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Paw Paw Pulls the Plug
on Cancer

On the best summer day in Minnesota, the sun shines bright on the corn leaf, giving all the power the chlorophyll needs to take 6 carbon atoms, and 6 oxygen atoms (leaving 6 left over to form oxygen gas for us to breathe) and combine them with 12 hydrogens to make the sweet corn even sweeter. Glucose is born. These 12 hydrogen atoms bond to the carbon ring, storing energy in this sweet substance.

Along about the end of August, farmers pull pickup trucks into the parking lots of towns and cities and the feeding frenzy begins. Families that regularly don't eat together find a renewed bonding experience as dozens of ears are stripped of their husks. Ultimately, it is the energy from a strong summer sun that is harvested, prepared, and consumed.

Interestingly enough, the above scenario also takes place in our bodies, at an atomic level. Let's take a look at that.

Glucose comes to us in a ring of carbons. A six carbon ring is split into two three carbon chains. These chains enter the famous Krebs cycle to finish the harvesting job. Temporarily, hydrogen atoms bond to a useful intermediate that is known as NAD, and so it becomes NADH. (Nicotinamide adenine dinucleotide reduced, for us laypeople.) Eventually that hydrogen atom will be stripped off. When a hydrogen atom is stripped off, energy is released from the breaking of the bond. The body then grabs this hydrogen and bonds it with oxygen. In the end, we have energy and water (one hydrogen bonded to two oxygen atoms).

There is a very interesting complex of proteins that make up this aerobic factory. It is located within the inner membrane of the mitochondrion, the small cigar-shaped energy factory within the cytoplasm of our cells.

Five distinct respiratory complexes (processes) exist, each with a specific purpose. Respiratory complexes one and two transport hydrogen molecules from their respective carriers, NADH and FADH2, into a holding area called the intermembrane space, splitting off electrons for transfer to complex three, carried there by handy little carriers known as ubiquinone (appropriately named because they are so ubiquitous or widespread). One of the forms of ubiquinone is also known as CoQ10. [Co-Q10 is needed by every cell in the body for energy production. See our July ’03 Newsletter for an important link between Statin Drugs and the suppression of CoQ10 production by the liver.]

Hydrogen atoms collect, making a charged chemical battery. When that charge builds up, the hydrogen atoms travel back down inside through respiratory complex five, giving up their energy to a phosphate bond on a handy little molecule with two phosphates already attached, making it three phosphates, also known as ATP or adenosine triphosphate. That new phosphate bond is a portable power supply for many cell functions. When the bond is released, the energy is harvested and the molecule shifts back to its 2 phosphate form, ADP (or adenosine diphosphate), which is ready to be recharged in respiratory complex five again. Again, we get energy and water. (Ever notice how when you expend energy, you sweat?)

Now in respiratory complex four, oxygen molecules are transported by special heme (from the word hematin; a deep red iron-containing group; think of hemoglobin, which is deep red) groups to join up with hydrogen to form H2O or water. Once in a while, oxygen gets loose from the heme groups and recklessly has a life of its own. It makes a new reactive molecule—H2O2 or hydrogen peroxide —using a little more oxygen than before. When respiratory complexes one and two are working right, plenty of hydrogens are available for the water formation, keeping the cell in good shape. When they are not working right, the peroxide molecules can trigger release of cytochrome c, another electron carrier, which sets off a cascade of reactions leading to a very severe consequence, the orderly destruction of the cell by programmed cell death, or apoptosis. (This word has the second "p" silent across the Atlantic in the UK, but well-trained scholars here in the US insist on keeping "pop" in apoptosis.)

So where does Paw Paw come along? And how does it affect cancer?

Paw Paw belongs to the family of plants known as the Annonaceae. One of its well-known cousins is Annona muricata or Graviola. Paw Paw has some very long chains of carbon atoms. The special carbon chains are called the Annonaceous acetogenins. These acetogenins have certain features in common (and a few differences) that contribute some very interesting modifications to the energy cycle mentioned above.

One key feature is the gamma lactone ring. This is at the end of the carbon chain. Some acetogenins have one ring, some have two, a few have none, and at least one has three. These molecules have been studied extensively at Purdue University by a team led by Dr. Jerry McLaughlin. Many other researchers, both at Purdue and elsewhere have spent many years uncovering their chemical structures as well as testing them for their anti-cancer and insecticidal properties. Their work has been published well over one hundred times in science journals.

We told you about drug company that hid the results of their secret testing of graviola, but Dr McLaughlin’s research has been freely disseminated since he began.

Dr. McLaughlin's research team has isolated 28 compounds from graviola. Each year, they find still more. In 2003 the first double ring structures were isolated. Expect even more compounds to be found.

Back to the gamma lactone ring. It turns out that for most tissues, this double ring structures provide just the right length and shape to reach down a series of more than 100 protein pieces in respiratory complex one to fit perfectly into the right place, the PSST subunit. They fit like a glove. The researchers discovered that three OH groups in the right places stop NADH from giving up its hydrogen. (You’ll see why this is important soon.)

The lactone ring (an acetogenin) comes in many varieties. One double ring structure that seemed to out perform the others in stopping the process mentioned above was Bullatacin. It was so effective that Purdue elected to patent it. So, unlike the widely-held belief that plant materials cannot be patented, Bullatacin was.

Why is it important to stop NADH from giving up its hydrogen?

By interfering with the harvesting of the hydrogen's energy, the hungry cancer cell can no longer run its energy production (metabolism) wide open. Cancer cells use up glucose at very high rates. Breast cancer cells have 17 times the glucose uptake capacity of their normal tissue counterparts. [See also the article Cancer Loves Sugar.] So their rate of respiration is up to 17 times that of normal breast tissue. By shutting down respiratory complex one, the rest of the mechanism is strongly affected. Respiratory complex four, being starved for hydrogen, more readily forms hydrogen peroxide, leading apoptosis, that cell to programmed cell death we mentioned. [Hydrogen peroxide is one of the oxidative cancer therapies we’ve mentioned in our Alternative Cancer Therapies article.]

Because you do not want to inhibit the reactive peroxide, it is highly recommended that, while on a Paw Paw regimen, you avoid using strong antioxidants.

Why many chemotherapy drugs are useless against cancer.

One interesting feature in slowing down ATP production by the acetogenins is the fact that certain cancer cells have overexpression (a fifty cent word scientists use “more than the average”) of a pump that is powered by ATP energy. This pump, the "ABCB1" efflux pump to be exact, protects the cancer cell from harmful agents like chemotherapy drugs. (Forty-eight ATP driven pumps have been found in the body. Ten can pump drugs. Three are known to be involved in multi-drug resistance.)

After a round of chemo, most of the ordinary cancer cells succumb to the drugs, but some, with this special protective pump, expel the drugs. So they continue to grow, becoming the majority. These drug resistant cells grow to dominate the tumor. And since they are resistant, drug therapy becomes less and less effective and cancer can no longer be controlled. But when the ATP producing mitochondrion has its power plugged pulled by the acetogenins, the cancer tumor cells lose their resistance given to them by this pump and can be killed more easily. No ATP means no power to the pump.

Dr. McLaughlin and his team have discovered at least 50 different acetogenins in Paw Paw. Their activities were tested with various cancer cell culture lines and it was discovered that many were very active at low concentrations. Compounds from graviola were also tested. The best acetogenins came from the double ring compounds in Paw Paw. (In currently available products, a comparison was run by Dr. McLaughlin's staff to see how active the products were in the brine shrimp activity assay, a screening test for anticancer activity. The two brands tested required 24 times and 56 times, respectively, that of Paw Paw to produce the same effect. This is quite remarkable when you realize that the actual content of the Paw Paw capsule is only 12.5 milligrams of the acetogenins. The other materials have hundreds of milligrams of plant material.) When at least seven drug companies decided to "pass" on the patented molecules owned by Purdue, Dr. McLaughlin decided that he would still go ahead somehow to make Paw Paw's acetogenins available to people. After he retired from Purdue, a job opening at an herbal supplement company for a chief scientific officer paved the way.

Beginning there in 1999, he started work on the product. After extensive research to discover the best way to extract the compounds and to make sure that they were safe for human consumption, he decided to conduct a human trial. The study began with twenty stage 4 cancer patients under the care of a Reno, Nevada physician named Dr. James Forsythe. Their cancers were varied, but all were refractory (resistant) to conventional treatments. In the first few months of the trial, seven died. The other thirteen lived for at least two years with their doctor calling them "stable."

By the end of the human trials, ninety-four patients with diagnosed cancers of various types had participated. Dr. McLaughlin has reported that as many as 8 in 10 found some benefit from using the Paw Paw. Many continued some form of conventional treatments; though some opted to take the Paw Paw only. The results of the trial will be published in a journal. It was hoped to be published in 2004, but it might take a little longer, as it is a very controversial paper.

Paw Paw is a twig extract that comes in a standardized form in capsules. It is patent pending. There are many inferior Paw Paw products, so be careful to get the standardized capsule product. One capsule is taken four times a day with food. This applies to a person of a body weight of between 150-170 pounds. Larger people may decide to take slightly more. Thin people may decide to take a little less.

Side effects are very slight, BUT should be noted. Paw Paw has the power to make people throw up. It is a natural emetic, like ipecac syrup. At the concentration given, most people do very well. Some report feeling better after a couple weeks. This may be due to the cancer cells using less energy, making more available to the rest of the body, or it may be due to the lactone rings providing a lift not unlike the herb kava. At the time of this writing, between 3000 and 5000 people are using Paw Paw in the US. We expect to see a lower percentage of success as more people use it, because that is typical pattern in all trials. We do not know precisely which types of cancer respond best as yet. People in the human trial realized benefits six to eight weeks into their regimen. People who respond to it should expect to continue taking it long term, perhaps for the rest of their lives. But this is true of anyone beating cancer. You have to continue some sort of regimen the rest of your life. You have to make changes in diet and lifestyle that keep your entire body healthy, as cancer is a systemic disease, affecting the entire system.

Rarely, someone might develop an allergy to Paw Paw just as they could to strawberries.

Dr. McLaughlin does not recommend taking Paw Paw for prevention. He reasons that a healthy person does not need to take antibiotics. So unless a person was addressing a particular condition, he does not recommend casually using it. It does have other uses as an herb. It appears to be anti-viral (some reports of shingles being controlled by it), anthelmintic (kills worms), anti-fungal (e.g. toe nail fungus), insecticidal (the Minnesota state bird), and antiparasitic. It is an ingredient in a very effective lice shampoo which also works well against fleas on dogs.

Dr. McLaughlin spoke to an audience in Columbus, Ohio about his life's work shortly after he retired for a second time. This lecture is available for viewing on video or listening to on audio at

For those who wish to purchase Paw Paw, the product that Dr McLaughlin's created is available at or you can write to [email protected].


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