Guilt

[jfz9580m]

20. I can relate

Last edited Thu Aug 7, 2025, 11:15 PM - Edit history (21)

(This post and others need more work to be legible. But I will complete them another time. I have too much to do and am neither wealthy nor bright enough to gawk admiringly at Trump all day ;-/).


I lost my mother to multiple myeloma in Nov 2021 and am kinda over it finally. But it was hard.

My mom’s cancer story was odd. She was on 750 mg of this medication prescribed for diabetes Metformin for about a year and half at least. And then she saw this news story in 2020, (just around the time Covid was really starting to make itself felt) where some batches of Metformin were being recalled in the US due to high amounts of NMDA?
No NDMA.
https://www.ihs.gov/nptc/pharmacovigilance/medication-safety-resources-archive/2020/metformin-extended-release-nmda-recall/

Mom wasn’t even in the US and her brand was different. But that news story scared her, because we have lost a lot of people to cancer on her dad’s side (1 glioblastoma, 2 cases of breast cancer, 1 case of prostate cancer and my mom). So 5 cases in two generations.

And she was only pre-diabetic and figured it would be okay to stop using it. She didn’t tell her doctor. She had a good diabetologist, but it’s awkward to broach a news-story to go off meds so she stopped it sometime May 2020 end early June 2020. Her health deteriorated rapidly at that point.
She had complained a few times of tiredness and pain a few times maybe in previous years, but nothing very serious. She had vomited once in response to a Renerve?-a vitamin B injection.

But this was very rapid deterioration. She went from basically being fine to really ill by July 2020. Dad and I were shocked-she lost a lot of weight.
It is a silent cancer and only detectable by later stages I think. So maybe that is common.

Anyway our oncologist diagnosed it very fast and she started cancer treatment mid August 2020. We were lucky in finding an excellent oncologist-he was not just competent, he is also a really nice person.

Meanwhile I looked up PubMed to see how Metformin affects multiple myeloma. I was expecting to see a positive correlation between Metformin use and multiple myeloma. I think looked at all cancers more than multiple myeloma specifically. Can’t remember precisely. At any rate I was surprised to find many articles indicating that Metformin is considered to worst case have no effect on cancer and best case maybe actually check smouldering myeloma from progressing

Normally I am not much for sleuthing of that sort and I don’t second guess doctors (well okay reefer madness aside).

But it seemed odd that it was so soon after stopping metformin that she declined in health that rapidly. Could be a coincidence I suppose but what if it was not.

I was very close to my mom and couldn’t bear the thought of losing her. So I showed some of the articles to my oncologist and requested him to let her be on Metformin during her treatment. I also got her tested for lactic acidosis (one potential serious side effect of Metformin) on my own discretion. And it wasn’t an issue. I have all the lab reports somewhere. I really should organize them at some point.

My onc is pretty cool. He is a good scientist so not someone to jump enthusiastically on some sort of “Metformin Yes!” bandwagon because you show him a few studies. But at least he didn’t find it objectionable and there are other reasons Metformin is not the worst thing.
It’s a medicine without too many side effects.

So we started this course of treatment. And she was doing really well. I was her caregiver full time and used to ensure that she took all her meds. I got some support from Smart Patients which DUer Captain Queeg recommended. That was a good site. There was a nice lady called Jules on there.
I haven’t been able to stand looking at it after mom left us.

But she really improved after a slightly rough start where she needed a couple of blood transfusions. By Jan 2021 she was doing really well. We were so happy and relieved. Things finally seemed okay.
By around March or February of 2021 she was well enough that I let her start taking her own meds etc. I was a bit worried she might shirk on the meds. She is normally very rational but the cancer was sort of draining her and it was hard for her to keep stuff down, but you can’t shirk your meds so I used to ensure she took all of them…a rather grim lot too Acyclovir …I remember that one.

She was so well by March that she had started watering plants in the garden etc. So I thought I would let her start managing her own meds. She had stopped getting sick even the day after chemo. For MM it was this pretty standard regimen of Bortezomib, Dexamethasone and I can’t recollect the rest but I kept a dairy I plan to scan at some point. We followed everything to the letter. None of that Apple Cider Vinegar dreck (couldn’t watch that thing ..scary damn show..not only that scammer Belle Gibson..that other woman refusing cancer treatment and she’s also based on a real person who refused cancer treatment and died. Scary messing with cancer like that. Cancer is not “hysteria”).

I generally trust doctors and our oncologist did everything he could to make life easier for us including recommending this really useful home healthcare checkup lab. That was so helpful during covid. He is awesome - overworked but so competent and thorough regardless and always so cool. My mom was very fond of him.

But it’s to be expected that doctors in general are overworked in these parts- we can’t train and educate oncologists at the rate at which people pop out babies.

Anyway, things seemed to be going well, but sometime in July or August of 2020 maybe she started getting sick again after the chemo. I was distrait with some stuff I wouldn’t bother with today in August. But mom was okay. Though it was worrying that she had started getting sick again.

But by October she started doing really badly again and in November it drastically accelerated and then she told me that she had halved her Metformin dose around July-August (roughly) just around when she started getting sick again. And she stopped it entirely sometime in Sept-early Oct (she was not sure).

She did it of her own accord. Not sure why.
It’s silly..she always hated taking it because for some reason it’s this bitter and large pill rather than something like a gel capsule that goes down easily. And since I had requested our onc to put her on it, she saw it as in no way a necessary part of her treatment. She had this feeling it was just some whim of mine.

I had this hunch that whether it is outright beneficial or not, sometimes when you get on some medications it’s better to stay on them. And I have at least 3 data points indicating the mom responded to it in a positive way. There’s also a person to person variation probably.

I am myself cautious about outright any specific claim where it is related to science or medicine when it has not been rigorously verified enough to be a part of any gold standard of care and is only being explored as an adjunct. (As an aside, I am wrapping up a correction to some old work where the original model I had in mind for analysis of an experiment struck me as inadequate and I have come up with what I consider a better analysis. I’ll see..)

I didn’t have the time or energy to parse all literature about Metformin and Multiple Myeloma. So since I couldn’t really assess the quality of the papers, while I did feel she shouldn’t go off it, I didn’t know enough to be that sure what the right thing to do is.

When I found out I started her on it immediately. But then I took her to the hospital and they didn’t want to put her on it. She left us a few weeks later.

I was pretty devastated. I felt guilty and still do, because had I continued to give her meds I would have noticed immediately when she started getting sick again. But more than guilt, it was just painful to lose her and think that it was possibly preventable had I known that she went off it.

I don’t know if Metformin helps or not in the end. But i do suspect that once you go on any medication that at the very least has some effect on cancer, you should not go off it suddenly.

These are some of the papers I found on it later. Many of them are from China, but though Xi Ping is a douchebag, I see no reason to be more suspicious of science coming out of China than of any science to the extent that it depends on the quality of the specific paper. In general there does seem to be an indication that Metformin has an anti myeloma effect. But I did find at least one paper arguing the other way and I have not been able to go over these papers and assess their quality. But the real world dynamics of caregiving are not that black and white and mom definitely seemed to respond well to Metformin and badly to going off it. So in conjunction with the rough trend shown by these papers, I did feel she should have stayed on it and by now i have stopped having this sense of savage regret that I didn’t she had gone off it so I could have prevented that:


This is a basic research paper on Fission Yeast that I think is my best bet re a simple model for understanding the anti-proliferative mechanism behind Metformin’s general anti-tumor action:

https://www.nature.com/articles/s44324-024-00048-9
Reversal of metformin’s anti-proliferative effect in fission yeast efr3 and dnm1 (DRP1) mutants with elongated mitochondria

These refer to different cancers and indicate a positive effect net that Metformin has wrt checking cancer:

https://www.sciencedirect.com/science/article/pii/S1347861317301147
Effects of metformin on proliferation and apoptosis of human megakaryoblastic Dami and MEG-01 cells. Liang et al. 2017

Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial-Dependent Biosynthesis. Griss et al. 2015.
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002309

Metformin - its potential anti-cancer and anti-aging effects. Podgorica et al. 2017.

These refer to different cancers and indicate potential negative effects to be cautious about wrt use of Metformin for cancer:

This one is related to lung cancer and indicates why you have to understand the specific mechanism of action beyond a rough correlation. Things don’t always line up as neatly as you wish they would wrt human health. More broadly it is what helps a type of huckster (the Apple Cider Vinegar type) to confuse people anecdotes and sketchy use of statistics:

https://pubmed.ncbi.nlm.nih.gov/35740881/
Metformin Induces Resistance of Cancer Cells to the Proteasome Inhibitor Bortezomib

These are specific to Multiple Myoma and indicate a positive effect net that Metformin has wrt checking cancer:

https://pubmed.ncbi.nlm.nih.gov/36762777/
Metformin attenuates multiple myeloma cell proliferation and encourages apoptosis by suppressing METTL3-mediated m6A methylation of THRAP3, RBM25, and USP4
Chen et al. 2023

Reduced Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma in Type 2 Diabetes Mellitus: Will Metformin Never Stop Its Pleasant Surprises? Stella Papachristou , Djordje S Popovic , Nikolaos Papanas (2022)

Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells
Ameet K Mishra, David Ding (2019).

This review says that low dose Metformin prevents progression of myeloma from MGUS to MM, but higher doses have adverse effects. I can’t access it to see what the doses are.
Repurposing Metformin in hematologic tumor: State of art. Min Hu , Yan Chen , Tao Ma , Li Jing. 2023

The Risk of Multiple Myeloma Is Reduced in Metformin Initiators: A Retrospective Cohort Study in Taiwanese Patients with Type 2 Diabetes Mellitus. Chin-Hsiao Tsen. (2022).

This one shows, quoting from the abstract:
“Co-treatment with the anti-diabetic agent metformin suppressed GRP78 and enhanced the anti-proliferative effect of bortezomib.”
Molecular chaperone GRP78 enhances aggresome delivery to autophagosomes to promote drug resistance in multiple myeloma. Malek et al. 2015.

[iObesityasaPossibleRiskFactorforProgressionfromMonoclonal Gammopathy of Undetermined Significance Progression into Multiple Myeloma: Could Myeloma Be Prevented with
Metformin Treatment? Dantas De Cunha Junior et al. (2015).

Metformin and chidamide synergistically suppress multiple myeloma progression and enhance lenalidomide/bortezomib sensitivity. Mao et al. (2024).

Metformin confers sensitisation to syrosingopine in
multiple myeloma cells by metabolic blockage and inhibition of protein synthesis. Vreken et al. 2023.

Influence of metformin on HIF‑1 pathway in multiple myeloma. Kocemba‑Pilarczyk et al. (2020)
To quote from the paper:

Results: Our results showed, for the first time, that metformin inhibits HIF-1 signaling in MM cells. Moreover, we demonstrated the effect of metformin to be mainly oxygen dependent, since the HIF-1 pathway was not significantly affected by metformin in anoxic conditions as well as after application of hypoxic mimicking compound, ­ CoCl2. Our data also revealed that metformin triggers the growth arrest without inducing apoptosis in either normoxic or hypoxic conditions.
Conclusions Taken together, our study indicates metformin as a promising candidate for developing new treatment strategies
exploiting HIF-1 signaling inhibition to enhance the overall anti-MM effect of currently used therapies, that may considerably benefit MM patients.

Metformin Inhibits Multiple Myeloma Serum-induced Endothelial Cell Thrombosis by Down-Regulating miR-532. Gao et al. (2022).

“Conclusions: Metformin played an inhibitory effect on MM serum-induced HUVEC thrombosis, suggesting that metformin could serve as a novel antithrombotic approach for MM patients.”


This one’s more about the general association between diabetes and mm:
Diabetes mellitus and multiple myeloma; common features of two distinct entities
et al (2022)

This was the paper that I really wanted to take a better look at as it goes the other way (in common parlance..too weary to put it
professionally). It’s the only one I have seen so far that explicitly indicates that.

The antidiabetic drug metformin acts on the bone microenvironment to promote myeloma cell adhesion to preosteoblasts and increase myeloma tumour burden in vivo
Beatriz G et al (2021)



I’ll update this post with the entire list including the one that explicitly indicated went counter to this. Those are the ones that strike one the most.

I was thinking indifferently that I really should read them at some point after I am done with this paper I am completing.

Anyway I am fortunate in having mom’s oncologist as my oncologist now..I do preventive care to some extent within reason and so I went to him for a preventive check up last year and so far nothing except something called a TR3 nodule to keep an eye on.

But I have been putting off a colonoscopy..
I will get around to it. I don’t drink anymore (or very rarely-can’t remember the last time I had a drink. Maybe Fall 2024?). However I used to drink sometimes and heavily (society you know ;-/..or not) so I really should get around to it.

Life feels like one endless colonoscopy session most days, so I have been shirking that one ;-/.