The intravenous (IV) route of DCA has a number of therapeutic advantages, including:
1) higher blood levels because pulsed IV dosing can achieve a higher concentration than is feasible with an oral dosage
2) a longer washout period to reduce the potential for neurotoxicity
3) a bypassing of the digestive system, which is particularly significant for advanced-stage cancer patients.
I want to collect here all the details about the intravenous DCA. Below, I wrote out all the information on the doses and schedule of intravenous DCA in published treatment reports.
1. A Novel Form of Dichloroacetate Therapy for Patients With Advanced Cancer: A Report of 3 Cases
http://alternative-therapies.com/at/web_pdfs/s202khan.pdf
https://www.ncbi.nlm.nih.gov/pubmed/25362214
Case 1: A 79-year-old male sought therapy for metastatic colon cancer
The first dose of 3000 mg (41 mg/kg) of IV DCA was administered on December 22, 2011, together with 50 g of IVC. The second DCA infusion was given 6 days later at a dose of 3500 mg (48 mg/kg) together with 35 g of IVC. A third DCA infusion at a dose of 3700 mg (50 mg/kg) and 50 g of IVC were given 8 days after the second dose.
Case 2: A 43-year-old male sought therapy for metastatic angiosarcoma of the right femur.
IV DCA was started at a dose of 3000 mg (47 mg/kg) weekly and escalated in a 2-week period to 5000 mg (47 mg/kg) twice per week. No side effects were observed. Following a total of 4 months of IV DCA therapy, an MRI demonstrated stability.
2. Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067498/
A 57 years old female.
The plan consisted of addition of high dose oral vitamin D at 10000 international units per day, a change of oral vitamin C to vitamin C 50 g intravenous (i.v.) weekly, and addition of dichloroacetate sodium (DCA) 3000 mg i.v. (49 mg/kg) weekly (manufacturer: Tokyo Chemical Industry, United States). To reduce the risk of DCA side effects, 3 natural supplements were prescribed: Alpha lipoic acid (racemic) 500 mg i.v. with each DCA dose, oral R-alpha lipoic acid 150 mg 3 times a day, oral acetyl L-carnitine 500 mg 3 times a day, and oral benfotiamine 80 mg twice a day.
DCA was increased to 4000 mg i.v. (66 mg/kg) weekly. The only side effect noted at the higher DCA dose was mild post-infusion sedation.
…DCA i.v. was continued, and the dose was increased to 4500 mg i.v. weekly.
3. Pharmacokinetics and pharmacodynamics of dichloroacetate in patients with cirrhosis
https://ascpt.onlinelibrary.wiley.com/doi/full/10.1053/cp.1999.v66.a101340
http://sci-hub.tw/https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1053/cp.1999.v66.a101340
Stock dichloroacetate solution (100 mg/mL) was prepared by dissolving sodium dichloroacetate (>99%, TCI America, Portland, Ore) in 0.45% sodium chloride under aseptic conditions, sterilized by 0.22 micron filtration, and tested for sterility and pyrogenicity before use. It was stored at 4°C, where it is stable for >1 year. Purity and stability were verified by negative chemical ionization gas chromatography—mass spectroscopy (NCI-GC/MS, models 5890/5989A, Hewlett-Packard, Pleasanton, Calif) as described previously. Stock dichloroacetate solution was diluted in 0.9% sodium chloride to a final dichloroacetate concentration of 60 mg/mL on the morning of the infusion protocol.
Intravenous dichloroacetate, 35 mg/kg, was infused for 30 minutes. This dichloroacetate dose was chosen for a near-maximal response of plasma lactate concentration without the somnolence commonly associated with larger doses, even in healthy volunteers. After completion of the stable isotope infusion protocol, subjects were allowed to eat and drink for the duration of the study. All subjects were discharged and sent home 24 hours after the single dichloroacetate administration.
4. Preparation and Stability of Intravenous Solutions of Sodium Dichloroacetate (DCA)
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Unfortunately, I can not find any more information on how to prepare an intravenous DCA solution.
I found a ready-made DCA solution, but still can not find where to buy it.
If you have any information about intravenous DCA, share it!
1) higher blood levels because pulsed IV dosing can achieve a higher concentration than is feasible with an oral dosage
2) a longer washout period to reduce the potential for neurotoxicity
3) a bypassing of the digestive system, which is particularly significant for advanced-stage cancer patients.
I want to collect here all the details about the intravenous DCA. Below, I wrote out all the information on the doses and schedule of intravenous DCA in published treatment reports.
1. A Novel Form of Dichloroacetate Therapy for Patients With Advanced Cancer: A Report of 3 Cases
http://alternative-therapies.com/at/web_pdfs/s202khan.pdf
https://www.ncbi.nlm.nih.gov/pubmed/25362214
Case 1: A 79-year-old male sought therapy for metastatic colon cancer
The first dose of 3000 mg (41 mg/kg) of IV DCA was administered on December 22, 2011, together with 50 g of IVC. The second DCA infusion was given 6 days later at a dose of 3500 mg (48 mg/kg) together with 35 g of IVC. A third DCA infusion at a dose of 3700 mg (50 mg/kg) and 50 g of IVC were given 8 days after the second dose.
Case 2: A 43-year-old male sought therapy for metastatic angiosarcoma of the right femur.
IV DCA was started at a dose of 3000 mg (47 mg/kg) weekly and escalated in a 2-week period to 5000 mg (47 mg/kg) twice per week. No side effects were observed. Following a total of 4 months of IV DCA therapy, an MRI demonstrated stability.
2. Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067498/
A 57 years old female.
The plan consisted of addition of high dose oral vitamin D at 10000 international units per day, a change of oral vitamin C to vitamin C 50 g intravenous (i.v.) weekly, and addition of dichloroacetate sodium (DCA) 3000 mg i.v. (49 mg/kg) weekly (manufacturer: Tokyo Chemical Industry, United States). To reduce the risk of DCA side effects, 3 natural supplements were prescribed: Alpha lipoic acid (racemic) 500 mg i.v. with each DCA dose, oral R-alpha lipoic acid 150 mg 3 times a day, oral acetyl L-carnitine 500 mg 3 times a day, and oral benfotiamine 80 mg twice a day.
DCA was increased to 4000 mg i.v. (66 mg/kg) weekly. The only side effect noted at the higher DCA dose was mild post-infusion sedation.
…DCA i.v. was continued, and the dose was increased to 4500 mg i.v. weekly.
3. Pharmacokinetics and pharmacodynamics of dichloroacetate in patients with cirrhosis
https://ascpt.onlinelibrary.wiley.com/doi/full/10.1053/cp.1999.v66.a101340
http://sci-hub.tw/https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1053/cp.1999.v66.a101340
Stock dichloroacetate solution (100 mg/mL) was prepared by dissolving sodium dichloroacetate (>99%, TCI America, Portland, Ore) in 0.45% sodium chloride under aseptic conditions, sterilized by 0.22 micron filtration, and tested for sterility and pyrogenicity before use. It was stored at 4°C, where it is stable for >1 year. Purity and stability were verified by negative chemical ionization gas chromatography—mass spectroscopy (NCI-GC/MS, models 5890/5989A, Hewlett-Packard, Pleasanton, Calif) as described previously. Stock dichloroacetate solution was diluted in 0.9% sodium chloride to a final dichloroacetate concentration of 60 mg/mL on the morning of the infusion protocol.
Intravenous dichloroacetate, 35 mg/kg, was infused for 30 minutes. This dichloroacetate dose was chosen for a near-maximal response of plasma lactate concentration without the somnolence commonly associated with larger doses, even in healthy volunteers. After completion of the stable isotope infusion protocol, subjects were allowed to eat and drink for the duration of the study. All subjects were discharged and sent home 24 hours after the single dichloroacetate administration.
4. Preparation and Stability of Intravenous Solutions of Sodium Dichloroacetate (DCA)
Solutions for injection (100 mg/ml) were prepared by weighing DCA in a laminar flow hood and, using autoclaved utensils, dissolving it in 0.9% (154 mEq sodium chloride per liter) saline solutions. The solution was filtered through a sterile 0.2 u,m nylon Posidyne filter into a sterile pyrogen-free evacuated container. The solution was then transferred asepticaliy to commercially obtained sterile pyrogen-free vials.
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Unfortunately, I can not find any more information on how to prepare an intravenous DCA solution.
I found a ready-made DCA solution, but still can not find where to buy it.
If you have any information about intravenous DCA, share it!
Excellent info. Thank you!
ReplyDeleteThat's what the authors of the www.dcaguide.org website kindly replied to my letter about the question of intravenous DCA:
ReplyDelete"We are aware of the great advantages of I/V solutions, specifically, the lower toxicity and higher blood concentrations.
DCAGuide previously had plans to make a guide on how to make a I/V solution.
Most of the people could be able to prepare such solutions at home, however, the biggest problem is that you need the I/V solution to be sterile. Unsterile I/V solutions can cause bacterial or viral complications which are not the best thing for someone who has a tumor.
To achieve sterile conditions and to make such a I/V solution - one must use a laboratory with certain equipment for making the product totally clean
from bacteria and other microorganisms."
A little information about intravenous DCA from the Ottawa Integrative Cancer Center website:
ReplyDelete"Patients at the OICC are typically started at a dose of 20mg/kg intravenously and slowly titrated up to a therapeutic dose of between 50 mg/kg and 80 mg/kg. Intravenous DCA is given up to two times a week and doses are increased at each administration. All intravenous doses of DCA are immediately followed by intravenous alpha lipoic acid as well as intravenous B complex administration."
http://www.oicc.ca/uploads/dca-health-professional.pdf
And another recipe for the preparation of a DCA solution for intravenous administration:
ReplyDeletehttp://ufdc.ufl.edu/AA00011845/00001/41x
"Preparation of DCA Injection Solution
Two and one half grams of DCA were dissolved in 19 ml istonic saline and 6 ml sodium phosphate injection solution (276mg of monobasic sodium phosphate per
mililiter of H20) to give a final concentration of 100mg/ml. Early batches were sterilized by autoclaving at 121' for 30 minutes after passage through an 0.22 Posidyne Nylon 66 microfilter (Pall) (Baumgartner, et al. 1986).
However, when the stability of DCA was tested at high temperature, it was found that DCA has a decomposition half life of 41 hrs at 100" and pH 7.4. Later sample
preparation was made by first weighing DCA powder aseptically. The DCA was then aseptically transferred with on-line 0.22 p filtration and then added to a pyrogen-free container. Thioglycolate and Blood Agar tests were performed to test for bacteria and fungi. A lymulus lysate test was also performed for pyrogens.
Samples of the injection solution were assayed by gas chromatography."
I also wrote letters to many clinics (including Medicor in Canada) and DCA sales sites about the possibility of buying a DCA solution. Medicor from Canada is ready to sell DCA solution, but they can not send it to Russia.
In the end, if I can not buy the official DCA solution, I will have to analyze all the available recipes and order the preparation of DCA solution in the local laboratory.
By the way, in the Medicor Cancer Centers one of the documents specifies the price for intravenous DCA:
ReplyDeleteDCA iv, 250mg / ml x 30ml (7500mg), 1 vial - 145 $ CDN (= 113USD).
http://medicorcancer.com/wp-content/uploads/New_Patient_Package.pdf
And a little more about the preparation of DCA solution from the old study of 1980:
ReplyDeleteMetabolic Effects and Pharmacokinetics of Intravenously Administered Dichloroacetate in Humans
https://link.springer.com/content/pdf/10.1007/BF00421855.pdf
"DCA was supplied in 10 ml ampules as the sodium salt, 100 mg/ml, in phosphate buffer, pH 7 (Ciba-Geigy Corp., Summit, NJ). On the morning following an overnight fast, DCA was diluted in 130 to 200 ml normal saline and infused at a constant rate by a Harvard infusion pump into a superficial forearm vein for 30 min. Doses of 1, 5, 10, 15, 20, 25, 30, 35 and 50 mg/kg body weight were administered in increasing strength, each subject being studied once at a single dose. Blood samples were drawn from a superficial vein in the other arm at 30 or 60 min intervals over a 12 h period. Blood pressure, pulse and electrocardiogram (ECG) were monitored intermittently, and subjects remained fasting and supine throughout the study."
And by the way, one of the interesting conclusions:
"There are differences in the effects of orally versus intravenously administered DCA on plasma lactate and alanine. In diabetic patients receiving 50 rag/kg of DCA orally for seven days, depression of plasma lactate and alanine persisted several days beyond cessation of DCA treatment (8). In contrast, the lactate and alanine concentrations after intravenously administered DCA had returned to or toward basal levels within 12 h of drug administration. The reason for this discrepancy in response between chronic oral dosing and single dose intravenous drug administration is unknown, although even in the intravenous studies, lactate and alanine concentrations remained depressed up to 8 h after elimination of DCA from the plasma."
I wrote a lot of letters to different clinics about the DCA solution preparation advice, but I did not receive any answers.
This study (2017 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661062/) concluded that hypoxia is the cause of the resistance of glioblastoma cells to DCA:
ReplyDelete"...we examined the effects of DCA on viabilities of GBM cells cultured under normoxia or hypoxia... Interestingly, in GBM28 and GBM37, DCA treatment at 5, 10, or 20 mM induced significant levels of cell death under normoxia, but DCA at all doses failed to induce cell death under hypoxia , implying that hypoxic adaptation prevailed DCA effects in these cells.
...Overall, these results indicated that DCA effects on inducing cell death under normoxia varied, from no effect in U251 to moderate effects in GBM28 and GBM37, whereas all three GBMs were resistant to DCA treatment under hypoxia."
The authors also consider the effects of chrysin on glioblastoma cells and its synergy with DCA. Although food additives with chrysin are commercially available (for example, https://www.iherb.com/pr/MRM-Chrysin-500-30-Vegan-Capsules/4647), there is almost no information on the effects of oral administration. Therefore, it is unclear whether to combine chrysin with DCA.
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What conclusions can we draw from this study? Maybe, think about the combination of hyperbaric oxygen and DCA?
Unfortunately, I do not find information about the benefits of hyperbaric oxygen outside of radiation therapy. On the contrary this study (2018 https://www.ncbi.nlm.nih.gov/pubmed/29785863) concludes: "Hyperbaric oxygen inhibits production of CD3 + T cells in the thymus and facilitates malignant glioma cell growth."
Can there be other ways to reduce the hypoxia of glioblastoma cells for the effect of DCA?
By the way, can there be more effective inhibitors of HIF1α (instead of chrysin) for addition to DCA?
DeleteInterestingly, anti-angiogenic therapy with Avastin can restore normal blood flow, reduce hypoxia and thus make cells more sensitive to DCA. Maybe that's why in experiments on mice there was strong synergy of Avastin and DCA?
DeleteAlthough there might be a short period following Avastin treatment where vascular flow is normalized ("vascular normalization"), most studies show that Avastin eventually worsens hypoxia (by stopping the growth of new blood vessels).
DeleteThe results of the study you posted are difficult to make sense of. In theory, a hypoxic tumor should be more (not less) reliant on the Warburg effect, more productive of lactic acid, and more vulnerable to DCA treatment.
I rarely find cell culture studies very reliable.
My understanding of the Avastin + DCA synergy is that Avastin increases hypoxia, causing cells to rely more heavily on the Warburg effect (fermentation of pyruvate to lactic acid outside the mitochondria, rather than oxidative phosphorylation inside the mitochondria), thus becoming more sensitive to DCA. In other words I drew the opposite conclusion. Fortunately (for science, not for the animals) that study was done in mice, and wasn't just a cell culture study.
I found this study with another kind of cancer:
ReplyDelete2017 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584284/
Inhibition of COX2 enhances the chemosensitivity of dichloroacetate in cervical cancer cells
"...we for the first time revealed that DCA could upregulate COX2 which impeded the chemosensitivity of DCA in cervical cancer cells. Mechanistic study showed that DCA reduced the level of RNA binding protein quaking (QKI), leading to the decay suppression of COX2 mRNA and the subsequent elevation of COX2 protein. Inhibition of COX2 using celecoxib could sensitize DCA in repressing the growth of cervical cancer cells both in vitro and in vivo. These results indicate that COX2 is a novel resistance factor of DCA, and combination of celecoxib with DCA may be beneficial to the treatment of cervical cancer."
Can these findings on the synergy of DCA and celecoxib (celebrex) be applicable to glioblastoma?
I want to try DCA for my father.
ReplyDelete