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Cancer’s Sweet Tooth

Cancer loves sugar, and sugar really loves cancer.  Isn’t that sweet?  Actually, no, it’s more like a match made in hell – because sugar (glucose) makes many types of cancer grow faster.

Scientists have long known that cancers soak up glucose like a sponge; in fact, German physiologist Otto Warburg, who found that tumors extract glucose at a rate 20 to 50 times higher than do normal cells, won the 1931 Nobel Prize for for his research on metabolism.  Lew Cantley told me that.  Cantley, Ph.D., is a world-renowned scientist and Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.  I recently interviewed him for the Prostate Cancer Foundation’s website, pcf.org.

Cantley has spent much of his career studying the interplay between sugar and cancer.  His studies suggest that it’s not so much the amount of glucose in your bloodstream that helps promote cancer, as it is the level of insulin, the hormone made by the pancreas that controls glucose.  Insulin helps turn glucose into immediate energy, and also helps your body pack it away for longer-term storage.  Briefly, when you eat, your blood sugar goes up; this causes your pancreas to say, “Hey! We need to make more insulin!”  Insulin, like Paul Revere, then travels rapidly throughout the land, telling the cells to let the glucose in, either to be used right away or saved in muscles, fat cells, and the liver.

Why does a tumor suck up more glucose?  “The main reason,” says Cantley, “is that insulin can turn on the glucose transporters (proteins on cell membranes that carry glucose into cells), similar to those in the liver, muscle and fat.  The presence of those glucose transporters on tumor cells is in part regulated by insulin.  That’s why I keep focusing on the insulin.”

Cantley began studying the insulin receptor in the 1980s, when he was on the faculty at Harvard University.  A few years later, after moving to Tufts University, he discovered an enzyme called phosphoinositide-3-kinase (PI3K); PI3K signals cells that insulin is present; the cells, in turn, open the valve that lets in sugar.  Normally, PI3K does good and vital work, helping cells survive, grow and proliferate.  But sometimes it goes awry; in Type II diabetes, this PI3K pathway becomes sluggish, cells don’t respond appropriately to insulin and become insulin-resistant.  But in cancer, even in someone who’s insulin-resistant, PI3K does its job too well; glucose floods in, tumor cells feast on sugar and grow faster.  “What we now know is that mutations in the PI3K pathway make tumor cells hyperactive in response to insulin.”

In many cancers – sugar-loving cancers; not all cancers are addicted to sugar, but many are – PI3K is like a power switch that drives growth.  “PI3K is the most frequently mutated cancer-promoting gene in humans,” says Cantley.  It may be involved in as many as 80 percent of cancers, including breast cancer, bladder cancer, and certain brain tumors.

What about prostate cancer?  Well, one of the most common genetic events in prostate cancer is the loss of a gene called PTEN; cancer just knocks this gene out.  “PTEN makes an enzyme that reverses what PI3K does.  PI3K makes a lipid, and PTEN destroys that lipid; you have to have a balance between those two enzymes to keep growth under control.  But in prostate cancer, and in breast cancer , the loss of PTEN activates production of this lipid that drives cell growth.

“This tells us we probably should try to keep insulin levels as low as possible if we have cancer, to try to keep the tumor from growing.   If we can keep the diet under control, or exercise to keep glucose levels and insulin levels low, we have a much better chance of slower growth of the tumor.  Our research would also argue that pharmacological intervention would be more effective if we keep insulin levels low.”

Even better:  Keep insulin levels as low as possible anyway, whether you have cancer or not.  “This is a powerful potential cancer-prevention mechanism,” says Howard Soule, Ph.D., Executive Vice President and Chief Science Officer for the PCF.  “Reducing processed sugar may turn out to be even more important for cancer prevention than treatment.”

Can we learn to use cancer’s sweet tooth as a weapon against it?  Cantley’s research has already led to the development of several PI3K-inhibiting drugs: idelalisib, approved by the FDA in 2014 for treatment of lymphoma and leukemia and alpelisib, approved in 2019 for treating breast cancers with mutations in PI3K.  But Cantley also believes that changing the diet – to one low in sugar, but also low in other carbohydrates, which can cause blood sugar to spike – can make cancer-fighting treatments work even better.  In a landmark 2018 paper published in Nature, Cantley and colleagues showed in mice that by severely restricting carbohydrates “and keeping the insulin level low, tumors would respond much more dramatically to drugs that are already approved to treat them.  Tumors we had never been able to shrink in mice, we could shrink with a low-glucose diet.

“That’s my obsession now, to get that message out there.  Endocrinologists tell patients to exercise more and eat less sugar to keep diabetes under control, but for me, it’s even more critical to keep insulin levels low in order to get better outcomes for cancer patients.”  Cantley’s research suggests that “if you have a mutation in the PI3K pathway that causes cancer, and you’re eating a lot of simple carbohydrates, every time your insulin goes up, it’s making the tumor grow.”

How can this knowledge help slow the growth of prostate cancer?  Here’s one example:  “For prostate cancer patients with low Gleason scores who are on active surveillance, it makes perfect sense to pay a lot of attention to what you eat.  Try to keep your consumption of sugary drinks as low as possible.  Keeping sugar down is the best thing you can possibly do.”  It used to be, Cantley notes, Japanese men hardly ever got prostate cancer.  “But second-generation Japanese Americans have prostate cancer in similar rates to Caucasians.  It’s clearly lifestyle,” the Western diet.  “The truth probably is that some Japanese men in their 90s had some level of prostate cancer, but didn’t consume enough sugar for the cancer to advance.”

Here’s another:  If you are on ADT for metastatic prostate cancer, you are more likely to gain weight, and also to develop insulin resistance.  One way to fight this is by limiting your sugar and simple-to-digest carbs.  Bonus: keeping insulin down may also help slow down the cancer.  Watch out for protein drinks, too; many are loaded with sugar.

What about the ketogenic diet?  It’s low in carbs and high in fats.  “I’m not preaching the ketogenic diet; I don’t eat it myself,” says Cantley, who says he weighs the same now as he did in high school.  “I eat what my grandparents ate:  a healthy diet, lots of raw vegetables, some animal fat, healthy vegetable fats, an intermediate amount of protein.  I don’t avoid fats, but I prefer olive oil on salads, and healthy fats from fish and avocado,” instead of loading up on butter and cheese.  “I eat more protein than the ketogenic diet would recommend, and I do occasionally eat rice and pasta.”

But here’s the kicker:  “The one thing I’m fanatic about is not drinking anything with sugar:  no orange juice, no apple juice, no soda.  I’ll eat an orange, but I won’t grind it up and drink it.”  Sugar in liquid form is rapidly digested, which results in “glucose peaks, followed by insulin peaks.”

What about alcohol?  “A dry martini is probably safer than wine; there’s not much sugar in there.”  However, Cantley adds, “I do drink wine, but as low in sugar as possible.”

Exercise is a great way to divert sugar into someplace safe:  the muscles.  “Muscle is where you store a lot of sugar in your body.  If you drink a sugary drink after exercising, your insulin goes up, and you drive all that glucose into your muscle.  Whether you’re exercising at the time you drink a sugary drink, or you just put on muscle from exercise in general, there’s still a benefit: insulin won’t spike.”   However, exercise doesn’t make it safer to drink a lot of sugary drinks, because…

Sugary drinks are bad.  It’s not just sodas; sweet teas and coffee drinks have more sugar than you may realize.  Even sports drinks are loaded with sugar.  In 2019, Cantley and colleagues published another landmark paper in Science, involving mice with polyposis syndrome (mice genetically predisposed to developing polyps in the colon).  They demonstrated that sugary drinks can dramatically drive the growth of intestinal polyps.  “We gave mice high-fructose corn syrup, and their polyps grew two to three times faster.”  Fructose is a different sugar from glucose, and although “fructose is not consumed by tumors, it goes straight to the liver and turns into fat.  Fructose makes you fat.  But the other issue is that intestinal epithelial cells can directly consume fructose.  We think this explains why there has been a doubling to tripling rate of colorectal cancer in young adults.”

Consuming sugar in liquid form is worse than having that same amount of sugar in solid form.  Cantley explains:  “If you eat an apple, it takes a long time to get to the colon.  By the time it gets there, all that sugar has leached out.  But if you have that same amount of sugar in a drink, that watery sugar gets to the colon pretty quickly.  That’s independent of the insulin elevation (discussed above), and it’s another scary reason why young people should avoid drinking sugary drinks, no matter how much you exercise.  You may be a champion marathon runner, but if you’re drinking sugary drinks all the time to keep up your energy, this is a real warning that you should pay attention to.”

Now, back to prostate cancer:  Would taking a PI3K-inhibitor help slow cancer’s growth?  As is often the case with prostate cancer, it’s not that simple.  It turns out that there are two different kinds of PI3K, an alpha and a beta form that can contribute to prostate cancer.  “When prostate cancer loses PTEN, it uses PI3K alpha and beta form redundantly to drive the tumor.”  This means that a drug that targets only the alpha form probably won’t be as effective in prostate cancer as in other forms of cancer, where only the alpha form of PI3K is involved.

However, “our preclinical findings are overwhelmingly supportive, and the retrospective data in patients strongly suggests” that one day, in addition to surgery, radiation, hormonal therapy or other treatments for prostate cancer, patients will be prescribed a precision diet to make the treatment more successful.  “The more we learn about cancer metabolism, we are understanding that cancers are addicted to particular things.  For many cancers, that thing is sugar.”

In addition to the book, I have written much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

©Janet Farrar Worthington

 

 

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The Spare Tire and Your Risk of Lethal Prostate Cancer

Note: I’m not fat shaming!  I am excited, because here is something you can do to lower your risk of dying of prostate cancer!

Fat is flammable.  There’s so much fat in bacon grease, you can use it as a fire starter.   You can also take a can of Crisco, stick a wick in it, and make an emergency candle.      

Unfortunately, the same is true for us:  excess body fat is like lighter fluid for prostate cancer.   Visceral fat, that “spare tire” around the abdomen, is even worse.  It’s not subcutaneous fat – the surface fat you can “pinch an inch” with.  It’s deep inside the belly, an evil pillow that settles over and wraps itself around our abdominal organs.

Visceral fat is the Jabba the Hutt of fat: a notorious villain in several important health problems.  Visceral fat raises your risk of heart disease, diabetes, metabolic disturbances, dementia, and in women, breast cancer.

Now, for the first time, it’s also been shown to raise your risk of getting prostate cancer – the aggressive kind that needs to be treated.  The kind of prostate cancer that kills.

Why is visceral fat so bad?  Because it’s like a blobby smokestack, polluting our bodies with its troublesome emissions.  “Visceral fat is a living, biologically active entity,” says medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation (PCF).  Like the chest-bursting alien in Ridley Scott’s iconic movie, it’s alive! And it’s up to no good.

Among other things, visceral fat messes with your hormones.  It lowers testosterone and raises estradiol, a form of estrogen.  It churns out inflammatory chemicals called cytokines, which can raise your blood pressure, affect blood clotting, and raise your risk of heart disease and stroke.  Cytokines also have a bad influence on your insulin resistance; this rising tide of glucose raises your risk of getting diabetes.

Like Charlie Brown’s friend, Pigpen, visceral fat also sheds – not dust, but fatty acids, which go right to the liver.  These fatty acids lower your good cholesterol and raise your bad cholesterol.

No one had connected visceral fat to prostate cancer until very recently.  In a study published in Cancer, which I recently covered for the PCF’s website, scientists led by Lorelei Mucci, Sc.D, of Harvard’s T.H. Chan School of Public Health, and Sarah Markt, Sc.D., now at Case Western, investigated body fat distribution and the risk of prostate cancer.  You might say that their study, of Icelandic men in the Age, Gene/Environment Susceptibility-Reykjavik Study, has shaken up the apple cart of what we understand about body fat.

Speaking of apples, visceral fat goes with the “apple” body shape.  This is bad, because the fat surrounds so many vital organs.  But what if you’re a “pear?”  If you’re a pear shape, you carry your fat lower, in the hips and thighs. This fat is usually subcutaneous fat, usually not thought to be as dangerous as visceral fat.

Guess what?  For prostate cancer, thigh fat is bad, too.  This study found that men with greater visceral abdominal fat as well as men with greater thigh subcutaneous fat are more likely to get advanced or fatal prostate cancer.  Visceral fat even raises the risk of advanced or fatal prostate cancer in men with a lower body mass index (BMI – for how to calculate yours, see below); this suggests that the location (even for a modest pot belly) is more important than the overall amount of body fat.

            Risk Goes Up with Higher BMI:  Each BMI increase of 5 was associated with a 52 percent higher risk of advanced prostate cancer, and a 56-percent higher risk of fatal prostate cancer.  Obese men – with a BMI of 30 or higher – were 2.5 times more likely to develop advanced disease, and 2.6 times more likely to die of prostate cancer.  For about every four-inch increase in waist circumference, the risks of getting advanced prostate cancer and dying of it went up significantly – by 40 percent and 45 percent, respectively.

This study may lead to important changes in medical practice.  “We are working very hard to save the lives of men who have advanced, aggressive prostate cancer, notes Simons.  “To do this, we are trying to understand in depth the genetics and consequences in the biochemistry of the disease, and are looking for ‘’druggable” targets for new classes of drugs.  Here is a risk factor for aggressive disease that can be changed!  If this applies to you, we want you to know what a difference you can make in your risk of dying of prostate cancer.”

Note:  Stress makes it harder for you to lose weight.  If you are stressed, your body makes more cortisol, and cortisol makes your body store more visceral fat.  On some ancient level, your body may be thinking:  “Oh, no, times are hard! We’re going to starve!  Better hang on to this fat!”  So, in addition to other ways to lose the fat – exercise and eating a smarter diet with fewer carbs and sugar – you might consider stress management strategies like meditation, relaxation techniques, and deep breathing.  It might help your body let go of the fat.

 

What’s My BMI? 

BMI, or body mass index, is a measure of body size – and whether you’re at a good weight for your height.  It’s pretty simple, and requires just these two things: your weight and your height.  That’s it.  You can do it yourself with this formula:  BMI = weight in pounds x 703/in2. 

Or, you can use a BMI calculator.  There are plenty of them online.  The National Heart, Lung, and Blood Institute has a BMI calculator and even a free BMI calculator app you can download.  A BMI of 18.5-24.9 is considered the healthy range; between 25.0 and 29.9 is considered overweight, and a BMI over 30 is considered obese.  Also, men with a waistline that measures 40 inches or more are more likely to have too much visceral fat.

 

In addition to the book, I have written about this story and much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

© Janet Farrar Worthington

 

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Sugartown

In 1993, I actually wrote that sugar and carbs were fine. Want to be healthy? Eat more pasta and healthy grains, I wrote. Fats were the big evil. I was so wrong – but this was what the studies showed. This is what many doctors believed. Fat was our enemy. Fat was the reason we were becoming – not nearly so much as we are now, I might add – a nation of lard butts.

For decades, this was reflected in packaged “healthy” foods. Eat as many cookies as you want: yes, they’re chock full of carbs and junk calories, but no worries! They’re LOW FAT. This was the new food gospel, and we saw it proclaimed on our grocery store shelves – low-fat chips, ice cream, cakes. Guilt-free! Breakfast cereal – great! It’s got NO FAT! We saw the birth of olestra, which not only had no fat – it was indigestible! Side effects included gas, cramps, bloating, diarrhea, and, most appalling of all, “anal leakage.” Lays potato chips, Ruffles, and Doritos at the time that were “FAT FREE” and contained olestra had the word “WOW” in huge letters right there on the bag. I guess they meant the taste, but maybe they were referring to what happened when you ate it, as in: “Wow! I just pooped my brains out!”

In 1967, Nancy Sinatra had a hit song called “Sugartown.” She sang, “I got some troubles, but they won’t last. I’m gonna lay right down here in the grass, and pretty soon all my troubles will pass” (most likely, she did not mean “pass” in the olestra way) “ ‘Cause I’m in shoo-shoo-shoo, shoo-shoo-shoo, Sugar Town.” There were about five more “shoos” in that line, but you get the drift.

Sugartown was the place to be. We believed it because of review articles like one that appeared in the New England Journal of Medicine (NEJM) the same year as “Sugartown” – 1967. It discounted evidence that linked sucrose consumption to coronary heart disease. Doctors believed it. They told their patients. Their patients believed them.

It turns out that this particular study was secretly funded by the Sugar Research Foundation (SRF). Now we know, thanks to a bombshell article recently published by University of California-San Francisco scientists in the journal, PLoS Biology, that the SRF (now defunct) was completely evil. It manipulated the science.

It not only “discounted evidence linking sucrose consumption to blood lipid levels and hence coronary heart disease,” report the study’s authors, Cristin Kearns, Dorie Apollonio, and Stanton Glantz. It also “withheld information from the public” linking sugar to changes in the microbiome that can lead to bladder cancer.

But it’s not just the SRF, which later became the International Sugar Research Foundation (ISRF); it’s a bunch of sugar industry trade associations. And it wasn’t just back in the 1960s. All of these groups have “consistently denied that sucrose has any metabolic effects related to chronic disease beyond its caloric effects,” Kearns, Apollonio and Glantz state. In other words, the main side effect these groups are willing to acknowledge is that sugar makes you gain weight.

Let’s take a moment here for me to say that I love sugar. I do. I love cookies, and chocolate cake, and coconut custard pie, and Mexican Coke with real cane sugar instead of corn syrup.  But I really limit it.  I don’t like food Nazis, who tend to be snarky and condescending and who alienate people who really could benefit from what they’re trying to say by making snide statements like, “What’s next, a deep fried stick of butter?” (I actually read that this week in a nutrition magazine that means well, but its tone is so snotty that it’s off-putting.)

That’s not what I’m trying to do at all. What I’m writing about here is the disturbing idea that sugar has been linked to serious illnesses and that the sugar industry has suppressed this information. If we had known six decades ago, maybe a lot more people would be alive now, and maybe our country wouldn’t be struggling so hard with obesity, heart disease, and diabetes.

In case you’re wondering, Kearns, D.D.S., M.B.A., is an assistant professor at the University of California San Francisco (UCSF) School of Dentistry. Stanton Glantz, Ph.D., is Distinguished Professor of Tobacco Control in the Department of Medicine at UCSF. He’s seen this same kind of twisting and distorting of medical evidence a lot; the tobacco industry did it for years. Dorie Apollonio, Ph.D., is an associate professor in the Department of Clinical Pharmacy at UCSF. Together, these UCSF researchers make a formidable team.

Now, back to the 60 years of manipulating the science and hiding the harmful effects of too much sugar. As recently as 2016, the Sugar Association issued a press release blasting findings from a study published in Cancer Research. In that study, done in mice, scientists found that dietary sugar induces increased tumor growth and metastasis when compared to a non-sugar starch diet. But instead of saying, “Hey, you know, maybe you might want to consider not eating so much sugar – all things in moderation,” the Sugar Association doubled down, stating that “no credible link between ingested sugars and cancer has been established.” Nothing to see here, move along, move along. Look over there – doughnuts with sprinkles!

In this PLoS paper, the UCSF scientists lay out a trail of damning evidence. In that first project in the 1960s, one group of rats was given a diet of 75 percent fat but no sugar. A second group of rats ate a diet of less fat, just 15 percent, but 60 percent sucrose, and their little bodies metabolized all that sugar as a carbohydrate. The sugar-eating rats developed thiamine deficiency, which then led to heart failure. But in the rats that ate more complex carbohydrates and no sugar, the gut bacteria, or microbiome, changed and actually started synthesizing thiamine.

This study intrigued SRF scientists, who thought that maybe, if the microbiome could be adjusted, the gut could tolerate sugar better. This idea led to Project 259, in which scientists led by W.F.R. Pover at the University of Birmingham in the UK studied the effect of sugar in the gut between 1967 and 1971. Pover’s team showed, in rats and guinea pigs, that eating more sugar led to higher levels of triglycerides; in turn, this led to higher levels of beta-glucoronidase in urine – a finding that’s linked to bladder cancer – and in an internal document, scientists described this research as “one of the first demonstrations of a biological difference” between rats that eat a lot of sugar and rats that don’t.

Project 259 didn’t just link sugar consumption to cancer, but to hypertriglyceridemia, an elevated level of triclycerides (a type of fat) that raises the risk of heart disease, say the UCSF scientists, and these findings stayed hidden for decades until the UCSF scientists uncovered them. Also suppressed was evidence linking higher doses of sugar to other “renal disorders, urinary tract infections, and renal transplant rejection.” Eat sugar – reject your donor kidney!

Even worse, the sugar industry did what every good magician knows how to do: misdirect. In previous research, published in the Journal of the American Medical Association (JAMA), Glantz and Kearns, with colleague Laura Schmidt, examined SRF internal documents and historical reports and found that the SRF secretly funded studies, including one published in 1965 in the NEJM, “promoting fat as the dietary culprit in coronary heart disease.”

Imagine there’s a gunshot, and the killer quickly places the murder weapon in somebody else’s hands and starts shouting, “He did it! It’s that guy!” and then slinks away. That’s what the sugar industry did.

For six decades, we have blamed fat – and as a society, we now look more and more like the tubby earthlings on the big spaceship in the Pixar movie, “Wall-e.” We’re huge, and we’re unhealthy.

Sugartown is not so sweet.

©Janet Farrar Worthington

 

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Gout Hates Your Joints

If an illness can have a stereotype, gout has one: its poster boy is a portly, wealthy gentleman who drinks too much red wine and eats too much rich food. In literature, gout is an Epicurean affliction, the runoff of opulence and “disease of kings.”

In fact, gout attacks the poor as well as the rich; it’s more like a creepy shadow that follows other diseases, piggybacks off of their risk factors, and kicks sick people when they’re down. It is also becoming more common. Read more

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