May 2010

  

A Miracle Plant from the Amazon Region

Latin Name: Annona Muriaca 

GRAVIOLA

 

THE SANE HEALING SOLUTION and CANCER CURE – SCIENTIFICALLY PROVEN!!!!!

 “The time has come” – how many times we are hearing this sentence, nevertheless it is true because we are living in times of huge challenges changes and shifts where secrets of many different aspect of life are getting revealed to be known by the public – people also are more courageous to speak out what all should know and YES, if millions KNOW a fact, those who are hiding solutions, will have to surrender.

 

The biggest lie about Cancer Treatments and Chemo Therapy 

The Powers of Graviola (Guanabana in Brazil – Soursop USA)

1)   Beats 12 kind of types of cancer such as Breast Cancer, Abdominal Cancer, Ovary Cancer, Uterus Cancer, Lung Cancer, Prostate Cancer, Boon Cancer, Pancreas Cancer,

Skin Cancer, Blood Cancer (Leukemia), Bladder Cancer, Liver Cancer 

NO SIDE EFFECTS, NATURAL CURE !!!

Salubrious way back to a healthy state

2) The Fruit contains a substance called ACETOGENIN that has been proven as 10.000 (ten thousand times) stronger as ACETOGENIN, the drug used for Chemo therapy all over the world with the result of 90% to 10% survivors only – a Bingo Game with the life of people in all nations because the cure is already known

3) As it is a NUTRIENT it works from INSIDE OUT – eating up the cancer cells, any kind of viruses, bacteria etc. Nutrients have no side effects on our body!!! – unbelievable, miraculous, BUT TRUE (I had the honor to experience many people with cancer even in a very advanced state who  were getting well with a Power Juice containing Graviola and there are 1000s in Latin America who had the chance to know about it since 9 years of applications. Solution, Real Cure and permanently heal without Chemo. In case that the doctors ordain Chemo this Special prepared Juice has the powers to protect the healthy cells from burning and allows just the cancer cells to be destroyed, no nausea, no hair loss, neither any other common side effects taking that power plant of healing simultaneously.

MY own mother would not be alive without Graviola and further Amazon Juices 

It is TIME TO SHARE and to SHAKE the World of Cancer and to shift the 90% to 10% into a 10% to 90% of survivors !!

here is the chance to learn about a fact that there is something that has the power to cure cancer, that it has been scientifically proven and that it has been hidden away from people because it comes from Mother Nature and can not be patented in any way.

 

General Information: About the Plant

Graviola is an ever green tree growing in the Amazon region of Brazil and in other countries that are touched by the Amazon Forest. It also grows in the tropical rainforest of North America. He grows up to 15 meter high covered with green, long and glossy leaves. His divine fruit is green sometimes a bit yellow shining, has the form of a human heart with a skin looking kind like a big cactus. Its white fruit flesh is eatable and people can buy it on the local Markets. The diameter of the fruit is 20 to 40 cm and local people are eating it out of the hand, the pulp is used to produce a refreshing sour-acid drink or as sorbet

Indian Tribes use Graviola as medicine since Centuries  

Graviola counts with a very long history in the tribal herbal natural medicine. There are Healing substances in every part of the plant: a part of the powerful effects of the fruit we find high effective substances in the leaves, the roots, the trunk, the bark and the seeds. Indian Tribes know about the value of that miraculous tree and they are using the different parts tor multiple and diverse diseases and health Imbalances. Some examples

In Brazil Roots, Trunk and leaves are used as sedative tee and against nervousness, in other Latin America countries as sedative and as heart tonic medium, also for Diabetes. The leave tee is also used for lever problems and mixed with olive oil it is used for Rheumatism, Arthritis and Osteoarthritis pain in Peru. In Brazil they prepare a mixture out of an immature fruit mixed with Olive oil as extern treatment against Arthritis and Rheumatism.

Leaves are also used against Parasites in Brazil and against Catarrh in Peru.

Fruit, Seeds and Leaves are applied against fever, all kind of parasites, worms, diarrhea, in Brazil also to help increasing the milk of women after giving birth.

In other countries such as Haiti, West Indies and Jamaica are using Graviola as anti spasmodic, sedative, coughs and flu, as nerve strengthening tee, for asthma, hypertension and all kind of parasites, diarrhea and problems at childbirth.

 

Graviola and Science -

Cancer Research – Scientific Results on Graviol

The Graviola Fruit is already under research since the late 39 of last century – At that Time the science found out that the plant has components, natural principles and properties called “Annonacaeous Acetogenins“, natural chemicals that are confirmed to be highly effective against many kind of tumor cells with components that are found as toxins that kills the cancer cells in a very specific way. Simply spoken Graviola has components that are able to isolate every cancer cell, to build a kind of bubble around it avoiding that the cancer cell can get any further nutrient, so it dies. The dead cancer cells are eliminated by the own body system without any side effects. Those components are hidden in all parts of the tree and in different combination they are used for many different kind of disease. They are documented as anti-microbus, anti-parasitic, antitumorous, anti-cancerous, anti-depressive and anti-spasmodic. Several study results have been published but few people reacted. 

Since 1976 profound researches of the National Cancer Institute of the USA resulted in curing an “Adenocarcinoma” of the large intestine after short time. The therapeutic effect confirmed the power of Graviola and her components. This powerful component has been discovered by the German Research Scientist and Oncologist Helmut Keller and with three more Scientists they realized many studies on Graviola. As the Plant does NOT ALLOW any chemical process without losing the healing powers never nobody got to know about this effective cancer treatment. WHY??? – because it only works in natural form and a plant cannot be patented in any form, so the Pharmaceutical  World and the Monopoles could not get any profit from it and that is the reason they hided the information. Result:

Graviola contains very active, cytotoxic effects against cancer cells with a chemo therapeutic power that is

10.000 x stronger as Adriamicin, the drug that is used for traditional Chemo Therapy, – without any kind of side effects!.

(Since a while the HSI is offering now the copies of the results that can be bought for 25,00USD)

After the confirmation that Graviola can cure naturally Cancer the National Health Institute has indicated 20 Labs to studies the plant during 20 years without any result to transform the active principles into a valid remedy. At the end they gave up and let the miraculous findings in the drawer of their institute

Since 1996 other groups of scientists did researches on Graviola and found out that the fruit possesses characteristics against tumor formation and that it produces selective toxins against different kinds of cancer cells, without attacking healthy cells. They confirmed the findings of their results were published 8 different clinical studies. 

The different studies of different laboratories resulted in incredible findings that the Acetogenines of Graviola have an unbeatable component in prevention of enzyme formations, which are only found in the diaphragm by tumors and cancer cells. That is the reason, why they are poisonous only for cancer cells without attacking healthy cells. The Acetonines recognize the sick cells isolates the individual cancer cells and for missing nutrients the cancer cell dies.

In the year 1997 a small group of scientists found out, that Graviola contains also alkaloids which have an anti-depressive effect. In the same year the PARDU UNIVERSITY published the information that they discovered even more powers within Graviola. Their clinical studies confirmed that the “Annonacae Acetonine” in Graviola are so effective, that they do not only kill normal cancer cells, but that they are also very effective in killing those cancer cells that are resistant on Chemo Therapy. This investigation explained how that is possible: Those cancer cells that survive the Chemo Therapy are developing resistance against many other kind of drugs, called Multi-Drug-Resistant (MDR) what makes them immune against any treatment and leads the patient 100% to death

After 20 Year of research the Pharma Industry got aware of the Plant and started research by their own seeking a form and way to transform the active principles and components into a cancer remedy. They also failed. Graviola does not allow any kind of chemical reproduction. It is reconfirmed that Graviola only works as it grows in nature and it beats cancer better then any synthetic drug or heavy poison rays. Until today many different groups of scientists are still researching to create a similar product as Annonacins and it still works only like it grown in Nature. 

All that information has been kept in secret because Pharmacies could not transform it into something that would give them a huge profit. So they gave proof that they are not really interested in heal people but in making huge profits from those who are already sufficiently hidden by the disease itself. Why would somebody create so many unnecessary pain when there is something much stronger and without any life threatening side effect.  

At the end of the nineties one of the Scientists who was part of one of the research teams broke the silence for reasons of consciousness and some of the reports were accessible for the medicine world. Simultaneously some people from Brazil got kind of divine guidance to go to the Amazon and to study the Plants of the Rainforest. They were integrating the native people to learn from them as their knowledge about healing plants of the Rainforest is reaching back in time for many centuries.

The good thing is that for one time in this world the science is NOT finding a way of manipulation – the power of healing cancer lies in Graviola and several  further plants that God preserved to be used like the Almighty lets it grow. It is a blessing for Mankind and a gift from Mother Earth – A wake up call to become conscious and to start honoring the gifts we have forgotten that they exist. When we destroy the rainforests we destroy the lungs of our planet and without oxygen all life will die. We need to open up our hearts to understand that all what we experience has a solution and all what we suffer of different kind of disease has a natural way of cure in nature.

 

Graviola shows us the way

 

Nutritive Values of Graviola

Minerals                                                                                                                  

Iron, potassium, calcium, copper, magnesium, manganese, sodium, phosphorus, sulfur,   Selenium, zinc,   

Vitamins:                                                                                                                                                          

Vitamin A, Vitamin B1,  Vitamin B2, Vitamin B3,  Vitamin C 

In addition

Dietary fibers, Tannin, Proteins, Lipides      

                                                  

Ethno-medical Uses of Graviola in different Tropical Countries and USA 

Latin America

Brazil:

Abscesses, Tumors, Edemas, Worms, all kind of Parasites,  Bronchitis, Breathing Difficulties, Coughs, Diabetes, Digestive Imbalances, Dysentery, Intestine Parasites, the Intestinal/Colic Attacks, Fever, Liver Problems, Neuralgias, Nervousness, general Body Pain, Rheumatism, Tetanus

Peru 

Tumors of all kind, Intern Ulcers, Parasites, Lice, Hypertension Diabetes, Dysentery, Indigestion, Inflammation, Flu, Liver Disorders, Spasms, Fever and as a Sedative

Panama:

Tumors, Ulcers, Parasites, Worms, Digestive Disorders (Dyspepsia), Diarrhea and Kidney Problems: Renal Insufficiency – Renal Failure

Mexico:

Tapeworm, Indigestion, Diarrhea, Dysentery, Fever, Chest Colds, Ringworm, Scurvy, Styptic (bleeding)

 

The Carribean:  

Colds, chills, fever, flu, diarrhea, indigestion, nervousness, palpitations, rash, spasms, skin disease, and as a sedative and calmative agent

Curacao:

Gallbladder Problems, Nervousness, as a Sedative and Calmative Agent, Childbirth

Haiti:

Parasites, Lice, Flu, Digestive Sluggishness, Diarrhea, Fever, Coughs, Pain, Weakness, Wounds, Pellagra, Nervousness, Cardiopathy, Spasms, Sedative, Lactation Aid after Childbirth,

Jamaica:

Parasites, Worms, Asthma, Fevers, Heart Disease, Hypertension, Lactation Aid after  Childbirth, Nervousness, Sedative, Spasms, Tetanus, Water Retention and general Weakness,

Trinidad:

Ringworms, Blood Cleaning Agent, Hypertension, Palpitations, Fainting, Insomnia, Lactation Aid after Childbirth, Flu, 

USA:

Cancer, Tumors, Ulcers, Fungal Infections, Intestine Parasites, Hypertension, Depressio

Asia – Malaysia 

Furuncles, Coughs, Colds, Diarrhea, Dermatosis, Hypertension, Rheumatism, and to Reduce Bleeding

British West Indies:

Tumors, Intestine Parasites, Asthma, Childbirth, Lactation Aid, Hypertension 

Other Countries:

Cancer, Kidney Problems, Bladder Insufficiency, Liver Disorders, Dysentery, Malaria, Stomach Problems, Ringworm, Lice, Parasites, Childbirth, Asthma, Hypertension, Heart Disease, Arthritis, Scurvy and as a Sedative

 

Native Wisdom

 After learning about ethnological medicine and their high evolved knowledge we should ask ourselves who is more advanced. They have no hospitals and they have NO CANCER or did you ever see a Native in a Cancer Department of a Hospital? They do not have Laboratories, they don’t transform any plant into a pill and they are heal.

 The Natives still show us today how to live with nature and how nature provides all what we need for a healthy life. What do we as the so called Civilized World with Nature and with ourselves? We allow destructive exploitation, depletion, exhaustive cultivation, robber economy, not only with Mother Nature but also with our own lives. We burn the candle at two ends disrespecting the holiness of our body. We abuse a maximum and the end is deadly disease. Is that a wonder? No it is just a consequence of our issues, our habits, our believe systems and our actions, of out thoughts, words and the ability to look away when things are not in harmony with the cosmic order. We just don’t care when it does not hit us personally. To heal really we have to heal ALL THE REALMS we are living in otherwise we only get a momentum cure. Can you feel that? It is NOT a question of understanding but of feeling!!!!! We shot our feelings down

You go against your feelings and you get sick!!!

How many times a day we do that???? We have to come back to the heart and stand up to safe the natural resources that are still intact like the rainforest as biggest source of healing plants that exists in our world

A German Doctor made holiday in the Amazon Region and he was wondering how many natural remedies are there on the market. He took some of the to try and as I started to teach in Germany about Graviola and the Rainforest he showed up and said: I am director of a Hospital and I was looking for a way to make people the Amazonian Healing Powers available. I our Hospital we have a new system and are open for alternative healing methods. We offer open Seminaries and you can come whenever you want to talk about cancer and other disease. I did for Diabetes ….. it was amazing

So the Western Countries are learning about Graviola and the Healing Powers of Graviola, the miraculous fruit that brings never ending surprises to people with cancer and other heavy disease. Graviola is a chance for all those who are hidden by Cancer or one of the other diseases of civilization. 

This Article  is a Wake up Call and a Chance to survive Cancer. I

Graviola is not only a miracle against cancer cells, but has also components (results of researches) that can eliminate other chemicals like cortisone, drugs and all kind poisons in our body. This is UNIQUE as Cortisone remains into people’s bodies forever with the horrendous side effect that people are gaining weight fro nothing. Graviola is the power of life that is able to clean all poisons we are exposed today in our daily life in air, water and nutrients. It has the amazing natural potency to clean and to regenerate our body cells. Just remember that our body is the Holy Temple of Life that deserves all our respect because the body makes us the gift to be alive and to experience this wonderful personal journey on this beautiful planet, to have fun and grow in all senses when we maintain us in a healthy state.

This Plant and many others are a gift of Divine Source and Mother Earth preserved for our times to remember the love we should have for our divine vehicle, for ourselves and for all life. Divine Source and Mother Earth have the medium for people who have lost faith in the daily battle for survival

This fruit has the form of a huge heart to show you even by its form that only the heart can heal without any kind of human manipulation, pure and natural like it is given. 

A little insight of my own experiences:

As Multi-Dimensional Free Way Healer I learned to go straight to the cause of a disease that is created by denying feelings, psychic shocks, and heavy experiences on heart and soul level as well as body misuse of any kind. It can be karmic origin or even living on a place that is over poisoned by electricity or environmental. Nevertheless we can never get sick when our body defense is working properly and that opens the door to all what we experience. The way of cause and effect never fails and even incurable disease is curable by cosmic law. I always was driven to the Rainforest and I knew deep within that some kind of cure for the physical body should exist in that huge natural pharmacy of Mother Earth. I asked God to get something into my hands that helps people faster to understand and faster to heal so they can learn on big scale and not just one by one.

7 years ago – I was at about to travel to Germany and the day before a friend of my spiritual group from years ago over sudden crossed my way (we had moved both at the same time without thinking to exchange addresses). She asked me when I am going to travel again to Germany and if I could help the next time I go to open an enterprise that sells Amazon Natural Nutrients that are a power house of healing and there is nobody who speaks well German. Well, the word Amazon was hiding me like an electric shock and I was just going the next day… Is this the answer of my prayers I thought but I did not reacted so far as my journey had another purpose. After one week something drove me to get in touch and I felt the obligation to call and the representative came to my place to present the products, 7 at that time. He started to explain each product and as I held the bottle of a mixture of Graviola and 6 other anti cancerous components in my hands instantaneously my entire body was increasing tremendous heat waves and source transmitted: that is what you have asked for and of course I learned all I had to learn and stood in Germany for 9 month to get the information out there fighting the meanings and beliefs of traditional cancer cure

Within three weeks we had a intestine carcinoma disappearing, one prostate cancer patient who had the surgery marked, he was called into the hospital three days before the marked date for last examinations and o wonder all metastasis had disappeared. The doctors did not belief it and they said that those tumors cannot disappear just like that, that they are certainly hidden in some place and they ordained surgery anyways. Is this normal?   

A single mom with an 9 year old girl: after three chemo therapies and one surgery -close to death has a friend marries to a German knowing my mother – he head heavy heart surgery and just came back from Germany after 6 month Hospital – got the power juice and as he felt better after 3 days only he brought us this lady – she took three different juices at once at she was in a very advanced stat, no hair , no more faith and with a lot of fears to let her girl  behind alone – after 4 days she started to feel better after 10 days her hair started growing again, after 2 weeks she was sure that she will survive and she said: I am not going to tell this my doctor, I just will go there to the next control in 6 weeks and I will be safe. She did – as she had the next examination the result was so amazing that the doctor made a national seminary on her case, but nobody wanted to listen to her how she got better and she told me that this is not important for her – her life is more worthy then what doctors belief or not

There are so many cases I was testimony of that it would fill books and it would made you cry as it does with 100s of people when they hear at the annual gathering people telling their stories of survival in the last moment – their despair facing death and their families without a penny left because no assurance would take the bills anymore – family selling everything they have to safe a beloved one.

One friend of mine Brazilian  Plastic Surgery Specialist got Leukemia Myeloid and the needed urgently a cell transplant – she was on a list number 989 – I past 4 month with her working on her and finally we could access the products and the doctor of the enterprise said to her: You know that you are in the hands of God? Yes – but nevertheless we will give it a try – you got to take 5 different products and we found a sponsor – today she has a foundation for abandoned animals – she left her wheel chair behind and she is fine!!!! 

All those experiences are divine one by one but I think that more people need to know about it – from mouth to mouth it is just to slow – there are so many people suffering for nothing. The Lady who became director of the German enterprise had 5 types of cancer – 5 children – her best friend a director of a Hospital – he told her to go home and to spend the last time with her children – that his art has come to an end and that he is so sorry. At home a friend passed by and told her about those products – she loves life and she took one product only – after a week she felt stronger – her life powers came back she felt that she could make it and she said she would only go and show up front of her doctor and friend when she was fine. After 6 month she visited him in the hospital – he cried and asked what she did – she talked about the products and halleluiah the doctor today is working in his hospital with those products too. There is not only hope THERE IS HEALING OUT THERE and people need to be informed! 

———————————————————

Here some more evidence I found in different reports of the 100 strongest Underground Cures: 

CANCER “MAGIC BULLET” DISCOVERED – but drug giant hushes it up!

10,000 times stronger than chemotherapy with no adverse side effects

DARYL S. HAD 12 TUMORS IN HIS PROSTATE. But he received a cutting-edge treatment that helped save his life. And… In 3 months, his PSA dropped  AND THE TUMORS DISAPPEARED

HOW? Daryl’s secret was the help of an amazing tree that grows deep in the Amazon rainforest. Called Graviola, it may well prove to be the ultimate cancer-fighter. Studies by the National Cancer Institute already show that Graviola extract is 10,000 times stronger than top chemotherapy drugs…

Yet it’s incredible precision hunts down cancer cells while leaving healthy cells completely alone! Graviola just seems to “know” which cells to kill and which to avoid. There’s no nausea, no hair loss, no weight loss, no weakening of the immune system.

The news about Graviola sent shockwaves through HSI’s extensive medical network. But the story behind Graviola is just as shocking.

As we learned, this lifesaving discovery was very nearly denied to mankind. And I’m sorry to say the reason is that somebody sat on the research. The trail of evidence clearly shows…

For 7 long years, a billion-dollar drug company covered it up!

What’s more, this is undoubtedly not the first time that something like this has happened. Following is a textbook example of how modern drug research works, and how your health falls victim to the pursuit of money and power:

It all started in the early 1990s, when this well-known drug giant started pouring money into the search for a cancer cure..
What gave Jacqueline the power to CONQUER BREAST CANCER?

JACQUELINE HAD BREAST CANCER, but she also had a huge advantage in her battle. Best of all, it works by using your own body’s army of natural “killer cells.” So, it actually makes you feel more energetic, rather than sapping your strength. Like many such firms, they were intrigued by the healing powers of rainforest plants. They discovered that Graviola was being used by Amazon Indians to treat a huge range of diseases. And when they tested its cancer-fighting powers, bingo, they discovered a revolution…

But you can’t make megabucks from any cure UNLESS YOU PATENT IT…

And no one can patent a tree that’s been around for millions of years. So the drug firm tried for seven years to come up with man-made duplicates. But they hit a brick wall. Try as they might, they couldn’t match Mother Nature. Finally, they tossed in the towel…

Okay, they’re in business to make money. Fine. But let me ask you…

If the research files for this breakthrough were sitting on your desk, what would you do with them? Call a news conference? Send out press releases

At the very least, wouldn’t you publish them all in a prominent medical journal? After all, more than 6 million Americans have died from cancer in the last few decades.

Think how many might have been saved if a discovery like this had been available. But, instead of turning it over to independent researchers…….-

They boxed it up, put it on the shelf – AND TURNED OFF THE LIGHT

Happily, one courageous researcher just couldn’t live with that decision. He spilled the beans… and the result may turn out to be the most life-saving substance on earth. More clinical trials are needed, but more than 20 studies to date have already established that…

Graviola can wipe out 12 types of cancer cells, including breast, prostate, colon, lung and pancreatic tumors

Yet, unlike any chemotherapy drug, it leaves healthy cells undamaged.

A miracle? Perhaps. Yet even now, not one drug company we know of has picked it up and run with it.

WHY? Same reason. No one can legally patent it.

Are you starting to see?

AMAZON MIRACLE TREE fights much more than cancer

While scientific research on Graviola has focused on its cancer-fighting powers, the tree has been used for centuries by tribal healers to treat an astonishing array of diseases

 

hypertension

 

flu

 

ringworm

 

rheumatism

 

muscle spasm

 

diarrhea neuralgia

 

scurvy

 

malaria

 

insomnia

 

rashes

 

dysentery

 

arthritis

HSI-Reports

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My report continues here:

 

Healings -Cures – and Lies about Conventional Treatments 

True example: In Germany one of the Patients of Dr. D. Hamer (working on the psychic shocks for cancer cure) suffered breast Cancer and she was asked three times in the hospital if she is Jewish and she denied – she had family members who were but she wasn’t. She was wondering first why they asked that. The next day another doctor appeared in her Hospital room offering her a heavy treatment apart of the chemo therapy and he told her that people with cancer have only 10% chances to survive but she could be one of the 10% when she would accept this incredible expensive proposal. The got aware of why she was asked if she is Jewish and as it was not the same doctor, she answered, sorry I cannot do that as I am Jewish – the doctor replied: oh I didn’t know and leaving the room he remarked: you will be fine anyways……  can you believe that? But that is the truth about heavy and expensive treatments and people believe the Chemo (90% are not making it) and suffer for nothing…. The Lady reported the doctors and left the hospital. One thing is the big lie about Cancer – the other side has the solution and is not sufficiently known yet to help many people and children avoiding so much unnecessary pain. You will become porter of the secret – during May I will send out a report about the plant and how to get the juice product that is saving 1000s of lives since 9 years in Latin America and 5 other countries – not in USA yet apart of some friends of mine I sent the product to help them get well.

(She is German and the report is to find on Dr Hamer’s German Website)

 

Conclusion

What more can I say now as that I have experiences with Graviola since 7 years – As I learned by guidance how cases are set into motion that ends up in heavy disease or chronicle disease, even aids is one of the biggest lies, during this year I will publish more reports on products and natural powers for many of diseases that are used by the science to as a good income instead to inform about simple cures from inside out. Graviola helps reproducing the killer cells without our body that is the reason self defense it growing fast as the own body helps the nutrients to fight the sick cells in the body structure -any of them.

The latest studies in Brazil have confirmed that the product combination with Graviola has a component that kills even the Hospital Virus – this is a killer virus without cure until today that is 1000% deadly – we got results that are amazing.  In the meanwhile the component who does that that been found.

We are working to get information out to doctors and alternative healers. There is so much to learn and to do because the greatest shift has to be done in education. It is not easy to teach people who have been driven in only one direction to believe denying all other ways,even if their own life depends on that.

The reason of cancer is a psychic shock and it is not so difficult to learn about it – recreate your life from inside out and use the fruits, plants and natural elements that Mother Earth grows so we can get well. Let’s open our hearts and minds for the Amazon Rainforest and join people work fro the protection of this last wonder of an intact ecosystem and stop burning down 5000 square miles each day so some people can make their profit. They are killing life itself and we are the crown of creation and should honor all LIFE in first place as holy!!!! 

Healing of cancer is possible knowing about the cause of self creation and with the help of Mother Earth Cancer has no chance !!!!! 

Soon I will do some webinars on the topic and you will be informed……

More Information about Graviola and the power products and where to get them:

Info: mdfwhealing10@gmail.com -  

For automatic news – sign up for the free newsletter and email teachings at: www.2thepowerofspirit6.com/sq more about my work: www.2thepowerofspirit6.com

 If you want to help people get well inform your family members, your friends, your colleagues, your associations, your communities you can share that report…..; it is time to stop monopoles and manipulations. It is time to honor life and to love the fellow as ourselves…….. 

GRAVIOLA HAS THE POWER TO PREVENT and it is just a fruit in the Garden of Life –

GRAVIOLA is reproduced in plantations to let the Rainforest intact……

Blessings and time for reflection 

And don’t forget: Miracles of life are there for everybody

 

Regina E.H.Ariel

The Life Extension Pathway, Resveratrol etc. and Cancer Control: Mitochondrial Biogenesis Duality, the Metabolic Mechanism and Practical Applications.

Gregory S. Bambeck Ph.D. and Michael Wolfson  J.D., M.B.A.

Kent, Ohio U.S.A. 44240

 

SUMMARY STATEMENT: Cancer, heart disease and diabetes II, the three largest killers of the first and second world nation’s human beings (85%), and their disease antithesis, a healthy squirt from the fountain of youth, are finally defined under a singular unifying global hypothesis. Experimental molecular mapping proves that the regulatory pathway mechanisms define it as a true, real and clinically demonstrated system for the first time. Publicly available, practical and easily workable disease blocking and life extension implementation are readily available to anyone. There are three sections: ABSTRACT; PATHWAY MECHANISMS; PRACTICAL APPLICATIONS. Read on!

 

 

ABSTRACT

 

Full mitochondrial biogenesis is a two phase temporal process consisting of an early phase primarily associated with anabolism, cell replication and the making of over a thousand constitutive mitochondrial proteins that create new, but NADH to OX/PHOS inefficient mitochondria. Between these replication events, cell homeostatic controls up regulate a late phase set of mitochondrial respiratory chain proteins that create efficient NADH to OX/PHOS associated with a shift toward catabolism and autophagy of dysfunctional mitochondria and other cell debris. The early phase (neogenesis) supports cell growth, rejuvenation and whole body vitality in the short term, while the late phase (regenesis) supports cellular housekeeping and repair functions in the life extending long term. The immediate upstream effector of mitochondrial biogenesis is the mitochondrial proliferator co-activator (PGC-1alpha). Its up regulation institutes neogenesis and its down regulation institutes regenesis. Caloric restriction (CR) activates regenesis by up regulating adenosine monophosphate activated kinase (AMPK), while cancer activates neogenesis in the absence of regenesis by down regulation of the same AMPK pathway, upstream of PGC-1alpha. Recent 'rediscoveries’ show that a cancer cell metabolism proposal of 1980, is correct in its many metabolic particulars. Most cancer cells are mutationally glycolytic fetal enzyme driven 'sugar junkies’ supported by obligate mitochondrial ATP production inefficiency. Cancer cells are stuck in this cell growth drive state (metabotype), and become relentlessly replicative under the influence of mitogens. Recent genuine discoveries show that inhibition of the life extending CR pathway supports this 'sugar junkie’ growth state by creating and maintaining inefficient and neogenic mitochondria in the presence of forced hyperglycolysis. Blocking fetal glycolysis and re-establishing the CR pathway pattern creates the regenesis of efficient mitochondria and halts cancer cell growth, and can sometimes even initiate cancer cell apoptosis. We describe the pathway mechanism as a unidirectional feedback loop starting with the CR target, AMPK, and how it regulates mitochondrial biogenesis, the reactive oxygen species (ROS) output, of which, feeds back to AMPK. We also make sense of CR mimetic resveratrol, and its bioavailability in this context, and further employ these understandings to envision simple nutriceutical and lifestyle synergies to fight cancer, the major diseases of aging and even aging itself.                                                                                                     

PATHWAY MECHANISMS                                                             

                                                                                                                                                                                                    

To make this easy to understand, we wish to start with some rules of the road. First, when we use the adjective 'chronic’ or prefixes like 'hypo’ or 'hyper’, we are referring to aberrant, unnatural or man-made over impacts upon normal homeostatic systems or typical physiological shiftings in standard metabolic systems. These words are used to emphasize a principal or powerful effect of some kind. Second, since CR is the 'gold standard’ of life extension, we will use it as a 'home base’, or reference point, that most of our forays will diverge from, and then return to. Third, we will focus primarily on the unidirectional multi-toggle switch feedback cycle from AMPK to target of rapamycin (TOR) to PGC-1alpha to ROS to sestrin (SESN) and back to AMPK, with the up regulation of AMPK effectively down regulating every other component of the cycle downstream of it. Since the system is a closed feedback loop, everything is upstream of everything else as well as downstream of everything else, like the proverbial snake that eats its tail. However, extrinsic factors affecting any component can over ride their immediate upstream regulators, as we will often point out. Memorizing, or keeping a note pad with this simple AMPK, TOR, PGC-1alpha, ROS, SESN circuit, as a principal reference point, keeps the discussion grounded.

 

We will begin with a brief outline of the CR pathway. Most simply put, CR activates AMPK which down regulates TOR. Down regulated TOR shifts cell metabolism away from anabolism and toward catabolism, initiates autophagic clean up of cell debris, such as dysfunctional mitochondria and down regulates PGC-1alpha. When down regulated, PGC-1alpha results in the regenesis of existing mitochondria by initiating the transcription of mitochondrial respiratory chain proteins that efficiently link NADH to OX/PHOS ATP production. This causes mitochondrial ROS production to fall, which in turn, down regulates the ROS sensor, SESN. SESN then down regulates its stimulation of AMPK, causing the circuit to rebalance back toward its homeostatic center. Note here that active SESN up regulates AMPK and inactive SESN fails to activate, so its up regulation is active while its down regulation is passive. Thus, continued CR will bypass SESN and chronically up regulate AMPK to constantly enhance the CR pathway to reduce mitochondrial ROS. Elevated ROS is the principal life shortening component in the system, and thus, its repression is the largest single life extender known. This example demonstrates that increased AMPK activity causes a decrease in all the other four (TOR, PGC-1alpha, ROS, SESN) components in the unidirectional feedback loop. Conversely, decreased AMPK activity, as in p53 dysfunctional cancer cells, causes the up regulation of the same four components down stream of it, which incidentally, causes the neogenesis of inefficient mitochondria.                                                 

 

As exemplified by our CR model, AMPK to TOR to PGC-1alpha are the principal mitochondrial biogenesis inputs and their responses, while ROS to SESN are the principal mitochondrial outputs and their responses. We know that there are many steps between each of these five major toggle switches and that there are also myriads of branching pathways and gene up and down regulations stemming into and from each toggle switch, but they will be mentioned in passing only as needed, because it is the central unidirectional cycle that is critical to the cancer, diseases of aging decline and life extension metabolics we key on, herein. Very elegant and evolutionarily apt extensions of this central and related circuits and their nutrient sensing pathways can be found in Science, vol.327, 3/5/2010 p.1210 and vol.328, 3/16/2010 p.324. Lastly, the central focus, here, is on cellular bioenergetics and metabolics because these functions hail back to single cell eukaryotes and have finally earned their seat at the cancer cell control systems round table along with telomeres, growth factors, apoptosis etc. Later, we will see how the AMPK, TOR, PGC-1alpha, ROS, SESN circuit is the exact same circuit controlling cancer and life extension, albeit operating in the opposite direction. We shall also see that cancer 'cure’, or at least control, and CR share the exact same circuit when operating in the same direction, with mutationally driven hyperglycolysis being the lone but critical cancer stand out. But first, let’s look at each major component in the system.

 

AMPK stands at the headwaters of the CR pathway. AMPK monitors cellular energy charge by being sensitive to the AMP/ATP ratio, which generally represents the fuel nutrient availability in the cell. High concentrations of the energy rich ATP molecule represent fuel nutrient sufficiency and concomitant low AMP. Conversely, high AMP and low ATP indicate low fuel availability as in CR, which up regulates AMPK via AMPK kinase. Increases in AMPK can inhibit TOR by countermanding the growth factor pathways that activate TOR. Things that activate AMPK inhibit TOR, and things that inhibit AMPK activate TOR. Things that activate AMPK initiate the CR pathway and support life extension and inhibit the cancer metabotype. Standing directly upstream of AMPK, SESN activates AMPK when it self is activated by the cancer cell growth suppressor (p53) or by ROS, mostly of mitochondrial origin. The P53 protein is pro-apoptotic and its inhibition or dysfunction is found in about half of all cancers. Components or systems that reduce AMPK activity shorten life expectancy and promote the cancer metabotype. CR mimetics extend life expectancy and inhibit the cancer metabotype.

 

This last effect is exemplified by the anti-type II diabetic drug, metformin which is a direct activator of AMPK, causing the typical CR reduction in insulin resistance and the downstream inhibition of TOR. Metformin has been found to increase life expectancy in cancer victims, diabetics and healthy animals. Direct activation of AMPK by metformin enhances the ROS activated SESN switch or can over ride SESN inactivation by faulty p53. Intracellular concentrations of resveratrol in the 20 to 50 uM range activate AMPK similarly to metformin. Dietary free resveratrol rarely attains concentrations above the low single digits of uM. Metformin is our best known chemical example of a CR mimetic.

 

Now, let us take a brief tour of TOR. In our unidirectional metabolic loop activator model, TOR is the first primary target downstream of AMPK. TOR is a major NADH/NAD redox sensor and a master metabolic regulator switch involved in a dizzying array of integrated pathways, which can be found in a web search under 'mammalian target of rapamycin’. Fortunately, several major converging and diverging pathways impinge upon and emerge from TOR, allowing us to simplify matters. For instance, mitogens, growth factors, hormones and AMPK act upon TOR through a common intermediate called TSC2. Thus, in a functionally simplified sense, TOR responds to a delicate balance of AMP/ATP energy charge, NADH/NAD redox state, fuel nutrient availability, mitogens, growth factors, growth factor suppressors and genotoxic ROS load. TOR outputs are as multifunctional as its inputs, but are most commonly associated with the integrated regulation of mutually exclusive anabolic or catabolic systems.

 

The down regulation of TOR by elevated AMPK activity (by CR, for example) institutes a shift toward catabolic efficiency in support of the caloric restriction demands for maximum energy output from maximum fuel conservation under nutrient fuel limiting conditions. In this regimen, another TOR pathway institutes increased mitochondrial respiratory efficiency through the regenesis pathway, and still another TOR pathway up regulates the autophagy of cellular debris and dysfunctional mitochondria. Cellular efficiency, ROS reduction and elevated housekeeping functions increase life expectancy and foster disruption of the cancer metabotype. This process can also be enforced by the TOR inhibitor and foreign tissue rejection suppressor, rapamycin. Rapamycin can facilitate life extension by pulling an end around AMPK and directly inhibiting TOR to switch the cellular drive state from anabolism to catabolism, and also very importantly, push mitochondria into the state of regenic efficiency by down regulating PGC-1alpha.

 

Finally, as the last major element in the mitochondrial biogenesis input side of the unidirectional loop, a short summary of PGC-1alpha function might be in order. When PGC-1alpha is activated, it turns on over a thousand genes which are devoted to the very complex but singular mega-function of building more mitochondria (neogenesis). As we saw, when TOR is up regulated, it in turn, up regulates PGC-1alpha, and the building of all of the mitochondria except the respiratory chain, is instituted. The respiratory chain transcription elements can only be constructed when PGC-1alpha is down regulated, later. Chronic stimulation of PGC-1alpha via chronic up regulation of TOR by growth hormone keeps mitochondria in a state of neogenesis with impoverished regenesis, which is a high ROS generator.

 

This nowhere more manifest than in the cancer cell metabtype. When mitochondrial respiratory NADH to OX/PHOS coupling is compromised by neogenesis without regenesis, the mitochondria, although primarily catabolic in function, actually enhance anabolism by supporting increased glycolisis and, thereby, shift the balance of glycolytic products,  mitochondrial feedstocks and NADH reducing power toward cell building, all supported by an increase in the glycolytic to mitochondrial ATP production ratio. In his dissertation at Kent State University on mitochondrial alterations in a lymphoblastic lymphoma transplanted into DBA/1J mice, in 1980, Bambeck reviewed dozens of cancer type cell mitochondria, and saw a pattern. He provided a detailed catabolic chart, a general NADH cell nutrient and building block flow chart and an extensive narrative describing these connections. The AMPK, TOR, PG C-1alpha mitochondrial input side of the CR pathway, only now available, finally supply the control elements that prove his hypothesis, which we have just begun to re-discover in the last two years. It is surprising how accurate this thirty year old description is, considering there was no awareness of AMPK, TOR, PGC-1alpha or the vast array of intermediate connections in this regulatory pathway, at that time. However, even today, our new knowledge still boils down to the control of redox, energy charge and metabolites, which could be monitored even, at that time, in the absence of this modern regulatory pathway knowledge. This was done by constructing metabolic flow charts under different drive states and deducing where control links must exist, even if they were, as yet, unknown.

 

Just as metformin can bypass SESN by directly up regulating AMPK and rapamycin can bypass AMPK by directly down regulating TOR, T3 thyroxine in its non-shivering thermogenesis mode, can mostly bypass TOR by up regulating PGC-1alpha. In addition to ignoring the TOR anabolic/catabolic toggle, this can help illustrate the temporal duality of PGC-1alpha function.

 

A single dose of T3 thyroxine binds to nuclear DNA upstream of the mitochondrial biogenesis activator master control system and the PGC-1alpha binding co-activator, and begins transcription. Within five hours, activated PGC-1alpha causes more than 1,000 nuclear genes that are specific to the building of new respiration impoverished mitochondria to begin transcription. These very long mRNAs contain the code for their respective gene products as well as the leader sequences for their respective mitochondrial targets. These mRNAs are exported from the nucleus to the cytoplasm to form translational polysomes where mitochondrial outer membranes become confluent with endoplasmic reticulum. Depending on their signal sequences, these mitochondrial proteins are ferried to their mitochondrial home compartments to take up functional residence. After about 48 hours the thyroxine and PGC-1alpha signal system decays and a late set of nuclear and mitochondrial genes specifying the components of the respiratory chain are activated, causing these poorly coupled neogenic mitochondria to become efficient ATP producing regenic mitochondria. In chronic hyperthyroidism, the neogenic phase is powerfully up regulated relative to the regenic phase and the resultant ROS damage is severe enough to dramatically shorten life. A common term for early hyperthyroidism termination is 'burnout’, because unlike TOR and its anabolic activated neogenesis function, the thyroxine activation is catabolic.

 

In the thyroxine activated neogenic phase, there are also a set of uncoupling proteins (UCP) that are produced that allow NADH protons to 'leakback’ into the mitochondrial matrix without their chemiosmotic potential being captured and stored as high chemical energy ATP. Although this an over simplified description, the net result is that the uncaptured energy becomes manifest as heat, which is easy to measure. Thyroxine also supports catabolism by shifting fuel sources from low energy per carbon sugar to high energy per carbon lipid, and if need be, protein. However, when PGC-1alpha is up regulated by TOR, anabolism is supported and glucose is the preferred fuel. This difference becomes not only important, but highly magnified when we consider the cancer metabotype, later. Chronic up regulation of PGC-1alpha, whether anabolically driven by growth hormone stimulation of TOR or catabolically driven by direct stimulation of thyroxine as in hyperthyroidism, results in an incomplete mitochondrial biogenesis stuck in a high ROS producing neogenic state which can induce cancer and shorten life span via ROS produced genotoxicity and stochastic randomization of proteins compounded by the absence of phagocytic housekeeping functions and DNA repair systems. Chronic neogenesis in the absence of regenesis is not only a cancer cell metabotype inducer but a cancer cell metabotype maintainer, as well.

 

Another way to uncouple NADH from ATP production is for mitochondria to export NADH to the cytoplasm via the NADH/NAD shuttle system. In growing and dividing cells, the redox and energy charge states always lag, so this system is employed more heavily. Also, in non dividing quiescent cells, citrate in excess of krebs cycle needs can inhibit the 'committing’ enzyme phospho fructo kinase (PFK) at the headwaters of glycolysis. Fetal PFK is often elevated in cancer cells. Although it is an inefficient ATP and NADH producer, glycolysis can run at explosively fast rates when stimulated. For the sake of brevity, we will not distinguish between the two uncoupling forms in this document.

 

The above described AMPK to TOR to PGC-1alpha portion of the closed unidirectional loop are the inputs to the mitochondrial neogenesis/regenesis system. The ROS to SESN portion represent the ROS output feedback loop to AMPK. Although the exact mechanism of the mitochondrial output of ROS to SESN is still to be articulated, its requisite path and net results are unambiguous. Increases in ROS eventually leads to activation of SESN, which in turn, activate AMPK to inhibit TOR to down regulate PGC-1alpha to institute mitochondrial regenesis to reduce ROS. SESN gene knockout drosophila die prematurely of age related disorders, and the anti-oxidant vitamin E protects life length function in SESN gene knockouts.

 

The system, as so far described is more elucidative of life extension than it is of the generation and maintenance of the cancer metabotype, soon to be discussed. Basically, life extension via the CR upregulation of AMPK occurs, mostly due to the reduction of ROS caused by mitochondrial regenesis of efficient ATP producing mitochondria. This essentially puts the adult organism in an extended holding pattern until nutrient energy supplies can support fecundity and other energy intensive functions such as immune surveillance, wound healing and muscle building.

 

Here is how resveratrol probably fits into the picture. In dietary quantities, free resveratrol enters interstitial cells in too low a quantity to mimic caloric restriction by more than a very modest degree. In these quantities, it up regulates mitochondrial neogenesis more so than regenesis by a moderate but significant up regulation of thyroxine. The purported mechanism is via its mimicry of beta-estradiol activation of hypothalamic stimulation of thyroxine stimulating hormone releasing hormone. But, resveratrol is also a powerful anti-oxidant. In this mixed effect, it acts as a caloric restriction meta-mimetic rather than an actual AMPK stimulating mimetic. It does not significantly up regulate AMPK, but it activates PGC-1alpha without up regulating TOR, so it is not acting like growth hormone, either. This is a huge difference because, like CR elevation of AMPK, it is definitely not anabolic and it sports its own catabolic influence. On the other hand, it is unlike thyroxine stimulation in that it scavenges ROS, evoking a regenesis rather than a neogenesis result, another net outcome of CR. Regardless, resveratrol is more neogenic than regenic in these quantities. How much its mixed CR mimetic function plays into this tortuous scenario, is anybody’s guess, and its numerical impact on the ROS load is unknown. The largest evidence supporting this scenario is that dietary resveratrol’s cancer killing and life extension functions, as seen at in vitro concentrations, some ten times higher, are not significantly manifest. At the dietary levels it would be prudent to force a neogenic default to regenesis just to hedge the bet toward a definitive CR like outcome. Vigorous endurance exercise after an over night fast would probably turn the trick via creating a sugar depletion oxygen debt. In humans, resveratrol followed by exercise, even without fasting, converts glycolytic fast twitch white muscle fibers into aerobic red slow twitch fibers, and increases mitochondrial cell volume from about5% to 30%, with regenic characteristics. Similar results occur in fasting runners in the absence of resveratrol. The experiments we need are rather obvious.

 

The in vitro life extension and cancer apoptotic effects of  resveratrol in the 20-50 uM range are so enticing that this dietary bioavailability deficiency should soon be overcome. Already, free resveratrol serum levels well above the 20-50 uM target range are being reported, industrially. Also, synergistic molecules like quercetin and co enzyme Q with antioxidants are in the mix. Still, TOR down regulation and mitochondrial regenesis are requirements for full CR impact. We explore these issues in the practical applications section, later. But, for now, our metabolic feedback loop attentions divert their focus onto the cancer metabotype.

 

 

 

From a genetic perspective, cancer cells appear insane. Between the chromosomal inversions, insertions and uneven cell divisions that render cells into a heterogenous mix of  hundreds to thousands of genes in polyploidy or haploidy, add to this, the changed protein complement and its post translational miss modifications, and the result becomes a bewildering array of changes from any given cancer’s not quite fully differentiated stem cell progenitors. Although each cancer cell type retains many of the characteristics of its parent cell type, shot gun analysis, such as 2D electrophoresis and tryptic digest multi-gradient HPLC (high performance liquid chromatography) and MALDI-TOF (matrix assisted laser desorption ionization-time of flight) mass spectrometry, demonstrate that no two cancers are alike and that a given cancer is not even like itself. A cancer tumor seems as if it is composed of a heterogenous thematic of a precursor cell type engaged in a hyper-Darwinian selection for survival in an organism that is desperately trying, but failing, to kill it.

 

Fortunately, even cancer cells must obey the laws of thermodynamics, and they must do so within the constraints of the metabolic tool kit of sugar, amino acid, lipid and nucleotide apportionments and redox (NADH/NAD) and energy carriers (AMP/ADP/ATP) that permit the cell to grow and divide, so as to be able to grow and divide, and so on. Note here, that the sugar and carbohydrates are the cheapest energy source in the earth’s biotic food web. Lipid is a bit pricier, but proteins and nucleotides are very expensive because phosphate and redoxable nitrogen are nutrient limiting, pretty much, planet wide. Thus, sugar is the preferred fuel during cell growth and division (especially during hypoxia), while lipids, proteins and nucleotides are preserved as building materials. These nutrient limitations and metabolic requirements were fixed in stone a billion years before the first multicellular organism existed. In addition, cancer cells share a lot of features with fetal cells. Very importantly, they are always outrunning their fuel and oxygen supply needs, so they take on a hypoxia metabotype that induces blood vessels to grow toward them. This blood vessel growth is called angiogenesis. They also dramatically increase their glycolytic rate, in some cases well over 1000%. Most importantly of all, this changes the glycolytic to mitochondrial ATP production ratio by even a greater percentage, due to mitochondrial paucity and/or inefficiency. Like fetal cells, they become glucose junkies as they parasitize the sugar making hepatic gluconeogenic processes of their host, but unlike fetal cells, they cannot turn glycolysis off.

 

Because of this hypoxia and its anabolic requirements, cancer cell growth is always neogenically out pacing its regenic function. Many books have been and still will be written about fetal and enviromental bioenergetics and its evolutionary and organismal growth condition implications, and especially now, even more so, that the primary elements of the CR pathway have been clarified, and implicate cancer and other diseases of aging. But, for now, the main points, described above, will suffice.

 

How all this CR based AMPK feedback loop stuff fits together to arrive at cancer cell intermediary metabolism is an astonishing wonderment and a stunning new achievement. We grant many laudits and heaps of praise for the scientists who slogged through years and hundreds of thousands or even millions of man hours to elucidate the particulars of the regulatory loop and its myriad of attendant pathways. Even though cancer research and CR authors (as well as diabetes and cardiovascular researchers) may not yet know it, their results show that the cancer metabotype and the CR pathway are the exact same pathway, albeit operating in basically opposite directions and under different conditions, with the AMPK loop and mitochondrial neogenesis vs. regenesis as core control elements in both cases, and with cancer cell glycolysis providing its own caveat. The fact that type II diabetes and cardiovascular hyperplasia and cardiac hypertrophy are also outcomes of this pattern, is even more amazing. Readers of this document would easily understand and be pleasantly surprised by the basic cancer connection if they read (and this is a must read) New Scientist, 5/15/2010 p.6, a brief outline, of which, is below, after the Warburg correction discussion.

 

In the last two years, cancer researchers have proven that the particulars of glycolytic and aerobic metabolism in cancer cells are precisely as previously described in 1980. At that time the hypothesis corrected a flaw in the Warburg aerobic glycolysis hypothesis by postulating that cancer cell mitochondria suffered from an ATP production shortfall resulting in an anaerobic to aerobic ATP differential as opposed to Warburg’s mitochondrial oxygen consumption deficiency concept. This is an important difference because it changes the NADH/NAD, ATP/ADP and substrate flows in the cell. It was also described, in detail, how this shortfall was integrated with glycolytic fetal enzyme activation to force the system to amplify the, as then poorly understood, anabolic command system, to operate in an irreversible state of  cell growth and division, we previously have coined as the cancer metabotype. Interesting methods of attack designed to kill or renormalize cancer cells were envisioned at that time. With our new found knowledge, we might wish to revisit some of these strategies, in a search for synergies. It is remarkably serendipitous how the 'rediscovery’ of this forgotten system during the last two years is so similarly identical in such a wide array of particulars. In all cases, whether as old discoveries, rediscoveries or new discoveries, the results unambiguously show that the cancer metabotype is obligately and inextricably intertwined with the CR pathway, and with mitochondrial over neogenesis with a paucity of regenesis. It is this synthesis that is the really new stuff.

 

As an overview, from a metabolic standpoint, most cancer cells are stuck in mutationally up regulated fetal enzyme induced hyper glycolysis supported by down regulated AMPK to TOR etc. driven mitochondrial neogenic ATP production deficiency, in ways that the cell cannot recover from, as it can in fetal cells, at least in normal in vivo circumstances, short of artificial intervention. Under the influence of increased mitogen drivers and decreased or dysfunctional cell growth suppressors, the cell is forced into irrepressible and irreversible rounds of growth and division. We ignore metastasis and other issues, here, as we are focused on the ancient metabolic drive states of cancer cell induction and maintenance as opposed to progression.

 

What the researchers in the New Scientist review article found was that blocking fetal pyruvate kinase enzyme driven glycolysis with dichloroacetate 'reawakened’ (their words) mitochondrial regenesis (our words), re-establishing normal glycolytic to mitochondrial ATP production ratios and metabolite flow, and brought cancer cell growth to a virtual halt in brain glioblastomas. Furthermore, previous hospital records showed that up regulation of AMPK with metformin in diabetic lung cancer victims increased survival times. This is the first time, in humans, for it to be shown that CR and anti-cancer therapies share the exact same AMPK control circuit, and with an anti-diabetes drug, to boot. We must also note that the system has been shown to work in numerous mouse cancers, and this is one time in cancer research that mice and men really share an ancient and attackable metabolic control pathway. This is just the early 'sledgehammer’ phase of the human work. More sophisticated assaults are envisioned with excited expectancy. Let us hope that we don’t have to find too many fetal enzyme blockers, because even thirty years ago, we knew of other such fetal enzyme supporting changes in glycolysis and its attendant anabolic NADPH providing pentose phosphate shunt, in different cancers.

 

Reducing hyperglycolysis and increasing mitochondrial efficiency are the two key elements in slowing the impact of age related like cancer, type II diabetes and cardiovascular dysfunction. For instance, in the aging adult, cardiovascular ROS damage institutes mitogenic and hyperplasic thickening in the intima of the vascular tree, and ventricular hypertrophy concomitant with mitochondrial decline and a steady state shift from efficient high energy lipid catabolism to low efficiency glucose catabolism. Contrast this to hypoxic fetal conditions, when birth provides abundant pulmonary oxygen followed by full cardiac mitochondrial biogenesis, a rapid shift from carbohydrate to lipid catabolism, a conversion from parasitic high affinity fetal hemoglobin F to free living lower affinity adult hemoglobin A and a decrease in ROS production. The first is a stop-gap response to ROS induced genetic damage, while the second is a finely tuned genetic system response to an energy opportunity. Both are mediated by the AMPK, TOR etc. feedback loop, and judicious stimulation of this loop via CR or its mimetics are shown to yield significant inhibitory impacts on these exact forms of cardiovascular decline. Type II diabetes is a similar whole body response to the same type if insults found in cardiovascular decay, and can be staved off by direct metformin activation of AMPK that lowers insulin resistance and creates cellular housecleaning and mitochondrial regenesis. Metformin has been in use from long before we were even aware of such things as the sestrin feedback loop, mitochondrial neogenesis, regenesis and its relation to fetal hyperglycolysis!

 

Both neogenesis and regenesis are critical to retaining a juvenile youth state in adult cells. By analogy, neogenesis is like a construction crew that builds a new house but leaves a mess of construction related debris. Regenesis is like the housecleaning and maintenance follow up that makes the house into a livable home. In the aging adult non-dividing cell, both functions are deficient with regenesis being the more deficient, as aging cells tend to progress toward debris ridden hyperplasia. Declining growth hormone and androgenous steroids inhibit neogenic and rejuvenative functions while ROS exacerbates 'rusting out’ functions and abundant nutrition inhibits regenic functions. This may explain why CR seems to have virtually no impact if started before early middle age. This also may explain how chronic neogenesis, as with growth hormone, yields short term gains with long term 'burnout’. Conversely, it may explain how chronic regenesis, as with CR, yields long term gains, but with serious quality issues. Perhaps periodic neogenesis with a rapid default to regenesis, as is much more typical of juvenile cells, may provide an optimal result.

 

A review of these mechanisms has left the two of these authors quite breathless when we consider the scope of its medical implications, both in terms of the medical monetary cost savings, and in terms of the staggering number of quality human life years which might be added to the aggregate. It is quite nifty how key elements of the three greatest killers of the human race, along with a healthy squirt from the fountain of youth, all fit within the framework of a singular, unifying and global hypothesis. Thus, from all that has been articulated in the above document, we define the system.

 

PRACTICAL APPLICATIONS: THE FUTURE BURNS BRIGHT

 

One might consider this to be the wild hypothesis part of the document, but based upon the aforementioned findings, the proposals might actually be more sound than a lot of the stuff that peppers the grocery store checkout stands. However we remind everyone that we are not medical doctors, and therefore, not licensed to practice medicine. Nor is it our intention to do so. Any use of the information contained in same is at the reader’s discretion. We specifically disclaim any and all liability arising directly or indirectly from the use or application of any information contained in any of these articles. What we write here, is more so, of a free speculation of ideas engaging over the counter phytonutrients and life style choices.

 

Recent longitudinal studies show us that dietary sugar is killing us more resolutely than either saturated fat or high protein content, as found in animal products. The diseases of aging, such as diabetes, heart disease and cancer, kill the vast majority of us and excess dietary (extracellular) sugar is a main and growing culprit. However, the previously outlined AMPK, TOR, PGC-1alpha, ROS, SESN cycle shows that the system’s relentless decay yields to the diseases of aging, in spite of dietary sugar, due to intracellular metabolic shifts over time. In other words, even though sugar powered the creation of our lives from inception to birth, it will eventually kill us even if we don’t eat it. This is 'natural’ aging, and the data clearly shows that unnatural or supra-natural efforts must be made to obtain the unnatural or supra-natural state called life extension beyond the natural or normally expected limit. Face it, caloric restriction (CR) is draconian and is only natural in the sense that, in nature, food sometimes runs out. No organism exists that will 'naturally’ CR itself in the presence of adequate food. Mega doses of anti-oxidants or a hundred bottles of wine worth of resveratrol a day is, decidedly, unnatural.

 

 That being said, such things have been found to stand the test of time. For instance, the Chinese have been drinking a high resveratrol Japanese knotweed root extract, called itadoli tea, for millennia with claimed beneficial results and no known ill effects save for some occasional intestinal discomfort, found to be mostly due to emodin, a co extract, which incidentally, is not found in modern concoctions. The remainder of this brief discussion is mostly devoted to some unnaturally 'natural’ stuff that folks might do without having to live a supplement menagerie supported life in near anorexia with its attendant impediments to muscularity, wound healing, immune function, fecundity and others. The focus, here will be on forcing a default state to mitochondrial regenesis, which is the heart and soul of life extension and the inhibition of cancer cell induction and maintenance. Thus, the discussion will completely avoid the well worn school marm admonitions such as 'eat your vegetables,’ 'take your vitamins,’ 'exercise regularly,’ 'drink plenty of water,’ 'keep your weight down,’ 'don’t eat between meals,’ 'brush your teeth after every meal,’ 'don’t eat anything that you can’t fit into your mouth,’ 'holy cow, that sure is a big fish’ and other common sense standard fare that we won’t even mention, here.

 

It is difficult to tell how much of dietary resveratrol is neogenic and how much is regenic. It cannot be heavily neogenic due to its TOR bypass, catabolic and anti-oxidant functions plus its average life expectancy increasing and rejuvenative outcomes in the absence of increased cancer induction or any true life length reduction. Standard dietary resveratrol also cannot be very strongly regenic because there is no appreciable up regulation in AMPK, no real reduction in cancer incidence, no increase in cancer cell apoptosis and no true life extension. However, much mitochondrial biogenesis is observed, but how much of this is neogenesis converted to regenesis is unknown because most investigators were unaware of the difference.

 

Progressive nutriceutical supply companies recognize this and are actively pursuing remedies. The essential problem is simple. When resveratrol is eaten, well over 90% of it is sulfonated and glucuronidated in the intestines and in the liver via the hepatic portal system, rendering it water soluble for targeting it for kidney removal to the urinary tract. Free, unmodified dietary resveratrol is typically less than 2 uM during its one and a half hour elevated blood plasma phase following ingestion. Glucuronate and sulfate derivatized resveratrol do not cross interstitial cell membranes and the low free resveratrol in cell microsomal fractions indicate that the interstitial cell extracellular sulfatases and glucuronidases have no general impact. This may not be true at sites of inflammation, but the desired whole body effect appears not to be there. Although we have no retention or turnover numbers on free intracellular resveratrol, it does not appear to accumulate over time.  Experiments have shown that serum soluble free resveratrol concentration in the 20 uM range definitely impact the CR/AMPK pathway. For instance, DMSO solubilized resveratrol, when injected into mice, causes all the desired AMPK and downstream effects in brain tissue.

 

As mentioned earlier, nutraceutical suppliers are being very ingenious in their attempts to get serum resveratrol concentrations up to the CR mimetic range. One supplier shows, graphically, how micronization of resveratrol dramatically increases free resveratrol up to and well beyond the minimal required AMPK activating range. Other suppliers are creating encapsulated, solubilized and time released formats. One supplier provides lozenges for sublingual delivery. Resveratrol mixed with synergizers such as quercetin and co enzyme Q, are also offered. We eagerly await their time based serum data, and even more so, their intracellular AMPK up regulation data.

 

Here’s a quick and dirty home remedy. You can dissolve up to about 500 mg of resveratrol in a shot of 86 proof booze, or flavored schnaaps for the more faint of heart. Solubility is mostly dependant upon alcohol content, so the same should hold for a glass of wine, but it may take a while to dissolve. Besides, the smaller the volume, the better it is for non-intestinal absorption. Take a slug, swirl it around in your mouth for a full minute before swallowing, kick back, and enjoy. Dissolving is what you might call the nanonization technique. It has been shown to enhance buccal and aerodigestive absorption by as much as 800% above dietary methods, and it does not increase the kidney metabolite load one whit. Anyway, many of the medical gurus out there tell us that 10-20 grams of ethanol a day, is good for us.

 

Then, there’s the stretch (or even strain) of your imagination beyond the orbit of Pluto, plan. Human beings have daily circadian and monthly lunar cycles for a reason. Anyone who has read about the circadian melatonin cycle knows what we’re talking about. The fact that human females have a lunar cycle length receptivity cycle, and that in small, tight knit groups, cycle together, is no accident. The seasonal based cycle was replaced by the lunar cycle because conditions made it happen. What made it happen, you query? We never thought you would ask.

 

The mutational force is the primary evolutionary driver, but it is accidental, generational and is usually a losing proposition, with rare selective advantage. But, the winners support population survival in the form of multi-generational adaptation. The selection advantage of a switch from a seasonal to lunar cycle must have been powerful, simply because it was forced into existence. Consider the following. Over 99% of the last two million years, or so, of human evolution, has been devoted to the slow steady conversion from gathering, to scavenger gathering, to hunter gathering, while the remaining less than 1% is called civilization. Having excellent 3-D color vision, but poor night vision, the night light of the full moon became a great advantage as it advanced geographical food acquiring range and easier pickings. Being bipedal and having prehensile dexterity in a shrinking dryas ecosystem were great evolutionary pre-adaptations and opportunity vs. death drivers for proto-humans.

 

This dynamic food energy switch created full moon super-nutrition followed a remaining month of being trapped in standard fare. This tuned up a monthly cycle of high, then haphazard nutrition, which caused elevated body fat that could conveniently support fecundity, two weeks after the full moon, during the pitch black nights of the new moon. Since nobody looks ugly in the dark, and besides, there being nothing else to do but stumble around like blind idiots, a nutritional match was made in heaven. In addition, sexual glue is social glue. This was already operating in the context of a proto-hominid large brained noisy critter, with its ecological niche pushing a movement toward even more brain growth, symbolic representation as language and a pre-civilization social tool kit simply awaiting large enough population numbers to invent neat stuff like cities, war and jacuzzies. Thus, the African stage was set, and fortunately for us, all four acts played out before we, as the genetic evidence shows, were almost extincted.

 

This pattern would also be reflected as a natural nutrient driven cycle of low and high AMPK activity and a regular neogenesis and regenesis cycle, which may have assisted us in becoming the longest living primate. The long parturition period, the interminable time stretch from birth to sexual maturity and the creation of history, in the need for elders to pass all that big brained accumulation to the next generational batch of dull witted dimbulbs that seem to arise with each generation, could have helped to assist this life lengthening admixture. In the context of this paper, that is, if there still is any context, this kind of long winded speculative wannabe has just got to be followed with a circadian/lunar cycle recipe format.

 

The advent of commercially available high concentration bioavilable resveratrol would open the door to possibilities that will really bring the troops home. At full dose, it would bias the system toward true CR mimicry of AMPK driven mitochondrial regenesis, while at one tenth full dose, it would bias the system toward the neogenic meta-mimicry we described in detail, before. Since neogenesis takes several days to complete, while regenesis is much quicker, a circadian/lunar cycle plan that forces the system into lengthy defaults to life extending regenesis, might look something like this: Low dose neogenic resveratrol could be coordinated with anti-oxidants, dietary nutrient loading and/or power based exercise for five to seven days, or so, then followed by high dose resveratrol coordinated with daily food avoidance between dinner and breakfast and/or high oxygen utilizing endurance exercise prior to breakfast in a more extended time frame, say about three weeks, to entrench mitochondrial efficiency, cellular house cleaning and a shift away from glucose toward fat burning. Here we have something for everybody. Lounge lizards could reap the benefits of the phytonutrient pattern only effect, while the more restless spirits among us could enhance those effects by dietary and exercise regimens. Either way, organs and tissues other than cardiovascular and skeletal muscle could become larger recipients of resveratrol’s benefits. Numerous daily, weekly and monthly variations of the theme could be envisioned. One plan might be to include one meal a day to cause chronic fasting default to regenesis and/or with exercise to assist regenesis with glucose nutrient debt and/or a CR mimetic to activate the AMPK life extension loop.

 

A very interesting rat study of intermittent CR has put the world of CR afficionados on its ear. Using alternate days of ad libitum food supply and total fasting, in rats, results in no long term CR, as the rats make up for fasting by feasting between fast days, while ending up with life extension comparable to CR. This more or less jives with the down regulation of PGC-1alpha to regenesis turn on time frame. In fact, this study is the actual proof of principle, since life extension by CR can’t happen without it. This also jives with our notion that, at least partial neogenesis followed by regenesis, won’t hurt life extension, and you can avoid the misery and downside risks of genuine CR.

 

An interesting question emerges here. Since regenesis is a CR long term life extension holding pattern, how long is it good for? By this, we mean: Once mitochondria become efficient, how long do they stay efficient before they need restimulated to become efficient again? In other words, how many days of feast can one 'get away with’ before each day of fasting? If regenesis is good for a week, then a one day a week fast is a small price to pay. Not only that, if 18 hours of fasting works as good as 24, then all one would needs do is miss breakfast once a week. Can this be supplemented with a low dose resveratrol regimen that would accentuate the effect?

 

We need experiments and we need them earlier rather than later. But rats live five or more years, and rats are not people, (as opposed, off-times, to the other way around). Over the counter metformin is over a decade away, if ever, and rapamycin is too dangerous to become street legal in any time, dimension or reality. Metformin, when used with growth hormone to mechanistically force the system to toggle back and forth between neogenesis and regenesis could ultimately turn out to be the greatest anti-aging plus rejuvenation achievement of all time. This could truly cause cells to behave more like they do in the juvenile stage. The timing, dosage and testing required in such a scenario would be critical. This is playing with some real big mojo, here, and it would be illegal without a prescription under a doctor’s care. Only people, at least in their early middle years, say past thirty, could participate in such a program, safely.

 

Fortunately, at present, we have resveratrol, which is freely obtainable and we know enough about CR and mitochondrial neogenesis and regenesis, to get answers, fast, and in humans instead of rats. Human volunteers and tissue biopsies that measure CR via AMPK activity and mitochondrial biogenic state from krebs cycle enzymes vs. cytochrome content, can allow us to follow the system status through time. The system is well enough defined, by now that the meanings of these assays point to causation rather than correlation. A wide array of experiments could be rapidly conducted, and could pinpoint which timings, conditions and regimens are optimal, whether there are any down sides and what other items might be included. Ideally, we may find a CR mimetic dose schedule of resveratrol, a better mimetic or a mixture of synergistic components that require no life style changes outside of normal prudent health practices … except for that magic pill, of course.

 

AFTERWORD

 

 Not very surprisingly, there is very little cross talk between the cancer metabolism, cardiovascular disease, diabetes, life extension and diet/exercise research communities. Today’s specialization doesn’t really allow for it, and the areas of work do seem far afield of one another. But there are other reasons. For one, the cancer metabolism field, although rather ancient, is perceived to be actually, new. This has much to do with the hugely bitter and public battle that led to Warburg’s demise in 1956. The whole field of research became verboten, and one liners like “that was proven false a long time ago” and “we don’t even look into that area any more” were almost sheep mentality mantras. Another reason is that, who would have ever guessed that any such connection between cancer and life extension could even possibly exist, and even if it did, that it would simultaneously lead to the fountain of youth and the slaying of the monster hiding under the bed. Throwing in cardiovascular disease and diabetes, to boot, is more icing than any cake can stand. But in reality, it isn’t too big to believe, because this is all soon to become common knowledge. Anyone who reads the three review papers referred to in this article can readily observe that it has become too obvious by now for the connections not to be seen by droves of scientists. And we don’t mean the small connections. We mean the big ones, the really big ones.

 

Gregory S. Bambeck Ph.D.  e-mail: gregorybambeck@yahoo.com

Michael Wolfson  J.D., M.B.A.  e-mail: mwolfson@stanfordalumni.org

 

Copyright © by Gregory Bambeck and Michael Wolfson  June 11, 2010.