the next four and a half years. Those who gave blood had a 60% lower risk of dying from cancer.
Wait—they cut the risk of dying from cancer by more than half just by donating blood? That is a massive reduction in cancer death just from donating blood. Again, another shocking result.
Of course, we have to ask whether this is credible and what mechanisms there could be. It appears that iron may feed cancer in a few ways, both directly and indirectly. First, iron-driven oxidation can lead to DNA damage and mutations that initiate cancer. Then there is the fact that cancer cells often express far more iron-uptake receptors on their surface than normal cells, so they love to absorb iron.
Additionally, excess iron can affect immune cells, especially macrophages. It can shift M1 macrophages, which target cancer, toward M2 macrophages, which may suppress immune responses. That is not a good thing.
At this point I want to add a couple more points about bloodletting. Is it all iron? I believe iron plays a huge role, but it is also worth noting that phlebotomy in general can lower blood pressure, blood glucose, and LDL cholesterol. We know LDL is causally involved in atherosclerosis from genetic studies, although LDL and glucose did not fall in all cases, such as one study in people with hemochromatosis.
Still, because we do not have a heme-iron absorption cap and Western populations are getting large amounts of iron from animal foods, I cannot help but think we are eating too many animals—to the point that we benefit from literally draining our own blood of the animal-based iron and fats we have accumulated. That appears to massively lower heart attack risk, insulin resistance, and cancer risk. Clearly we are doing something wrong. We have too much blood in us.
So how many people are actually too high? I would say 75 is a decent risk cutoff. That is where higher insulin resistance shows up. Looking at NHANES US data, the median ferritin for men is 99, and for women it is 40. For postmenopausal women it is around 65.
So it is fair to say that about half of the population is over 75, meaning about half the population is rusting inside to a degree that will increase disease risk.
Finally, there is a population that has it much worse in terms of hemochromatosis, and that is Irish people. Whether because of surviving the potato famine or generally surviving a harsh environment with low iron availability, they may have evolved to use iron more efficiently. This means that when they do get enough iron, they are much more likely to get hemochromatosis.
Certain people in northwestern Ireland are seven times more likely than the general population to get it. This is due to a mutation affecting the brake on our iron system—hepcidin, which I talked about in my “vegans have increased plant iron absorption” video. Hepcidin directly blocks iron absorption, and these individuals do not have enough of it.
White Europeans are highest on average. Indigenous North Americans are also quite high, and then it declines from there.
A small side tangent: the thiamine-IBS video I made is also related. People of Irish descent are higher in that area as well, again probably because of historically low nutrient availability in their environment. If you want to learn about thiamine, digestion, and dysautonomia, check out my thiamine video.
In the end, it is obviously a smarter choice to rely on plant iron in a world where many diseases are driven or worsened by excess iron. Again, we cannot control heme-iron absorption in the same way. We may have around 150 million people with ferritin above 75, which lines up fairly well with insulin resistance numbers.
So whether it is iron in animal products alone, or the animal fat as well, bloodletting appears to be literally saving lives—creating an 88% lower heart attack risk or a 60% lower cancer mortality risk. Those numbers are mind-boggling. I think we should study this more and really examine that cutoff.
Are there maybe negatives to being between 15 and 30 ferritin for things like hair or other issues? I want to see all the research.
Let me know what you think in the comments. Have you had your iron checked? Do you have iron issues? Do you think my assessment that the population is rusting is accurate? Feel free to like, subscribe, and all that good stuff. Check out my Greece trip linked below if you are interested. Thanks for watching. I will see you in the next one.
Summary
The speaker argues that excess iron in modern Western populations acts like a kind of internal “rusting,” driving oxidative damage, insulin resistance, cardiovascular disease, and cancer. He uses the analogy of rust to describe iron oxidation and highlights two related processes: iron accumulation in tissues, particularly as hemosiderin in overt iron overload states such as hemochromatosis, and the Fenton reaction, where iron and hydrogen peroxide generate highly reactive hydroxyl radicals.
He then extends the argument beyond overt hemochromatosis. His main claim is that disease risk may rise well below classical iron-overload thresholds, especially at ferritin levels that are still considered normal in standard laboratory ranges. He suggests that modern reference ranges reflect what is common, not necessarily what is optimal.
The video links lower ferritin, especially in vegetarians and vegans, with better metabolic health. The speaker highlights studies suggesting that blood donation or phlebotomy lowers heart attack risk, insulin resistance, and possibly cancer mortality. He interprets this as support for the idea that excess iron is a widespread and underappreciated driver of chronic disease.
A major dietary theme is that heme iron from animal foods is more dangerous than plant iron because it is more readily absorbed and less tightly regulated. He argues that Western diets push ferritin into a harmful range and that plant-based eating may protect partly by lowering body iron stores.
He also discusses high-risk populations, especially people of Irish ancestry, because of hereditary hemochromatosis-related variants affecting iron regulation. He closes by suggesting that a substantial share of the population may have ferritin levels high enough to increase disease risk and that this possibility deserves much more study.
What is novel in the video
The core biology is not novel. The links between iron, oxidative stress, hemochromatosis, the Fenton reaction, and tissue damage are well known. The relationship between iron overload and risk in certain diseases is also established.
What is more distinctive is the framing and synthesis:
- “Rusting from the inside” as a unifying metaphor: This is rhetorically strong and helps connect iron chemistry, oxidative stress, atherosclerosis, diabetes, and cancer into a single narrative.
- The claim that “normal” Western ferritin may often be too high: That is the main provocative thesis.
- The emphasis on blood donation/phlebotomy as a possible broad public-health intervention rather than just a treatment for hemochromatosis: That is presented much more strongly than is typical.
- The interpretation of vegetarian/vegan metabolic advantages partly through iron burden rather than only through fat, weight, fiber, or calorie density: This is an interesting angle, though not demonstrated as the dominant explanation.
So the novelty is mainly interpretive, not mechanistic.
Critique
Strengths
The talk does a good job explaining why iron is biologically double-edged. Iron is essential, but its redox activity can become harmful when poorly controlled. The speaker is right that ferritin is not simply “the higher the better,” and he is also right that overt iron overload can damage the liver, pancreas, and heart.
The video is also strongest when it points out that “normal range” does not necessarily mean “optimal range.” That is an important general principle in medicine.
Another strength is that the speaker does not rely only on abstract chemistry; he tries to connect mechanisms to epidemiology and intervention studies, especially phlebotomy trials and observational work on ferritin and disease risk.
Weaknesses and limitations
The biggest problem is overreach. The video moves too quickly from:
- iron can promote oxidative damage,
- high iron overload states are harmful,
- some studies associate higher ferritin with worse outcomes,
to the much broader conclusion that roughly half the population is materially “rusting” in a clinically important way because ferritin is above about 75.
That conclusion is much stronger than the evidence presented in the transcript.
Ferritin is not a pure iron-overload marker
A major issue is that ferritin is also an acute-phase reactant. It rises with inflammation, infection, liver disease, metabolic syndrome, alcohol use, and other conditions. So when ferritin correlates with diabetes, cardiovascular risk, or cancer outcomes, ferritin may partly be:
- a marker of iron stores,
- a marker of inflammation,
- a marker of liver injury,
- or all three at once.
The speaker acknowledges reverse causation briefly, but he does not really grapple with how much of the association may be due to confounding.
Intervention evidence is intriguing but not definitive
The strongest part of the case would be randomized trials of iron reduction with hard clinical endpoints. The transcript mentions striking effects of blood donation/phlebotomy, but those effect sizes are so large that they invite caution. Very large benefits in observational studies can reflect healthy-donor bias, selection effects, or residual confounding. Even randomized evidence needs careful scrutiny around study design, endpoint definition, sample size, and replication.
So while the intervention signal is interesting, the video presents it with more confidence than seems warranted.
Mechanistic plausibility does not prove population-level causality
The mechanism is plausible: iron can catalyze oxidative chemistry, damage beta cells, worsen liver insulin handling, and potentially support tumour biology. But mechanistic plausibility is not enough to show that iron is a major driver of common chronic disease in the general population at ordinary ferritin ranges.
The jump from “possible mechanism” to “dominant public-health explanation” is not justified in the transcript.
Overemphasis on heme iron as the central explanation
The video strongly favors the view that animal-derived heme iron is a main driver of excess body iron and disease. That may be part of the story, but the transcript underplays other major determinants:
- total energy excess,
- adiposity,
- inflammation,
- genetics,
- alcohol,
- liver status,
- age,
- sex and menopausal status,
- insulin resistance itself.
In other words, iron may be one contributor without being the master variable.
The “half the population” claim is too assertive
The argument that half the population is at increased risk because half may be above ferritin 75 is not adequately supported here. Even if ferritin above 75 correlates with some outcomes in some cohorts, that does not establish a universal pathological threshold across sexes, ages, ethnic groups, and clinical contexts.
That is probably the weakest inferential step in the talk.
Some statements are oversimplified or slightly muddled
A few examples:
- Ferritin is described in a somewhat loose way as essentially an iron oxide storage form. That is directionally understandable for a lay audience, but biochemically it is more specific and regulated than the metaphor suggests.
- The hepcidin discussion is somewhat simplified and may confuse regulatory pathways with particular population histories.
- The evolutionary claims about Irish ancestry and famine adaptation are presented too confidently relative to the evidence shown in the transcript.
- “We have too much blood in us” is rhetorically memorable but biologically imprecise.
Rhetoric sometimes outpaces nuance
The talk is engaging, but phrases like:
- “the population is rusting,”
- “super-rust,”
- “we are eating too many animals to the point that draining our blood saves lives,”
make the argument vivid at the cost of precision. This can be useful for public communication, but it risks pushing a contested hypothesis as though it were near-settled.
Bottom line
This is a thought-provoking and mechanistically plausible argument that excess iron, even below classic hemochromatosis thresholds, may contribute to cardiometabolic disease and cancer risk more than is usually appreciated.
Its main value is as a hypothesis-generating synthesis:
- iron is biologically dangerous when poorly controlled,
- ferritin may deserve more nuanced interpretation,
- heme iron and iron reduction strategies may be worth more study.
But the video overstates the certainty and scale of the evidence. The transcript does not justify the strongest claims, especially that around half the population is pathologically “rusting” or that ferritin above 75 is a broadly applicable disease threshold.
A fair verdict would be:
Interesting, biologically plausible, and worth investigating further — but presented with substantially more confidence than the evidence in the transcript can support.
If you want, I can also turn this into a claim-by-claim table with columns for claim, evidence presented, strengths, weaknesses, and verdict.
I asked another question of Claude: Is it accurate to describe ferritin as Iron Oxide?
No, it’s not accurate — and the distinction matters both chemically and biologically.
What ferritin iron actually is
The mineral core of ferritin is best described as ferrihydrite — a hydrated iron(III) oxyhydroxide with an approximate formula of Fe₅HO₈·4H₂O or sometimes written as 5Fe₂O₃·9H₂O. It is:
- A poorly crystalline, hydrated iron(III) oxyhydroxide phosphate
- Not an oxide in the strict sense — it contains hydroxyl (OH⁻) and phosphate groups integral to the structure
- More accurately an oxyhydroxide than an oxide
Why “iron oxide” is misleading
| Property | Iron oxide (Fe₂O₃, haematite) | Ferritin core (ferrihydrite) |
|---|---|---|
| Formula | Fe₂O₃ | ≈ Fe₅HO₈·4H₂O |
| Water content | Anhydrous | Heavily hydrated |
| Crystallinity | Well-crystalline | Poorly crystalline / amorphous |
| Phosphate | Absent | Present (up to 1 P per 8 Fe) |
| Biological solubility | Very low | Relatively mobilisable |
The hydration and poor crystallinity of ferrihydrite are not incidental — they are what makes ferritin iron biologically accessible. Haematite-like iron oxide would be essentially insoluble and unavailable for mobilisation.
The oxidation chemistry at the ferroxidase centre
Iron enters ferritin as Fe²⁺ (ferrous), is oxidised to Fe³⁺ at the ferroxidase centre (using O₂ or H₂O₂ as oxidant), and then migrates to the core as ferrihydrite. So the process involves oxidation, but the product is not an oxide — it’s an oxyhydroxide mineral.
Bottom line
Calling ferritin “iron oxide” is a common shorthand but chemically imprecise. The correct terms are ferrihydrite or iron(III) oxyhydroxide. This distinction is particularly important in your research context because the redox lability and phosphate content of the ferrihydrite core directly govern iron bioavailability, Fenton reactivity of the labile iron pool, and ultimately the mitochondrial and nuclear oxidative stress dynamics central to the Genomic Failure Hypothesis.
This has been an interesting topic because of looking at various people’s different circumstances and in particular the way that TRT skews iron metabolism.
I may be unique in doing weekly full panel blood tests (ie the discount full panel that any lab operates, which does not always include ferritin, but mainly does). Hence I have my ferritin figures since 2022. And here they are:
420 337 358 329 332 404 371 412 325 204.6 364 202 337 176.2 176.2 319 172.9 205 253 205 145 175 157.9 165.7 171.4 190.9 180.4 173.4 222 176.7 ng/ml 298 291 mgc/L 202.5 187.8 174.9 140.4 155.4 170.5 123.2 150 152.6 147.6 168.7 177 201 165 203 168 165 164 154 142 ng/ml 164.16 129 126 134.42 118 116.07 115 120.45 96 going down? 102.5 93 79.02 95 122.54 166 109 95 115.63 161 112 105 97 110 96 99 112 92 68.3 99.5 103.21 96 101.3 108 93 101 56 52.3 56.1 71.3 45.38 83.3 58.06 78.7 76.82 77.4 57.91 71.7 47.66 24.4 60.19 51.9 63.7 56.42 69.8 35.96 67.7 74.41 73.8 72.33 75.9 56.04 63 65.76 55 61 50.79 67.2 63.64 48.6 40.8 24.22 52.63 39.92 38.59 36.08 35.83 33.15 28.84 34.3 20.2 37.40 44.3 30.1 36.2 28.08 19.07 22.25 34.25 89 50.74 34.89 32.01 32.52 25.96 12.43 47 30.71 47.65 47.85 39.01 30.71 33.86 39.53 53 48 39.31 67 44.92 41.91 61 46.96 43.87 58.89 76 60.23 48.7 49.65 50.6 55.1 62 70 72 59.75 37.8 56.23 44.94 35.76 22.75 low iron 37.72 37.14 48 40.31 48.85 41.76 40.66 48.44 45.79 36.34 71 62 67.78 57.72 39.36 30.35 59.77 60.27 76 58.63 70.55 55 46 54.3
The first thing you can say from those is that ferritin is quite variable week to week. It think it probably moves in a sort of range of 15 (the units are the same number in US and Europe even if the units vary because the numerator and denominator vary by the same number).
It would need a bit more work on looking at the variability between ferritin tests to see how variable it is on a day or between days, but clearly you cannot take it as a biomarker like height.
I cannot find who gave the link to this website for some reason: Iron Status Interpreter
Edit 31/3 - it was @Kebossit on a renal thread who I thank.
However, that is a useful start on looking at iron status. I have not tried to work out how reliable it is.
It has changed since I last looked at it as it used to refer to Peter Attia saying ferritin should be in a range of something like 30-400.
Clearly there is a minimum iron level below which people have symptoms like hair loss, but obviously if there is enough iron in haemoglobin then the symptoms which result from a shortage of oxygen do not appear. Hence you cannot just rely on ferritin to judge this.
We know that GPs go for 30 and neurologists go for 70 (because of the dopamine pathway in the brain) - which is why RLS is a potential symptom of iron deficiency.
A few weeks ago I did a chatGPT review of iron and mitophagy. It is a bit long and the conclusion is simply that less iron is better for mitophagy. It has a lot of links to original papers. I have created a share which is:
There is some work in human cells and biopsies from humans
There are, however, as far as I can tell no actual trials into seeing the effects of keeping iron bouncing along the bottom.
Obviously I am doing that myself in a biohacking manner. I have a hypothesis that a highly variable heart rate whilst sleeping is symptomatic of increased autophagy. The only evidence for this, however, is from my own experimentation.
I do think, however, the evidence is that for mitophagy lower ferritin is better, but realistically there are problems from low iron. I am not persuaded that the GP threshold of 30 is right and clearly if there is a nephrologist threshold of 10 then that is wrong. I do think it is important to maintain enough iron for dopamine metabolism, but that gives really an upper limit of 70 and one need to consider symptoms.
This was last night’s sleep tracker. I fasted yesterday and my Monday iron figures were:
Hb 145 g/l Ferritin 54.3 mcg/l CRP 0.4 mg/l Albumin 41.7 g/l MCV 92.5 fl Iron 7.1 mcmol/l TSat 13.1% TIBC 54.3 mcmol/l
TSat is low which is a sign of low iron. These things move quite rapidly, however.
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I thought it would be worth getting a chatGPT analysis of ferritin and hair.
Conclusion:
So the fairest summary is: under 15 ng/mL = clearly deficient; under 30–40 ng/mL = the range most often associated with hair shedding in the literature; around 40–60 ng/mL = commonly proposed as more supportive for hair growth; 50 ng/mL and above may be associated with better treatment response in some TE data, but this is not yet a universal proven threshold.
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Yes, this is true. And you can use a much smaller needle than 25g. I use a 29 gauge for my subq injections and it works just fine, especially since my T is in a base of MCT oil, which is thinner than other oils commonly used as bases for testosterone.
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I cannot WAIT for this peptide to be available in one way or another. It is the answer to our prayers for those of us who have to deal with elevated hematocrit and low ferritin issues from TRT. We can control lipids, blood pressure and even mitigate or prevent cardiac hypertrophy from androgens (telmisartan, nebivolol, cilnidipine, etc) but the Hct/ferritin conundrum is still a big thorn in our sides.
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I’m glad you appreciate it and I agree that people should be careful.
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Your values fluctuate surprisingly much. I don’t have data on what typical fluctuations are but mine appear to fluctuate far less and normally they shouldn’t move fast unless you just had an episode of something that caused acute inflammation. It can jump pretty fast when sick becaue it’s an acute phase reactant.
Mine are also all over the place, between 25 and 100.
I should I should put in this topic the fact that rapamycin is known to reduce both WBC and RBC. WBC tends to be more immediately affected because the half life of Neutrophils is quite short. This may not be obvious for people who don’t do frequent blood tests and take rapamycin frequently, but I can see the effects in my RBC because I do weekly tests and don’t take rapamycin more frequently than every 6 weeks.
Hence although it may not be obvious there will be a small amount of anaemia from weekly rapamycin (or fortnightly
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I came across this the other day… I don’t think its been posted,
A historical cohort study of the effect of lowering body iron through blood donation on incident cardiac events
A historical cohort study published in the journal TRANSFUSION by researchers from the University of Kansas School of Medicine and the Community Blood Center of Greater Kansas City investigates the “iron hypothesis”. This framework suggests that lowering body iron through blood donation may protect against atherosclerotic cardiovascular disease by limiting the oxidation of low-density lipoprotein (LDL) cholesterol.
The researchers designed a retrospective analysis tracking 1,508 frequent blood donors (individuals who donated more than one unit of whole blood annually from 1988 to 1990) and compared them against a control group of 1,508 casual donors (individuals who donated only a single unit during that same three-year period). By surveying the participants a median of 10 years later, the researchers evaluated the incidence of acute myocardial infarction, coronary angioplasty, bypass surgery, and death.
The data indicate that frequent whole blood donation is robustly associated with cardiovascular protection. Cardiac events occurred in 6.3 percent of the frequent donors compared to 10.5 percent of the casual donors. After adjusting for demographic and lifestyle differences, frequent blood donation yielded a 40 percent reduction in cardiovascular event risk (Odds Ratio 0.60). Notably, the protective effects were more pronounced in post-menopausal women than in men, providing compelling circumstantial evidence that offsetting the cessation of menstruation-induced iron loss is highly cardioprotective.
The impact score of this journal is 3.3, evaluated against a typical high-end range of 0–60+ for top general science, therefore this is a Medium impact journal.
Paper: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1537-2995.2002.00186.x
It always worries me as to how much " After adjusting for demographic and lifestyle differences," has an effect on the figures.
I would be interested in such a study which looks at the iron load directly. It is like vitamin D studies that don’t report 25OHD levels.
What argument would that be?
We need to be told what the adjustment was, how it was calculated and what the results would have been had the adjustment not been made. Also the basis of the assumptions in the adjustment and a sensitivity analysis.
The process of adjusting for confounders is a matter of judgment and to have a purely objective approach is hard. Hence in understanding the reliability of the conclusions we need to understand how the statistics were changed.
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