Tamoxifen has ruined my life

[tommyg130]

Ever since I took tamoxifen when trying to come off steroids I really just broke completely. Severe mitochondrial dysfunction.

As I’ve desperately tried to get myself better I’m understanding why I was messed up so bad.

The CYP p450 enzyme/ gene mutations. If you read that basically this specific gene cyp2d6 is largely involved with the metabolism of drugs and cholesterol pregnenolone etc. But very specifically tamoxifen. Which I happen to take in large doses (of course) this is a very studied gene that they look at to tailor cancer treatment drug approaches.

So with these mutations you can either be an “extensive” or “very poor metabolizer”. I’m struggling to figure which one I am as I am attempting to reverse engineer what I have done.

I either need to use a cyp inhibitor or cyp inducer. I think I was a poor metabolizer which didn’t allow me to convert tamoxifen in my body and let it get cleared and detoxed appropriately. Which led to down regulation of the cyp enzyme. In which I could benefit from a cyp enzyme inducer.

Any thoughts on this please

 

[Perry Staltic]

Do you take any other drugs?

 

[tommyg130]

Do you take any other drugs?

No. I did a steroid cycle, then used tamoxifen off label as an HPTA restart. Then I went on trt. Then I came off. And now I’ve been on nothing. The tamoxifen made me go crazy and develop this insane sensitivity to indoor to light and sound.

 

[Perry Staltic]

Maybe you could look into to natural cyp2d6 inhibitors/inducers

Effect of health foods on cytochrome P450-mediated drug metabolism - Journal of Pharmaceutical Health Care and Sciences

Background Health foods have been widely sold and consumed in Japan. There has been an increase in reports of adverse effects in association with the expanding health food market. While health food-drug interactions are a particular concern from the viewpoint of safe and effective use of health...

jphcs.biomedcentral.com

 

[tommyg130]

Thing is I dont

Maybe you could look into to natural cyp2d6 inhibitors/inducers

https://jphcs.biomedcentral.com/articles/10.1186/s40780-017-0083-x[/URL

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Maybe you could look into to natural cyp2d6 inhibitors/inducers

Effect of health foods on cytochrome P450-mediated drug metabolism - Journal of Pharmaceutical Health Care and Sciences

Background Health foods have been widely sold and consumed in Japan. There has been an increase in reports of adverse effects in association with the expanding health food market. While health food-drug interactions are a particular concern from the viewpoint of safe and effective use of health...

jphcs.biomedcentral.com

Thank you..!thing is I don’t know which .. based on what I did I’m not sure what my mutation and that tamoxifen means.. I don’t know if I need to use an inhibitor or inducer.. I suppose try one of each and see how I feel

 

[AspiringSage]

Could you describe the symptoms of the mitochondrial disfunction in more depth? This might aid people in helping you find options. If you don’t mind adding what dose of tamoxifen did you take and for what duration? This can really help others with harm reduction.

 

[tommyg130]

Could you describe the symptoms of the mitochondrial disfunction in more depth? This might aid people in helping you find options. If you don’t mind adding what dose of tamoxifen did you take and for what duration? This can really help others with harm reduction.

Lost 35lbs in 4 months despite eating 4k calories. Went from a very high division 1 collegiate level athlete to not being able to do air squats. Extreme hypoxia. dissociation/schizophrenia. Sensitive to every supp and food. scared of my own shadow. I’m literally deteriorating. Destroyed gut. Can’t even drink liquids. Cholesterol of over 400 with non readable steroid hormones. Because that’s another thing CYP enzymes are responsible for. That conversion of cholesterol to pregnenelone.

40mg for about 3 months. 40mg is a really high upper limit dose for anybody. Let alone this gene. The gene is very studied and used for cancer patients to determine protocols to help prevent toxicity. Towards the end I took only 5mg and it still ****88 me up still.. that’s when I knew I really messed up taking 40mg.

 

[miquelangeles]

You can easily get sucked into endless rabbit holes with genes, enzymes and individual substances that will get you nowhere. Probably better if you focus on addressing the depression and PTSD first. Most everything else is downstream and would resolve by itself. Some low risk/high reward things you can do are bright light therapy, PEMF therapy, grounding/earthing, tension and trauma release exercises also called "self-induced therapeutic tremors". You might benefit from prescribed antidepressant medication for 6-12 months while you implement other strategies. Tricyclics like doxepin are safer than SSRIs and particularly useful when there is weight loss involved. Very similar in structure to cyproheptadine.

 

[Whichway?]

From the SNP table above, can you tell me are variants with the circles against them the ones that you have been verified to have via genetic testing?

The rsXXXXXXX are gene variations. Depending on which ones you have. I can look them up to see whether they increase or decrease the activity of CYP2D6. Then you can make a more informed choice from there.

 

[Pablo Cruise]

I think the po

Ever since I took tamoxifen when trying to come off steroids I really just broke completely. Severe mitochondrial dysfunction.

As I’ve desperately tried to get myself better I’m understanding why I was messed up so bad.

The CYP p450 enzyme/ gene mutations. If you read that basically this specific gene cyp2d6 is largely involved with the metabolism of drugs and cholesterol pregnenolone etc. But very specifically tamoxifen. Which I happen to take in large doses (of course) this is a very studied gene that they look at to tailor cancer treatment drug approaches.

So with these mutations you can either be an “extensive” or “very poor metabolizer”. I’m struggling to figure which one I am as I am attempting to reverse engineer what I have done.

I either need to use a cyp inhibitor or cyp inducer. I think I was a poor metabolizer which didn’t allow me to convert tamoxifen in my body and let it get cleared and detoxed appropriately. Which led to down regulation of the cyp enzyme. In which I could benefit from a cyp enzyme inducer.

Any thoughts on this please

I think you are working on theories of the Cytochrom 450p system that may not be applicable. I would think some good supplements like NAC, Glutathione, Curcumin and a good diet will return you to normal. As another said, I think you are going down a rat hole trying to postulate a remedy to your perceived problems.

 

[mostlylurking]

Ever since I took tamoxifen when trying to come off steroids I really just broke completely. Severe mitochondrial dysfunction.

Can you share why you took the tamoxifen? The way this is worded, it sounds like you took it as part of trying to get off of steroids.

I'll try to focus on the "severe mitochondrial dysfunction". The two main things I think to focus on are thyroid function and thiamine status/function. Have you looked into these?

Thyroid function in postmenopausal breast cancer patients treated with tamoxifen - PubMed

<p>Thyroid function was evaluation in 26 postmenopausal women with breast cancer before and at various time intervals during treatment with tamoxifen. Tamoxifen treatment suppressed plasma levels of FT3 and FT4 (p < 0.005 for both) and elevated plasma concentrations of TBG (p < 0.005 and TG (p...

pubmed.ncbi.nlm.nih.gov

"Thyroid function was evaluation in 26 postmenopausal women with breast cancer before and at various time intervals during treatment with tamoxifen. Tamoxifen treatment suppressed plasma levels of FT3 and FT4 (p < 0.005 for both) and elevated plasma concentrations of TBG (p < 0.005 and TG (p < 0.025). In general, these changes became significant after 6 months of treatment. Plasma TSH increased significantly after 1 y of treatment (p < 0.025). A fall in FT4 and FT3 combined with increase in TSH suggests a reduced bioavailability of T4 and T3 during tamoxifen treatment. The increase in TG may reflect a reduced synthesis or liberation of T4 resulting in a reduced plasma level of FT4. Our findings suggest that tamoxifen influences the thyroid hormone levels, not only by modulating plasma TBG, but also by interfering with hormone synthesis or secretion in the thyroid gland."
-end-
Sounds like Tamoxifen can wreak havoc with thyroid hormones to me. A good endocrinologist might be able to help you. Reading all you can about thyroid via Ray Peat's articles would be a really good idea before you hand yourself over to a stranger. Start with this one: Thyroid: Therapies, Confusion, and Fraud

Thiamine deficiency/functional blockage will wreak havoc on mitochondrial function. Thiamine is required as a co-enzyme in several steps in the krebs cycle. Many pharmaceutical drugs block thiamine function. Foods that contain thiaminase block thiamine function. Coffee and black tea block thiamine function. I supplement with high dose thiamine hcl; it corrected my metabolic mitochondrial function. I've been working on this problem for several years. I've learned that the thyroid needs thiamine to function and that too much thyroid hormone can block thiamine function. The two things need to be in sync.

I also found this article:

Ameliorating effect of coenzyme Q10, riboflavin and niacin in tamoxifen-treated postmenopausal breast cancer patients with special reference to lipids and lipoproteins - PubMed

The study figures the altered lipid and lipoprotein levels in the untreated and TAM-treated breast cancer patients. On combination therapy with Co Q10, riboflavin and niacin, it counteracts the tamoxifen-induced hyperlipidemia to normal levels.

pubmed.ncbi.nlm.nih.gov

Conclusion: The study figures the altered lipid and lipoprotein levels in the untreated and TAM-treated breast cancer patients. On combination therapy with Co Q10, riboflavin and niacin, it counteracts the tamoxifen-induced hyperlipidemia to normal levels.
-end-
Ray Peat always recommended niacinamide, never niacin. I've found niacinamide very helpful. Here's good info on niacinamide: Ray Peat, PhD Quotes on Therapeutic Effects of Niacinamide – Functional Performance Systems (FPS)

another article of interest:

Tamoxifen and its active metabolites inhibit dopamine transporter function independently of the estrogen receptors - PubMed

As one of the primary mechanisms by which dopamine signaling is regulated, the dopamine transporter (DAT) is an attractive pharmacological target for the treatment of diseases based in dopaminergic dysfunction. In this work we demonstrate for the first time that the commonly prescribed breast...

pubmed.ncbi.nlm.nih.gov

"Abstract: As one of the primary mechanisms by which dopamine signaling is regulated, the dopamine transporter (DAT) is an attractive pharmacological target for the treatment of diseases based in dopaminergic dysfunction. In this work we demonstrate for the first time that the commonly prescribed breast cancer therapeutic tamoxifen and its major metabolites, 4-hydroxytamoxifen and endoxifen, inhibit DAT function. Tamoxifen inhibits [3 H]dopamine uptake into human DAT (hDAT)-N2A cells via an uncompetitive or mixed mechanism. Endoxifen, an active metabolite of tamoxifen, asymmetrically inhibits DAT function in hDAT-N2A cells, showing a preference for the inhibition of amphetamine-stimulated dopamine efflux as compared to dopamine uptake. Importantly, we demonstrate that the effects of tamoxifen and its metabolites on the DAT occur independently of its activity as selective estrogen receptor modulators. This work suggests that tamoxifen is inhibiting DAT function through a previously unidentified mechanism."
-end-

Vitamin B1 on testosterone, estrogen, DHT and dopamine » TESTONATION

Here’s why every Alpha Energy male needs vitamin B1 for high androgens and feeling awesome. Low vitamin B1 can lead to low energy, low dopamine (low mood), low testosterone and infertility and estrogen dominance. According to Dr Marrs and Dr Lonsdale, measurable thiamine deficiency has been...

men-elite.com

"A thiamine deficiency stresses the mitochondria and decreases ATP production. Less ATP in the brain decreases an enzyme that regulates dopamine levels and can lead to low levels of dopamine and bring feelings of tiredness, no motivation or focus, etc…


It is shown that a thiamine deficiency induces degeneration of dopamine neurons (8)."

also this: This B-Vitamin Can Raise Dopamine (Thiamine tetrahydrofurfuryl disulfide - TTFD)

As another said, I think you are going down a rat hole trying to postulate a remedy to your perceived problems.

I agree. I think modern medicine has gone down the wrong path with all that mumbo jumbo about genes. I think it's more productive to focus on the body's environment (food, supplements, sleep pattern, etc.) which you can actually do something about.

 

[Santosh]

Lost 35lbs in 4 months despite eating 4k calories. Went from a very high division 1 collegiate level athlete to not being able to do air squats. Extreme hypoxia. dissociation/schizophrenia. Sensitive to every supp and food. scared of my own shadow. I’m literally deteriorating. Destroyed gut. Can’t even drink liquids. Cholesterol of over 400 with non readable steroid hormones. Because that’s another thing CYP enzymes are responsible for. That conversion of cholesterol to pregnenelone.

40mg for about 3 months. 40mg is a really high upper limit dose for anybody. Let alone this gene. The gene is very studied and used for cancer patients to determine protocols to help prevent toxicity. Towards the end I took only 5mg and it still ****88 me up still.. that’s when I knew I really messed up taking 40mg.

Same thing happened to me after 3 months lf intensive aromasin use.
People on steroid forums call me crazy and tell me it's in my head.

 

[Santosh]

You can easily get sucked into endless rabbit holes with genes, enzymes and individual substances that will get you nowhere. Probably better if you focus on addressing the depression and PTSD first. Most everything else is downstream and would resolve by itself. Some low risk/high reward things you can do are bright light therapy, PEMF therapy, grounding/earthing, tension and trauma release exercises also called "self-induced therapeutic tremors". You might benefit from prescribed antidepressant medication for 6-12 months while you implement other strategies. Tricyclics like doxepin are safer than SSRIs and particularly useful when there is weight loss involved. Very similar in structure to cyproheptadine.

You are being very dismissive of something you don't know or don't understand.

I've been on the same path as Tommy because of permanently altered aromatase secondary to aromasin use.

It's not in our head, the last thing we need is an SSRI. Do you even understand Peat's principles and know that SSRI is the worst med you could ever swallow ?