14 replies to this topic

[Florian Xavier]

to prevent or cure cancer ?

– Curcumin known as tumeric, Isoflavone from soybeans, Indo-3-Carbinol from cruciferous plants, C-phycocyanin from spirulina, Reservatrol from grapes, and Quercetin, a flavonoid present in fruits, vegetables, and tea

http://www.scienceda...31122103901.htm

[joelcairo]

The "super cocktail" inhibited cancer growth by over 80% while killing 100% of the cancer cells? Huh?

I thought the Science Daily article got the specifics wrong, so I found the original paper. The abstract says much the same thing. I haven't read the full study; perhaps the discrepancy is the result of looking at different time periods or different concentrations.

http://www.jcancer.org/v04p0703.pdf

Also from the abstract: "The compounds were ineffective individually." Again, huh? This is hard to believe given the enormous amount of in vitro evidence supporting all of these compounds (except C-phycocyanin perhaps, which I am not familiar with). But again, this is presumably due to the exact experimental conditions.

Final thought: There's certainly nothing magic about this particular combination. Given how powerfully anti-cancer the individual compounds are, who would have predicted this experiment WOULDN'T work? It would probably be easy enough to come up with a totally different cocktail that works just as well.. EGCG, apigenin, pterostilbene, tocotrienols, etc.

Edited by joelcairo, 07 December 2013 - 06:51 PM.

[Florian Xavier]

sometimes combinations of drugs cancel each' others effects.

[joelcairo]

That can happen, and who knows maybe one of these substances was contributing nothing or actually making the overall formula less effective. Without detailed testing of every possible combination, there's no way to be certain of that.

I'm glad to see this work is being published. I'm a big proponent of combining a spectrum of anticancer compounds rather than relying on just one or maybe two interventions, so having supporting evidence is important. I'm just saying that there's no reason to believe that there's anything unique about this particular combination of phytonutrients.

[niner]

They said that the drugs were used at 'bioavailable levels', so I checked the concentration of resveratrol they used (0.5e-6 ug/ml), since I'm familiar with its PK. That concentration works out to 2 uM, which is technically achievable in humans, but you'll need repeated large (or well-formulated) doses to come close to the conditions of the experiment, where cells were constantly soaked in these compounds. I would imagine that the other compounds are similar. It would be interesting if they could try a series of leave-one-out experiments, and see if they could replicate the results with fewer compounds.

[RWhigham]

"I found the original paper."  http://www.jcancer.org/v04p0703.pdf

Cancer Fighting Super Cocktail - made from 6 over-the-counter supplements http://www.cancerdef...niversity/3375/  From the original paper, the cocktail takes 8 days to kill 100% of cancer in vitro.

 

Unfortunately, the Indole-3-carbinol concentration seems to be unattainable in vivo, and if attainable, might be too toxic.

 

When this thread started, the curcumin concentration also appeared unattainable. But with the introduction of UltraCur® from Ultrabotanica, it should now be attainable by taking 4 capsules at a time twice daily (for the 8 days). A plot of blood concentration vs time from Ultrabotanica would help verify this.

 

The 6 ingredients and their concentrations from the paper are:

 

Indol-3-Carbinol 4 ug/ml - appears to be 40x the concentration safely attainable in humans

Curcumin 2.25 ug/ml  - 4 capsules of Ultrabotanica UltraCur®, repeated twice daily

Quercetin 1.5 ug/ml - 1 capsule of Now Foods 100 mg EMIQ, repeated twice daily

Genistein 3 ug/ml - 2 capsules of Vital Nutrients Genistein  (once daily, half-life is 46 hrs)

C-phycocyanin 50 ug/ml - 2-3 heaping tablespoons of Nutrex hawaiian spirulina daily

Resveratrol 0.5 ug/ml - 2-10 caps (1-5 g) per dose of Mega Resveratrol, three doses/day

 

Supplement calculations:

 

Indol-3-Carbinol 4 ug/ml

http://cebp.aacrjour...tent/15/12/2477 "No detectable I3C was found in any plasma sample regardless of I3C dose or sampling time." (I3C doesn't survive human stomach acid). The I3C metabolite 3,3′-diindolylmethane (DIM) is found instead. A 400 mg dose of I3C gave about 50 ng/ml of DIM in the blood. A 1,000 mg dose gave about 600ng/ml, but more than 1,000 mg gave no further increase.  A 200 mg dose of Bioresponse® DIM gives 90 ng/ml of DIM in plasma. A larger dose had little effect. So about 0.1 ug/ml of DIM in vivo is the best we can do. (Bioresponse® Dim is micronized for 2x better absorption).

 

Curcumin 2.25 ug/ml

One capsule of UltraCur® is reported to give a plasma level = 610 ng/ml at peak. http://www.longecity...pplement/page-2 To get 2.25 ug/ml peak reuqires, 2.25ug/0.61ug = 3.7 < 4 capsules. A human has about 5L of blood.  2.25 ug/ml x 5,000ml = 11.25 mg in blood.  4 capsules contain about 50 mg of curcumin - more than enough. A human has about 40L of fluid.  2.25 ug/ml x 40,000ml = 90 mg.  8 capsules contain about 100 mg, so tissue saturation is plausible with a repeated 4 capsule dose.

 

Quercetin 1.5 ug/ml

Enzymatically modified isoquercitrin (EMIQ) is water soluble.  Bioavailability of oral EMIQ is 35% (in rats) https://www.ncbi.nlm...pubmed/19952424  "According to pharmacokinetic data, the absorption of EMIQ is up to 40 times greater (Cmax) and 15 times greater (AUC) than that of quercetin and reaches peak levels in the bloodstream in just 15 minutes." http://naturalfactor...tin-emiq-en-us/  To get 1.5 ug/ml in 5L of blood at 35% absorption takes (1.5ug x 5,000)/0.35 = 21 mg of EMIQ. To get 1.5 ug/ml in 40L of body fluid takes 8x as much = 168 mg of EMIQ.  Now Foods EMIQ has 100 mg/capsule, so tissue saturation is plausible with a repeated 1 capsule dose. (Non EMIQ quercetin can have 40x less bioavailability and take up to 7 hrs to peak).

 

Genistein 3 ug/ml

 https://www.ncbi.nlm.nih.gov/pubmed/12587954/  "the absolute oral bioavailability of genistein in male and female rats was 7 and 15%".

"Pharmacokinetic parameters Cmax, Tmax and AUC were similar to those reported in humans, which supports the use of the rat model for genistein toxicity studies." https://www.ncbi.nlm...les/PMC4010305/ Half life is long at 46 hours. Oral absorption is close to 90%, but there is extensive 1st pass metabolism in the liver. To get 3 ug/ml in 5L of blood at 7% bioavailability takes (3 ug/ml x 5,000)/0.07 = 214 mg of genistein. Vital Nutrients Genistein has 125 mg/capsule, so 2 capsules are required. To get 3ug/ml in 40L of body fluid may not more, because the blood concentration half-life of 46 hr makes it plausible that body fluids are saturated.

 

C-phycocyanin 50ug/ml

This comprises about 9% of Nutrex hawaiian spirulina. 1 tsp (3 g) has 270 mg. Several authors say its bioavailability is "high", although  its altered by the gut, and then again by cells into very biologically active forms. To get 50 ug/ml in 5L of blood at 50% availability takes (50 ug x 5,000)/0.5 = 500 mg which is about 2 tsp of spirulina. To get 50 ug in 40L of body fluid takes 8x as much = 16 tsp, but it may build up (I didn't find half-life data), so 2-3 heaping tablespoons daily would be enough.

 

Resveratrol 0.5 ug/ml

Resveratrol has high absorption but low bioavailability. About 70% of an oral dose is absorbed, but its mostly excreted as metabolites in the urine. The intestines and liver metabolize it such that only trace amounts of unchanged resveratrol are found in plasma.  https://www.ncbi.nlm...pubmed/15333514 (2012). There has been extensive research into enhanced delivery methods. https://www.ncbi.nlm...pubmed/21978644   Commercially available micronized resveratrol at 5 g/dose almost works. After a 5 g dose, it reached a peak of 0.5 ug/ml is one patient out of six, averaged about 0.15 ug/ml in 4 of the patients, and only reached 0.05 ug/ml in a 6th patient. The peaks occurred from 2 to 4 hr after dosing, then concentration dropped quickly and became undetectable at 8 hrs.  https://www.ncbi.nlm...les/PMC3173869/   Micronized resveratrol (Mega Resveratrol, 120 capsules, 500 mg/capsule, 99% pure trans-resveratrol) is about $90 for 60 g. It would likely take 15 g per day for 8 days to approximate the desired amount. This would take two bottles at $180. However, the metabolites which have 20x greater concentration than the unchanged resveratrol are also active against some types of cancer, so this could be over kill. So 1g to 5g 3x/day may suffice.  http://www.sciencedi...308814612004967  NB: The original paper used pure trans-resveratrol from Sigma.

 

Comment:

The resveratrol alternative, pterostilbene, is similar to resveratrol and is much more bioavailable, although not studied in this combination. If I had cancer, I would add it to the stack. The impossible concentration of I3C may have been essential. However, lower concentrations of this stack for a longer time, say 8-12 weeks, may also be effective.

 

Edited by RWhigham, 31 December 2016 - 07:37 PM.

[YOLF]

How is DIM metabolized? For I3C to outperform DIM, it's obviously producing competition for metabolism somewhere. So what can be added to it? It appears that Genistein often works in combination. Is there a coadministration study demonstrating higher levels of DIM in the blood when taken in combination?

 

What type of toxicity are we talking with the I3C? Can it be bypassed? I3C isn't absorbed and gets turned into more than just DIM, so perhaps the DIM isn't directly responsible for the toxicity? Who did this study? Are they likely to have wasted their time with unobtainicillin? Or are they thinking circles around us?

[RWhigham]

What type of toxicity are we talking with the I3C?

 

I3C toxicity:

https://ntp.niehs.ni...arbinol_508.pdf   "After subcutaneous administration of 500 mg I3C/kg body weight, 3 out of 4 rats died."  After administration of 0.3 mg I3C/kg BW guinea pigs showed signs of intoxication the first dose, exhibited moderate depression, trembling, tachypnea, polypnea, irregular breathing and increased vesicular lung sounds after 2nd dose. After 4th dose on day 4 sacrificed guinea pigs showed hepatic steatosis and interstitial pneumonia with septal hyperemia. After beagle dogs were given 100 mg/kg BW daily one was moribund by week 5 and had to be sacrificed. The dose was reduced for the other dogs. etc for mice

 

Dim toxicity:

http://cancerres.aac...upplement/170.1  In beagle dogs the average concentration of DIM reached 5 ug/ml with sufficient dose, but DIM was very toxic at that level.

 

I3C vs DIM  https://bioresponse....-13C-vs-DIM.asp "Because I3C gets converted in the stomach to intermediaries that have undesirable side effects, I would not recommend its use." Dr. H. Leon Bradlow. DIM has not shown toxicity at recommended doses.

Edited by RWhigham, 01 January 2017 - 07:43 AM.

[Danail Bulgaria]

Thats all very nice. Only it is only for a breast cancer.

 

How about the male's cancer - the prostate cancer. Do you know such an effective combination for it?

[RWhigham]

 

 

Thats all very nice. Only it is only for a breast cancer.

Actually, all breast cancer is not the same. This cocktail was only tested on a particular line of breast cancer cells. However, to me it's plausible that it should have wider efficacy. I thought all cancers were similar? 

[Danail Bulgaria]

Unfortunatelly, not.

 

The cancers are different depending of the tissue they come from. They differ in everything - morphology, malignency, efficiency of drugs, whatever you say.

Because of the difference of the morphology the pathoanatomist can say if this is a primal tumor or a metastase.

The most malignant cancerin the human body is the malignant melanoma from the melanocitic cells of the skin. The least worst from all cancers is the skin basal cell carcinoma, which originates from the babal histological layer of the skin.

Drugs against cancer of the blood cells don't have any effect on the cancers of the skin.

[YOLF]

Thats all very nice. Only it is only for a breast cancer.

 

How about the male's cancer - the prostate cancer. Do you know such an effective combination for it?

 

I seem to remember that I3C and DIM, as well as many other forms of aromatase inhibition in the right group of men lead to a decrease in prostate cancers or higher recovery rates.

 

As for blood cancers being different, they don't need to penetrate into tissues in order to be effective. Do skin cancer drugs work against blood cancers?

 

I'm not saying all cancers are the same, but something like p53 activation seems to be widely beneficial against them and a common feature shared by a variety of research... For instance, Resveratrol is great against a variety of cancers and is both a potent p53 activator as well as a potent aromatase inhibitor. I believe turmeric/curcumin has similar properties.

 

I think the data in this case would side with this cocktail and many of it's ingredients being widely effective.

[YOLF]

 

What type of toxicity are we talking with the I3C?

 

I3C toxicity:

https://ntp.niehs.ni...arbinol_508.pdf   "After subcutaneous administration of 500 mg I3C/kg body weight, 3 out of 4 rats died."  After administration of 0.3 mg I3C/kg BW guinea pigs showed signs of intoxication the first dose, exhibited moderate depression, trembling, tachypnea, polypnea, irregular breathing and increased vesicular lung sounds after 2nd dose. After 4th dose on day 4 sacrificed guinea pigs showed hepatic steatosis and interstitial pneumonia with septal hyperemia. After beagle dogs were given 100 mg/kg BW daily one was moribund by week 5 and had to be sacrificed. The dose was reduced for the other dogs. etc for mice

 

Dim toxicity:

http://cancerres.aac...upplement/170.1  In beagle dogs the average concentration of DIM reached 5 ug/ml with sufficient dose, but DIM was very toxic at that level.

 

I3C vs DIM  https://bioresponse....-13C-vs-DIM.asp "Because I3C gets converted in the stomach to intermediaries that have undesirable side effects, I would not recommend its use." Dr. H. Leon Bradlow. DIM has not shown toxicity at recommended doses.

 

 

Ok, it looks like it's getting harder, but if we could identify and reduce the toxicity caused by metabolism of I3C or even DIM in the liver and perhaps some other organ systems, this could be doable.  I'm thinking a sufficiently skilled pharmacology expert could come up with an off the shelf solution to make this feasible and that this is why the research was done. 

[Danail Bulgaria]

The skilled pharmacology expert may not be able to help for new molecules, because information of how they interract with opther medications is not yet available.

 

If I3C and DIM are already used in the medical practice for several years, then an oncologyst prescribing these medications, and following the patients would be the best source. 

[pamojja]

Looks almost like a tiny fraction of the latest LifeExtension suggestions for cancer adjuvant therapy:

 

 Cancer Adjuvant Therapy (2016, LEF).pdf   1.37MB   4 downloads

• Apigenin: 20 – 50 mg daily
• Astaxanthin: 6 – 12 mg daily
• Astragalus: 2000 – 4000 mg daily
• Blueberry: 900 – 1800 mg daily
• Chrysin: 900 – 1800 mg daily
• Curcumin: 400-2400 mg daily of a BCM-95® extract with food
• Coenzyme Q10: 200-400 mg daily with food
• Cruciferous vegetable concentrate blend: 1 – 2 capsules daily
• Enzymatically Modified Rice Bran: 500 – 1000 mg daily with food
• EPA-DHA fatty acids: 4000 – 8000 mg daily of fish oil concentrate supplying up to 2800 mg EPA and 2000 mg DHA with food
• Gamma Tocopherol: 400 – 1000 mg daily with food
• Garlic: 1200 – 4800 mg daily with food
• GLA (gamma-linolenic acid): 700 – 900 mg daily with food
• Grape Seed Extract: 300 mg daily
• Green Coffee Extract: (standardized to 50% chlorogenic acid): 400 mg three times daily, before meals
• Green Tea Extract: Up to 3000 mg daily of EGCG without food
• Indole 3 Carbinol (I3C): 200 – 600 mg daily
• Lignans : 75 – 125 mg daily
• Lipoic acid (Sodium R-lipoate): 600 – 1200 mg daily on an empty stomach
• Lycopene: 15 – 45 mg daily with food
• Melatonin: 10 – 50 mg between 8-10pm
• Panax ginseng: 200 – 2000 mg daily of standardized to contain 4-7% ginsenosides
• Pomegranate: 280 – 375 mg daily of punicalagins
• Proteolytic Enzymes: 2 – 10 pills, 3 times daily on an empty stomach of a formula containing pancreatin, papain, trypsin, and
chymotrypsin
• PSK (Coriolus versicolor): 3000 mg daily of a 40% polysaccharide extract
• Pterostilbene: 1 – 3 mg daily
• Quercetin: 1000 – 3000 mg daily
• Reishi: 980 – 3000 mg daily of standardized to contain 13.5% polysaccharides and 6% triterpenes
• Selenium: 200 – 400 mcg daily with food
• Silibinin: 225 – 450 mg daily
• Sulforaphane: 400 – 1600 mg daily (broccoli extract)
• Vitamin C: 4 – 12 g daily
• Vitamin D3: 2000 – 10௘000 IU daily with food, based on individual blood testing. Optimal blood levels of vitamin D are 50 – 80 ng/ml.

 

Edited by pamojja, 04 January 2017 - 06:37 PM.