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Most chemotherapy drugs are approved by the U.S. Food and Drug Administration (FDA) without evidence that they benefit survival or quality of life.

By 2030, the number of new cancer cases in the United States is expected to skyrocket by 45%, from 1.6 million to 2.3 million every year. Are we really winning the war on cancer? Sadly, in general, no, despite the hundreds of new anticancer drugs that have been introduced.

As I discuss in my video How Effective Is Chemotherapy?, the war on cancer has been likened to the war on terror. No matter how many drone strikes you do, it’s nearly impossible to kill all the bad guys, and no matter how precise the bombing, one must always consider the collateral damage. Toxicity from cancer therapy can be debilitating—and not just health-wise. There is also “financial toxicity.”

Some patented anticancer drugs can cost nearly a thousand dollars a day. Even with health insurance, the average cost to patients with stage IV breast cancer, for example, can run about $190,000. It’s bad enough to have to fight for your life; you shouldn’t have to face bankrupting your family at the same time. Sadly, it remains a common problem today.

Who can forget the apocryphal story of Walter White in “Breaking Bad,” who worked two jobs with health insurance and still couldn’t afford his cancer care? Now, not everyone is willing to start their own meth lab, but many are willing to go for broke. A large portion of cancer patients reported their willingness to declare bankruptcy or sell their homes to pay for treatment. Aren’t the high prices of cancer medicines justified if innovative, new treatments offer patients significant benefits? You may be shocked to find out that “many FDA-approved cancer drugs might lack clinical benefit.”

Well, then how did they become FDA-approved? “Most approvals of cancer drugs are based on flimsy or untested surrogate endpoints, and postmarketing studies rarely validate the efficacy and safety of these drugs on patient-centred endpoints.” Let me explain what that means. New chemotherapy drugs are increasingly approved based only on surrogate endpoints, which means instead of looking at what we really care about—survival or quality of life—drugs are being approved based on things like “response rate” or tumor shrinkage. But who cares if the tumor shrinks if it doesn’t actually extend your quantity or quality of life? It’s kind of counterintuitive, but just seeing a tumor shrink on a CT scan or an MRI is not necessarily correlated with improvements in symptoms or survival. In fact, most studies that have actually followed people over time found low correlations with survival. The most recent comprehensive analysis found 91% of studies of such validation trials found little correlation with overall survival.

Of 36 new chemo drugs approved by the FDA based on these kinds of surrogate endpoints, once they were actually put to the test in the real world, only one in seven was shown to extend life, half explicitly flopped, and the rest remain untested, revealing “that most cancer drug approvals have not been shown to, or do not, improve clinically relevant end points.” “Exorbitant drug prices are bad enough for treatments that work. Charging vulnerable patients for drugs without evidence that they actually improve patients’ survival and quality of life is unconscionable.”

Why doesn’t the FDA require proof that chemo drugs actually benefit patients before it approves them? Some drug companies say that requiring randomized, controlled trials with “meaningful measures” would take too long, but the study time reduction using surrogate endpoints rather than overall survival is estimated at just 11 months. So, instead of it taking 7.3 years to come to market, on average, it would take 8.2 years. Of course, we want to get these drugs out as soon as possible, but only if they’re actually going to help people.

Do cancer drugs improve survival or quality of life? “You don’t need to know, according to our broken regulatory system” in the United States—and things are not much better over in Europe. A systematic evaluation of chemo drug approvals showed that most entered the market without evidence they benefited survival or quality of life. Even years later, there was still no conclusive evidence that they offered any benefit, and, when they did, the gains were often marginal.

That’s why you see editorials in the Journal of the National Cancer Institute with titles like “Hans Christian Andersen and the Value of New Cancer Treatments,” alluding to Andersen’s tale The Emperor’s New Clothes. “These studies all converge on a singular conclusion: only a minority of new cancer drugs approved by US and European regulatory authorities in recent years deliver clinically meaningful benefits to patients…” In fact, some cancer-related deaths may be hastened, or even caused, by the toxic effects of chemotherapy rather than the cancer itself. Based on a review of tens of thousands of cancer patients, in as many as 27% of cases, the cancer treatment itself caused or hastened death. But it might be worth that risk if the potential benefit is large enough. That’s the subject of my next blog.

Doctor’s Note

What about preventing cancer in the first place? See Fighting the Ten Hallmarks of Cancer with Food and How Not to Die from Cancer.

Coming up? How Much Do New Chemotherapy Drugs Extend Life?.

If you care about your health so much that it would be unthinkable to light up a cigarette before and after lunch, maybe you should order a bean burrito instead of a meaty one.

According to the Global Burden of Disease Study, diets high in processed meat, like bacon, ham, hot dogs, lunch meat, and sausage, may kill more than 100,000 people every year, due largely to heart disease, but also cancer and diabetes. This results in millions of healthy years of life lost every year around the world, as you can see below and at 0:29 in my video How Much Does Meat Affect Longevity?.

It doesn’t take much either. The Union of Concerned Scientists estimated that if Americans could cut down to just an ounce of processed meat a week, thousands of cancer deaths could be averted every year. But that’s on a population scale. How can we better understand our individual risk?

In the last few blogs, I’ve talked a lot about the NutriRECS meat papers published in the Annals of Internal Medicine. Though the panel discarded its own findings, analyses determined that a reduction in red and processed meat consumption is in fact associated with a 13% lower risk of premature death—and that’s using its own numbers. What does a 13% difference in mortality risk actually mean? To get a better handle on it, let me introduce the concept of microlives.

Acute risks, like skydiving or riding a motorbike, could result in an accident. A good way to compare such risks is with a unit known as a micromort, defined as a one-in-a-million chance of sudden death. (I made a really fascinating video about it.) “However many risks we take don’t kill you straight away: think of all the lifestyle frailties we get warned about, such as smoking, drinking, eating badly, not exercising, and so on. The microlife aims to make all these chronic risks comparable by showing how much life we lose on average when we’re exposed to them: a microlife is 30 minutes of your life expectancy.”

Why is that? Well, someone in their 20s—say a 22-year-old man or a 26-year-old woman—may have, on average, about 57 years of life left. That’s about 20,000 days, or 500,000 hours, or a million half hours. So, that’s how they define a microlife—a reduction of one of the million half hours we may have left. What would, on average, cost a 30-year-old man one microlife?

• smoking two cigarettes
• drinking two pints of strong beer
• living every day 11 pounds (5 kg) overweight

See how helpful this can be in terms of comparing risks? So, drinking a pint of strong beer shortens your life expectancy as much as smoking one cigarette would. If it’s unthinkable to have so little respect for your own health that you’d light up twice a day, maybe one cigarette in the morning and one at night, then it should be just as unthinkable to be 11 pounds overweight.

Alternatively, you can compare life-extending behaviors. For example, eating at least five servings of fruits and vegetables a day may add an average of four years onto your lifespan for men and three years for women. That’s up to twice as beneficial as exercising every day. But guess what—exercise for 20 minutes, and the payoff is an extra hour of life (two microlives). So, for everyone who says they don’t have time to exercise, it’s like a 3-to-1 return on investment! Give 20 minutes of your life to get 60 minutes of life. Beyond that, there’s a bit of diminishing returns, but exercise an hour a day and get back more time than you put in, as you can see below and at 3:45 in my video.

So, what about meat? Each burger is associated with the loss of one microlife; it’s as if each burger were taking 30 minutes off your life. So, in terms of your lifespan, one burger appears to equal two cigarettes. If lighting up at lunch seems unimaginable, maybe a bean burrito is a better choice.

Processed meat is even worse. Here are a few ways to put it into perspective:

• Imagine two people who are completely identical except in one way: One person eats about 50 grams of processed meat a day (roughly one large sausage or a few strips of bacon), and the other eats none. Eating that single serving of processed meat every day is expected to take about two years off the length of that first person’s life. That’s two fewer years with loved ones, grandkids, or a spouse, and two more years of being mourned.
• Or think about it on a day-to-day basis. Eating a bologna or ham sandwich every day—just two slices of deli meat—is expected to take about an hour off life each day. If there never seem to be enough hours in the day, you may effectively have one less depending on what you pack for lunch.
• Another way to think about it is in terms of “effective age.” Eating 50 grams of processed meat a day is expected to add about two years to a person’s “effective age,” meaning the annual risk of death is similar to that of someone two years older.

In summary, wrote the chair of nutrition at Harvard and his colleagues, the NutriRECS meat recommendations “suffer from important methodological limitations and involve misinterpretations of nutritional evidence. To improve human and planetary health [as a side bonus], dietary guidelines should continue to emphasize dietary patterns low in red and processed meats and high in minimally processed plant foods such as fruits and vegetables, whole grains, nuts, and legumes,” that is, beans, split peas, chickpeas, and lentils.

Let me end with a quote from Dr. Dean Ornish about the Annals of Internal Medicine meat papers that suggested people should continue to eat meat with abandon. His Lifestyle Heart Trial was one of the many studies the meat panel ignored. It showed that a plant-based diet and lifestyle program could reverse the progression of even severe coronary heart disease, a top killer of men and women. The control group actually made modest reductions in meat similar to those in the Annals review and showed continued worsening of their atherosclerosis. “I take solace,” Ornish said, “in knowing that the light drives out the darkness. But, these days, the light has to be very bright indeed. Caveat emptor. Don’t be fooled. Your life may depend on it.”

Doctor’s Note

If this concept of comparing different risks is interesting to you, I think you’ll love my micromorts video: Micromorts: How Risky Is It to Go Under Anesthesia?.

This is the final blog in an eight-part series on how industries impact dietary and health guidelines. If you missed any of the others, see the related posts below. 

I have a number of videos on longevity, including this popular one: How to Increase Your Life Expectancy 12 to 14 Years.

Big Meat downplays the magnitude of meat mortality.

A series of studies published in the Annals of Internal Medicine found a statistically significant association between lower consumption of red and processed meats and lower total mortality (meaning living a longer life), lower cardiovascular disease mortality, as well as lower risk of dying from cancer—across the board. Yet, remarkably, the authors of these studies concluded that people should ignore all the other dietary guidelines and keep eating meat to their heart’s content (or rather discontent).

They offered three reasons why their panel reached a conclusion at odds with other contemporary dietary guidelines that advise people to cut down on meat. One reason is taste. In short, people who enjoy eating meat, enjoy eating meat. I talked about this in my last blog, but in short, taste preference probably should not be a major factor in developing dietary guidelines. Many people don’t want to exercise more or stop smoking or drinking, but that doesn’t change the science; it shouldn’t change the public health recommendations.

A second reason they explain why their recommendations differ from everyone else’s is that other guidelines didn’t use the so-called GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach, and no wonder, since GRADE was largely created to evaluate evidence from drug trials. There are grading systems for dietary and lifestyle approaches, but the meat panel chose to inappropriately apply GRADE, which similarly “could be misused to undermine recommendations about secondhand smoke, air pollution, trans fats, or physical inactivity”—you name it. I have three blogs delving deep into all that, but this blog is about the third reason they give for ignoring meat reduction advice: Other guidelines didn’t highlight the “very small magnitude” of the effects of meat consumption. In other words, even if meat does cause heart disease, cancer, diabetes, and death, it doesn’t cause that many heart attacks, doesn’t kill that many people, doesn’t cause that much cancer to offset all those taste benefits.

Of course, it matters what people replace the meat with. Replacing even 3% of calories from animal protein with plant protein is linked to living longer. Eggs appear to be the worst. Yes, replacing red meat protein with plant protein sources may lower overall mortality by more than 10%, but eliminating egg protein could mean more than 20% lower risk of premature death. So, if someone reduces meat consumption by replacing a burger with an egg salad sandwich, that particular reduction in meat could mean more mortality.

But maybe the meat panel researchers concluded there was such a small effect only because “major bodies of evidence were omitted, [and] relevant studies excluded because the authors didn’t like the results.” It’s not that there aren’t tons of randomized controlled trials about meat; it’s just that they appeared to cherry-pick a few to fit their agenda, discarded studies that even met their own criteria, and wrongly rejected randomized controlled trials clearly showing that meat increased risk factors like cholesterol or blood pressure. Why wasn’t the PREDIMED trial included? What about the hundreds of randomized trials on the DASH diet?

What about the Lyon Diet Heart Study? It involved randomizing people to a more Mediterranean diet that included a significant drop in meat consumption, as you can see below and at 3:32 in my video How Big Meat Manipulated the Science.

Compared to the control group, those on the lower-meat diet experienced a 70% reduction in mortality from all causes put together. Why did the meat panel exclude that study? They excluded it because, in their words, it reported “an implausibly large treatment effect.” In other words, it worked too well.

That’s no surprise, given that this so-called NutriRECS meat panel was partnered with—and had multiple people on the payroll of—Texas A&M AgriLife, which receives millions of dollars of meat industry money every year. So, it’s probably not shocking to find out that they also excluded research that compared health outcomes of vegetarians to meat eaters. As they described it, they were interested in “realistic decreases in meat consumption,” like cutting out three servings a week. In fact, the study that they mostly relied on, the Women’s Health Initiative, achieved only a difference of 1.4 servings of meat per week. That amounts to a difference in meat consumption of just half an ounce each day—about a fifth of a hamburger.

“Participants in the Women’s Health Initiative reduced meat intake only modestly, resulting in a modest reduction in mortality related to breast cancer. This finding in no way supports the notion that there is ‘No need to reduce red or processed meat consumption for good health.’ Rather, it shows that modest dietary changes yield modest benefits. As an analogy, if studies showed that modest reductions in tobacco use yielded only modest health benefits, it would be inaccurate and dangerous to suggest that there is ‘No need to reduce tobacco use for good health.’”

“To say that small increases in meat consumption only cause small increases in the risk of disease doesn’t mean that eating meat is good for you,” said Dr. Dean Ornish. “That’s like saying that smoking 24 cigarettes a day increases your risk of lung cancer only a little more than smoking 20 cigarettes a day”—and being careful not to include any studies that compared smoking 24 cigs to smoking none—“and then erroneously concluding that smoking isn’t that bad for your health.”

Despite ignoring and excluding evidence, the meat panel “nonetheless found entirely consistent, clinically meaningful, statistically significant adverse effects of eating more meat and processed meat on all-cause mortality, on cardiovascular disease, on cancer, and on diabetes. That they did so despite the obstacles they put on the path to this finding is nearly incredible, and directly bespeaks the magnitude of adverse effects of meat and processed meat intake on health.”

Based on their meta-analyses of large cohorts, dietary patterns with just a moderate reduction in the consumption of red and processed meats were associated with lower total mortality by 13%, lower cardiovascular disease mortality by 14%, lower cancer mortality by 11%, and a 24% reduced risk of type 2 diabetes. We spend tens of billions of dollars a year trying to tweak risk factors by about this magnitude. And this one intervention—a reduction in meat consumption—appears to do all those things at the same time. There are statin drugs that can reduce heart disease risk, but they actually increase risk for type 2 diabetes and have little effect on cancer. If there was a drug that did as much for your health, it would be a multi-billion-dollar blockbuster.

The chair of nutrition at Harvard estimates that moderately reducing red meat consumption could prevent 200,000 deaths each year. Now, the meat panel can call that a very small effect if they want to, but I imagine it’s no small effect to those 200,000 families.

The numbers are on par with the amount of cancer and heart disease attributable to secondhand smoke and based on the same kind of studies—population studies. (They didn’t randomize people to sit in smoky rooms all day for a couple years.) But no rational person who looks at the public health data around the effectiveness of smoke-free zones would argue that people should continue exposing themselves to secondhand smoke; so, why do the same for red meat and processed meats?

The smoking analogy is actually a good one. “[I]magine researchers select studies with extremely small between-group differences in the number of cigarettes smoked per week. They avoid any studies that actually compare smoking to non-smoking [i.e., meat-eating to vegetarian]. They find that despite the small differences in exposure, there is still a clear and consistent benefit of smoking less. They then apply methods of grading the evidence that strongly favor randomized trials over all other methods. Since there are few if any randomized trials of smoking, they conclude that they have very low confidence in the reliability of their own findings. On that basis, they publish guidelines recommending—that the public simply continue to smoke. After all, they reason, people who smoke like smoking.” That really does sum up the Annals of Internal Medicine papers in a nutshell.

That reminds me of a quote from a famous paper published in 1959, compiling all the most poignant evidence linking smoking and lung cancer, after coming up against those same charges of inadequate proof. This quote could just as well have been written about the state of science on meat today. If the mountain of evidence they found “had been made on a new agent, to which hundreds of millions of adults were not already addicted, and on one which did not support a large industry, skilled in the arts of mass persuasion, the evidence for the hazardous nature of the agent would be generally regarded as beyond dispute.”

Doctor’s Note

See this video for more on How Smoking in 1959 Is Like Eating in 2019.

This is the seventh in an eight-part series on how industries impact dietary and health guidelines. The first six parts are in the related posts below.

The final blog, coming up, is How Many Minutes of Life Does a Burger Cost?.