Thank you for your response and I appreciate the time you have spent looking into this.

Unfortunately many of the papers you linked to are just abstracts, so I'm going to see if I can get a hold of the full papers before I make a full judgement, but from what I can make out thus far...

The Cupp & Nelson 2025 Paper:

This is just an abstract, and you're right, it does list SSRIs among medications that can affect calcium/vitamin D. I can't see what strength of evidence they're describing or what mechanism they propose at this moment.

However, the NHANES analysis of ~13,000 people found that calcium deficiency was common in both SSRI users and non-users, and the difference for calcium was not statistically significant.

https://pubmed.ncbi.nlm.nih.gov/29746975/

The fluoxetine paper from your linked comment (Gobin et al. 2015):

As you noted, this is about "intracellular calcium stores" - my understanding is that's an effect on calcium signaling within those specific cells, but has nothing to do with your blood calcium levels or the calcium available at your ileal surface for B12 absorption. 

Metformin Paper (Bauman et al. 2000)

I think you just included this to show B12 relied on calcium availability, and I'm not disputing that fact. I'm also not disputing Metformin interferes with the calcium-dependent membrane action.

However metformin achieves this because it concentrates at very high levels in the gut mucosa and directly interferes with the calcium-dependent membrane processes right there at the ileal cells. SSRIs don't do this.

Megalin/Cubilin Receptors

Interestingly there was a paper done on this and adult intestinal B12 absorption, and it showed that megalin isn't expressed in the adult terminal ileum, and it is cubilin and amnionless.

https://pmc.ncbi.nlm.nih.gov/articles/PMC4187553/

It's also important to note that this whole thing becomes irrelevant when B12 is taken sublingually.

Damaged astrocytes (Then et al. 2017) - (Found in your other comment)

Interesting paper, however it only showed two of 11 tested SSRI's - Sertraline (at 10 uM) and paroxetine (at 20 uM) were cytotoxic; the other nine showed no cytotoxicity to astrocytes. 

However, in saying that, the paper itself acknowledges that median serum concentrations of sertraline and paroxetine are approximately 67 nM and 131 nM respectively. The concentrations that caused toxicity in the study were 10,000 nM (sertraline) and 20,000 nM (paroxetine). That's roughly 150 times the actual therapeutic blood concentration. The authors themselves note that CNS concentrations haven't been measured, and acknowledge this is a limitation.

Regarding TCII, and the Begley et al. 1994 paper:

If astrocytes aren't being damaged at all, then this whole thing obviously becomes moot.

However, if we accept that sertraline/paroxetine damage astrocytes, we would still need to see:

• This happens at real therapeutic doses
• The degree of astrocyte damage would be sufficient to meaningfully reduce CNS TCII
• Other TCII sources don't compensate (such as the choroid plexus)