Wanted to share some research on curcumin which may alleviate the endoplasmic reticulum stress identified in this paper. The gist is that while there is some research suggesting curcumin reduces ER stress, there are good reasons to doubt this.
There are a number of papers to suggest curcumin has anti-ER properties. This paper summarises a lot of these papers:
https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.767493/full#B12
Confusingly, curcumin has also been found to kill cancer cells by triggering ER stress. How can one compound cause ER stress in some cells but reduce it in others?
This makes me wonder how accurate the studies are. My theory is that the curcumin is interfering with the tests scientists are running and that is causing them to appear to trigger or reduce ER stress (depending on what the researchers' hypothesis is). That is backed by this paper which lists the various ways curcumin can interfere with assays used to measure the level of chemicals in cells:
https://pmc.ncbi.nlm.nih.gov/articles/PMC5346970/
That paper points out that there have been over 120 clinical trials run on curcumin and no double blinded, placebo trial has found any significant effect. It "provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead".
I asked ChatGPT and Claude about my hypothesis. ChatGPT thought curcumin could both increase and decrease ER stress - this may have been because it didnt want to contradict its prior answer. It also agreed with my point about curcumin interfering with assays but pointed out some of the studies did try to avoid this through various methods. E.g. one paper used a luciferase essay which is less suspectible to interference by curcumin. Overall ChatGPT had moderate confidence that curcumin did decrase ER stress generally and increase it in cancer cells.
By contrast, Claude agreed that the contradiction was difficult to justify and we should be cautious.
Another factor to consider is curcumin has low bioavailabililty. The doses used in the studies far exceed what you can get through supplementation. That means that eating curcumin is unlikely to affect our cells. So if you do take it, make sure you can a version with enhanced bioavailability.
Curcumin also interferes with other drugs and supplements so be careful if oyu are taking it.