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
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).
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).
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)
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
I would not deny that there are benefits in having lower iron levels with ferritin on an uninflamed basis below 100. However, it is more complex below that and particularly below 75 and it may require a form of cycling.
Noted John.
As I’ve said before I think I have an iron absorption problem (maybe allied to gluten sensitivity, based on SNPs I have).
That said, my HsCRP remains low so not too concerned
I don’t think we really know exactly where things should lie. It is obvious that there is a point at which it is too low and a point at which it is too high. The level for brain iron looks to be higher than that for anemia. Questions that are hard to answer are the speed to which the reduction in brain levels occurs. Hence you could have a sufficiency in the brain and take ferritin below the maintenance level, but it will take a while before that will affect the brain negatively.
I can understand neurologists wanting higher ferritin, but probably this should guide GPs as well.
“ Glucagon, a key hormone in maintaining euglycemia during fasting, also exerts broad metabolic effects, including regulation of lipid oxidation, adiposity, insulin sensitivity, and metabolic rate. However, its role in aging and longevity remains largely unexplored, a significant omission given the extensive research on dietary restriction and insulin signaling in lifespan modulation. Here, we investigated the impact of hepatic glucagon receptor (GCGR) signaling on lifespan using a liver-specific GCGR knockout (LKO) mouse model. While male LKO mice exhibited normal lifespan, female LKO mice displayed a significant reduction in survival. Strikingly, and in contrast to prevailing expectations based on metabolic improvements, this shortened lifespan in females occurred despite marked enhancements in metabolic health, including reduced body weight and adiposity, preferential glucose oxidation, elevated metabolic rate, and enhanced glucose tolerance and insulin sensitivity throughout adulthood.”
In patients with type 2 diabetes (T2D) treated with ICDs, the arrhythmic effect of empagliflozin appears more pronounced in men than in women, according to a subanalysis of the EMPA-ICD trial published Jan. 22 in JACC: Asia.
The randomized, double-blind EMPA-ICD study evaluated 150 patients across 31 centers in Japan. The study included men and women aged ≥20 years with T2D and cardiovascular disease who were being treated with an ICD or cardiac resynchronization therapy defibrillator (CRT-D). The patients (83% men) were randomized 1:1 to receive either empagliflozin 10 mg daily or placebo between April 2019 and April 2021. Patients were evaluated for adverse events and clinical status every three months.
The primary endpoint, detected by ICDs/CRT-D over 24 weeks, was the change in the number of ventricular arrhythmias (VA), including nonsustained ventricular tachycardia, as well as sustained ventricular tachycardia and ventricular fibrillation.
Looking at the primary outcome in men, there was a significant reduction in the number of VA events in the treatment group while they increased in the placebo group (–2.10 events vs. +2.25 events; p<0.001). In contrast, in women there was a slight increase in VAs in the empagliflozin group while there was a slight decrease in placebo group (+0.55 vs. –0.08 events; p=0.35). This translated to a rate ratio in men of 0.33 for empagliflozin vs. placebo (p<0.001), a 67% reduction in arrhythmia events. In women, there was no significant difference between groups, with a rate ratio of 1.78 (p=0.35). Moreover, a significant interaction between sex and treatment was observed, suggesting a sex-specific treatment response (p=0.006).
Miyo Nakano, MD, et al., note several limitations to their analysis, including the small number of female participants, the short follow-up period and the lack of diversity within the patient population. Despite limitations, they write “these results suggest that sex-related differences in arrhythmic substrate, comorbidities and pharmacokinetic properties of SGLT2 inhibitors may influence treatment response.” Furthermore, research is needed to understand these sex-differences in treatment and pharmacokinetics to develop appropriate treatment strategies in women.
Zydus Lifesciences announced tentative approval from the US FDA for its Dapagliflozin Tablets (5mg and 10mg). This SGLT2 inhibitor, used for type 2 diabetes, targets a significant US market segment where the reference drug (Farxiga) reported annual sales of USD 10,486.9 million. The approval signifies Zydus’s expanding product portfolio in the crucial US market and adds to its 430 US FDA approvals. Zydus Lifesciences Secures Tentative USFDA Approval for Key Diabetes Drug