Juvenon Health Journal volume 11 number 1 march 2012
By Benjamin V. Treadwell, Ph.D.
You’ve probably heard the expression “sugar high.” Sugar-laden foods do make us feel good while we’re eating them. We can become “addicted” to the taste and the energy burst, too, always wanting more. But could sugar possibly be as damaging to our health as addictive drugs?
Scientists are beginning to answer “yes,” especially regarding one life-threatening health concern: cancer. Almost a century of research has led to their response. In this issue of the Health Journal, we’ll take a closer look.
Today’s theories connecting sugar and cancer can be traced back to the discovery of a link between diet and tumors. Nobel Laureate Peyton Rous is credited with being the earliest (1920s) to observe that the amount of food consumed had a direct correlation to tumor growth in animals.
Chicago pathologist Albert Tannenbaum confirmed Rous’ findings in 1942. By putting rats with tumors on a semi-starvation diet, he demonstrated a significant reduction (in some cases to zero) not only in tumor growth, but also in the incidence of cancer itself.
Around this same time, scientists were also studying the connection between caloric restriction (CR) and longevity. In multiple experiments, rats on CR lived longer, compared to control animals given a continuous food supply.
Tannenbaum’s CR rats also enjoyed a longer lifespan due to cancer inhibition. In both cases, there were no excess calories in the rats’ diets. Looking at it another way, the rats weren’t fat.
Similar to the rat’s, the human body needs energy homeostasis – where calories taken in do not exceed energy put out – to be healthy. What if too much food disturbs the balance? Research continues to provide more detailed answers. The common denominator seems to be excess tissue levels of the food metabolite glucose. In other words, too much sugar.
Glucose is one of the body’s primary sources of energy. It also stimulates the pancreas to make insulin, a hormone necessary for transporting the glucose from the blood into tissues (fat, liver, muscle). But what happens when there’s more glucose in the blood than the body needs for energy?
The level of blood insulin increases, allowing more glucose to be transported into tissues. The unused glucose is converted to fat. The result? Not only more fat stored in fat tissues, but also in places where it normally wouldn’t be, like muscle cells, liver cells, and pancreas insulin-producing beta cells.
The consequences of overdosing, so to speak, on glucose/sugar can be broader than creating a fat rat or human. When energy homeostasis is disturbed, the switches (biochemical pathways) regulating our body’s metabolism are stressed, sometimes so severely as to impair their normal functions. Studies indicate this impairment can progress to serious health concerns, such as type II diabetes and cancer.
Following the Pathway
For more than 80 years, scientists investigating type II diabetes and cancer were like two ships passing in the night. Neither paid much attention to the others’ discoveries.
Clinicians specializing in type II diabetes, for example, had observed the connection between the condition and obesity. They were also aware of the higher incidence of cancer in both obese and diabetic patients. But several other health concerns, such as atherosclerosis and Alzheimer’s disease, are also associated with diabetes and obesity.
So, until recently, many dismissed the potential commonalities between cancer and diabetes as indirect and complex. Now, there’s provocative evidence supporting a role for the insulin-signaling pathway in both. A critical piece of the diabetes puzzle, these common pathways may also be pivotal to promoting, and perhaps even initiating, cancer.
Insulin-Glucose-Cancer Cell Connection
Studies have shown that cancer cells are over-loaded with receptors for growth factors, including insulin. Compared to normal cells, they also need nine or more times the glucose to produce energy.
An abundance of glucose in the blood activates the insulin-signaling pathway, causing the pancreas to release an abundance of insulin. Working with the plentiful receptors on the cancer cell, the insulin transports large quantities of glucose into these cells to be burned for energy. Overeating can create the perfect environment for this process. But, why does the cancer cell require so much glucose?
Another Nobel Prize winner, Otto Warburg, seems to have found the answer in the 1920s. His experiments showed cancer cells rely on less efficient aerobic glycolysis for converting glucose to energy. Instead of the 36 ATP’s (Adenosine triphosphate) produced from one glucose molecule by normal cells, cancer cells produce only four.
This phenomenon, also known as the Warburg Effect, answered one question and posed another. Why would the cancer cell, which needs so much energy/glucose, favor the less efficient glycolytic pathway to produce it?
Building Material Bonus
Interestingly, while aerobic glycolysis produces much less ATP/energy, it also shifts parts of the glucose molecule into tributary pathways. These pathways excel in producing substances that build new cells to expand the cancer volume. One of these molecules also protects the cancer cell from oxidants that can damage its cells and impair cancer growth. In other words, the less efficient mode of energy production actually allows cancer cells to thrive and grow.
In other words, the less efficient mode of energy production actually allows cancer cells to thrive and grow.
The More Receptors The Merrier
Once they are thriving, it seems cancer cells can also grow with normal levels of glucose. How? An initially high intake of sugar-laden calories seems to increase not only insulin and insulin receptors on the cancer cells, but also the cell receptors for the insulin-like growth factor (IGF-1). The more receptors, the more glucose can be transported into the cancer cell, feeding its “addiction” even with normal glucose supply.
Where Do The Cancer Cells Come From?
Researchers agree that the change in metabolism, brought on by excess blood glucose from diet and the associated increase in the growth factors, insulin and IGF-1, plays a major role. However, there are two prominent hypotheses as to the exact mechanism.
Damaged DNA or Activated Mtor (Mammalian Target of Rapamycin)?
Lewis Cantley, director of the Cancer Center at Beth Israel Deaconess Medical Center (part of Harvard Medical School) believes that high levels of glucose and glucose metabolites (produced during the conversion of glucose to energy), result in toxic substances. These toxic substances damage DNA, causing mutations that convert a normal cell to a cancerous one.
A cancer researcher at the Massachusetts Institute of Technology (MIT), Robert Weinberg, developed another theory. Studies have shown that high glucose activates mTOR, a regulatory molecule. This molecule, in turn, interferes with an important mechanism that recognizes old, cancer-prone cells and kills them. So, according to the Weinberg hypothesis, high glucose effectively allows cancer cells to escape death and thrive.
Each hypothesis is supported by experimental evidence and may prove to be, at least partially, correct. Although they disagree on the mechanism, Cantley and Weinberg both identify high levels of glucose and insulin as instrumental in cancer development and growth.
What if there was something we could take to normalize blood glucose and insulin?
Backtracking a little, high levels of these substances also play key roles in type II diabetes. Preliminary evidence indicates a very promising side effect for diabetics taking Metformin, a synthetic prescription drug modeled after a plant-derived nutrient. They not only have lower glucose and insulin levels, but also a lower incidence of cancer. 40-50% lower!
Which brings us to another intriguing question. Can we prevent cancer by taking an agent, like Metformin, on a regular basis? It turns out several plant neutraceuticals may have the potential to reduce blood glucose-insulin and return the insulin-signaling pathway to homeostasis (balance). One very promising natural compound is berberine.
Research is ongoing and future Health Journals will revisit natural compounds with Metformin-like effects. In the meantime, avoiding excess caloric intake, especially of sugar-laden foods, seems to be a wise course of action.
answers your questions.
question: I read your recent article about the health benefits of the strawberry-derived plant nutrient fisetin. It clearly seems exciting in that it has been demonstrated, in animal models, to improve mental sharpness, as well as protect the brain from degenerative changes associated with aging. My question is how you came up with the quantity of fisetin, your suggested 50mg daily dose, which would be effective in humans, since the research seems to be entirely done in animals. – S
answer: Thank you for an excellent question. Fisetin is one of the key nutrients in Juvenon’s new Youthful Memory supplement. Our recommendation of 50mg per day was determined according to a formula, used by many supplement and pharmaceutical companies, to translate what’s given in an animal study to a human equivalent dose (HED).
This formula was published in 2007 by a research team from the University of Wisconsin. The group noted extrapolating an animal dose to an HED, based on body weight alone, yielded unrealistic, potentially unhealthy and scientifically incorrect mega-doses.
They proposed metabolism, which is associated with the ratio of weight to body surface area, must be taken into account for accurate conversion. A mouse’s metabolism, for instance, eliminates a drug/nutrient from the body 10 times faster than a human’s. Thus, mice would require a lot more of the drug for an effect, as compared to people.
Dr. Benjamin V. Treadwell is a former Harvard Medical School professor and member of Juvenon’s Scientific Advisory Board.
The “News Focus” section of a recent issue of Sciencefeatured an article on potentially exciting developments in cancer research. “Unraveling the Obesity-Cancer Connection,” by Gary Taubes, chronicles theories, experiments and epidemiologic studies regarding the link between diet and cancer.
Surprisingly, this correlation has appeared in medical literature for nearly a century. As early as the 1920s, a seminal paper, by Nobel Prize-winner Peyton Rous, revealed tumor growth in animals was inhibited by a semi-starvation diet.
Chicago pathologist Albert Tannenbaum confirmed Rous’ findings in 1942. In his experiments, feeding rats a diet just sufficient to keep them alive significantly increased their lifespans, in part by inhibiting tumors. Tannenbaum proposed the diet denied tumors the large amounts of blood sugar they need to grow.
The effects of a semi-starvation diet led investigators to focus on the opposite condition, obesity. Epidemiologic studies established a connection with cancer. In fact, a 2004 team noted excess body fat seems to be associated with one quarter to half of frequently diagnosed types of cancer.
Parallel epidemiology revealed a higher incidence of cancer in type II diabetics. What’s the connection between the two populations? The keys seem to be the blood levels not only of glucose, but also of insulin (commonly known for its role in diabetes) and a related hormone, insulin-like growth factor (IGF). These two hormones may be critical factors in activating metabolic pathways involved in cancer growth.
Scientists have discovered some types of cancer cells (prostate, colorectal, and breast cancer, for example) have a much higher presence of insulin and IGF receptors than healthy tissue to assure the delivery of sufficient glucose. Previous research demonstrated cancer cells require nine to 10 times more glucose than normal cells for growth because they use an inefficient energy-producing pathway, glycolysis. So, reducing caloric intake would, in turn, reduce blood glucose and, consequently, blood insulin levels, starving these cancers.
A recent study, reported with this article, seems to support this hypothesis. Type II diabetics took the glucose/insulin-reducing drug, Metformin. The drug seemed to mimic the effect of semi-starvation, reducing the normally higher incidence of certain cancers in diabetics by 50%. But what about the cancers that didn’t respond?
One researcher from Harvard Medical School, Lewis Cantley, may have the answer. He discovered a new enzyme, Phosphoinositol 3 kinase (PI3K), the final gate, so to speak, in the insulin-signaling pathway for glucose uptake. Subsequent research demonstrated some of the most malignant cancers have a mutated, permanently “open” form of PI3K. Glucose/insulin-reducing drugs did not inhibit growth of those cancers.
The work Gary Taubes summarizes is exciting. Putting insulin, IGF and PI3K at the center of a growing wave of research worldwide, it could lead to new therapeutics for certain types of cancers and a better understanding of PI3K’s role in others. The evidence is compelling so far. But as Canadian oncologist Pam Goodwin puts it, after studying insulin and breast cancer since the 1990s, “All it’s done is help us form a hypothesis. We need to proceed from here very, very carefully.”
This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.