Phlorizin & Phloretin: a powerfull glucose transport inhibitor

Summary 

I know and like Phloretin since long time ago but today I came across a very interesting (old) patent that is based on Phlorizin (a derivative of Phloretin) as an anti cancer treatment. Based on the science behind, safety and case reports, I think this is very interesting and below I will share the information I find most relevant from this patent.

Phloretin/Phlorizin, are very well know Glut1, SGLT1 and SGLT2 inhibitors. These are transporters responsible for transporting glucose into the the cells. For example, glucose symporter SGLT1, co-transports one glucose molecule into the cell for every two sodium ions it imports into the cell. In the cancer cells, some of these transporter are over expressed and their inhibition will lead to energy depletion or may even lead to the death of the cancer cell. Indeed, malignant cells are very much dependent on glucose and when deprived of glucose are unable to maintain their energy (ATP) levels for periods longer than four hours whereas normal cells have no difficulty in maintaining their ATP levels in the absence of glucose (Biochem et Biophysica Res Comm. 82:787, 1978). (Ref). As a result, if not killing the cancer cells,  Phlorizin or Phloretin can at least increase the effectiveness of chemotherapies or other anti cancer therapies by lowering the drug resistance capabilities of cancer cells.

Phloretin/Phlorizin are safe substances and are natural phenols found in apple tree leaves. “One need not fear giving an excessive quantity of phlorizin, however, since this substance has proven to be non-toxic and is rapidly excreted in the urine.” (Ref.)

Apple Polyphenols and Longevity http://www.lifeextension.com/magazine/2012/4/Apple-Polyphenols-Longevity/Page-01

Case reports (from the patent Ref.)

EXAMPLE 1

A thin female 57 years of age entered with sarcoma of duodenum resected 3 years prior. Patient was jaundiced and work up indicated obstruction of common bile duct. Tumor was debulked around porta hepatis and cholecystojejunostomy was done. Patient was then given life time dose of radiation and chemotherapy. Pathology report of patient was a leiomyosarcoma. About one year later, the tumor recurred in the umbilical area requiring further debulking at which time large portion of abdominappleal mass was resected.

Further debulking was done from the abdominal wall, transverse colon and hepatic region. The tumor was not possible to completely resect at any surgery and each time the lesion was more extensive. The patient again became jaundiced and another laparotomy with debulking was performed. A T-tube was placed in the common duct and a gastroenterostomy was performed.

The patient was treated with antibiotics for cholangitis and infection of abdominal wall wound. She was then started on phlorizin given continuously for 12-24 hours with local heat. Systemic temperature rose to 40° C. Vinblastin and Mitomycin C were given I.V. in very small doses. The entire tumor mass became necrotic. Massive necrosis of necrotic tumor became liquified and infected and have required multiple drainages with catheters placed by radiographers under x-ray control. Bowel wall which was replaced by nectrotic tumor tissue has communicated with a large intraabdominal abcess which has been drained. Sepsis is now being controlled. CT scans show multiple areas of tumor liquification and cavitation. The patient’s survival with large necrotic masses is questionable but patient is being supported and sepsis seems under control.

EXAMPLE 2

A 51 year old female had a low anterior resection for cancer of rectum. At time of surgery, hepatic metastases were discovered. Had full course of radiation to pelvis, post surgery. She was treated with 5 FU, Mitomycin C and Novotrome without response. Was starated on 8-12 hour phlorizin plus the same chemotherapeutic agents. Made an immediate response with regression of tumor and no further bowel obstruction.

EXAMPLE 3

A 57 year old male had a melanoma over right scapula removed. There was a local recurrence and a local infection with paraincisional melanosis. This was removed with lymph nodes. Pathological diagnoses was Clark level two melanoma. 7 years later, a cerebral recurrence was found. There were two lesions in frontal lobes and one in parietal area. Was treated with radiation without response. All therapy was then abandoned and the patient was told he had 60 days to live.

The patient was started on small doses of Vincrestine, methyl CCNU and received phlorizin by bolus 5 grams and mild heat to head by RFTT. There was a 50% reduction of lesion by NMR scan. NMR scan of brain was negative. He had a recurrance and was treated but chemotherapy omitted. The lesion did not respond and patient died.

EXAMPLE 4

46 year old female developed a melanoma of the right leg during pregnancy. An excision of primary with lymph node desection and removal was done. Pathology reported that lymph nodes were positive for melanoma. Metastases appeared in head and lungs. Patient was placed on Vincristine and Precarbizone. Severe pain in abdomen probably caused by hemorrhage into a liver mets. She was treated with a bolus of 5 grams o±phlorizin and decadron to lower any possible inflamatory response from necrotic tumor tissue along with RFTT of 50 watts to head and the chemotherapy which had previously been unsuccessful. Vincristine Methyl CCNU and procarbozine was restarted in small doses. The lesion in her brain completely resolved on CT scan. The liver and abdominal diseases had increased and patient died in June of liver and abdominal disease without any recurrance in the head.

EXAMPLE 5

38 year old female developed a melanoma of left axilla which was widely excised with adjacent lymph nodes. Lymph nodes were negative for metastases. She developed plural effusion with multiple nodules in left lung. Received 50.0 mg 5 F.U. and 5 mg. mitomycin C intraplurally. Heated with 100 watts R.F.T.T.. Given vincrestine procarbozine CCNU but did not respond. Chest was drained again in September. Received same treatment plus phlorizin over 12 hours. Responded and now is tumor free for past 11 months.

EXAMPLE 6

A 39 year old woman presented with total obstruction from stomach and a large bowel fistula from previous surgery. She was unable to take any food by mouth. She underwent treatment with R.F.T.T. to area of obstruction after 8 hours of continuous phlorizin infusion. Small doses of chemotherapy were also administered I.V. Patient responded with disappearance of complete gastric outlet obstruction. She is now on full diet and the Fistula has spontaneously closed.

EXAMPLE 7

Patient had carcinoma of breast and previous mastectomy but experienced a large recurrence in the axilla. Because of a generalized vasculitis poorly understood she did not receive chemotherapy but only received phlorizin and heat treatment. She was given a bolus containing 2.5 grams of phlorizin and 75 watts of R.F.T.T. to axilla. Lesion dried up and CT scan was negative.

EXAMPLE 8

34 year old male had a resection of sigmoid and descending colon for cancer of colon. Pathological report described perivascular invasion, lymph node invasion and diffuse periotoneal seeding. All lymph nodes could no be removed. Was treated with 5FU Mitomycin and a bolus of phlorizin. Now has normal CT scan of liver and abdomen. C.E.A. 2.8 and has remained tumor free for 1 year.

EXAMPLE 9

54 year old female with cancer of breast amputated and was placed on chemotherapy and tomoxifen and local radiation. There was a metastases to the 4th ventricle of the brain on CT scan. Patient told no treatment possible and was sent to a terminal cancer hospital.

Was treated with mild heat, phlorizin and decadron without chemotherapy. CT scan now negative and patient remains well.

EXAMPLE 10

62 year old executive had adenocarcinoma of lung with metastases to brain. Three separate lesions appeared in brain on CT and NMR scans. Brain was radiated without response. Lung also radiated without response. Patient was started on 5FU mytomycin and phlorizin. CEA was 8.2. Scan has improved and only 1 small lesion is now visable in brain and 2 have disappeared. Lung lesion has disappeared. No other soft tissue metastases.

EXAMPLE 11

Primary tumor in colon was resected. Patient underwent liver resection for right hepatic metastatic colon cancer. No other tumor seen. Developed recurrent bowel obstruction and peritoneal seeding. Repeated bowel obstructions respond each time to chemotherapy and phlorizin. Laparotomy with a colostomy slowed massive tumor regression. Has improved long term survival.

EXAMPLE 12

56 year old man had cancer of rectum resected. Recurrance three years later in abdomen was treated with a bolus, heat mitromycin and 5FU. Patient developed renal shut down from obstructed ureters. There were liver metastases and abdominal tumor present. Patient was given 8-12 hour phlorizin plus chemotherapy as above and has responded with tumor regression and ureter is no longer obstructed.

EXAMPLE 13

78 year old female had anterior resection for cancer of rectum. She developed a recurrance one year later with radiation to pelvis. No response occured and the bowel was obstructed so a laparotomy was done and an end colostomy performed. Liver metastases were found. Laparotomy and exenteration was done for colovesical fistula. Biopsies were all positive for cancer post exenteration. Patient was treated with 8 hour infusion of phlorizin. Chemotherapy and heat were administered. All biopsies turned negative and there was no evidence of pelvic cancer. Pelvic biopsies were negative Liver metastases remain stable.

EXAMPLE 14

Nasopharangeal cancer treated by radiation and chemotherapy. Pathology was a poorly differentiated squamous cell carcinoma. Lesion spread to both sides of neck. Progressed on chemotherapy. Phlorizin was added by bolus to regime. Patient progressed very slowly. Eight hours of phlorizin was instituted with chemotherapy. Tumor regressed by 80%.

EXAMPLE 15

58 year old female had a right colon resection for carcinoma. The cancer had perforated the bowel wall and there was peritoneal seeding visable. All of the tumor could not be resected. CEA was 13.9 Was treated postoperatively with 5 FU Mitomycin C and phlorizin infusion plus mild heat. Last CT scan was negative for tumor and C.E.A. remains at low level of 3.0.

EXAMPLE 16

80 year old female with massive liposarcoma of left lower leg. Patient has had repeated resections of tumor mass of left lower leg. Patient was injected with mitomycin C and Vinblastin with phlorizin. Because of the shortage of phlorizin, it was injected intralesionally and a tourniquet applied to prevent reabsorption. The lesion has resolved with a 90% regression in tumor size. Requires occasional therapy with heat RFTT and chemotherapy but has not required further surgery.

EXAMPLE 17

48 year old female who had upper G.I. discomfort. She had been working with x-rays for 20 years. Exploratory laparotomy revealed cancer of stomach with diffuse metastases over peritoneum. The patient gradually deteriorated and developed partial bowel obstruction. She received 8-12 hours phlorizin infusion plus 5FU and mitomycin C and RFTT to area of obstruction. Obstruction resolved and went home to Texas. Returned 6 weeks later with another obstruction. Retreated. Mass reduced in size and obstruction overcome. Responds well to treatments.

EXAMPLE 18

54 year old obese female with metastases hypernephroma to brain, scalp and lungs. Primary tumor had been removed some years previously. Patient had failed chemotherapy and was dying. Phlorizin given in bolus of 2 grams with Lonidamine I.V. Heat given to head with conductive R.F.T.T. of 50-100 watts. Necrosis of tumor occurred immediately and patient went into acute cerebral edema requiring immediate neurosurgical decompression. The necrotic tumor was scooped out from brain. Pathology report confirmed that dead tumor tissue had caused acute edema. Tumor of scalp also became necrotic and disappeared leaving a scar biopsy free of tumor. CT scan now confirm that tumor in head had disappeared. Patient now alive and well.

EXAMPLE 19

37 year old male with massive liver cancer. The biopsies disclosed a carcinoid tumor but a search for the primary tumor did not disclose any intestinal primary. He was operated upon and the tumor proved to be completely unresectible. Patient was placed on high doses of chemotherapy both before and after surgery but it failed completely.

Patient had received phlorizin by bolus plus previously failed chemotherapy and lonidamine but responded only slowly. Therefore, he was switched to long term phlorizin over 12 to 24 hours with the same chemotherapy and heat regime and has responded to long infusions of phlorizin. The long infusion technique depleted the cell of glycogen and made it impossible for damage of cancer cell to be repaired. The results have been dramatic with marked response in weight gain, strength, well being. Tumor size has decreased significantly on direct palpation and CT scan. CT scan shows necroses of hepatic metastases.

All the examples above have been published in the following patent https://www.google.com/patents/US4840939

One of the inventor in the patent cited above was Dr. Harry H. LeVeen, a great man, former chief of surgery for 23 years at what is now the Veterans Affairs Medical Center in Brooklyn. There, in the 1970’s, he devised the LeVeen shunt, the first successful device for diverting fluids from the abdomen back into the bloodstream Ref

Mechanism

As discussed above, the anticancer effect of this component is due to the inhibition of Glut1, SGLT1 and SGLT2, transporters responsible for the transport of glucose inside the cells. As a result, is prohibiting glucose entry into the interior of the cell, impairs the vitality, metabolism, and repair and injury to cells caused by outside forces and changes sublethal cellular damage to lethal damage thus enhancing the effect of chemotherapy, radiation and heat.

Safety

Phlorizin is relatively non-toxic and has been administered to man parenterally and by mouth in wafer form. Doses as high as 15 grams have been administered in a single oral dose (J Clin Invest. 13:749, 1934). It has been given intravenously and subcutaneously to humans. Phlorizin by inhibiting glucose entry into the renal tubular cell causes glycosuria but since it also inhibits glucose entry into intestinal mucosal cells, absorption from the intestines is inhibited and sugar may be present in the feces. (Ref)

If for any reason it is necessary to interrupt the therapy, it can be counteracted with glucose infusions.

Preparation and administration

In rats, 10.4% of the ingested dose was recovered in urine after 24 h (Ref).

It should be used as IV since with oral therapy, much of the dose appears in the stool.

The dosage required to effectively inhibit cancer growth is easily determined since the patient acts as his own bioassay. The concentration which makes the tumor cells impermeable to glucose, makes other normal cells in the body also impermeable to glucose. When the dosage is adequate to prevent glucose entry into cells, the proximal tubular cells can no longer absorb glucose and glucosuria occurs. When total blocking of glucose absorption into the cell occurs, glucose then appears in the urine in almost the same concentration that it is present in the serum depending on the degree of water absorption of the urine. The correct dosage of the composition of the invention can be determined by measuring the glucose clearance, which approaches 125 cc’s per minute and which is the same as the xylose and inulin clearance. The creatinine clearance is a good substitute since it is only slightly higher than the inulin clearance.

Clinical experience has shown that, the composition of the invention is preferably administered in a continuous drip, approximately 1 mg per kilo of body weight per hour as a maintenance dose after total phlorizination to completely abolish glucose entry into cells. An initial loading dose of 4-6 mg per kilo of body weight is usually desirable to completely phlorizinize a patient as evidenced by the failure of the tubular cells to absorb glucose. This can be given by a slow push or over a ten minute interval. The duration of the effects last approximately one to one and one-half hours when administered intravenously as a single dose. With oral therapy, much of the dose appears in the stool. That glucose reabsorption in the kidney is completely blocked can be determined by comparing clearance of glucose to the clearance of xylose after administration.

Generally, it has been found that the administration of a total dosage of about 200-1000 mg of phlorizin or the indicated derivative per kilogram of body weight is an adequate dose in most patients. One need not fear giving an excessive quantity of phlorizin, however, since this substance has proven to be non-toxic and is rapidly excreted in the urine. The effect of phlorizin is dependent on a critical concentration in the extracellular fluid which will completely block all of the receptors sites for glucose.

The composition is generally administered during intervals of chemotherapy or radiation therapy by heating, radiation or chemotherapeutic drugs. Complete phlorizination for twenty-four hours prior to therapy reduces cellular glycogen levels and renders the therapy more effective. This dose is sufficient to reduce the blood glucose concentration to low levels and to partly or completely deplete cellular glucose. Further inhibition of glucose entry into the cancer cell is extended to the time of patient therapy by heat, chemotherapy or radiation and continued for 24 hours post therapy. The patient should be carefully observed for salt depletion. If for any reason it is necessary to interrupt the therapy, it can be counteracted with glucose infusions.

For I.V. infusion of phlorizin ten grams of phlorizin or the indicated analogs are dissolved in 20 ml of 95% ethyl alcohol which is then mixed with 930 ml of warm or hot 0.5 normal sodium chloride solution to which one ampule of sodium bicarbonate (50 mq in 50 ml H2 O) has been added. This mixture may require heating until it is warm enough to fully dissolve the phlorizin. After initial administering of the loading dose, the infusion is slowed to 10-15 ml per hour depending on body weight.

Summary of the above on preparation:

  1. phlorizin and not phloretin is preferred because of better water solubility of phlorizin
  2. Because of its poor oral absorption, the compositions of the invention is administered IV, dissolved in a suitable carrier such as 1/2 normal saline.
  3. 10g of phlorizin are dissolved in 20 ml of 95% ethyl alcohol (i.e. 50mg phlorizin/ml ethanol) which is then sterilized using a 0,22ug syringe filter  and than mixed with 930 ml of warm or hot 0.5 normal sodium chloride solution (1/2 normal saline) to which one ampule of sodium bicarbonate (50 mq in 50 ml H2 O) has been added. This means that every ml of nearly 1000ml solution will contain 10mg phlorizin.
    I am not sure if it i specifically required 0.5 normal saline or simply normal saline (i.e. 0.9%) is also fine.
  4. This mixture may require heating until it is warm enough to fully dissolve the phlorizin.

Summary of the above on administration:

  1. An initial loading dose of 4-6 mg per kilo of body weight is usually desirable to completely phlorizinize a patient. This can be given by a slow push or over a ten minute interval. (The duration of the effects last approximately one to one and one-half hours when administered intravenously as a single dose.)
    Note that according to the patent some patients receive a bolus loading dose of 2g or even 2.5g phlorizin, which for a person of about 65kg that is 30mg/kg, i.e. much higher than indicated above.
  2. Preferably, following the loading dose, the solution is further administered in a continuous drip, approximately 1-2 mg per kilo of body weight per hour as a maintenance dose for the next 8 to 24 hours (usually 8-12 hours). This means that for a 50kg person, 50mg-100mg phlorizin will be administrated every hour, i.e. about 5ml-10ml of the solution every hour
  3. During the above chemo or others treatments will be performed to increase their effectivness
  4. Note that upon prolonged exposure to aqueous solutions phlorizin hydrolyzes to phloretin and glucose. So if administrated for longer time maybe it would be better to produce new solution every few hours.

Update 16.01.2016: Prepared the solution as indicated above and it looks great for IV – very soluble in NaCl solution (did not used sodium bicarbonate)

Storage:

Powder at 4C; Solution at -20C for ax one month http://www.abcam.com/Phlorizin-ab143144.pdf

Source

CAS 60-81-1: Various chemical companies such as Cayman: http://www.caymaneurope.com/app/template/Product.vm/catalog/11576
Carbosynth: http://www.carbosynth.com/carbosynth/website.nsf/(w-productdisplay)/56CD657845777A2D802573EB0072A5C9
I am nut sure if this source can be trusted but the claim is >95% at low cost: https://www.badmonkeybotanicals.com/organic-apple-root-phloridzin-extract

References

In vitro and in vivo study of phloretin-induced apoptosis in human liver cancer cells involving inhibition of type II glucose transporter http://onlinelibrary.wiley.com/doi/10.1002/ijc.24189/full

Phloretin (Ph), a natural product found in apples and pears with glucose transporter (GLUT) inhibitory activity, exerts antitumor effects. However, little is known about its effects on human liver cancer. The purpose of this study is to test the cytotoxic effects of Ph on HepG2 cells and to identify the underlying molecular pathways. Human hepatocellular carcinoma specimens and HepG2 show a high level of GLUT2 transporter activity in the cell membrane. Real-time PCR and MTT assays demonstrate that Ph-induced cytotoxicity correlates with the expression of GLUT2. Flow cytometry and DNA fragmentation studies show that 200 μM Ph induces apoptosis in HepG2, which was reversed by glucose pretreatment. GLUT2 siRNA knockdown induced HepG2 apoptosis, which was not reversed by glucose. Western blot analysis demonstrates that both intrinsic and extrinsic apoptotic pathways in addition to Akt and Bcl-2 family signaling pathways are involved in Ph-induced cell death in HepG2 cells. Furthermore, using flow cytometry analysis, a mitochondrial membrane potential assay and Western blot analysis, we show that cytochalasin B, a glucose transport inhibitor, enhances the Ph-induced apoptotic effect on HepG2 cells, which was reversed by pretreatment with glucose. Furthermore, we found significant antitumor effects in vivo by administering Ph at 10 mg/kg intraperitoneally to severe combined immune deficiency mice carrying a HepG2 xenograft. A microPET study in the HepG2 tumor-bearing mice showed a 10-fold decrease in 18F-FDG uptake in Ph-treated tumors compared to controls. Taken together, these results suggest that Ph-induced apoptosis in HepG2 cells involves inhibition of GLUT2 glucose transport mechanisms.

Treatment of cancer with phlorizin and its derivatives https://www.google.com/patents/US4840939

Malignant, neoplastic cells are treated by inhibiting glucose transport into the cell by administering phlorizin, phloretin or its analogs while concurrently administering adjunct therapy such as heat, radiation or chemotherapy. In this manner, the cells are prevented from growing or repairing the damage caused by the adjunct therapy, which can be administered in dosages that would otherwise be non-lethal if used alone.

SGLT Inhibitors as New Therapeutic Tools in the Treatment of Diabetes http://iqanda-cme.com/assets/pdf/Kinne.pdf

Recently, the idea has been developed to lower blood glucose levels in diabetes by inhibiting sugar reabsorption in the kidney. The main target is thereby the early proximal tubule where secondary active transport of the sugar is mediated by the sodium-D-glucose cotransporter SGLT2. A model substance for the inhibitors is the O-glucoside phlorizin which inhibits transport competitively. Its binding to the transporter involves at least two different domains: an aglucone binding site at the transporter surface, involving extramembranous loops, and the sugar binding/ translocation site buried in a hydrophilic pocket of the transporter. The properties of these binding sites differ between SGLT2 and SGLT1, which mediates sugar absorption in the intestine. Various O-, C-, N- and S-glucosides have been synthesized with high affinity and high specificity for SGLT2. Some of these glucosides are in clinical trials and have been proven to successfully increase urinary glucose excretion and to decrease blood sugar levels without the danger of hypoglycaemia during fasting in type 2 diabetes.

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

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Fred
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Fred

Daniel,

My wife receives TPN (IV nutrition) due to total bowel blockage. She receives a 1500cc bag from 8p to 8a each night. It occurred to me I could add a cancer fighting agent to the bag.

Base formula
Dextrose 150G
Aminosyn 75G
Intralipid 50G
Water for Inj. 420ml

Electrolytes
KCL 40 mEq
Pot. Phosphates 30 mEq
MgSO4 20 mEq
Ca Gluconate 10 mEq

Vitamins, trace elements and medications
Zinc Sulfate
Selenium 60 mcg

I was thinking of adding phlorizine to the 12 hour bag to set up therapies the next day.

Any thoughts anyone?
Thanks!

Fred
Member
Fred

Also Daniel you write that long administration will degrade phlorizin effects. I suppose I can add phlorizin to the IV bag during last 3-4 hours.

Also, it is unclear to me if phlorizin effects cancer cells more relative to healthy cells. The TPN bag contains 150 to 200G dextrose so this addition is interesting to me. TPN is what keeps my wife living for now but I don’t like all the glucose involved. If some of the glucose can be inhibited from entering cancer cells while healthy cells are allowed to feast that would be great.

Ergin
Member
Ergin

There is stg very special about phlorizin.Very interesting.Respects more search.
https://www.ncbi.nlm.nih.gov/m/pubmed/9889076/

Ergin
Member
Ergin

Hi Daniel,
There are too much price difference between 99% and ≥99%.
Which one did you use?
http://www.sigmaaldrich.com/catalog/product/sigma/p3449?lang=en&region=TR
http://www.sigmaaldrich.com/catalog/product/aldrich/274313?lang=en&region=TR
And there is phloretin,phloridzin dihydrate?
Thanks
Ergin

Emad
Member
Emad

Hi Ergin

what you think about this source https://www.badmonkeybotanicals.com/organic-apple-root-phloridzin-extract

it looks incredibly cheap , but I wonder its effect

what is the source that you are trying to get ?

Ergin
Member
Ergin

Thank you Emad,At last i took your attention to phlorizin.Daniel also tried to take our attention to this and sal before it is too late.
I am sure we will find a good way with you.

Emad
Member
Emad

Thanks for your help Daniel

I know how hard is it to read all these comments and questions even when you don’t have family visiting

wish a nice weekend for you and the entire family

Alex
Member

DO have a very nice weekend.
Thank you!

Ergin
Member
Ergin

Thank you very much Daniel,
Have a nice weekend.

Emad
Member
Emad

Hi Ergin

you mean , we will find a good way with both you and me !

Ergin
Member
Ergin

Yes Emad,Together we will be more powerful.
I am happy about your enterance into phlorizin subject.
I wonder if sal+phlorizin works without chemo or not?
Lots of treatments should work with phlorizin.
What do you think?

Emad
Member
Emad

Hi Ergin , yes I’m really focusing on phlorizin

if things go well , maybe my next protocol will be : Sal + 3-BP + Phlorizin + DCA + chemo

if there is something missing in this protocol , it would be MG , I believe in the statistics made by Prof Ray , as I never ever so incredible results like it !

the above looks like the strongest protocol in the world

if it just didn’t work properly then maybe a gun shot in the head will solve the problem hah 😀

Alex
Member

You may want to add Metformin on top of that to make it a little spiced up eh?
DCA MAY not work well with Sal. same feelings i had with CA+DCA
One is trying to inhibit, the other is trying to speed up things.
Maybe even metformin will not be a good idea. Cancer cell metabolism will slow down
What about 3-BP+Phlorizin+Dca+Chemo+Cimetidine+HyperThermia Locally.?! Maybe a little Arte here and there, a little aspirin and or diclofenac.
Save your bullets dear Emad.
Munition is low…

Emad
Member
Emad

why you are saying that DCA may not work well with Sal ?

yes sorry I didn’t mention metformin as my mother is using it now and will continue

also will add diclofenac soon

Walter
Member

I am asking myself the same question if SAL and DCA may work together or not. I found this paper which rather concludes a synergistical effect: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496345/
What do you think on it?

Alex
Member

Dear Walter.
I am no scientist, doctor etc. I have no medical training at all.
The reason i said that SAL, DCA combination may not be the best is because SAL in my limited understanding is meant to shut things down while DCA is doing the opposite, starting things up.
The research is likely correct compared to my humble, possibly wrong opinion.
On the other side of things:
SAL in my possibly wrong opinion is somewhat similar to Aspirin, the aspirin my mother takes with DCA, that now is making her pain worse, possibly meaning that it helps DCA in killing the cancerous cells.
I say possibly but the latest marker values indicate the rate of growth is reduced considerably with time.
This again was obtained with Metformin all the way and Lansoprazole.
A small ray of hope.

Many Many Thanks.
Alex

Alex
Member

Metabolic inhibitors i believe will decrease the volume of the blood vesels in the tumor.
It sounds to me like they would be best administered after chemo, just after. To somewhat close the doors behind.
Cheers

Ergin
Member
Ergin

:)))First a head shot to me,than yourself please.
Emad may be heat +above is the strongest.But can you reach a hyperthermia in Libya?

Emad
Member
Emad

No unfortunately we have only guns here in Libya :)))

but really what do you think about MG ?

I’m always thinking about the statistics , 78% respond , and 38% of them cured !!

the problem when using a treatment that we really believe in then it just doesn’t work , we feel like we did the best and failed

we need to think with our minds not hearts

Alex
Member

remind me please,
what is it that you used with paracetamol that decreased the marker with 1 point?
i remember something like that, and it may hold some answers to our quest in finding the solution

Emad
Member
Emad

we used 10 cycles of Taxotere , the first 6 were very good with DCA

the other 3 didn’t work and the markers climbed , so Taxotere cannot work alone

then the last cycle we again used taxotere but we didn’t have DCA , so we added several things , metformin , paracetamol , chloroquin , lansoprazole , sulfasalazine , cimetidine

the markers declined a little bit from 740 to 714 , but we stop some of them lately when received DCA

we continued on metformin 1g , chloroquine 200mg , lansoprazole 60mg

when added with DCA , the markers declined first to 670 then to 460 , but when DCA stopped for 3 days before chemo (which is a bad mistake) the markers climbed to 560

i felt that DCA are the major role in our fight , and the others are maybe have little on no benefit , so we stopped them

Ergin
Member
Ergin

Emad,While Daniel is not around here ,we can make some gossip:)
When i was searching MG ,i found an article.
https://www.ncbi.nlm.nih.gov/pubmed/11707430/
Brain mixing knowledge about MG.It helps chemo,and diabetic patients responds chemo better than the others because of more MG in their blood. What can you say about it:)?

I also have MG at home and afraiding it to use.
Also you can not use it with DCA and metformin as Daniel said before.

Ergin
Member
Ergin

And i wonder if SGLT1 inhibition is too much necessary for our purpose.
I bought oral dapagliflozin(SGLT2 inhibitor) from pharmacy but waiting to use before chemo.
There are different types below but very very expensive.But i put them only to have knowlodge.

Inhibitor Name SGLT1 SGLT2 SGLT4 SGLT5 SGLT6
Dapagliflozin ++++
Canagliflozin +++
Empagliflozin (BI 10773) + +++ + ++ ++
Sotagliflozin (LX4211) +++ ++++

Ergin
Member
Ergin

True chart should be this.(copy paste didnt work)

Inhibitor Name SGLT1 SGLT2 SGLT4 SGLT5 SGLT6
Dapagliflozin ++++
Canagliflozin +++
Empagliflozin (BI 10773) + +++ + ++ ++
Sotagliflozin (LX4211) +++ ++++

Ergin
Member
Ergin

Oh my god!I couldnt create a chart.
In summary Dapagliflozin and Canagliflozin inhibits only SGLT2.
Phlorizin and others inhibit both SGLT1 and SGLT2.
The othes are expensive and iv and not proven yet.
I wonder if we can achive our target with oral dapagliflozin.
How can we test?The urine or blood?

Alex
Member

Urine+Blood is best Ergin
take care brother,
Very important to tell your mother how much you lover her.
No money in the world will help her more, no treatment will help as much as real love and motivation, ambition and tenacity.
I hope for the best for you and your mother, good luck! Try to relax this weekend a little.

I don’t know what to do… i am “stuck-blocked”.
I think Daniel can help very much, all of us, but he is very busy+disclaimer
I have no experience and time is against us all.
Markers go up, i don’t know what to do, doctors don’t know what to do……
Nobody seems to know anything or have no interest in it
Treatments go very nice in the lab tests but they don’t seem to do be sufficient in real situations.
I will wait for this last test to see personally and then i send you the results from past to present. Maybe your doctor will say something.
Nobody seems to actually know about this cancer problem, as if it’s not even a real problem in the world.
There seems to be a divided society, “normal” and cancer society. Very separated……
Normal people have problems with the weather outside and get frustrated over it….. i have a problem with not knowing why my mother’s body emits a smell even after shower. It’s strong when she feels bad.
Nobody knows…
Sometimes i feel i am very stupid, asking questions and not getting answers from qualified people, kinda makes me realize… you know… they are only aware of what others discovered, they didn’t discover anything. Not as dumb as i thought
I’m somehow certain that if i were to be a doctor in medicine for 30+ years, i would know a little more about cancer.
And even if not me, someone… someone else who is actually motivated, interested, curious.
I don’t know what i am doing, now more than ever we need help, guidance for effective, strong treatments.
I don’t know what is good and what is not.

Take care,
Alex

PaulF
Member

Hi Alex

I feel your frustration. It is so difficult to come up with the correct protocol.

My sister has to have her chest cavity drained every few days due to the pleural effusion. In her last draining there was a lot of tissue in the fluid.
Anyone have any idea what this would be?

Paul

Alex
Member

tissue?
This could be good… could be tumor cells dying.
If i am not mistaken, your syster didn’t have surgery, the liquid seems to me, from my basic knolege that it is coming out due to massive inflamation, an immune system response to the tumor/s.
Sounds to me like anti-oxidants and metabolic inhibitors could help a great deal, besides the usual liquid drain.
You want more and more more and more more and more tests done, auto-immune, metals, minerals, immune system, endocrine, glands, etc. everything possible, the more you know the better.
Maybe someone else may have a better opinion

Ergin
Member
Ergin

Drugs sold in nearly all pharmacies.(SGLT inhibitors)

”The predominance of SGLT2 over SGLT1 expression in tumors
is potentially advantageous for the development of novel
therapies to treat pancreatic and prostate tumors with SGLT2
inhibitors approved by the Food and Drug Administration for
diabetes treatment. For those tumors that express SGLT1, the
current development of SGLT1 and dual SGLT1/2 inhibitors for
diabetes may also prove to be useful in cancer therapy.”
http://www.pnas.org/content/112/30/E4111.full.pdf

”Scientists have, for the first time, demonstrated the importance of sodium-dependent glucose transporters (SGLTs) in delivering glucose to pancreatic and prostate cancer cells. Their study results show promising evidence that current SGLT inhibitor drugs (such as those commonly used to treat diabetes) could potentially be used to block glucose uptake and reduce tumor growth in these cancers.”
https://www.sciencedaily.com/releases/2015/07/150720145325.htm

Ergin
Member
Ergin

It is a very old article but good knowledge about total phlorizination.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC435965/pdf/jcinvest00731-0086.pdf

Ergin
Member
Ergin

And here it says it is very hard to reach total phlorizination by oral usage of phlorizin
https://www.jci.org/articles/view/100618/version/1/pdf/render

Ergin
Member
Ergin

Dear Daniel,
Phlorizin is on the way,2 weeks later we will try.
I mean after we reach total phlorizination after some hours with necessary dosages(no glucose in blood),
if we want to use chemoteraphy we have to give premedication like dexamethasone as we always did before.
But when we give dexamethasone,the blood glucose levels goes very high with some patients like
my mother or with all patients i dont know.Is there a mechanism that convert stg to glucose in body after premedication?
In phlorizin patent it is not clear.They only say,very small dosages chemo they gave.Is it because of a possible reaction because they dont give premedication like dexamethasone?
Or without glucose in healthy cells,chemo also damages them?
Why very small dosages chemo they gave after phlorizination?
Kind Regards
Ergin

Ergin
Member
Ergin

Here is a link about clinical trials on HSP inhibitiors.
Results are disappointing.
http://www.tandfonline.com/doi/full/10.1080/13543784.2017.1302428

sirsna
Member
Ergin
Member
Ergin

Dear Ieva,
If you really want to use,i will send you phlorizin%99 purity 10 gr from sigma unopened box which is enough for you to try i think.
If you accept ofcourse.And can you find hyperthermia or are you taking radiotherapy and dont respond well?When will be your next chemo?

Kind Regards
Ergin

sirsna
Member

Thank You for Your good intentions!
I can not answer correctly about next steps as I should clarify them for myself. My carboplatin/docetax is finished as they usually give 6-8 cycles. Now I must do something local with liver, but MRI is needed to decide (chemoembolization/radioembolization/etc). I have few options for systemic maintenance therapy from my oncologist, but she is relaxed and leaved it to decide myself :). She could give me Xeloda. I have done somatic gene mutation test and send it to one clinical trial with 11 medications in NKI. So they decided that I can enroll and they could give me Olaparib. But I am not sure at all that this could give me something :). As I have only one somatic allele changed in BRCA1. And I do not believe much in those targeted therapies.
So, as You see, not much certainty.

Ergin
Member
Ergin

Olaparib is a very expensive drug.Will they give it free?Here 1 year usage for a patient is nearly 100.000 euros.

sirsna
Member

yes, without medication cost, but with other costs, just I am not sure, that this is for my case, as I do not have germline mutation in brca, I even do not have full somatic mutation in brca, just “copy number”. Maybe I should try this is drug because I could not afford to pay it myself and maybe this is some great chance? I don`t know. I talked with theoretical profesor in genetics, but we do not have much experience here with this, and he said I should not focus on brca in my case.

Ergin
Member
Ergin

Here patients are taking signatures for government to give it freely.Is it really very effective?
My experience:Some targeted terapies fit very good to some patients like bevacizumab (avastin).
If i were you,i would think about to enter trial if it is really free and doesnt harmful.Avastin has serious side effects for example.

Ergin
Member
Ergin

BTW phlorizin is a perfect natural substance as you very well know😀.
No serious side effects,a big opportunity for patients to try.

Ergin
Member
Ergin

Complete phloriziniation (no sugar inside a tumor) is directly cytotoxic.But doing it half does not mean that it is not effective when used with other powerful chemo,radioterapy or hyperthermia.If you can do,complete phlorizination is perfect.
My idea is combining it with Donc’s fasting protocol for some days.Before and after treatments.Doing it after treatments is very very important because cancer uses SGLT to repair itself which we totally or partially block it with phlorizin.

ovidiu
Member

Synergistic inhibition of colon cancer cell growth by a combination of atorvastatin and phloretin.
https://www.ncbi.nlm.nih.gov/pubmed/29399200

Ergin
Member
Ergin

Super finding.Thanks alot Ovidiu.

Ergin
Member
Ergin

SGLT1 inhibitor (Phlorizin) sensitized prostate cancer cells to EGFR inhibitors (Gefitinib and Erlotinib).

http://onlinelibrary.wiley.com/doi/10.1002/pros.22692/full

Ergin
Member
Ergin

Phloretin+Cisplatin:

https://www.spandidos-publications.com/10.3892/ijo.2015.3304

The aim of the present study was to evaluate the anticancer effects of phloretin on NSCLC cell lines and the results revealed that phloretin could exert anticancer effects on NSCLC cell lines and it also enhanced the anticancer effects of cisplatin.

Ergin
Member
Ergin

For patients who is new to GLUT can directly read 4.Discussion on this article.A good summary.
https://www.sciencedirect.com/science/article/pii/S1021949817300856

marcosbomber901
Member

Hi Ergin
I’m going to use phlorizin for my wife,which was the product that you bought in Sigma Aldrich ?.The CAS number does not match, but i think that phlorizin dihidrate is the same product.

Ergin
Member
Ergin

Hi Marcos,
Yes it is same product.
Good Chance!

marcosbomber901
Member

My doctor wants to apply florizina before chemotherapy and 3BP,but you do not have 8-12 hours of time for your application before the chemotherapy according to the protocol described by Daniel.Then you can apply a bolus of phlorizin de 6mg per kg,what would be 360 mg,that dissolved in 7.2 ml ethanol would give us 50 mg of phlorizin per ml of ethanol.
How much saline solution would be necessary for this mixture?.

Ergin
Member
Ergin

Hi Marcos,
Please read every sentences very carefully.Did you show the 2 articles to your dr?
Drs mostly does not have time to read.
There are different strategies in that article if you read carefully.
First they give a dose bolus(fast) to make cancer cells cannot take anymore glucose.After that they use low doses
for maintanance the sugar deprivation.
Do you need help for the protocol?

Ergin
Member
Ergin

And please begin with low dose.
You have to choose 1 of the below for the begining.
1.Low dose chemo with high dose+ long duration phlorizin?
2.Normal dose chemo with low dose phlorizin.?
How many grams of phlorizin do you have?

Ergin
Member
Ergin

Btw will you use hyperthetmia with phlorizin?

Ergin
Member
Ergin

Hi Daniel,
Very interesting,i did not know that.Thanks for this link.
Btw i dont take any mails from this website anymore.
Do you know the reason?
Kind Regards
Ergin

Ergin
Member
Ergin

Yes you are right,all mails goes to junk.

marcosbomber901
Member

Hello Ergin and Daniel thanks for their respuestas.Comenzare Phlorizin with usual chemotherapy and bolus dose of quick application.I can make the mixture that Daniel described on this site and manage only rapid infusion of 10 minutes, and store the rest at -20 C ?.What would be the only protocol to manage rapid infusion in 10 minutes that lasts 1.5 hours?.I am trying to raise money for combined with hyperthermia because here is very expensive 450 euros per session,This would next to an inhibitor of HSP90 as a 17-dmag or celastrol or EGCG.
I have 15 gr of Phlorizin.

marcosbomber901
Member

I have put the protocol that my doctor has proposed in the forum to bear your valuable opinions.a greeting

Ergin
Member
Ergin

Hi Marcos,
It would be honour for me to help you if you accept ofcourse in anything you need.
Please write me from private.

marcosbomber901
Member

thank you Ergin.Very friendly as always

Ergin
Member
Ergin

Hi Marcos,I understand that you only want to use only
10 min fast infusion.I believe you will see a benefit.
For intramuscular injection you will need 25grams of phlorizin for a 50 kg person.That means 500 mg/kg.
As you know there are 2 patents.There are 3 years between them.Later they begin iv i think.
Fasting overnight is must.And also if she can not eat after treatment for some hours,it would be better.
And dr can give phlorizğn also after chemo with small dosages.

Ergin
Member
Ergin

Marcos,tobe honestly i understand you are using translator to communicate with us.We are also talking private.But i really dont understand what you understand.So i prefer to talk with you here.Please open a post on forum side or we wish it from Dear Daniel.

Ergin
Member
Ergin

Please dont forget me and Daniel are both here to help you and the believers of the powerfull phlorizin.
We both loose our lovely patients and we know the truth about cancer.The truth is do everything by yourself.
Take your own risk.I highly appreciate what you are doing but please find someone who knows good English.a

marcosbomber901
Member

Hi Ergin
The publication is open in the forum with the protocol that my wife is going to continue.The title is endometrial cancer protocol stage 4.
I know that Daniel and you help me in everything I have no doubt

Ergin
Member
Ergin

If you enter this website ,be sure that you or your patient will live longer than drs expected.But you will never understand.
This is the truth.
My English is not enough to write the whole story.
But if you are in this page,you have a chance about a cure.

marcosbomber901
Member

Hi Ergin.
I know that the cure is possible, thanks to all of you who write on this page.

Ergin
Member
Ergin

Hi my friend Daniel,
You have a wonderful website which includes full of knowledge.You gave too much time.Really too much time.
If i have read 10.000 papers in 2,5 years,i cannot imagine how many you read…
Could you please tell me the difference between a stage 2 and stage 4 cancer patient?
And how many cured patients you have seen?
Yes cure is a wonderfull word.And may be out of this world.
One day in the past,you said me that nothing is considince.
Yes Daniel you were right.

If all the cells in our body is living by the help of glucose and cancer cells has to be alive and has to divide contibiously by using glucose,you know the drug.

We worked too much about hyperthermia…and phlorizin with fasting…

Alex
Member

Bro, i hope you are ok.
We are still here…. despite all the problems.

What are you trying to say?

Alex

Ergin
Member
Ergin

Yes Alex you are right.It looks like an unlogical message.
I missed too many sentences.Forgive my excitement.
It should be 1000 papers ofcourse not 10 thousand.
I heard some good news about phlorizin just like in the article.Some people are doing fasting very serious.

I hope Marcos will use phlorizin with a good protocol and she will get benefit.

Ergin
Member
Ergin

Interesting!
I hope everyone is ok:)

Ergin
Member
Ergin

I am sorry Daniel,
I have to write these words.Some of you may be thinking that i lost my mind after i lost my mom and dad in 2 months.

The Last month of my mom,she was crying for not to die.
She was praying for me to make her phlorizin with a surgery.
I prefer first 3 BP and salinomycin,although nurses said she has 1 month.Nurses are very clever and has a great experience.
Last month…..very hard,nothing works.Who knows when is last month?What are the clues?I talked too much how it comes.

I am seriously thinking to leave cancer world but not Daniel.
Noone is talking here about surgery.The most powerful option.And phlorizin with heat ofcourse.

Ergin
Member
Ergin

Hi Daniel,
I am again drunk.I miss mom too much.I feel i make air pollution here.I wrote my last words here on phlorizin page which makes me verry happy
I love you my BROTHER.

Ergin
Member
Ergin

Comment moderated

Ergin
Member
Ergin

Hi Daniel,
You are saying thanks to Ovidiu without reading the messages.
I am very sure that you never read his messages.
Bored erlotinib messages.
I will write you a message here.

Ergin
Member
Ergin

There are 2 types of engineers in the world.
1.You give his/her salary,tell them what to do.
Yes they work perfect.They stucked into a subject and they can work forever for you on a subject.
2.The one which i was thinking of you.Was!

Alex
Member

Brother, take care of yourself and family. Please!
And as a side-note. Mother had surgery, but that only addressed the bulk of the tumor, not the infiltrated cancerous tissues in her spine or micro-tumors in her lungs.
Surgery and chemo is life-saving for some people in some cases, that’s the reality, statistics etc…. The rest sadly, do not live much.

What you did, what Emad did, what i am doing and not to forget what Daniel did, was and is pure love. I’m not even sure the substances matter all that much, maybe some but then there is love and care.
I can be corrected sure… but it’s the way i see it in person with my mom, it’s what i personally believe.
I see other people who have not been cared for who have long died sadly.
I strongly believe the nursing part is highly important next to treatments, perhaps even more, to increase quality of life.

Yes some people may be “lucky” and benefit from some substance or treatment etc hugely, so yes anything is worth a shot, so long the risks are low to very low to none, supervised by their doctor.

So please, take care of yourself and your family.
PS, if you are coming, i would love to meet you.

Your brother, Alex

Ergin
Member
Ergin

Moderated