Dialing Down the Grim Reaper Gene

Only about 1 in 10,000 people live to be a 100 years old. What’s their secret? I discuss this in my video Animal Protein Compared to Cigarette Smoking.

In 1993, a major breakthrough in longevity research was published about a single genetic mutation that doubled the lifespan of a tiny roundworm. Instead of all worms being dead by 30 days, the mutants lived 60 days or longer. This lifespan extension was “the largest yet reported in any organism.” This methuselah worm, a “medical marvel,” is “the equivalent of a healthy 200-year-old human.” All because of a single mutation? That shouldn’t happen. Presumably, aging is caused by multiple processes, affected by many genes. How could knocking out a single gene double lifespan?

What is this aging gene—a gene that so speeds up aging that if it’s knocked out, the animals live twice as long? It’s been called the Grim Reaper gene and is the worm equivalent of the human insulin-like growth factor 1 (IGF-1) receptor. Mutations of that same receptor in humans may help explain why some people live to be a hundred and other people don’t.

So, is it just the luck of the draw whether we got good genes or bad ones? No, we can turn on and off the expression of these genes, depending on what we eat. Years ago I profiled a remarkable series of experiments about IGF-1, a cancer-promoting growth hormone released in excess amounts by our liver when we eat animal protein. Men and women who don’t eat meat, egg white, or dairy proteins have significantly lower levels of IGF-1 circulating within their bodies, and switching people to a plant-based diet can significantly lower IGF-1 levels within just 11 days, markedly improving the ability of women’s bloodstreams to suppress breast cancer cell growth and then kill off breast cancer cells.

Similarly, the blood serum of men on a plant-based diet suppresses prostate cancer cell growth about eight times better than before they changed their diet. However, this dramatic improvement in cancer defenses is abolished if just the amount of IGF-1 banished from their systems as a result of eating and living healthier is added back. This is one way to explain the low rates of cancer among plant-based populations: The drop in animal protein intake leads to a drop in IGF-1, which in turn leads to a drop in cancer growth. The effect is so powerful that Dr. Dean Ornish and colleagues appeared to be able to reverse the progression of early-stage prostate cancer without chemotherapy, surgery, or radiation—just a plant-based diet and lifestyle program.

When we’re kids, we need growth hormones to grow. There’s a rare genetic defect that causes severe IGF-1 deficiency, leading to a type of dwarfism. It also apparently makes you effectively cancer-proof. A study reported not a single death from cancer in about 100 individuals with IGF-1 deficiency. What about 200 individuals? None developed cancer. Most malignant tumors are covered in IGF-1 receptors, but if there’s no IGF-1 around, they may not be able to grow and spread.

This may help explain why lives appear to be cut short by eating low-carb diets. It’s not just any low-carb diet, though. Specifically, low-carb diets based on animal sources appear to be the problem, whereas vegetable-based low-carb diets were associated with a lower risk of death. But low-carb diets are high in animal fat as well as animal protein, so how do we know the saturated animal fat wasn’t killing off people and it had nothing to do with the protein? What we need is a study that follows a few thousand people and their protein intakes for 20 years or so, and sees who lives longest, who gets cancer, and who doesn’t. But, there had never been a study like that…until now.

Six thousand men and women over age 50 from across the United States were followed for 18 years, and those under age 65 with high protein intakes had a 75 percent increase in overall mortality and a fourfold increase in the risk of dying from cancer. Does it matter what type of protein? Yes. “These associations were either abolished or attenuated if the proteins were plant derived,” which makes sense given the higher IGF-1 levels in those eating excess protein.

The sponsoring university sent out a press release with a memorable opening line: “That chicken wing you’re eating could be as deadly as a cigarette.” It explained that “eating a diet rich in animal proteins during middle age makes you four times more likely to die of cancer than someone with a low-protein diet—a mortality risk factor comparable to smoking.” And when they say “low-protein diet,” what they actually mean is getting the recommended amount of protein.

“Almost everyone is going to have a cancer cell or pre-cancer cell in them at some point. The question is: Does it progress?” said one of the lead researchers. That may depend on what we eat.

“[T]he question is not whether a certain diet allows you to do well for three days,” a researcher noted, “but can it help you survive to be 100?” Excessive protein consumption isn’t only “linked to a dramatic rise in cancer mortality, but middle-aged people who eat lots of proteins from animal sources…are also more susceptible to early death in general.” Crucially, the same didn’t apply to plant proteins like beans, and it wasn’t the fat; the animal protein appeared to be the culprit.

What was the response to the revelation that diets high in meat, eggs, and dairy could be as harmful to health as smoking? One nutrition scientist replied that it was potentially dangerous because it could “damage the effectiveness of important public health messages.” Why? Because a smoker might think “why bother quitting smoking if my cheese and ham sandwich is just as bad for me?”

This reminds me of a famous Philip Morris cigarette ad that tried to downplay the risks of smoking by saying that if we think second-hand smoke is bad, increasing the risk of lung cancer 19 percent, drinking one or two glasses of milk every day may be three times as bad with a 62 percent higher risk of lung cancer. What’s more, doubling the risk is frequently cooking with oil, tripling our risk of heart disease is eating non-vegetarian, and multiplying our risk six-fold is eating lots of meat and dairy. So, they conclude, “Let’s keep a sense of perspective.” The ad goes on to say that the risk of cancer from second-hand smoke may be “well below the risk reported…for many everyday items and activities.” So, breathe deep!

That’s like saying we shouldn’t worry about getting stabbed because getting shot is so much worse. Or, if we don’t wear seatbelts, we might as well have unprotected sex. If we go bungee jumping, we might as well disconnect our smoke alarms at home. Two risks don’t make a right.

Of course, you’ll note Philip Morris stopped throwing dairy under the bus once they purchased Kraft Foods.


The IGF-1 story is so pivotal that it’s one of the first video series I ever produced for NutritionFacts.org. I’m so glad I was able to release this long-awaited update. If you want a blast from the past, watch the original series starting with Engineering a Cure.

For more parallels between the tobacco industry and the food industry, see:

What about the mobile phone industry? Does Cell Phone Radiation Cause Cancer?

For more on healthy aging and longevity, see:

It’s important to note the so-called low protein intake is actually the recommended protein intake, which is associated with a major reduction in cancer and overall mortality in middle age, under age 65. But did you notice that it says not among older individuals? All of this is covered in my video Increasing Protein Intake After Age 65.

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Pomegranates Put to the Test for Prostate Cancer

The pomegranate “has been revered through the ages for its medicinal properties”––so much so that it’s been used as a symbol for some medical organizations. A fruit seems to me a better representation of health than the American Medical Association’s snake on a stick.

The pomegranate is thought to be beneficial for a wide range of diseases, including several types of cancer, cardiovascular disease, and rheumatoid arthritis. Evidently even the cannibals love it as it improves the color of “kid meat.” The researchers were talking about baby goats, but the title of their study did make me do a double-take!

Most of the attention over the last decade has focused on pomegranates and prostate cancer. In vitro studies have shown that pomegranate extract can suppress the growth of prostate cancer cells in a petri dish by up to 95 percent. As you can see in my video Pomegranate vs. Placebo for Prostate Cancer, there is no real difference between what normal prostate cells look like under a microscope with a little or a lot of pomegranate extract; it doesn’t seem to have much of an effect on healthy cells. However, prostate cancer cells are decimated by pomegranate extract—at least in a petri dish, but what about in a person? If these results translated to the clinic, it could be dramatic, but we first need to try it out in people.

“Primary management of prostate cancer…consists of either radical surgery or radiation therapy.” Despite this, “a significant number of patients relapse and ultimately develop metastatic disease.” Even after radical prostatectomy, the cancer comes back in about one-third of the patients, as evidenced by rising prostate-specific antigen (PSA) levels. At that point, the treatment options are limited as the prostate has already been removed. The next step is essentially chemical castration, or hormonal ablation. Just like breast cancer can thrive on estrogen, prostate cancer can thrive on testosterone. We can try to wipe out testosterone, but that can have such negative side effects that anything we can do to delay that would be good. 

So, what about plants? Men in Asia appear to have the lowest prostate cancer rates in the world, up to ten times lower than men in North America. Is this simply because of genetics? No. When Japanese individuals move to the United States and start living and eating like us, their breast and prostate cancer rates shoot right up toward ours. It could be because of what they start eating more of: animal products, which are the strongest risk factor for prostate cancer worldwide on a country-by-country basis. Or, it could be because of what they’re eating less of in the United States, namely their traditional low-fat, high-fiber, generally plant-rich diet with soy products and green tea. So, did the researchers put the cancer patients on a plant-based diet? No, they just had them drink a cup of pomegranate juice every day. Why? Because the study was funded by a pomegranate juice company.

In the three years leading up to the study, participants’ cancer was steadily growing, as measured by the increase in their average PSA levels. Once they started the juice, their tumors continued to grow, but it looked like they were growing slower. In contrast, Dean Ornish and his colleagues got an apparent reversal in early prostate cancer growth with a plant-based diet and other healthy lifestyle changes. Indeed, PSA didn’t just go up slower—it trended down. And, when dripping the blood of the men on prostate cancer cells growing in a lab, the blood serum of those eating healthfully suppressed cancer growth nearly eight times better, whereas the blood of the men on the pomegranate juice suppressed cancer growth by only about 12 percent. Still, to see any effect from drinking a cup of juice a day is pretty impressive.

The problem is that there was no control group in the pomegranate juice study. We could say the patients acted as their own controls, before and after. It’s probably not just a coincidence that their tumors started growing slower right when they started the juice. But, a drug trial tried to do the same thing—treat men with recurring prostate cancer after surgery or radiation. In the drug group, tumor growth slowed in 55 percent of the men. A pretty effective drug, right? Well, the sugar pill worked 73 percent of the time. The placebo effect can be so powerful that it may slow cancer growth. This is why we need placebo-controlled trials. Maybe tricking people into drinking pomegranate-flavored Kool-Aid would have had the same effect. We don’t know until we put it to the test.

Finally, researchers did a randomized, controlled trial of pomegranate juice for prostate cancer, and the daily pomegranate intake had no impact. What do they mean, no impact? Twenty-five percent of the cancer patients appeared to shrink their tumors as soon as they started drinking the pomegranate juice, but 35 percent shrunk their tumors not drinking pomegranate juice. So, any effect appears just to be a placebo. It’s the same story with pomegranate extract pills: They seemed to work until they went head to head with sugar pills and fell flat on their face.


I love pomegranates! Unfortunately, the juice and extracts look no more promising today than when I produced my video Is Pomegranate Juice That Wonderful?.

For some foods that may actually affect prostate cancer progression, see:

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

The Effects of the Hops Phytoestrogen in Beer on Breast Cancer Risk

Hops have been used for centuries as a flavoring agent in beer, but “[o]ver the years, a recurring suggestion has been that hops”—and therefore beer—may be estrogenic, thanks to a potent phytoestrogen in hops called 8-PN, also known as hopein. Might beer drinking affect our hormones? I discuss this in my video What Are the Effects of the Hops Phytoestrogen in Beer?.

Even just the alcohol in beer can reduce testosterone levels in men, so when beer was tested as a source of estrogens, the alcohol was first removed. Researchers tested the equivalent of one can of beer every day for a month on the hormone levels of postmenopausal women, so as to not confound the results with her own estrogens, and they found significant alterations of hormonal levels during the beer month and then a return to baseline a week afterwards. But does this have any clinical effects, whether good or bad?

A cross-sectional study of about 1,700 women found that beer drinkers appear to have better bone density, perhaps because of the pro-estrogenic effects. They don’t recommend women start drinking beer for bone health, but suggest it may have beneficial bone effects for women who already drink.

What about helping with hot flashes? About half of postmenopausal and premenopausal women in the United States suffer from hot flashes, whereas the prevalence in Japan may be ten times lower, presumed to be because of their soy consumption. What about hops? There have been a few studies showing potential benefit, leading to a 2013 review suggesting that “hop extract may be somewhat effective in treating menopausal discomforts especially against hot flushes,” but that was before a study reported extraordinary results with about a half teaspoon of dried hop flowers. In the placebo group, the women started out having 23 hot flashes a week and continued to have 23 hot flashes a week throughout the three-month study. In the hops group, the women started out even worse with about 29 hot flashes a week, but then got down to 19 at the end of the first month, then 9, and finally just 1 hot flash a week. And similar findings were reported for all the other menopausal symptoms measured.

Animal estrogens work, too. Millions of women used to be on horse hormones—Premarin, from pregnant mares’ urine. That drug also took care of hot flashes, as well as  curtailed osteoporosis, but caused a pesky little side effect called breast cancer. Thankfully, when this was realized and millions of women stopped taking it, breast cancer rates fell in countries around the world.

The question, then, is: Are the estrogens in hops more like the breast cancer-promoting horse estrogens or the breast cancer-preventing soy estrogens? The key to understanding the health-protective potential of soy phytoestrogens is understanding the difference between the two types of estrogen receptors, alpha receptors and beta receptors. Unlike animal estrogen, the soy phytoestrogens bind preferentially to the beta receptors, and in breast tissue, they’re like yin and yang with the alpha receptors signaling breast cell proliferation. This explains why horse hormones increase breast cancer risk, whereas the beta receptors, where the soy binds, oppose that proliferative impact. So, do the hops phytoestrogens prefer beta, too? No. 8-PN is a selective estrogen receptor alpha promoter. “Surprisingly and in clear contrast to genistein [the soy], 8-PN is a much weaker” binder of beta than of alpha. So, that explains why hops is such a common ingredient in so-called breast enhancing supplements—that is, because it acts more like estrogen estrogen. Given the breast cancer concerns, use of such products should be discouraged, but just drinking beer could provide the exposure to the hops estrogen, which could help explain why beer may be more carcinogenic to the breast than some other forms of alcohol.


A phytoestrogen in beer? For more on the background of this issue, see The Most Potent Phytoestrogen Is in Beer.

Other videos on phytoestrogen include:

To learn more about dietary effects on testosterone, see:

What about “natural” hormones for menopause? See my video Plant-Based Bioidentical Hormones.

For more on the risks of alcohol in terms of breast cancer risk, see Breast Cancer and Alcohol: How Much Is Safe? and Breast Cancer Risk: Red Wine vs. White Wine.

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations: