Curcumin formulation - cancer/stroke


This webpage is a recipe for getting Curcumin into the bloodstream to help

kill cancer and increase brain function in stroke patients. 

The story is long but the recipe is potentially revolutionary. 

From Brad Culkin, Phd in chemical engineering and stoke survivor

My sisters mother in law is dying of cancer so I did research and found a cure in my opinion.

I take this Curcumin formulation now and I am getting over my stroke incredibly quickly. Cosmic Karma?

I'm CTO and founder of New Logic Research, a membrane separation based tech company in California. I am not a doctor and have no medical training. I do understand chemical transport through membranes. Chemical transport and absorption of curcumin through the lipid membranes of the gut into the blood is largly controlled by its bioavailability.  If you bear with me I will present evidence here on how to solubilize Curcumin and how to get Curcumin into your blood at high concentrations using basic principles of chemical engineering and some simple kitchen chemistry. I have a PhD in Chemical engineering. I'm 60 years old.

In December of 2009 I had an infarction which caused a stroke. Trust me when I say this powerfully motivated me to seek chemical agents that can induce Neurogenesis. This resulted in five years of a diligent effort first to do an internet discovery of Curcumin the promising molecule, and then to gain internet understanding of Curcumin.  My goal was to figure out the transport issues controlling its absorption and bioavailability.

Recently I have turned to researching Curcumin and cancer because a close relative is dieing of cancer even as I write this.
The promise of curcumin as a potential cure for cancer is obviously great.

For example this paper suggests that in theory based on in vitro (Petri dish) experiments, if one could reach blood levels corresponding to 2.5 grams Curcumin per 100 kg body weight every cancer cell in the body would die by necrosis in less than one hour while normal cells would remain unharmed.


http://mct.aacrjournals.org/content/3/9/1101.full.pdf+html


At half this dose 80% of cancer should be killed by apoptotic self destruction which is preferred over necrosis since it is much less destructive to collateral tissues. This is amazing work and a promising result.

So what is the current state of the art for commercial products attaining these blood levels in vivo? Unfortunately it's about 1000 times less than even one gram equivalent.  Below is a review of the current offerings of various super curcumin formulations.


http://www.nutritionj.com/content/pdf/1475-2891-13-11.pdf

The best of this lot, while admittedly being hundreds of times better than simply eating Curcumin powder, still achieves only a few mg per hundred kg body mass.  1/1000th of what's desired to kill cancer.

Now let's review some home remedies and I'm sorry to say, why they also won't get you to one gram absorbed and bioavailable.

It is widely known that Curcumin is nearly insoluble in water and so taking solid powdered Curcumin is a complete dead end. Apparently it is less widely known that Curcumin is only sparingly soluble in common oils and fats. The layman's measure of curcumin solubility is color. The notion that deep red is better than light red which is better than yellow when it comes to evidence of solubility is not foolish. I use it myself as a measure of solubility but like life, it's complicated. Curcumin can be dissolved into fat at high temperature and the deep red seen at high temperature is indeed Curcumin in solution, but as the fat or oil cools this solution precipitates microcrystalline Curcumin which, though still red colored, is not in solution at high concentration anymore and so is not likely to be significantly absorbed in the gut.

Sorry, but based on solubility data alone fat is not a viable carrier for getting grams of Curcumin into the blood for cancer therapy.

So let's talk about my own failures and experiments and one eventual success. My first approach to boosting bioavailability was to use a water miscible carrier solvent for the Curcumin.

There are four reasonably non toxic candidates:

1.) Ethanol,
2.) Glycerol
3.) Propylene glycol
4.)  DMSO.

Ethanol can carry about 1% and DMSO can carry about 2.5 % Curcumin. Glycerol and PG significantly less. This approach sort of works. With heating followed by cooling one can quickly make saturated solutions and I did get these vile solutions down by filling gel caps. But even by this method you won't easily deliver grams into the gut and of that delivered amount you won't absorb nearly 100% of the Curcumin in these solutions into the blood.

At 400 molecular weight, Curcumin is too big to pass through the water conducting pores of the gut. So the water miscible solvent can go through but the Curcumin it carries is blocked.

That leaves molecular diffusion of curcumin through the lipid bilayers of the epithelial cells lining the gut. But as noted Curcumin is only sparingly soluble in this kind of fat constituted membrane and to diffuse through this layer it must first dissolve into the layer. I'm sure I was getting significant drug through to my blood using ethanol and glycerol in this way, probably more than any commercial super Curcumin product but it was not grams quantity and I had to imbibe a lot of ethanol and glycerol. Enough to make me fat.

Technically it should be feasible to intravenously inject solvents plus Curcumin this way and achieve gram loadings especially using DMSO as the solvent. Maybe someday this will be a viable therapy. The distinct advantage of this approach is that not only does the solvent carry the drug into the body but it momentarily raises the drug carrying capacity of the blood serum at least for a few hours until it is metabolized or excreted. If very high levels of curcumin can preferentially kill cancer after just one hour of exposure this should be acceptable. This is not a home remedy though and will not be offered clinically anytime soon. A lot can go wrong when injecting stuff intravenously.

This solvent work was a valuable experience though because it helped me think plus it gave me a good sense of what 1% (ethanol) and 2.5% (DMSO) true solutions of curcumin look like. 2.5 % is pretty deep red. Like ruby stones in jewelry. Even a half inch path length through this is deep red. 1% is just reddish tinted, you get deep red only if the optical path length is several inches.

My next idea was to find a complexing agent to increase the aqueous solubility of curcumin while protecting it from hydrolysis simultaneously. At first this turned out to be a dead end because the known agents that complex with Curcumin in the literature are toxic bivalent metals or huge proteins like gelatin, pectin, and albumin, or large polysaccharides like cellulose, cyclodextrins, modified starch etc. you can't absorb these through the gut.

Another dead end was dispersants like polysorbate 80 and poloxal solid polymer solutions. Dispersants can speed the kinetics of dissolution and they can slightly increase solubility by supersaturating a solution but they can't shift solubility the way complexing agents can.

With that in mind here is a brief history of my thinking process and the final successful experimental efforts:

First of all, Curcumin water solubility increases with Ph. This suggests just drinking alkaline solutions could work. Unfortunately Curcumin destruction by hydrolysis also dramatically increases with Ph. At body temperature and mildly elevated Ph=8, Curcumin is about half destroyed in one hour. 90% is gone after 2 hours. Meanwhile solubility at Ph 8 is still very low. It's much worse at very high Ph like 10 or so where solubility is more reasonable. It's gone in minutes. This is evident by color change. The solution goes from red to brown. This color change is the hallmark of hydrolysis and absence of this change indicates reliably that something is complexing with Curcumin giving it increased stability.

It's known that Curcumin is stabilized by complexing agents. These are either metal ions that are unfortunately too toxic or proteins and polysaccharides which are way to big to diffuse from the gut into the blood. So it's checkmate right? Well, that's why we need  dumb luck sometimes.

A little known chemical factoid is that sodium carbonate is weirdly soluble in glycerol. It's about one to one so you can make a 50% solution of sodium carbonate in glycerol. This is very unexpected behavior. Normally ionic salts are not highly soluble in organic liquids. There is no water. It's pure glycerol and sodium carbonate , so the good news is any Curcumin you dissolve in this will not hydrolyze (separate). So I tried dissolving Curcumin in this atypical mixture and boy, is Curcumin ever soluble in this mixture.

And there's more. I now believe , based on experiment, Curcumin actually goes in and forms a complex with the glycerol and the carbonate in this dry mixture. The carrying capacity of this mixture is at least 20 % Curcumin w/w.

In all humility I'm pretty sure I'm the first to discover this.  I hereby gift this knowledge for patent purposes into the public domain. I truly believe it is an important improvement toward achieving by oral administration, very high plasma levels of curcumin in biologically active form. I now describe a practical procedure for home brew of this solubilized Curcumin material.

** This recipe is for experimental use only - talk to your doctor before taking any of this **

** This is only a theory.  Use at your own risk.  **

Curcumin recipe ingredients:

1.) Sodium carbonate. Make your own by placing food grade sodium carbonate  in a baking dish (pour it out of the box into the dish) and bake at 450 F for two hours. You now have food grade sodium carbonate.




2.) Glycerol food grade 99.7 % from Amazon or such. One gallon.




3.) Curcumin 95% powder from Purebulk dot com or from ebay. 100 grams.



Now:

1.) 4 ounces of glycerol in a paper cup. (No plastic, it melts.  Use a paper coffee cup.)

2.) Add two heaping teaspoons of sodium carbonate and stir with a bread knife until creamy.

3.) Microwave this until the first sign of smoke rises from the cup.

4.) Add two heaping teaspoons of curcumin powder. While still hot stir with the butter knife. (you can let it cool a little in the oven so it's not dangerous before adding)

Color should become super dark red verging on black and after cooling the consistency and color will be that of roofing tar or black honey.  New: I'd cook for three hours just to be sure you're saturated. Stir every half hour. Add water as needed to boiler pan. Slow boil is fine.

5.) Reheat this mixture in the microwave. Stop at the first sign of smoke vapor coming from the cup. This ensures thorough reaction.

*** You're done ***

This is a very strange and interesting material. First of all it's highly water soluble. Rinse your coated butter knife by agitation in a small bowl of warm water. The water will turn deep ruby red. This is the first evidence that you have Curcumin in solution and that the limiting concentration is extremely high.

Second, this color is stable for many hours even though the Ph is near 11. This is reliable evidence that the Curcumin is stabilized by some sort of complex formation. Third, if you lower Ph by adding vinegar the deep red color will quickly vanish and you will have a pale yellow suspension. This is just the acid form of curcumin forming which is now in the bowl as suspended yellow particles. Interestingly this is irreversible. Adding sodium carbonate and thus restoring the high Ph will not restore the red color.

The complex created by the dry melt reaction of sodium carbonate, glycerol, and Curcumin cannot be produced by reversible aqueous solution Chemistry. That's why I say it's kind of a miracle I just stumbled onto this synthesis doing dry kitchen chemistry.

For highest absorption and bioavailability I suggest enteric coating to gel caps. This is very important improvement. Taking proton pump inhibitors is not nearly as good as using enteric coated gel caps. 

The resulting high stomach Ph has another important benefit. Not many people realize this but the raising of stomach Ph should significantly increase the molecular weight cut off of your epithelial cell membranes in your gut. It's hard to say how much with certainty but this should have a large beneficial impact on diffusional transport and bioavailability of these relatively large Curcumin molecules complexed with glycerol.

First of all this method of solubilization produces potentially very high concentrations of water soluble Curcumin complex in the gut evidenced by the deep red color attainable.

Second this alkaline aqueous solution is unexpectedly stable even with its high Ph, evidenced by the long red color stability.

Third the concomitant high Ph should significantly lessen the molecular rejection of the epithelium cellular layer to diffusion transport into the blood. If as this evidence suggests the Curcumin must potentially enter the blood by diffusing as a complex with glycerol it should be released as this glycerol is metabolized away from the complex. This is very serendipitous if true. It's potentially practically important as well.

Even if one had a magic wand and could place molecularly dispersed Curcumin into a person's blood it is unlikely the blood itself could carry one gram or two grams of curcumin in solution. Blood serum is basically water plus albumin. The carrying capacity of water is near zero. Curcumin can form complexes with albumin and this gives hope that blood could have some non zero carrying capacity but albumin is not more than 10 Micromolar concentration in serum .

Even if serum albumin complexed that magic Curcumin one to one that means blood could carry no more than 10 micromolar Curcumin which works out to 0.25 gram per 100 kg person.
 

That paper cited above reached the 1 to 2.5 gram equivalent concentrations in vitro that killed the cancer by using ethanol as a solvent added to the medium in the Petri dish. This added amount was up to 1% ethanol which is 100 times the legal limit for ethanol so even the basic physical chemistry controlling Curcumin solubility in blood per se says whole gram per 100 kg loading in vivo is impossible without high levels of some solvent like ethanol or DMSO present or some complexing agent attached to the drug.

As noted above this solvent idea could actually work especially by solvent transfusion but only for a few hours until the solvent is cleared. My hope and belief, which is supported by experimental observation, is that the Curcumin mixture prep described here creates a complex of glycerol and Curcumin that can enter the blood intact by diffusion and this enables higher serum concentrations than possible with Curcumin alone.

Thus, Curcumin can be carried by the blood plasma as a glycerol/Curcumin complex at concentrations which would not be achievable by any other means save coadministration with intravenous water miscible solvent.

I take this black mixture currently:

1.) I am up to dosing of 16 ml daily of the mixture described here. I take the whole dose once before bedtime. This black honey like mixture is shelf stable. I heat the mixture about five seconds of microwave to get it lukewarm. This lowers viscosity so I can pipette the mixture into 000 gel caps. (500 Empty Gelatin Capsules "Size 000" - Bulk Clear Hard Gel Caps Amazon ) Each cap holds 1.6 ml. I take 10 caps.

I don't have cancer. I'm taking the mixture hoping to grow my brain back and though this is going miraculously well it's not relevant here other than that it's further evidence Curcumin is successfully entering my blood plus that it's a wonder drug.

One warning. Killing all your cancer in one hour may sound great but it's actually likely to be a dangerous idea.

Such a rapid and uncontrolled death of cells is called necrosis. When cells die this way they basically explode, spilling their contents around their cellular neighborhood. This is a disaster for the cellular neighbors as they get chewed up by protease enzymes that are released. You'll really probably prefer a type of controlled cancer cell death called apoptosis. This is a kind of polite cellular suicide where the cellular house is cleaned up before death so the neighbors won't have too much trouble. For this reason as well as common sense if this is in fact a viable way to jack blood levels of curcumin to levels thousands of times higher than ever before attained, please, don't be stupid.

** Start with a little, say, one daily gram of the mixture and observe. **

Even this is a lot but at least by calculation since its at most 20% Curcumin even if that's 100% Absorbed and bioavailable that one gram of secret sauce should induce about 10 micromolar blood levels which according to the cited study above will kill something like 10% of cancer by apoptosis. Even this rate will kill all the cancer in due time if the cancer cannot adapt.

** Anyway I currently take 16 gm per day of the Mixture and I'm doing fine. **

No side effects at all. I'm just saying don't be foolish. Even one gram should deliver blood levels containing one million times more Curcumin than eating turmeric or 95% Curcumin powder can possibly deliver.

Lightening in a bottle indeed.

Benefits of Curcumin:

* Protection for your brain and cognitive function

* Improved mental clarity and memory retention

* Better mood balance and more energy

* A healthier heart and more balanced cholesterol

* Fewer aches and pains and less stiffness

* Smoother, more youthful-looking skin

* Support for liver health and detoxification

* Antioxidant protection against free radicals

* An overall increased sense of vitality

How to make stomach absorbing Curcumin

1.) 4 ounces of glycerol in a paper cup. (No plastic, it melts.  Use a paper coffee cup.)

2.) Add two heaping teaspoons of sodium carbonate and stir with a bread knife until creamy.

3.) Microwave this until the first sign of smoke rises from the cup.  New: I'd cook for three hours just to be sure you're saturated. Stir every half hour. Add water as needed to boiler pan. Slow boil is fine.

4.) Add two heaping teaspoons of curcumin powder. While still hot stir with the butter knife. (you can let it cool a little in the oven so it's not dangerous before adding)

Color should become super dark red verging on black and after cooling the consistency and color will be that of roofing tar or black honey.

5.) Reheat this mixture in the microwave. Stop at the first sign of smoke vapor coming from the cup. This ensures thorough reaction. 

6.) Proton pump inhibitor. I take Protonic.  The idea is to prevent stomach acid

7.) Fill Empty Gelatin Capsules "Size 000"   Start with one.    (warm mixture so you can get curcumin into the capsule)

** This recipe is for experimental use only - talk to your doctor before taking any of this **

** This is only a theory.  Use at your own risk.  **

By Brad Culkin, PHD
 

UPDATE 3-2016  

I have made quite a lot of progress since I posted that recipe. Unfortunately my efforts to save my sisters mother in law was unsuccessful because she tried chemo one last time which caused heart failure and immediately killed her. I can say I have a friend diagnosed with Parkinson's who is greatly helped by my recipe plus another with eczema who is greatly helped. I pray you will have more luck. Here is my current protocol I am following for stroke recovery with truly miraculous results.
First you need to thoroughly dissolve curcumin in the solvent system of sodium carbonate plus glycerol. In an eight cup capacity Pyrex mixing cup add two cups glycerol plus four cups curcumin 95% powder plus one cup sodium carbonate for example Arm and Hammer washing soda. Stir this mixture to form a reddish viscous mixture that is homogeneous. Slight heating will make this easier. A few minutes of microwave on high power will do for this. Try not to form gas bubbles by heating the mixture too much.
Now cook the mixture on low power by microwave for three hours stirring every half hour or so. I use 10% power setting in a 1200'watt microwave oven. This works very nicely. The mixture will darken to almost black after three hours.
You will need to buy empty enteric coated gel caps. Enteric coating technology ensures the caps will delay dissolving until they are in the small intestine. This is important because stomach acid will destroy the solution of curcumin in glycerol carbonate mixture. My original recipe of adding a proton pump inhibitor to reduce stomach acid is not effective for this. The enteric gel caps are thus an important improvement. For a child size 0 is advised. eBay has these. Search under enteric gel caps.
Also buy a 100 ml size syringe also available on eBay. It helps to lubricate the rubber slider with vegetable oil each time you use the syringe and to disassemble the syringe and clean it after each use.
Also you should buy two capmquick brand size zero gel cap holders to make two times fifty gel caps in one sitting. Also on eBay.
Heat the cooked mixture to where the mixture is free flowing and will easily suck up into the syringe by pulling the plunger while the syringe tip is in the mixture. Try not to heat so much that gas is forming. Gas foaming is destructive to the mixture or I should say foaming is a reaction product of destroyed curcumin. Try to avoid this high temperature induced foaming. A little is ok. There is lots of curcumin in the mixture.
Anyway use the syringe to dispense the black goo mixture into the gel caps. Assemble them and now you have a supply of caps to use. The cooked mixture is shelf stable. I keep mine on top of the microwave for use as needed.
I weigh 100 kg. I take 30 size 00 enteric coated caps per day. Each 00
Cap holds 1 ml of black goo described above. If I take 35 to 40 I have mild side effects. Slight kidney pain I view as a warning.
I believe it is important to use high doses to get best results. I say this because curcumin is tightly bound by blood plasma proteins. Low doses are therefore not enough to saturate this system and so concentration inside the cells is low. As dose is raised a point is reached where plasma protein is saturated with bound curcumin. Now additional curcumin is free and available to enter the cells. This is an oversimplification because saturation is not a sharp event but the idea is valid. For a child the problem of dosing is very difficult and all I can offer you is these guidelines plus caution. The ballpark for side effects is 30 ml per 100 kg body weight. I take 10 g in the morning and 20 g at night the thinking being sleep combined with strong dosing is a good combination. I can definitely feel when the enteric coated caps reach my small intestine and burst about two hours after I take them. Not any stomach pain but ringing in my ears and a flushed feeling. It's fine to take them with food. I have an iron stomach so I hope your child is like me.
If you can share your cancer details with me I may have some thoughts on how best to proceed.
I hope this helps you. Good luck.

 


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