Therapies for hyperglycaemia-induced diabetic complications: from animal models to clinical trials
(see attachment)
From what I have read the neuropathy is short term once DCA is discontinued.Also I was giving her 1500mg of thiamine.
From what I've read thiamine may be useful in mild cases but not severe.
"BFT Treatment in Clinical Studies of Patients with Mild AD
Thiamine treatment does not exert significant beneficial effects in clinical trials of AD even at very high doses (3 g per day for 3–12 months) [51,52]. This was ascribed to a poor bioavailability of the vitamin and it was hoped that treatment with precursors of higher bioavailability would give better therapeutic effects. A study carried out in 1996 with TTFD (100 mg per day for 12 weeks) showed some improvement in cognitive function in mildly impaired patients [53] but no follow-up study was done. The first clinical trial of BFT treatment was conducted in 2016 on five patients with mild to moderate AD [28]. The patients, after receiving an oral dose of 300 mg of BFT per day during 18 months, had improved cognitive function independently of β-amyloid accumulation. As there were only five patients and no placebo control, these results could only be considered as preliminary, but they showed that it was worth continuing to explore this track. More recently, Gibson et al. [27] reported the results of a randomized placebo-controlled phase IIa clinical trial of a 12 month BFT treatment of patients with either mild cognitive impairment or mild to moderate AD. The participants were treated with BFT (300 mg orally twice a day) or placebo. In the blood of patients, there was a strong increase in concentrations of thiamine and ThDP, while there was a significant reduction in blood advanced glycation products (AGEs). Importantly, BFT treatment resulted in an improvement of cognitive functions of patients as assessed by several tests. The results of this pilot study are very encouraging and BFT appears to be a safe and cost-effective treatment of mild forms of AD."
Also, I can't find any studies of thiamine's effectiveness in mitigating DCA-induced neuropathy specifically. Do you have any references?
"Peripheral neuropathy appears to be a common side effect during chronic DCA treatment, even with coadministration of oral thiamine. "
I've posted about this before, I think it was a different study but showing similar results about thiamine supplementation in TNBC.
"The MDA cells showed a 3.5-fold increase in the cell proliferation in the 3µM thiamine group
thereby suggesting that thiamine supplementation promoted cell proliferation. This correlates with the evidence suggesting that a higher expression of TPK1 enzyme in malignant cells could have led to enhanced conversion of thiamine to its active form which would then support metabolic reactions to promote cell growth. "
https://getd.libs.uga.edu/pdfs/khatu_shivani_c_201812_ms.pdf
@j hi Johan.
I guess DCA could be a culprit. I will discontinue. You previously mentioned the combination of Metformin with Artovastin combined with 60mg of loranzaprole could have have been contributing as well. My question is with so many things possibly being a factor how do you you discontinue valuable cancer fighting tools?
Jens
@j Hi Johan
I did have a few references. I keep forgetting to post things that I find to help others as well. I will try to locate again.
Thanks.
Jens
@j hi Johan.
I guess DCA could be a culprit. I will discontinue. You previously mentioned the combination of Metformin with Artovastin combined with 60mg of loranzaprole could have have been contributing as well. My question is with so many things possibly being a factor how do you you discontinue valuable cancer fighting tools?
Jens
Hi Jens, that's a very good question. I think one needs to decide whether the treatment is actually curative and if not there needs to be a good reason in order to continue, for example, a treatment might not be curative but relieve pain or discomfort. If a treatment is not curative and is causing serious side effects that affect the quality of life, why continue? An oncologist will measure the success or failure of treatment using a CT scan or MRI, or cancer marker and look for a positive response to the treatment.
I looked at the protocol you posted in February and DCA isn't listed. When did you start DCA treatment? I know very little about it but it seems that the toxicity gets worse with each dose as it has an accumulating effect. At the start of DCA treatment there might be no side effects at all but in time and with each new administration clearance of the substance is slower, and that's when the side effects start showing.
Doxycycline attenuates peripheral inflammation in rat experimental autoimmune neuritis
@jens you had doxy on your protocol but discontinued it for the OV treatment in February. Have you reintroduced it since? If not, now may be a good time, it's a hifa inhibitor, it could help with neuropathy, it has anti-inflammatory properties, anticancer effects against TNBC and synergy with rapamycin.
Also, if DCA is causing (most of ) the neuropathy you might want to reconsider using atorvastatin and metformin in combination with apigenin.
@jens I read the article on DCA by Daniel, and I notice many of the drugs he mentions, to enhance the effect of DCA, such as Fenben and Metformin, are part of your protocol. Also, he mentions thiamin to deal with neuropathy.
He says to continue DCA until no sign of disease. When treatment is reducing cancer and the toxicity profile allows one to continue, this makes perfect sense. But if there's a progression of cancer during treatment, it does not, even more so if there's significant toxicity.
The article was written 6 years ago and in my view could use more information e.g. how to deal with neuropathy (vitamin B1 isn't good enough and in certain cancers such as TNBC may promote cancer proliferation, see above references).
@j Hi Johan.
I understand DCA could be the main factor but other than about 4 IV treatments she only had approximately 80grams total which is really not that long of a time frame I just am not clear to the cause. I really wanted to start her back on the Metformin do to it crossing the blood brain barrier. But she is deathly afraid of the neuropathy. Like you mentioned I just have concentrate now on trying to fix the numbness. Her quality of life went down dramatically even without the cancer.
Lourdes had a MRI of the spine today. I don't know why they didn't just do the whole Body Pet Scan.
Thanks
Jens
@j Hi Johan .
It amazes me how you find these research materials. I would not have conceived endostar and the hyperbaric oxygen would be able to do that to help alleviate necrosis. The question is how to a get endostar and or to find a doctor willing to give it. Since we have cheap access to the Oxygen Chamber I am going to try and source the endostar.
Thanks.
Jens
@j Hi Johan.
I had her ammonia and lactic acid tested about a year ago. The lactic acid was high at the time. Also the magnesium tested low. I had been giving her Epson salt baths 3 times a week for 30 min at a time. I will test her again.
Thanks.
Jens
@j Hi Johan.
I was giving her 200mg of Doxycycline and 200mg Azithromycin with the IVC. Now she still takes 200mg of Doxycycline. As you know since her complications we have not done any IVC or IV Curcumin.
Thanks.
Jens
@j Hi Johan.
I understand DCA could be the main factor but other than about 4 IV treatments she only had approximately 80grams total which is really not that long of a time frame I just am not clear to the cause. I really wanted to start her back on the Metformin do to it crossing the blood brain barrier. But she is deathly afraid of the neuropathy. Like you mentioned I just have concentrate now on trying to fix the numbness. Her quality of life went down dramatically even without the cancer.
Lourdes had a MRI of the spine today. I don't know why they didn't just do the whole Body Pet Scan.
Thanks
Jens
@jens Hi Jens, indeed that's not that much, she must be very sensitive to it and other drugs. Chemo and RX really seem to have made it much worse. I am acutely aware of the dilemma you're facing, and the DCA strategy is sound but however good a treatment might be it has to produce results and at an acceptable and tolerable amount of toxicity. Very tough choices.
Sometimes the patients with the worst side effects have the most reduction of cancer, I hope this new MRI shows this is what's happening!
@j Hi Johan.
I was giving her 200mg of Doxycycline and 200mg Azithromycin with the IVC. Now she still takes 200mg of Doxycycline. As you know since her complications we have not done any IVC or IV Curcumin.
Thanks.
Jens
In this study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747360/ mice were treated with 60, 30, or 15 mg/kg of doxycycline; 20 mg/kg of cyclophosphamide; or saline by oral gavage once a day, for 5 weeks
Human equivalent dose of 60 = 267.57 mg for a 55kg person.
The rapamycin + doxy study would be approx Rapamycin 18mg + Doxycycline 30mg (3x/week for 21 days) .
@j Hi Johan .
It amazes me how you find these research materials. I would not have conceived endostar and the hyperbaric oxygen would be able to do that to help alleviate necrosis. The question is how to a get endostar and or to find a doctor willing to give it. Since we have cheap access to the Oxygen Chamber I am going to try and source the endostar.
Thanks.
Jens
Sometimes it's not very useful because of the inability to get a drug off-label, but I know you have access to HBOT, maybe there's a substitute for Endostar (it suppresses angiogenesis). Maybe theobromine?
@j Hi Johan.
I had her ammonia and lactic acid tested about a year ago. The lactic acid was high at the time. Also the magnesium tested low. I had been giving her Epson salt baths 3 times a week for 30 min at a time. I will test her again.
Thanks.
Jens
The Epsom salt in bath water is great but I do think she needs some extra Mg orally, transdermal Mg isn't that reliable to boost mg levels in my view.
The PINK1 Activator Niclosamide Mitigates Mitochondrial Dysfunction and Thermal Hypersensitivity in a Paclitaxel-Induced Drosophila Model of Peripheral Neuropathy
Tanshinone II A Affects Diabetic Peripheral Neuropathic Pain via Spinal Dorsal Horn Neuronal Circuitry by Modulating Endoplasmic Reticulum Stress Pathways
https://pubmed.ncbi.nlm.nih.gov/31295750/
(Danshen)
@j Hi Johan.
She was receiving 2 Grams in the morning and 2 Grams in the evening
Thanks.
Jens
https://classic.clinicaltrials.gov/ct2/show/results/NCT01029925
https://thechi.ca/wp-content/uploads/2022/08/DCA-professional-July-22-2022.pdf
A wide range of DCA dosages are used from 6mg/kg (330mg for a 55kg person) to 100mg/kg/day (5,5 grams) for a 55kg person, but even at the low end of this dose severe side effect have been recorded to occur (clinical trial).
At 4 grams a day, this dose is at the high end of the range.
@j Hi Johan.
She was receiving 2 Grams in the morning and 2 Grams in the evening
Thanks.
Jens
https://classic.clinicaltrials.gov/ct2/show/results/NCT01029925
https://thechi.ca/wp-content/uploads/2022/08/DCA-professional-July-22-2022.pdf
A wide range of DCA dosages are used from 6mg/kg (330mg for a 55kg person) to 100mg/kg/day (5,5 grams) for a 55kg person, but even at the low end of this dose severe side effect have been recorded to occur (clinical trial).
At 4 grams a day, this dose is at the high end of the range.
According to a phase 1 study, the MTD (Maximum Tolerated Dose) and RP2D (highest dose with acceptable toxicity) were set at 6.25mg/kg BID (twice a day).
80 grams would be equivalent to 242 days at the MTD. I believe DCA is most likely what has been causing the increasing severity of the neuropathy, exacerbated of course by the recent carboplatin and radiation treatments and possibly cancer. I think it's the right decision to discontinue DCA.
Sorry, MTD is 6.25mg/kg "twice a day (BID)" I forgot the latter in my calculation, so that would be equivalent to about 120 days. Even at this reduced figure, you can tell there's an obvious risk of toxicity.
@jens, Hi Jens, here's a list with studies of mostly natural substances that may be useful in dealing with neuropathy, all of these substances have anticancer properties as well and there are many possible synergies to possibly increase effectiveness.
@j hi Johan. Thanks for thinking of others. Your work is extremely helpful. Especially for people that's are very as organised.Very useful indeed.
Jens
Jens
@j Johan. I cant keep thanking you enough. Another good resource. I will try to use all I can to help my wife walk again. It's good most of those are also cancer fighters. I keep seeing Emodin in a lot of your posts you must think highly of it.
Thanks
Jens
@j Johan. I cant keep thanking you enough. Another good resource. I will try to use all I can to help my wife walk again. It's good most of those are also cancer fighters. I keep seeing Emodin in a lot of your posts you must think highly of it.
Thanks
Jens
@jens You're welcome, Jens. It does keep popping up, but I really don't have any favorite substances, that said the combinations I think have the highest probability of efficacy against cancer are those on the homepage of my blog.
Hopefully, the new MRI brings good news.
Acupuncture To Improve Peripheral Neuropathy
https://www.henryford.com/blog/2021/04/how-does-acupuncture-improve-peripheral-neuropathy
