Note that the whole issue with subclinical deficiency is rooted in how the body prioritizes nutrients when they are scarce. When things are used for a lot of things in the body, they are prioritized when they are scarce. In the case of iron, it is used for many more things than for hemoglobin production, but hemoglobin production is perhaps the most important function of iron, because it is so essential to getting enough oxygen. Therefore the body prioritizes iron stores towards hemoglobin production when it doesn’t have enough iron for all the things it is used for in the body.
If you have adequate iron stores, and slowly get closer to deficiency, your body will first reduce available iron for less important things and later reduce it for hemoglobin production. When iron is so low that it’s starting to result in reduced hemoglobin production, chances are it’s already quite deficient for other processes the body uses iron for. Hence, why you cannot rely on hemoglobin as an indicator of iron deficiency. Yes, hemoglobin tells you whether you have enough iron to produce hemoglobin, but not whether you have enough for the other things requiring iron.
Note that iron is as an example a cofactor for enzymes required for respiration, so when your iron is about to get a little to low to produce hemoglobin it’s probably already too low to produce some enzymes important for respiration. That could explain why fatigue was reduced with iron supplementation without there being any change in hemoglobin levels becuase the extra iron was correcting subclinical deficiency elsewhere while hemoglobin levels were already good.
I don’t know how to put this nicely, but I’m getting tired of seeing almost everything you say pushed through the mitophagy/mitochondrial lens, because biology is not that simple.
You keep using mitophagy as an explanation across very different contexts without showing that it is actually the relevant or dominant mechanism in the specific case that is being discussed. In biology, being able to invent a connection is easy, becaue almost everything is connected to everything else in some way. What is hard is showing that the connection is causally meaningful and important in the pathway or outcome being discussed.
I am highly confident that in most of the cases where you have jumped to mitophagy as the cause, a careful analysis of whether the connection is meaningful would show that it is far less meaningful than you think.
This isn’t about mitochondria. It’s about how you reason.
You keep applying a preferred mechanism across unrelated contexts without doing the work of showing that it is actually the dominant or meaningful driver in that specific case. It could be mitophagy, iron, testosterone or anything, the point is, the pattern is the same.
Drawing a connection is easy. Giving reasoning or evidence for causal importance is the hard part, and that step is consistently missing in your responses.
I’ve read through your responses in this thread, and you haven’t provided reasoning that supports your claim that iron levels are meaningfully inhibiting mitophagy in this context, or that this would justify keeping iron “as low as possible.”
I’m not questioning that you’ve written about this elsewhere. Regular readers here are well aware that you have a website with written info on mitochondria.
The issue is that in these discussions on this forum here, you keep applying the same mechanism without demonstrating that it is actually the relevant or dominant driver in the specific case being discussed. Prior material on your website doesn’t replace that step.
Here is a response i posted today. I did not write it. However it gives “reasoning and evidence for causal importance.”
QED
The extent of the effect is substantial: Splicing is not merely a side effect of aging but a primary molecular driver of thymic failure. Because the thymus’s “educational” role is uniquely dependent on proteomic diversity, it is more sensitive to the age-related decline in splicing machinery than most other tissues
That example isn’t relevant to the point I’m making.
The issue isn’t whether you can provide detailed reasoning somewhere. It’s that in this thread, you made a specific claim (iron influences mitocphagy, which in turn influences the recommendation) without showing that it is actually a meaningful driver in that case.
Not every comment needs to spell out the full reasoning or evidence, but skipping that only works when the person making the claim has a clear track record of careful thinking and of being able to support their claims when questioned. When that track record is absent, claims need to be supported.
I don’t know much about lactoferrin, but you could try iron bisglycinate as well. Based on what I’ve seen with plant foods so far, it’s hard to get enough iron because of phytates.
Greger is like this, and IMO should be kept in mind. He’s very ideological.
The point is that this pattern comes up repeatedly (including here). The pattern of treating a plausible connection as the explanation for an effect, without first making sure, through reasoning or evidence, that it is actually significant and meaningful in that context.
You changed the wording. That changed the meaning of the phrase. I had proven your original meaning false. I can prove your changed meaning false. However, I am not going to waste my time. My view is that you disagree with me.
You tend to wish to play the man rather than play the ball. I prefer to stick to rational evidence based arguments about the science.
You obviously don’t recognise that you are insulting me. That may be a subtle point relating to my native language.
After this response I will not waste anyone elses time by engaging with you.
In this discussion of not too much and not too little iron (which I personally wrestle with), I wonder how much activity level matters. I would think (and I am acting on) that I need more iron than a sedentary person to perform well to provide the signal to my body to move well, be vigorous and resilient, be strong, heal fast, etc. An active body uses more iron: needs more, loses more. I aim for cycles of hard and easy, break down and rebuild. I also donate whole blood regularly (dump “old factors”) but struggle to keep my iron levels from falling (donate less often now). I’m struggling to establish of a proper level of iron (or how to measure). I’m in the weird place of donating blood and supplementing iron. Any useful thoughts?
I don’t think your activity changes what is the optimal level of iron in the body for you. What it does change however is how much iron you need to ingest through foods or supplements to maintain that optimal level. E.g. if two people want to maintain a certain ferritin level, the one who is exercising a lot or donating blood will need to ingest more iron to maintain that level.
One could argue though that someone that donates blood regularly might want to aim for slightly higher iron stores, because his iron will fluctuate more from slightly lower right after each donation and then rising until the next one. So to not go too low you might want to aim for a little bit higher level than someone that doesn’t donate blood.
My understanding is that athletes have higher iron needs (higher hemoglobin ie more iron) and the greater iron losses: sweat, GI micro bleeding, foot strike, and can have more hepcidin which interferes with iron absorption.
Anyway, my last test results were:
Iron Binding Capacity: 370
Iron: 140
Iron Saturation: 38
Ferritin: 26
Yes. That is sensible. I was imagining that perhaps a person who is trying to slow aging without being active could have a different relationship with iron. Perhaps not. Extreme CR is often touted as a way to extend lifespan but the body adapts to far lower calorie intake making an active lifestyle more difficult…. but if a person is not active perhaps much lower calories is another way to get some of the benefits of exercise. This is the model I was imagining. But not for me. No way.
The compounding effect of hard exercise and frequent blood donation is tough to overcome with diet (intake of iron). I’ve tried. I had to slow down my whole blood donations and increase iron supplementation. I’m still on the low end.
Checking with chatGPT as a starter it is true that endurance athletes particularly can lose more iron “The main reasons are exercise-related hemolysis, small gastrointestinal blood losses, hematuria, sweat losses, and transient exercise-induced rises in hepcidin that can reduce iron absorption.”
There seems to be an argument that Hb should be higher yes, but to a great extent that iron is recycled. Hence there is a question as to whether the normal age linked increase in iron levels is counterbalanced by some activity. It seems clear that endurance exercise does cause iron loss.
I would think your frequent blood donation is far more significant than activity even if it is endurance exercise.