Cancer

THREE STAGES OF CANCER (救命飲食)

from http://www.amazon.com/China-Study-Comprehensive-Nutrition-Implications/dp/1932100660/ref=sr_1_11?ie=UTF8&s=books&qid=1220640890&sr=1-11

Cancer proceeds through three stages initiation, promotion and progres­sion. To use a rough analogy, the cancer process is similar to planting a lawn. Initiation is when you put the seeds in the soil, promotion is when the grass starts to grow and progression is when the grass gets completely out of control, invading the driveway, the shrubbery and the sidewalk.

So what is the process that successfully “implants” the grass seed in the soil in the first place, i.e., initiates cancer-prone cells? Chemicals that do this are called carcinogens. These chemicals are most often the byproducts of industrial processes, although small amounts may be formed in nature, as is the case with aflatoxin. These carcinogens genetically transform, or mutate, normal cells into cancer-prone cells. A mutation involves permanent alteration of the genes of the cell, with damage to its DNA.

The entire initiation stage can take place in a very short period of time, even minutes. It is the time required for the chemical carcinogen to be consumed, absorbed into the blood, transported into cells, changed into its active product, bonded to DNA and passed on to the daughter cells. When the new daughter cells are formed, the process is complete. These daughter cells and all their progeny will forever be genetically damaged, giving rise to the potential for cancer. Except in rare instances, completion of the initiation phase is considered irreversible.

At this point in our lawn analogy, the grass seeds have been put in the soil and are ready to germinate. Initiation is complete. The second growth stage is called promotion. Like seeds ready to sprout blades of grass and turn into a green lawn, our newly formed cancer-prone cells are ready to grow and multiply until they become a visibly detectable cancer. This stage occurs over a far longer period of time than initiation, often many years for humans. It is when the newly initiated cluster mul­tiplies and grows into larger and larger masses and a clinically visible tumor is formed.

But just like seeds in the soil, the initial cancer cells will not grow and multiply unless the right conditions are met. The seeds in the soil, for example, need a healthy amount of water, sunlight and other nutrients before they make a full lawn. If any of these factors are denied or are missing, the seeds will not grow. If any of these factors are missing after growth starts, the new seedlings will become dormant, while awaiting further supply of the missing factors. This is one of the most profound features of promotion. Promotion is reversible, depending on whether the early cancer growth is given the right conditions in which to grow This is where certain dietary factors become so important. These dietary fac­tors, called promoters, feed cancer growth. Other dietary factors, called anti-promoters, slow cancer growth. Cancer growth flourishes when there are more promoters than anti-promoters; when anti-promoters prevail cancer growth slows or stops. It is a push-pull process. The pro­found importance of this reversibility cannot be overemphasized.

The third phase, progression, begins when a bunch of advanced cancer cells progress in their growth until they have done their final damage. It is like the fully-grown lawn invading everything around it: the garden, driveway and sidewalk. Similarly, a developing cancer tumor may wander away from its initial site in the body and invade neighboring or distant tissues. When the cancer takes on these deadly properties, it is considered malignant. When it actually breaks away from its initial home and wan­ders, it is metastasizing. This final stage of cancer results in death.

PROTEIN AND PROMOTION

To go back to the lawn analogy, sowing the grass seeds in the soil was the initiation process. We found, conclusively, through a number of experi­ments, that a low-protein diet could decrease, at the time of planting, the number of seeds in our “cancerous” lawn. That was an incredible finding, but we needed to do more. We wondered: what happens during the promotion stage of cancer, the all-important reversible stage? Would the benefits of low protein intake achieved during initiation continue through promotion?

Practically speaking, it was difficult to study this stage of cancer be­cause of time and money It is an expensive study that allows rats to live until they develop full tumors. Each such experiment would take more than two years (the normal lifetime of rats) and would have cost well over $100,000 (even more money today). To answer the many ques­tions that we had, we could not proceed by studying full tumor develop­ment; I would still be in the lab, thirty-five years later!

This is when we learned of some exciting work just published by oth­ers3’ that showed how to measure tiny clusters of cancer-like cells that appear right after initiation is complete. These little microscopic cell clusters were called foci.

Foci are precursor clusters of cells that grow into tumors. Although most foci do not become full-blown tumor cells, they are predictive of tumor development.

By watching foci develop and measuring how many there are and how big they become, we could learn indirectly how tumors also develop and what effect protein might have. By studying the effects of protein on the promotion of foci instead of tumors we could avoid spending a lifetime and a few million dollars working in the lab.

What we found was truly remarkable. Foci development was almost entirely dependent on how much protein was consumed, regardless of how much aflatoxin was consumed!

This was documented in many interesting ways, first done by my graduate students Scott Appleton and George DunaiP. After initiation with aflatoxin, foci grew (were promoted) far more with the 20% protein diet than with the 5% protein diet.

Up to this point, all of the animals were exposed to the same amount of afiatoxin. But what if the initial aflatoxin exposure is varied? Would protein still have an effect? We investigated this question by giving two groups of rats either a high-aflatoxin dose or a low-aflatoxin dose, along with a standard baseline diet. Because of this the two groups of rats were starting the cancer process with different amounts of initiated, cancerous “seeds.” Then, during the promotion phase, we fed a low-protein diet to the high­-aflatoxin dose groups and a high-protein diet to the low-afiatoxin dose group. We wondered whether the animals that start with lots of cancerous seeds are able to overcome their predicament by eating a low-protein diet.

Again, the results were remarkable. Animals starting with the most cancer initiation (high-aflatoxin dose) developed substantially less foci when fed the 5% protein diet. In contrast, animals initiated with a low-aflatoxin dose actually produced substantially more foci when sub­sequently fed the 20% protein diet.

A principle was being established. Foci development, initially deter­mined by the amount of the carcinogen exposure, is actually controlled far more by dietary protein consumed during promotion. Protein dur­ing promotion trumps the carcinogen, regardless of initial exposure.

With this background information we designed a much more sub­stantial experiment. Here is a step-by-step sequence of experiments, carried out by my graduate student Linda Youngman. All animals were dosed with the same amount of carcinogen, then alternately fed either 5% or 20% dietary protein during the twelve-week promotion stage. We divided this twelve-week promotion stage into four periods of three weeks each. Period 1 represents weeks one to three, period 2 represents weeks four to six, and so on.

When animals were fed the 20% protein diet during periods 1 and 2 (20-20), foci continued to enlarge, as expected. But when animals were switched to the low-protein diet at the beginning of period 3 (20-20-5), there was a sharp decrease in foci development. And, when animals were subsequently switched back to the 20% protein diet during period 4 (20-20-5-20), foci development was turned on once again.

In another experiment, in animals fed 20% dietary protein during period 1 but switched to 5% dietary protein during period2 (20-5), foci development was sharply decreased. But when these animals were re­turned to 20% dietary protein during period 3 (20-5-20), we again saw the dramatic power of dietary protein to promote foci development.

These several experiments, taken together, were quite profound. Foci growth could be reversed, up and down, by switching the amount of protein being consumed, and at all stages of foci development.

The most significant finding of this experiment was this: foci devel­oped only when the animals met or exceeded the amount of dietary protein (12%) needed to satisfy their body growth rate.3’ That is, when the animals met and surpassed their requirement for protein, disease onset began.

This finding may have considerable relevance for humans even though these were rat studies. I say this because the protein required for growth in young rats and humans as well as the protein required to maintain health for adult rats and humans is remarkably similar.

According to the recommended daily allowance (RDA) for protein consumption, we humans should be getting about 10% of our energy from protein. This is considerably more than the actual amount required. But because requirements may vary from individual to individual, 10% dietary protein is recommended to insure adequate intake for virtually all people. What do most of us routinely consume? Remarkably, it is considerably more than the recommended 10%. The average American consumes 15—16% protein. Does this place us at risk for getting cancer? These animal studies hint that it does.

Ten percent dietary protein is equivalent to eating about 50—60 grams of protein per day, depending on body weight and total calorie intake. The national average of 15—16% is about 70-100 grams of protein per day, with men at the upper part of the range and women at the lower end. In food terms, there are about twelve grams of protein in 100 calories of spinach (fifteen ounces) and five grams of protein in 100 calories of raw chickpeas (just over two tablespoons). There are about thirteen grams of protein in 100 calories of porterhouse steak (just over one and a half ounces).

Yet another question was whether protein intake could modify the all-important relationship between aflatoxin dose and foci formation. A chemical is usually not considered a carcinogen unless higher doses yield higher incidences of cancer. For example, as the aflatoxin dose becomes greater, foci and tumor growth should be correspondingly greater. If an increasing response is not observed for a suspect chemical carcinogen, serious doubt arises whether it really is carcinogenic.

To investigate this dose-response question, ten groups of rats were administered increasing doses of aflatoxin, then fed either regular levels (20%) or low levels (5—10%) of protein during the promotion period.

In the animals fed the 20% level of protein, foci increased in number and size, as expected, as the aflatoxin dose was increased. The dose-response relationship was strong and clear. However, in the animals fed 5% protein, the dose-response curve completely disappeared. There was no foci response, even when animals were given the maximum tolerated afiatoxin dose. This was yet another result demonstrating that a low-protein diet could over­ride the cancer-causing effect of a very powerful carcinogen, aflatoxin.

Is it possible that chemical carcinogens, in general, do not cause cancer unless the nutritional conditions are “right”? Is it possible that, for much of our lives, we are being exposed to small amounts of cancer-causing chemicals, but cancer does not occur unless we consume foods that promote and nurture tumor development? Can we control cancer through nutrition?

NOT ALL PROTEINS ARE ALIKE

If you have followed the story so far, you have seen how provocative these findings are. Controlling cancer through nutrition was, and still is, a radical idea. But as if this weren’t enough, one more issue would yield explosive information: did it make any difference what type of protein was used in these experiments? For all of these experiments, we were using casein, which makes up 87% of cow’s milk protein. So the next logical question was whether plant protein, tested in the same way, has the same effect on cancer promotion as casein. The answer is an astonishing “NO.”In these experiments, plant protein did not promote cancer growth, even at the higher levels of intake. An undergraduate pre­medical student doing an honors degree with me, David Schulsinger, did the study (Chart 3.842). Gluten, the protein of wheat, did not produce the same result as casein, even when fed at the same 20% level.

We also examined whether soy protein had the same effect as casein on foci development. Rats fed 20% soy protein diets did not form early foci, just like the 20% wheat protein diets. Suddenly protein, milk protein in this case, wasn’t looking so good. We had discovered that low protein intake reduces cancer initiation and works in multiple synchronous ways. As if that weren’t enough, we were finding that high protein intake, in excess of the amount needed for growth, promotes cancer after initiation. Like flipping a light switch on and off, we could control cancer promotion merely by changing levels of protein, regardless of initial carcinogen exposure. But the cancer-promoting factor in this case was cow’s milk protein. It was difficult enough for my colleagues to accept the idea that protein might help cancer grow, but cow’s milk protein? Was I crazy?

THE GRAND FINALE
Thus far we had relied on experiments where we measured only the ear­ly indicators of tumor development, the early cancer-like foci. No~ it was time to do the big study, the one where we would measure complete tumor formation. We organized a very large study of several hundred rats and examined tumor formation over their lifetimes using several different approaches.

TURNING OFF CANCER

The effects of protein feeding on tumor development were nothing less than spectacular. Rats generally live for about two years, thus the study was 100 weeks in length. All animals that were administered afla­toxin and fed the regular 20% levels of casein either were dead or near death from liver tumors at 100 weeks. All animals administered the same level of aflatoxin but fed the low 5% protein diet were alive, active and thrifty, with sleek hair coats at 100 weeks. This was a virtual 100 to 0 score, something almost never seen in research and almost identical to the original research in India.

In this same experiment, we switched the diets of some rats at either forty or sixty weeks, to again investigate the reversibility of cancer pro­motion. Animals switched from a high-protein to a low-protein diet had significantly less tumor growth (35%—40% less!) than animals fed a high­protein diet. Animals switched from a low-protein diet to a high-protein diet halfway through their lifetime started growing tumors again. These findings on full-blown tumors confirmed our earlier findings using foci. Namely, nutritional manipulation can turn cancer “on” and “off.”

We also measured early foci in these “lifetime” studies to see if their response to dietary protein was similar to that for tumor response. The correspondence between foci growth and tumor growth could not have been greater.

How much more did we need to find out? I would never have dreamed that our results up to this point would be so incredibly consistent, bio­logically plausible and statistically significant. We had fully confirmed the original work from India and had done it in exceptional depth.

Let there be no doubt: cow’s milk protein is an exceptionally potent cancer promoter in rats dosed with aflatoxin. The fact that this promotion effect occurs at dietary protein levels (10—20%) commonly used both in rodents and humans makes it especially tantalizing—and provocative.