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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Just published: Anemia and Blood Biomarkers of Alzheimer Disease in Dementia Development 2026
JAMA Netw Open, Karolinska + Sapienza + KTH
They found that anemia was associated with:
- Higher levels of AD-related blood biomarkers (p-tau217, NfL, GFAP)
- A higher risk of developing dementia
They conclude:
These findings suggest that anemia may interact with neuropathologic processes, potentially accelerating dementia development.
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Recent lab results
Ferritin: 40
Iron: 77 (38-169)
TIBC: 412 (250-450)
UIBC: 335 (111-345)
Sat %: 19 (15-55)
For whatever reason, my body seems to be depleting iron slowly. I began a course of 100mg iron bisglycinate daily to improve my iron stores just a smidge to optimize them.
I absolutely do not believe in having an iron deficiency being a good thing like some people have suggested in here. I am not exactly iron deficient, but I am close. Improving the numbers slightly is in my best interest.
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OK. But I’m having a slightly anemic reaction to this study (ahem! apologies, couldn’t resist). To me the most relevant quote from the study was this:
“Anemia was defined according to World Health Organization criteria.”
And what is that? It’s hemoglobin below 12.0 g/dL for women and 13.0 for men.
If someone has such numbers, this is notable. Hardly anyone does (on this list).
Meanwhile, the relationship between iron status and anemia is a huuuuuge can of worms, as seen in this thread. Many of us have what might be seen as below range iron levels, but absolutely don’t have anemia according to WHO criteria.
As an example my numbers from my most recent LabCorp test:
TIBC - 405 ug/dL (ref. 250-450)
UIBC - 330 ug/dL (ref. 111-343)
Iron - 75 ug/dL (ref. 38-169)
Iron Saturation - 19% (ref. 15-55)
Ferritin - 20 ng/mL (ref. 30-400) flagged as Low by LabCorp.
And in the same test, my hemoglobin was 15.4 g/dL (ref. 13.0-17.7).
So, I certainly seem to be on the low side of iron status, but pretty robust hemoglobin number far from WHO anemia. As I’ve reported I don’t experience any of the typical anemia symptoms and my energy levels are fine.
How useful is this connection (anemia/AD) to most of those of us on this list who struggle with their iron status? I don’t know.
Also, if you dig into this study, it becomes ever more equivocal, with a variety of factors (BMI included, nutrition status etc.) and after adjustments barely on the border of significance. Like I said: anemic.
The signal may be there, but we need much stronger results, especially those which might allow us to define optimal iron biomarkers (which was not even the focus of this study).
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Even though they used a low cut off to define anemia, higher hemoglobin might still be better for those AD biomarkers. It’s a pity they didn’t report ferritin and other iron biomarkers.
As you said, it’s a big can of worms…
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There is an interesting question as to how the body prioritises Iron usage when iron stores are low. We have identified two key requirements - Haemoglobin and Dopamine although Iron is needed for other reasons. Hb is easy to measure. Neurologists say ferritin should be 70 for Dopamine adequacy. I don’t know what the studies are on this.
There are many other uses for Iron, but we also know higher iron levels (possibly over ferritin 100 without inflammation) are detrimental.
Very similar to my latest numbers. Your ferritin is slightly lower though.
“A study in Sweden found that older people with anemia (i.e., hemoglobin less than 12 g/dL in women and 13 g/dL in men) were 66% more likely to develop Alzheimer’s disease and have higher levels of biomarkers for Alzheimer’s than those who were not anemic (Valletta, JAMA 2026). However, this association does not prove cause-and-effect and there appeared to be little or no additional benefit to having much higher than adequate hemoglobin levels.”
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2847873
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Iron deficiency and dementia risk: evidence from the Swedish population-based cohort study AMORIS
Discussed just above:
Two exposure groups were defined: absolute iron deficiency (serum ferritin < 30 ug/L) and functional iron deficiency (transferrin saturation < 20% and serum ferritin ≥ 30 ug/L).
Compared with the reference group, absolute and functional ID was associated with increased dementia diagnosis (adjusted hazard ratio (HR) = 1.24, 95% confidence interval (CI): 1.18–1.42; HR = 1.21, 95% CI: 1.05–1.39, respectively), after adjusting for age, sex, education, and comorbidities.
That’s an interesting one @John_Hemming. So should one target transferrin saturation > 20% and serum ferritin ≥ 30 ug/L?
This is where the neural dopamine pathway comes in. I think that needs higher ferritin. 50-70 territory.
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Do you use topical or subq? Wouldn’t you expect the former to have a lesser effect on iron stores?
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No question. And it explains why extreme athletes like Lance Armstrong juice with EPO. Higher EPO equals higher HGB and a corresponding increase in performance.
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I’ve switched to topical compounded T cream, which is more expensive but should have a much less significant effect on hematocrit and iron stores (ferritin). In the mean time I’m also supplementing with heme iron and just playing the waiting game for ferritin to increase and hematocrit to gradually come down over the next couple of months.
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Dr. Greger does a deep dive into iron and health, ferritin and diabetes, cancer, neurological effects, anemia, optimal levels, supplementation and so forth.
The Iron Dilemma (via NutritionFacts.org)
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Summary
Greger’s iron episode argues a single thesis: most people carry more iron than is healthy, the “sweet spot” is a ferritin of 15–50, vegetarians sit closer to it, and excess iron drives diabetes and cancer via free-radical damage. He distinguishes iron stores (ferritin) from frank anemia, and closes with practical repletion advice for those who are actually deficient. The framing is consistently directional toward “less meat, more plants,” and the strength of evidence behind individual claims varies widely — the weakest claims carry the most rhetorical weight.
Key points as presented
- Ferritin measures stores; “normal” 30–300, but healthy ≈ 15–50; >50 starts toxicity risk, <12–15 too low.
- Iron is a pro-oxidant; we have no excretion mechanism, so stores rise with age.
- Higher iron → higher type 2 diabetes risk across the normal range (+20% at average ferritin, +43% at high), supported by Mendelian randomization and a small phlebotomy trial.
- Cancer as a “ferrotoxic disease”; a blood-donation RCT showed 60% lower cancer death.
- Vegetarians have lower ferritin but are not meaningfully more anemic (vegans 8% vs meat-eaters 9% in the British cohort).
- Iron deficiency without anemia has no demonstrated harms (one study, even showed “better memory”).
- Repletion advice: alternate-day dosing, vitamin C, bisglycinate, empty stomach; diet over supplements long-term.
What holds up
No iron excretion mechanism / stores accumulate with age — Correct. Regulation is absorption-only; men rise from adulthood, women post-menopause. (High)
Heme iron is less down-regulated than non-heme — Accurate, and it’s the mechanistic basis for heme iron tracking with cardiometabolic risk. (High)
Higher iron status associates with T2D, with some causal support — The observational association is robust (multiple meta-analyses), and MR provides some causal signal. Magnitudes (~20%/43%) are plausible. (Medium) — see caveats below.
Alternate-day dosing, vitamin C timing, bisglycinate tolerability — Aligns with current absorption/hepcidin science (Stoffel et al.). Bisglycinate’s ~2× bioavailability is reasonably supported. (Medium-high) — relevant to your own bisglycinate use.
~75% GI side effects / ~1-in-4 discontinuation on ferrous salts — In range for full-dose daily ferrous sulfate. (Medium-high)
Vegans not meaningfully more anemic than meat-eaters — Consistent with the EPIC-Oxford anemia data he cites; the anemia/low-stores distinction is correctly drawn. (Medium) — caveat: iron deficiency without anemia is genuinely more common in vegans, which he soft-pedals.
Menorrhagia as leading IDA cause in menstruating women — Correct for that population. (High)
What doesn’t hold up (or is overstated)
The “60% lower cancer death from donating blood” claim — This is the load-bearing overstatement. The source is the FeAST trial (Zacharski). Reality: 1,277 symptomatic peripheral-arterial-disease patients, mean age 67, 98.5% male — not healthy general-population volunteers, and “calibrated phlebotomy,” not voluntary blood donation. Critically, no difference was documented between treatment groups in all-cause mortality and the secondary outcome of death plus nonfatal MI and stroke — the trial’s primary endpoint was null. Cancer was a secondary substudy: reduced cancer incidence (HR 0.65, 6.0% vs 9.3%) and the cancer-mortality HR ≈0.39 that yields his “60%.” Single trial, unreplicated, secondary endpoint, narrow population. Presenting it as “a thousand cancer-free individuals randomized to donate blood” is misleading framing. Holds weakly; the framing does not hold. (Low) ScienceDirect + 3
Ferritin as a clean iron marker for the diabetes/cancer claims — Major omission: ferritin is an acute-phase reactant. It rises with inflammation, insulin resistance, fatty liver, and alcohol. Much of the “elevated ferritin → diabetes” association is confounded/reverse-causal — insulin resistance raises ferritin. MR partly addresses this, but MR results for iron→T2D are mixed across studies, not the settled “genetic evidence supports a causal link” he asserts. (Medium that some causal effect exists; Low for the clean magnitude he implies)
The n=6 phlebotomy/insulin-sensitivity study — Real (Fernández-Real), but six men. The ~40% effect is directionally consistent with MR but the study itself is far too small to “demonstrate” anything. He presents underpowered evidence as confirmatory. (Low as standalone proof)
“Iron deficiency without anemia is harmless” — Overstated via cherry-pick. The single study he leans on (the “better memory” finding is almost certainly a multiple-comparisons artifact) is contradicted by several RCTs (Verdon 2003, Krayenbuehl 2011, Vaucher 2012) showing iron repletion reduces fatigue in non-anemic iron-deficient women. The honest statement is “evidence is mixed,” not “no conclusive evidence of harm.” (Does not hold as stated)
The 15–50 “sweet spot” / “>50 = toxicity” — A defensible minority position presented as established. The optimal ferritin range is genuinely contested; mainstream deficiency cutoffs (<30, sometimes <45 with inflammation) and the upper bound are debated. Treating 50 as a toxicity threshold is the aggressive end of the literature. (Low-medium)
Bottom line
The mechanistic spine (no excretion, heme vs non-heme, iron as pro-oxidant) and the practical dosing advice are sound. The disease-prevention thesis rests disproportionately on one null-primary-endpoint trial’s secondary analysis and on a biomarker (ferritin) confounded by inflammation — neither acknowledged. It’s a reasonable hypothesis dressed as a settled conclusion. Net: directionally plausible, evidentially oversold. (Overall confidence in his strong causal framing: Low-medium.)
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Looking at this and not watching the video he does not seem to mention dopamine. Arguably that wants ferritin at 70. (whichever units)
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Sustained dysregulation of iron and glutathione homeostasis induces chronoferroptosis, a persistent ferroptotic adaptation in neuronal cells
https://www.nature.com/articles/s41420-026-03208-6
“Although iron accumulates in brain regions impacted by neurodegenerative diseases such as Alzheimer’s and Parkinson’s, how chronic elevated iron levels contribute to neuronal dysfunction remains unclear. Here, we show that sustained iron overload, but not acute exposure, leads to a state of ferroptotic stress where nerve cells remain viable but become hypersensitive to oxidative injury. Retinoic acid-differentiated SH-SY5Y neuronal cells were exposed to acute (6–8 h) or chronic (9 days) iron loading to model transient versus prolonged age-related iron stress. While acute iron exposure produced minimal biochemical changes and did not sensitize cells to oxidative or ferroptotic challenges, chronic iron exposure induced ferritin upregulation, mitochondrial superoxide accumulation, suppression of GPX4 expression, elevated lipid peroxidation and loss of cellular glutathione (GSH). In addition, chronic but not acute GSH depletion by buthionine sulfoximine (BSO) recapitulated the iron-induced phenotype. Cells under chronic ferroptotic stress exhibited increased sensitivity not only to the ferroptosis inducer RSL-3 but also to hydrogen peroxide. Ferrostatin-1 significantly mitigated these effects suggesting that lipid peroxidation drives this state. Together, these findings demonstrate that, in contrast with acute exposure, chronic disruption of iron homeostasis with consequent GSH depletion remodels cellular redox homeostasis over time, inducing a state we term chronoferroptosis: a persistent ferroptotic adaptation characterized by coordinated alterations in iron-handling and antioxidant defense proteins that may represent early vulnerability to neurodegenerative pathology. Thus, these studies highlight the importance of sustained stress paradigms for modeling the progressive nature of neurodegenerative diseases.”
Pop-sci article.
Long-Term Iron Accumulation Strips Neurons of Disease Resilience
"Neurodegenerative conditions like Alzheimer’s and Parkinson’s diseases afflict tens of millions of people worldwide, driven by a complex web of cellular vulnerabilities that scientists are actively racing to untangle. For years, an intriguing clue has hovered at the edges of neurodegeneration research: the gradual, progressive buildup of iron inside aging neurons. While this mineral accumulation appears harmless early in life, it eventually transforms into a catalyst for slow, widespread neuronal demise.
A breakthrough study finally unmasked the temporal mechanics behind this heavy-metal threat. By engineering the first-ever progressive cellular model of long-term iron accumulation, the team discovered that chronic iron exposure systematically dismantles a neuron’s internal defense systems over time. This chronic depletion leaves the cells fragile, defenseless, and highly vulnerable to secondary environmental stressors, a distinct, time-dependent degenerative pathway the researchers have named chronoferroptosis."
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