The finding that SGLT2 inhibitors can induce erythrocytosis without iron supplementation suggests that the abnormalities in iron diagnostic tests in patients with mild-to-moderate heart failure are likely to be functional, rather than absolute, that is, they are related to inflammation-mediated trapping of iron by hepcidin and ferritin, which is reversed by treatment with SGLT2 inhibitors.
Is that relevant?
I think so. I have personal interest in this because I take empa and have low iron and ferritin levels, but not even a hint of erythrocytosis. This tells me the story is likely much more complicated. But on the flip side I feel very under informed about iron handling in general. I should do a deeper dive, especially that iron is so critically involved in PD and other NDDs. I wonder what’s the best place to start. Suggestions?
I started to look at iron and PD and it seemed so complicated (and poorly understood) that I gave up. Let me know if you find something!
If anything, taking empagliflozin should cause elevation of your serum iron and ferritin because the empa reverses the chronic inflammation that is potentially driving the low iron/low ferritin, so in your case since you still have low ferritin despite empa, it’s more likely that you have a true iron deficiency. This would also explain why you aren’t seeing any significant erythrocytosis from empa, since there’s just not enough iron to do the job despite the stimulation for synthesis.
Have you had iron studies done which include both ferritin and transferrin saturation?
I’ve had my iron staus tested by LabCorp, several iron biomarkers. I suspect that my diet is key in that I consume few animal iron sources (fish, no other meat), metric tons of fiber, tanins, polyphenols and various food iron binding elements.
I am doing a lot of reading on iron ATM. It appears that inflammation can push up ferritn even when iron levels are low. It looks, however, that there are reasons for having low iron ar least from time to time, but not too low.
Although erythrocytosis can cause low iron i dont see how it works the other way.
Despite SGLT2 increasing RBC production it actually slightly reduces ferritin/iron, so just because someone might develop erythrocytosis does not mean their general iron production will also increase
Conclusion: Following empagliflozin treatment, serum levels of ferritin and inflammatory markers interleukin-6, CRP, and uric acid declined, indicating a significant relationship between SGLT2 inhibition, inflammation, and iron metabolism. Furthermore, the correlation between ferritin and inflammatory markers suggests that reduced ferritin levels may result from reduced inflammation.
The same is true of testosterone, which makes this independent to SGLT2s
https://journals.physiology.org/doi/full/10.1152/ajpendo.00184.2014
“TE also reduced serum ferritin 32% (P = 0.002) within 3 mo of treatment initiation without altering iron, transferrin, or transferrin saturation.“
If it turns out that you want to supplement iron, I’d recommend Proferrin. It’s a patented synthetic form of heme iron that is absorbed well with food and has minimal or no GI side effects compared to non-heme sources of iron (which need to be taken on empty stomach w/vit C, have numerous drug/nutrient interactions and tend to cause significant GI side effects in many people).
Thanks, I might resort to that.
I run a low ferritin and am sometimes anaemic. All iron metrics otherwise ok. Like to be poor absorption. I have genes for gluten ‘sensitivity’ (not actual Coeliac) so Im gluten a bit to see if my ferritin improves.
Im always asymptomatic.
Ferritin is definitely a marker of inflammation - so called acute phase reactant.
For this reason (I think) is one of the reasons it isn’t often used. You can see sky high ferritins with inflammation or malnutrition. The more typical iron panel is less prone to such deviations.
That being said, ferritin is a more sensitive marker and the one hematologists use to track deficiency and what their studies are often based on.
I like to think that longevity diet and meds that drive hsCRP into sub 0.5 territory might also drive ferritin a little low. The human body is never that simple but a correlation seems probable.
I do tend to think you want iron and ferritin as low as reasonable - or not anemic. Some people will have fatigue at borderline levels but if you don’t have that, then I’m not sure there is a problem (but that is an opinion).
FWIW, August 2025 my LabCorp numbers were:
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 by LabCorp as “LOW”
Hematocrit - 48.2 % (ref. 37.5 - 51)
December 03 2025 UCLA Lab:
Sedimentation rate, Erythrocyte - 4 (Normal range below/equal to 12mm/hr)
No symptoms except one: frequent low level RLS.
They’re definitely on the low end, but can easily be fixed with short-term iron bisglycinate supplementation
If a change is warranted my ferritin is currently around 40, but I want to try a period more like 20.
RLS could be symptomatic so I would definitely try some iron.
Incidentally have had a period of ferritin below 20 in the past. I just want to see what the broader effects are of a period more like that. I may then bring it back up to more like 40.
Ordinarily I eat meat and take a small amount of iron supplementation in a multi. However, when I am wanting to bring iron up I take some iron bisglycinate (normally when I am drinking).
My lowest ferritin was 12.43 (mcg/L), but iron was 17.5 mcmol transferrin was a bit high at 2.8 g/l and saturation 24.8% and TIBC 70.5% Haemoglobin was really high at 155 and HCT quite high. It may have been an odd week. The week before ferritin was 25.96 (mcg/L)
Reading up on RLS the ai says minimum ferritin 75, but that must take into account inflammation.
I have spent a bit more time on this (as I am looking at Iron at the moment). Brain Iron Deficiency can cause The “Wired But Tired” Feeling (Akathisia), Pseudo-ADHD (Focus & Motivation), Sleep Fragmentation, Anxiety and Panic Pica (The Ice Craving) (and RLS).
The reason is that Iron is a cofactor for Tyrosine Hydroxylase which produces dopamine. Hence you get a reduction in Tyrosine Hydroxylase activity without enough Brain iron. The medics use 75 (different units have same value) as the threshold. This is probably because if people are inflamed then ferritin will be higher, but still deficient.
If someone is trying to clear RLS then they go for 100 (units). The conventional wisdom is 50 is needed for effective brain function.
Hence there is a conflict between reducing iron levels to enable mitophagy and not reducing them so much that you end up with a shortage of iron in the brain.
Whichever way I have a blood test on Monday and I think after that I am likely to aim to increase ferritin. I may even aim for a target of 75. Again really to see what happens. I don’t have RLS or any of the other low brain iron symptoms particularly, but I can see a good reason why low ferritin should be a temporary state. I would like to have Monday’s test result before doing anything, however.
This is obviously relevant to why iron chelation would have caused symptomatic problems in PD @adssx
I’m a long-standing blood donor (60+ units over the years) as there seem to be health benefits. I have been turned away twice recently due to marginal anaemia (125), largely due to low ferritin. So I’m also looking for a sweet spot that I think is ferritin of 20-50, just so I can donate