Michael Greger's Blog

What are the pros and cons of relative risk, absolute risk, number needed to treat, and average postponement of death when taking cholesterol-lowering statin drugs?

In response to the charge that describing the benefits of statin drugs only in terms of relative risk reduction is a “statistical deception” created to give the appearance that statins are more effective than they really are, it was pointed out that describing things in terms of absolute risk reduction or number needed to treat can depend on the duration of the study.

For example, let’s say a disease has a 2% chance of killing you every year, but some drug cuts that risk by 50%. That sounds amazing, until you realize that, at the end of a year, your risk will only have fallen from 2% to 1%, so the absolute reduction of risk is only 1%. If a hundred people were treated with the drug, instead of two people dying, one person would die, so a hundred people would have to be treated to save one life, as shown below and at 1:01 in my video How Much Longer Do You Live on Statins?.

But there’s about a 99% chance that taking the drug all year would have no effect either way. So, to say the drug cuts the risk of dying by 50% seems like an overstatement. But think about it: Benefits accrue over time. If there’s a 2% chance of dying every year, year after year, after a few decades, the majority of those who refused the drug would be dead, whereas the majority who took the drug would be alive. So, yes, perhaps during the first year on the drug, there was only about a 1% chance it would be life-saving, but, eventually, you could end up with a decent chance the drug would save your life after all.

“This is actually the very reason why the usage of relative risk makes sense…” Absolute risk changes depending on the time frame being discussed, but with relative risk, you know that whatever risk you have, you can cut it in half by taking the drug. On average, statins only cut the risk of a cardiovascular “event” by 25%, but since cardiovascular disease is the number one killer of men and women, if you’re unwilling to change your diet, that’s a powerful argument in favor of taking these kinds of drugs. You can see the same kind of dependency on trial duration, looking at the “postponement of death” by taking a statin. How much longer might you live if you take statins?

The average postponement of death has some advantages over other statistics because it may offer “a better intuitive understanding among lay persons,” whereas a stat like a number needed to treat has more of a win-or-lose “lottery-like” quality. So, when a statin drug prevents, say, one heart attack out of a hundred people treated over five years, it’s not as though the other 99 completely lost out. Their cholesterol also dropped, and their heart disease progression presumably slowed down, too, just not enough to catch a heart attack within that narrow time frame.

So, what’s the effect of statins on average survival? According to an early estimate, if you put all the randomized trials together, the average postponement of death was calculated at maybe three or four days. Three or four days? Who would take a drug every day for years just to live a few more days? Well, let’s try to put that into context. Three or four days is comparable to the gains in life expectancy from other medical interventions. For example, it’s nearly identical to what you’d get from “highly effective childhood vaccines.” Because vaccines have been so effective in wiping out infectious diseases, these days, they only add an average of three extra days to a child’s life. But, of course, “those whose deaths are averted gain virtually their whole lifetimes.” That’s why we vaccinate. It just seems like such a small average benefit because it gets distributed over the many millions of kids who get the vaccine. Is that the same with statins?

An updated estimate was published in 2019, which explained that the prior estimate of three or four days was plagued by “important weaknesses,” and the actual average postponement of death was actually ten days. Headline writers went giddy from these data, but what they didn’t understand was that this was only for the duration of the trial. So, if your life expectancy is only five years, then, yes, statins may increase your lifespan by only ten days, but statins are meant to be taken a lot longer than five years. What you want to know is how much longer you might get to live if you stick with the drugs your whole life.

In that case, it isn’t an extra ten days, but living up to ten extra years. Taking statins can enable you to live years longer. That’s because, for every millimole per liter you lower your bad LDL cholesterol, you may live three years longer and maybe even six more years, depending on which study you’re reading. A millimole in U.S. units is 39 points. Drop your LDL cholesterol by about 39 points, and you could live years longer. Exercise your whole life, and you may only increase your lifespan by six months, and stopping smoking may net you nine months. But if you drop your LDL cholesterol by about 39 points, you could live years longer. You can accomplish that by taking drugs, or you can achieve that within just two weeks of eating a diet packed with fruits, vegetables, and nuts, as seen here and at 5:30 in my video. 

Want to know what’s better than drugs? “Something important and fundamental has been lost in the controversy around this broad expansion of statin therapy.…It is imperative that physicians (and drug labels) inform patients that not only their lipid [cholesterol] levels but also their cardiovascular risk can be reduced substantially by adoption of a plant-based dietary pattern, and without drugs. Dietary modifications for cardiovascular risk reduction, including plant-based diets, have been shown to improve not only lipid status, but also obesity, hypertension, systemic inflammation, insulin sensitivity, oxidative stress, endothelial function, thrombosis, and cardiovascular event risk…The importance of this [plant-based] approach is magnified when one considers that, in contrast to statins, the ‘side effects’ of plant-based diets—weight loss, more energy, and improved quality of life—are beneficial.” 

A Mayo Clinic visualization tool can help you decide if cholesterol-lowering statin drugs are right for you.

“Physicians have a duty to inform their patients about the risks and benefits of the interventions available to them. However, physicians rarely communicate with methods that convey absolute information, such as numbers needed to treat, numbers needed to harm, or prolongation of life, despite patients wanting this information.” That is, for example, how many people are actually helped by a particular drug, how many are actually hurt by it, or how much longer the drug will enable you to live, respectively.

If doctors inform patients only about the relative risk reduction—for example, telling them a pill will cut their risk of heart attacks by 34 percent—nine out of ten agree to take it. However, give them the same information framed as absolute risk reduction—“1.4% fewer patients had heart attacks”—then those agreeing to take the drug drops to only four out of ten. And, if they use the number needed to treat, only three in ten patients would agree to take the pill. So, if you’re a doctor and you really want your patient to take the drug, which statistic are you going to use?

The use of relative risk stats to inflate the benefits and absolute risk stats to downplay any side effects has been referred to as “statistical deception.” To see how one might spin a study to accomplish this, let’s look at an example. As you can see below and at 1:49 in my video, The True Benefits vs. Side Effects of Statins, there is a significantly lower risk of the incidence of heart attack over five years in study participants randomized to a placebo compared to those getting the drug. If you wanted statins to sound good, you’d use the relative risk reduction (24 percent lower risk). If you wanted statins to sound bad, you’d use the absolute risk reduction (3 percent fewer heart attacks).

Then you could flip it for side effects. For example, the researchers found that 0.3 percent (1 out of 290 women in the placebo group) got breast cancer over five years, compared to 4.1 percent (12 out of 286) in the statin group. So, a pro-statin spin might be a 24 percent drop in heart attack risk and only 3.8 percent more breast cancers, whereas an anti-statin spin might be only 3 percent fewer heart attacks compared to a 1,267 percent higher risk of breast cancer. Both portrayals are technically true, but you can see how easily you could manipulate people if you picked and chose how you were presenting the risks and benefits. So, ideally, you’d use both the relative risk reduction stat and the absolute risk reduction stat.

In terms of benefits, when you compile many statin trials, it looks like the relative risk reduction is 25 percent. So, if your ten-year risk of a heart attack or stroke is 5 percent, then taking a statin could lower that from 5 percent to 3.75 percent, for an absolute risk reduction of 1.25 percent, or a number needed to treat of 80, meaning there’s about a 1 in 80 chance that you’d avoid a heart attack or stroke by taking the drug for the next ten years. As you can see, as your baseline risk gets higher and higher, even though you have that same 25 percent risk reduction, your absolute risk reduction gets bigger and bigger. And, with a 20 percent baseline risk, that means you have a 1 in 20 chance of avoiding a heart attack or stroke over the subsequent decade if you take the drug, as seen below and at 3:31 in my video.

So, those are the benefits. In terms of risk, that breast cancer finding appears to be a fluke. Put together all the studies, and “there was no association between use of statins and the risk of cancer.” In terms of muscle problems, estimates of risk range from approximately 1 in 1,000 to closer to 1 in 50.

If all those numbers just blur together, the Mayo Clinic developed a great visualization tool, seen below and at 4:39 in my video.

For those at average risk, 10 people out of 100 who do not take a statin may have a heart attack over the next ten years. If, however, all 100 people took a statin every day for those ten years, 8 would still have a heart attack, but 2 would be spared, so there’s about a 1 in 50 chance that taking the drug would help avert a heart attack over the next decade. What are the downsides? The cost and inconvenience of taking a pill every day, which can cause some gastrointestinal side effects, muscle aching, and stiffness in about 5 percent, reversible liver inflammation in 2 percent, and more serious damage in perhaps 1 in 20,000 patients.

Note that the two happy faces in the bottom left row of the YES STATIN chart represent heart attacks averted, not lives saved. The chance that a few years of statins will actually save your life if you have no known heart disease is about 1 in 250.

If you want a more personalized approach, the Mayo Clinic has an interactive tool that lets you calculate your ten-year risk. You can get there directly by going to bit.ly/statindecision.

What is the dirty little secret of drugs for lifestyle diseases?

Drug companies go out of their way—in direct-to-consumer ads, for example—to “present pharmaceutical drugs as a preferred solution to cholesterol management while downplaying lifestyle change.” You see this echoed in the medical literature, as in this editorial in the Journal of the American Medical Association: “Despite decades of exhortation for improvement, the high prevalence of poor lifestyle behaviors leading to elevated cardiovascular disease risk factors persists, with myocardial infarction [heart attack] and stroke remaining the leading causes of death in the United States. Clearly, many more adults could benefit from…statins for primary prevention.” Do we really need to put more people on drugs? A reply was published in the British Medical Journal: “Once again, doctors are implored to ‘get real’—stop hoping that efforts to help their patients and communities adopt healthy lifestyle habits will succeed, and start prescribing more statins. This is a self-fulfilling prophecy. Note that the author of these comments [the pro-statin editorial] disclosed receipt of funding from 11 drug companies, at least four of which produce or are developing new classes of cholesterol-lowering agents,” which make billions of dollars a year in annual sales.

Every time the cholesterol guidelines expand the number of people eligible for statins, they’re decried as a “big kiss to big pharma.” This is understandable, since the majority of guideline panel members “had industry ties,” financial conflicts of interest. But these days, all the major statins are off-patent, so there are inexpensive generic versions. For example, the safest, most effective statin is generic Lipitor, sold as atorvastatin for as little as a few dollars a month. So, nowadays, the cholesterol guidelines are not necessarily “part of an industry plot.”

“The US way of life is the problem, not the guidelines…” The reason so many people are candidates for cholesterol- and blood-pressure-lowering medications is that so many people are taking such terrible care of themselves. The bottom line is that “individuals must take more responsibility for their own health behaviors.” What if you are unwilling or unable to improve your diet and make lifestyle changes to bring down that risk? If your ten-year risk of having a heart attack is 7.5 percent or more and going to stay that way, then the benefits of taking a statin drug likely outweigh the risk. That’s really for you to decide, though. It’s your body, your choice.

“Whether or not the overall benefit-harm balance justifies the use of a medication for an individual patient cannot be determined by a guidelines committee, a health care system, or even the attending physician. Instead, it is the individual patient who has a fundamental right to decide whether or not taking a drug is worthwhile.” This was recognized by some of medicine’s “historical luminaries such as Hippocrates,” but “only in recent decades has the medical profession begun to shift from a paternalistic ‘doctor knows best’ stance towards one explicitly endorsing patient-centered, evidence-based, shared decision-making.” One of the problems with communicating statin evidence to support this shared decision-making is that most doctors “have a poor understanding of concepts of risk and probability and…increasing exposure to statistics in undergraduate and postgraduate education hasn’t made much difference.” But that understanding is critical for preventive medicine. When doctors offer a cholesterol-lowering drug, “they’re doing something quite different from treating a patient who has sought help because she is sick. They’re not so much doctors as life insurance salespeople, peddling deferred benefits in exchange for a small (but certainly not negligible) ongoing inconvenience and cost. In this new kind of medicine, not understanding risk is the equivalent of not knowing about the circulation of the blood or basic anatomy. So, let’s dive in and see exactly what’s at stake.

Below and at 3:55 in my video Are Doctors Misleading Patients About Statin Risks and Benefits? is an ad for Lipitor. When drug companies say a statin reduces the risk of a heart attack by 36 percent, that’s the relative risk.

If you follow the asterisk I’ve circled after the “36%” in the ad, you can see how they came up with that. I’ve included it here and at 3:56 in my video. In a large clinical study, 3 percent of patients not taking the statin had a heart attack within a certain amount of time, compared to 2 percent of patients who did take the drug. So, the drug dropped heart attack risk from 3 percent to 2 percent; that’s about a one-third drop, hence the 36 percent reduced relative risk statistic. But another way to look at going from 3 percent to 2 percent is that the absolute risk only dropped by 1 percent. So, in effect, “your chance to avoid a nonfatal heart attack during the next 2 years is about 97% without treatment, but you can increase it to about 98% by taking a Crestor [a statin] every day.” Another way to say that is that you’d have to treat 100 people with the drug to prevent a single heart attack. That statistic may shock a lot of people.

If you ask patients what they’ve been led to believe, they don’t think the chance of avoiding a heart attack within a few years on statins is 1 in 100, but 1 in 2. “On average, it was believed that most patients (53.1%) using statins would avoid a heart attack after statin treatment for 5 years.” Most patients, not just 1 percent of patients. And this “disparity between actual and expected effect could be viewed as a dilemma. On the one hand, it is not ethically acceptable for caregivers to deliberately support and maintain illusive treatment expectations by patients.” We cannot mislead people into thinking a drug works better than it really does, but on the other hand, how else are we going to get people to take their pills?

When asked, people want an absolute risk reduction of at least about 30 percent to take a cholesterol-lowering drug every day, whereas the actual absolute risk reduction is only about 1 percent. So, the dirty little secret is that, if patients knew the truth about how little these drugs actually worked, almost no one would agree to take them. Doctors are either not educating their patients or actively misinforming them. Given that the majority of patients expect a much larger benefit from statins than they’d get, “there is a tension between the patient’s right to know about benefiting from a preventive drug and the likely reduction in uptake [willingness to take the drugs] if they are so informed,” and learn the truth. This sounds terribly paternalistic, but hundreds of thousands of lives may be at stake.

If patients were fully informed, people would die. About 20 million Americans are on statins. Even if the drugs saved 1 in 100, that could mean hundreds of thousands of lives lost if everyone stopped taking their statins. “It is ironic that informing patients about statins would increase the very outcomes they were designed to prevent.”

How can you calculate your own personal heart disease risk to help you determine if you should start on a cholesterol-lowering statin drug?

The muscle-related side effects from cholesterol-lowering statins “are often severe enough for patients to stop taking the drug. Of course, these side effects could be coincidental or psychosomatic and have nothing to do with the drug,” given that many clinical trials show such side effects are rare. “It is also possible that previous clinical trials”—funded by the drug companies themselves—“under-recorded the side effects of statins.” The bottom line is that there’s an urgent need to establish the true incidence of statin side effects.

“What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug?” That’s the title of a journal article that reports that, even in trials funded by Big Pharma, “only a small minority of symptoms reported on statins are genuinely due to the statins,” and those taking statins are significantly more likely to develop type 2 diabetes than those randomized to placebo sugar pills. Why? We’re still not exactly sure, but statins may have the double-whammy effect of impairing insulin secretion from the pancreas while also diminishing insulin’s effectiveness by increasing insulin resistance.

Even short-term use of statins may “approximately double the odds of developing diabetes and diabetic complications.” As shown below and at 1:49 in my video Who Should Take Statins?, fewer people develop diabetes and diabetic complications off statins over a period of about five years than those who do develop diabetes while on statins. “Of more concern, this increased risk persisted for at least 5 years after statin use stopped.”

“In view of the overwhelming benefit of statins in the reduction of cardiovascular events,” the number one killer of men and women, any increase in risk of diabetes, our seventh leading cause of death, would be outweighed by any cardiovascular benefits, right? That’s a false dichotomy. We don’t have to choose between heart disease and diabetes. We can treat the cause of both with the same diet and lifestyle changes. The diet that can not only stop heart disease, but also reverse it, is the same one that can reverse type 2 diabetes. But what if, for whatever reason, you refuse to change your diet and lifestyle? In that case, what are the risks and benefits of starting statins? Don’t expect to get the full scoop from your doctor, as most seemed clueless about statins’ causal link with diabetes, so only a small fraction even bring it up with their patients.

“Overall, in patients for whom statin treatment is recommended by current guidelines, the benefits greatly outweigh the risks.” But that’s for you to decide. Before we quantify exactly what the risks and benefits are, what exactly are the recommendations of current guidelines?

How should you decide if a statin is right for you? “If you have a history of heart disease or stroke, taking a statin medication is recommended, without considering your cholesterol levels.” Period. Full stop. No discussion needed. “If you do not yet have any known cardiovascular disease,” then the decision should be based on calculating your own personal risk. If you know your cholesterol and blood pressure numbers, it’s easy to do that online with the American College of Cardiology risk estimator or the Framingham risk profiler.

My favorite is the American College of Cardiology’s estimator because it gives you your current ten-year risk and also your lifetime risk. So, for a person with a 5.8 percent risk of having a heart attack or stroke within the next decade, if they don’t clean up their act, that lifetime risk jumps to 46 percent, nearly a flip of the coin. If they improved their cholesterol and blood pressure, though, they could reduce that risk by more than tenfold, down to 3.9 percent, as shown below and at 4:11 in my video.

Since the statin decision is based on your ten-year risk, what do you do with that number? As you can see here and at 4:48 in my video, under the current guidelines, if your ten-year risk is under 5 percent, then, unless there are extenuating circumstances, you should just stick to diet, exercise, and smoking cessation to bring down your numbers. In contrast, if your ten-year risk hits 20 percent, then the recommendation is to add a statin drug on top of making lifestyle modifications. Unless there are risk-enhancing factors, the tendency is to stick with lifestyle changes if risk is less than 7.5 percent and to move towards adding drugs if above 7.5 percent.

Risk-enhancing factors that your doctor should take into account when helping you make the decision include a bad family history, really high LDL cholesterol, metabolic syndrome, chronic kidney or inflammatory conditions, or persistently high triglycerides, C-reactive protein, or LP(a). You can see the whole list here and at 4:54 in my video.

If you’re still uncertain, guidelines suggest you consider getting a coronary artery calcium (CAC) score, but even though the radiation exposure from that test is relatively low these days, the U.S. Preventive Services Task Force has explicitly concluded that the current evidence is insufficient to conclude that the benefits outweigh the harms.

Do you know more about basic nutrition than most doctors?

“A poor diet now outranks smoking as the leading cause of death globally and in the United States, according to the latest data.” The top killer of Americans is the American diet, as you can see below and at 0:23 in my video How Much Do Doctors Actually Know About Nutrition?.

If diet is humanity’s number one killer, then, obviously, nutrition is the number one subject taught in medical school, right? Sadly, “medical students around the world [are] poorly trained in nutrition.” It isn’t that medical students aren’t interested in learning about it. In fact, “interest in nutrition was ‘uniformly high’ among medical students,” but medical schools just aren’t teaching it. “Without a solid foundation of clinical nutrition knowledge and skills, physicians worldwide are generally not equipped to even begin to have an informed nutrition conversation with their patients….”

How bad is it? One study, “Assessing the clinical nutrition knowledge of medical doctors,” found the majority of participants got 70 percent of the questions wrong—and they were multiple choice questions, so they should have gotten about a fifth of them right just by chance. “Wrong answers in the…knowledge test were not limited to difficult or demanding questions” either. For example, less than half of the doctors were able to guess how many calories are in fat, carbohydrates, and protein; only one in ten knew the recommended protein intake; and only about one in three knew what a healthy body mass index (BMI) was. We’re talking about really basic nutrition knowledge.

Even worse, not only did the majority of medical doctors get a failing grade, but 30 percent of those who failed had “a high self-perception of their CN [clinical nutrition] expertise.” They weren’t only clueless about nutrition; they were clueless that they were clueless about nutrition, a particularly bad combination given that doctors are “trusted and influential sources” of healthy eating advice. “For those consumers who get information from their personal healthcare professional, 78% indicate making a change in their eating habits as a result of those conversations.” So, if the doctor got everything they know from some article in a magazine while waiting in the grocery store checkout aisle, that’s what the patients will be following.

Of doctors surveyed, “only 25% correctly identified the American Heart Association recommended number of fruit and vegetable servings per day, and fewer still (20%) were aware of the recommended daily added sugar limit for adults.” So how are they going to counsel their patients? And get ready for this: Of the doctors who perceived themselves as having high nutrition knowledge, 93 percent couldn’t answer those two basic multiple-choice questions, as seen here and at 2:39 in my video.

“Physicians with no genuine expertise in, say, neurosurgery [brain surgery] are neither likely to broadcast detailed opinions on that topic nor to have their ‘expert’ opinions solicited by the media. Most topical domains in medicine enjoy such respect: we defer expert opinion and commentary to actual experts. Not so nutrition, where the common knowledge that physicians are generally ill-trained in this area is conjoined to routine invitations to physicians for their expert opinions on the matter. All too many are willing to provide theirs, absent any basis for actual expertise…” Or worse, they’re “often made on the basis of native bias and personal preference, at times directly tethered to personal gain—such as diet book sales—and so arises yet another ethical challenge.” That’s one of the reasons all the proceeds I receive from my books are donated directly to charity. I don’t want even the appearance of any conflicts of interest.

“In a culture that routinely fails to distinguish expertise from mere opinion or personal anecdote, we physicians should be doing all we can to establish relevant barriers to entry for expert opinion in this [diet and nutrition], as in all other matters of genuine medical significance.” I mean, we aren’t talking celebrity gossip. Lives are at stake. “Entire industries are devoted to marketing messages that may conspire directly against well-informed medical advice in this area.”

“Medical education must be brought up to date. For physicians to be ill-trained in the very area most impactful on the rate of premature death at the population level is an absurd anachronism….The mission of medicine is to protect, defend, and advance the human condition. That mission cannot be fulfilled if the diet is neglected.”

A possible starting place? “Physicians and health care organizations can collectively begin to emphasize their seriousness about nutrition in health care by practicing what they (theoretically) preach. Is it appropriate to serve pizza and soft drinks at a resident conference while bemoaning the high prevalence of obesity and encouraging patients to eat healthier? A similarly poor example exists in medical conferences, including national meetings, where some morning sessions are accompanied by foods such as donuts and sausage.”

It may not be the number of bacteria growing in our small intestine, but the type of bacteria, which can be corrected with diet.

When researchers tested more than a thousand patients suffering for longer than six months from symptoms typical with irritable bowel syndrome (IBS), such as excess gas, bloating, diarrhea, and abdominal pain, but who do not appear to have anything more serious going on, like inflammatory bowel disease, a significant percentage were found to be suffering from lactose intolerance—intolerance to the milk sugar lactose. In infancy, we have an enzyme called lactase in our small intestine that digests milk sugar, but, understandably, most of us lose it after weaning. “Although genetic mutation has led to persistence of lactase in adults, about 75% of the world’s population malabsorbs lactose after age 30” and have lactose intolerance. However, a third of the patients were diagnosed with small intestinal bacterial overgrowth (SIBO).

“The evidence for SIBO and IBS is shrouded in controversy, predominantly because of the fact that the [breath] tests used in clinical practice to diagnose SIBO are not valid,” as I’ve explored before. As well, the implications of having more versus fewer bacteria growing in the small intestine are unclear since the number doesn’t seem to correlate with the symptoms. It turns out it isn’t the number of bugs growing in the small intestine, but the type of bugs. So, it’s “small intestinal microbial dysbiosis”—not overgrowth in general, but the wrong kind of growth—that appears to underlie symptoms associated with functional gastrointestinal disorders, like IBS.

How can we prevent this from happening? The symptoms appear to be correlated with a significant drop in the number of Prevotella. Remember them? Prevotella are healthy fiber feeders, “suggestive of a higher fiber intake in healthy individuals,” while the bugs found more in symptomatic patients ate sugar, which “may reflect a higher dietary intake of simple sugars.” However, correlation doesn’t mean causation. To prove cause and effect, we have to put it to the test, which is exactly what researchers did.

“Switching a group of healthy individuals who habitually ate a high­-fibre diet (>11g per 1,000 calories) to a low­-fibre diet (<10g per day) containing a high concentration of simple sugars for 7 days produced striking results. First, 80% developed de novo [new] gastrointestinal symptoms such as bloating and abdominal pain that resolved on resumption of their habitual high-fibre diet. Second, diet­-related changes in the small intestinal microbiome were predictive of symptoms (such as bloating and abdominal discomfort) and linked to an alteration in duodenal [intestinal] permeability.” In other words, they developed a leaky gut within seven days. And, while some went from SIBO positive to SIBO negative and others from SIBO negative to SIBO positive, it didn’t matter because the number of bacteria growing didn’t correlate with symptoms. It was the type of bacteria growing, as you can see below, and at 3:12 in my video Fiber vs. Low FODMAP for SIBO Symptoms.

No wonder their guts got leaky. Levels of short-chain fatty acids plummeted. Those are the magical by-products our good gut bugs make from fiber, which “play an important role in epithelial [intestinal] barrier integrity,” meaning they keep our gut from getting leaky.

So, while we don’t have sound data to suggest that something like a low FODMAP diet has any benefit for patients with SIBO symptoms, there have been more than a dozen randomized controlled trials that have put fiber to the test. Overall, researchers found there was a significant improvement in symptoms among those randomized to increase their fiber intake. That may help explain why “high-fiber, plant-based diets can prevent many diseases common in industrialized societies.” Such diets have this effect “on the composition and metabolic activity of the colonic microbiota.” Our good gut bugs take plant residues like fiber and produce “health-promoting and cancer-suppressing metabolites” like short-chain fatty acids, which have profound anti-inflammatory properties. “All the evidence points to a physiological need for ~50 g fiber per day, which is the amount contained in the traditional African diet and associated with the prevention of westernized diseases.” That is approximately twice the typical recommendation and three times more than what most people get on a daily basis. Perhaps it should be no surprise that we need so much. Even though we split from chimpanzees millions of years ago, “there is still broad congruency” in the composition of our respective microbiomes to this day. While they’re still eating their 98 to 99 percent plant-based diets to feed their friendly flora with fiber, we’ve largely removed fiber-rich foods from our food supply. 

Even if we could accurately diagnose small intestinal bacterial overgrowth (SIBO), if there is no difference in symptoms between those testing positive and those testing negative, what’s the point?

Gastrointestinal symptoms like abdominal pain and bloating account for millions of doctor visits every year. One of the conditions that may be considered for such a “nonspecific presentation” of symptoms is SIBO, a concept that “has gained popularity on the internet in addition to certain clinical and research circles.” SIBO is “broadly defined as excessive bacteria in the small intestine” and typically treated with antibiotics, but “dispensing antibiotics to patients with the nonspecific, common symptoms associated with SIBO is not without risks,” such as the fostering of antibiotic resistance, the emergence of side effects, and the elimination of our good bacteria that could set us up for an invasion of bad bugs like C. diff—all for a condition that may not even be real.

Even alternative medicine journals admit that SIBO is being overdiagnosed, creating “confusion and fear.” SIBO testing “is overused and overly relied upon. Diagnoses are often handed out quickly and without adequate substantiation. Patients can be indoctrinated into thinking SIBO is a chronic condition that can not be cleared and will require lifelong management. This is simply not true for most and is an example of the damage done by overzealousness.” “The ‘monster’ that we now perceive SIBO to be may be no more than a phantom.”

The traditional method for a diagnosis was a small bowel aspiration, an invasive test where a long tube is snaked down the throat to take a sample and count the bugs down there, as you can see at 2:10 in my video Are Small Intestinal Bacterial Overgrowth (SIBO) Tests Valid?.

This method has been almost entirely replaced with breath tests. Normally, a sugar called glucose is almost entirely absorbed in the small intestine, so it never makes it down to the colon. So, the presence of bacterial fermentation of that sugar suggests there are bacteria in the small intestine. Fermentation can be detected because the bacteria produce specific gases that get absorbed in our bloodstream before being exhaled from our lungs, which can then be detected with a breathalyzer-type machine.

Previously, the sugar lactulose was used, but “lactulose breath tests do not reliably detect the overgrowth of bacteria,” so researchers switched to glucose. However, when glucose was finally put to the test, it didn’t work. The bacterial load in the small intestine was similar for those testing positive or negative, so that wasn’t a useful test either. It turns out that glucose can make it down to the colon after all.

Researchers labeled the glucose dose with a tracer and found that nearly half of the positive results from glucose breath tests were false positives because individuals were just fermenting it down in their colon, where our bacteria are supposed to be. So, “patients who are incorrectly labeled with SIBO may be prescribed multiple courses of antibiotics” for a condition they don’t even have.

Why do experts continue to recommend breath testing? Could it be because the “experts” were at a conference supported by a breath testing company, and most had personally received funds from SIBO testing or antibiotic companies?

Even if we could properly diagnose SIBO, does it matter? For those with digestive symptoms, there is a massive range of positivity for SIBO from approximately 4 percent to 84 percent. Researchers “found there to be no difference in overall symptom scores between those testing positive against those testing negative for SIBO…” So, a positive test result could mean anything. Who cares if some people have bacteria growing in their small intestines if it doesn’t correlate with symptoms?

Now, antibiotics can make people with irritable bowel-type symptoms who have been diagnosed with SIBO feel better. Does that prove SIBO was the cause? No, because antibiotics can make just as many people feel better who are negative for SIBO. Currently, the antibiotic rifaximin is most often used for SIBO, but it is “not currently FDA-approved for use in this indication, and its cost can be prohibitive.” (The FDA is the U.S. Food and Drug Administration.) In fact, no drug has been approved for SIBO in the United States or Europe, so even with good insurance, it may cost as much as $50 a day in out-of-pocket expenses, and the course is typically two weeks.

What’s more, while antibiotics may help in the short term, they may make matters worse in the long term. Those “who are given a course of antibiotics are more than three times as likely to report more bowel symptoms 4 months later than controls.” So, what can we do for these kinds of symptoms? That’s exactly what I’m going to turn to next.

In every grade school class photo, I seem to have a mess of tousled hair on my head. No matter how much my mom tried to tame my hair, it was a little unruly. (I sported the windblown look without even trying.) Later came my metalhead phase, with headbangable hair down to the middle of my back. Sadly, though, like many of the men in my family, it started to thin, then disappear. Studies show that by age 50, approximately half of men and women will experience hair loss. Why do some lose their hair and others don’t? How can we preserve the looks of our locks?

As I discuss in my video Supplements for Hair Growth, we don’t lose our hair by washing or brushing it too much––two of the many myths out there. The majority of hair loss with age is genetic for both women and men. Based on twin studies, the heritability of baldness in men is 79%, meaning about 80% of the differences in hair loss between men is genetically determined, but that leaves some wiggle room.

Look at identical twins, for instance: Identical twin sisters with the same DNA had different amounts of hair loss, thanks to increased stress, increased smoking, having more children, or having a history of high blood pressure or cancer.

Indeed, smoking can contribute to the development of both male and female pattern baldness because the genotoxic compounds in cigarettes may damage the DNA in our hair follicles and cause microvascular poisoning in their base.

Other toxic agents associated with hair loss include mercury; it seems to concentrate about 250-fold in growing scalp hair. William Shakespeare may have started losing his hair due to mercury poisoning from syphilis treatment. Thankfully, doctors don’t give their patients mercury anymore. These days, as the Centers for Disease Control and Prevention point out, mercury mainly enters the body through seafood consumption.

Consider this: A woman went to her physician, concerned about her hair loss. Blood tests indicated elevated mercury levels, which makes sense as her diet was high in tuna. When she stopped eating tuna, her mercury levels fell and her hair started to grow back within two months. After seven months on a fish-free diet, her hair completely regrew. Doctors should consider screening for mercury toxicity when they see hair loss.

In addition to not smoking, managing our stress, and avoiding seafood, is there anything else we can do to prevent hair loss?

We can make sure we don’t have scurvy, severe vitamin C deficiency. We’ve known for centuries that scurvy can cause hair loss, but once we have enough vitamin C so our gums aren’t bleeding, there are no data correlating vitamin C levels and hair loss. So, make sure you have a certain baseline sufficiency.

What about foods for hair loss? What role might diet play in the treatment of hair loss?

As I discuss in my video Food for Hair Growth, population studies have found that male pattern baldness is associated with poor sleeping habits and the consumption of meat and junk food, whereas protective associations were found for the consumption of raw vegetables, fresh herbs, and soy milk. Drinking soy beverages on a weekly basis was associated with 62% lower odds of moderate to severe hair loss, raising the possibility that there may be compounds in plants that may be protective.

A randomized, double-blind, placebo-controlled study of compounds in hot peppers and soy found significantly higher promotion of hair growth, and the doses used were reasonable: 6 milligrams of capsaicin a day and 75 milligrams of isoflavones. How does that translate into actual food? We can get 6 milligrams of capsaicin in just a quarter of a fresh jalapeño pepper a day and 75 milligrams of isoflavones eating just three-quarter cup of tempeh or soybeans.

Researchers also investigated pumpkin seeds and hair loss. For a few months, 76 men with male pattern baldness received 400 milligrams of pumpkin seed oil a day hidden in capsules (the equivalent of eating about two and a half pumpkin seeds a day) or took placebo capsules. After 24 weeks of treatment, self-rated improvement and satisfaction scores in the pumpkin group were higher, and they objectively had more hair—a 40% increase in hair counts, compared to only 10% in the placebo group. In the pumpkin group, 95% remained either unchanged or improved, whereas in the control group, more than 90% remained unchanged or worsened. Given such a pronounced effect, there was concern about sexual side effects, but researchers looked before and after at an index of erectile dysfunction and found no evidence of adverse effects.

The most common ingredient in top-selling hair loss products is vitamin B7, also known as biotin. Biotin deficiency causes hair loss, but there are no evidence-based data that supplementing biotin promotes hair growth. And severe biotin deficiency in healthy individuals eating a normal diet has never been reported. However, if you eat raw egg whites, you can acquire a biotin deficiency, since there are compounds that attach to biotin and prevent it from being absorbed. Other than rare deficiency syndromes, though, it’s a myth that biotin supplements increase hair growth.

Can we just adopt the attitude that it can’t hurt, so we might as well see if it helps? No, because there is a lack of regulatory oversight of the supplement industry and, in the case of biotin, interference with lab tests. Many dietary supplements promoted for hair health contain biotin levels up to 650 times the recommended daily intake of biotin. And excess biotin in the blood can play haywire on a bunch of different blood tests, including thyroid function, other hormone tests (including pregnancy), and the test performed to determine if you’ve had a heart attack––so it could potentially even be life or death.

What about drugs? We only have good evidence for efficacy for the two drugs approved by the U.S. Food and Drug Administration: finasteride, sold as Propecia, and minoxidil, sold as Rogaine. It’s considered a myth that all the patented hair-loss supplements on the market will increase hair growth. And they may actually be more expensive, with over-the-counter supplement regimens costing up to more than $1,000 a year, whereas the drugs may cost only $100 to $300 a year. As I discuss in my video Pills for Hair Growth, the drugs can help, but they can also cause side effects. Propecia can diminish libido, cause sexual disfunction, and have been associated with impotence, testicular pain, and breast enlargement, while the topical Minoxidil can cause itching, for example.

How do they work (if they work at all)? Androgens are the principal drivers of hair growth in both men and women. Testosterone is the primary androgen circulating in the blood, and it can be converted to dihydrotestosterone, which is even more powerful, by an enzyme called 5-alpha reductase. That’s the enzyme that is blocked by Propecia, so it inhibits the souping up of testosterone. This is why pre-menopausal women are not supposed to take it, since it could feminize male fetuses, whereas for men, it has sexual side effects like erectile dysfunction, which can affect men for years even after stopping the medication and may even be permanent. Indeed, up to 20% of people reporting persistent sexual dysfunction for six or more years after stopping the drug, suggesting the possibility that it may never go away.

Given the side effects of the current drug options, I encourage you to incorporate hair-friendly foods in your daily routine.

A randomized controlled trial investigates diet and psychological well-being.

“Psychological health can be broadly conceptualized as comprising 2 key components: mental health (i.e., the presence of absence of mental health disorders such as depression) and psychological well-being (i.e., a positive psychological state, which is more than the absence of a mental health disorder,” and that is the focus of an “emerging field of positive psychology [that] focuses on the positive facts of life, including happiness, life satisfaction, personal strengths, and flourishing.” This may translate to physical “benefits of enhanced well-being, including improvements in blood pressure, immune competence, longevity, career success, and satisfaction with personal relationships.”

What is “The Contribution of Food Consumption to Well-Being,” the title of an article in Annals of Nutrition & Metabolism? Studies have “linked the consumption of fruits and vegetables with enhanced well-being.” A systematic review of research found evidence that fruit and vegetable intake “was associated with increased psychological well-being.” Only an association?

There is “a famous criticism in this area of research—namely, that deep-down personality or family upbringing might lead people simultaneously to eat in a healthy way and also to have better mental well-being, so that diet is then merely correlated with, but incorrectly gives the appearance of helping to cause, the level of well-being.” However, recent research circumvented this problem by examining if “changes in diet are correlated with changes in mental well-being”—in effect, studying the “Evolution of Well-Being and Happiness After Increases in Consumption of Fruit and Vegetables.” As you can see below and at 1:37 in my video Fruits and Vegetables Put to the Test for Boosting Mood, as individuals began eating more fruits and veggies, there was a straight-line increase in their change in life satisfaction over time.

“Increased fruit and vegetable consumption was predictive of increased happiness, life satisfaction, and well-being. They were up to 0.24 life-satisfaction points (for an increase of 8 portions a day), which is equal in size to the psychological gain of going from unemployment to employment.” (My Daily Dozen recommendation is for at least nine servings of fruits and veggies a day.)

That study was done in Australia. It was repeated in the United Kingdom, and researchers found the same results, though Brits may need to bump up their daily minimum consumption of fruits and vegetables to more like 10 or 11 servings a day.

As researchers asked in the title of their paper, “Does eating fruit and vegetables also reduce the longitudinal risk of depression and anxiety?” Improved well-being is nice, but “governments and medical authorities are often interested in the determinants of major mental ill-health conditions, such as depression and high levels of anxiety, and not solely in a more typical citizen’s level of well-being”—for instance, not just life satisfaction. And, indeed, using the same dataset but instead looking for mental illness, researchers found that “eating fruit and vegetables may help to protect against future risk of clinical depression and anxiety,” as well.

A systematic review and meta-analysis of dozens of studies found “an inverse linear association between fruit or vegetable intake and risk of depression, such that every 100-gram increased intake of fruit was associated with a 3% reduced risk of depression,” about half an apple. Yet, “less than 10% of most Western populations consume adequate levels of whole fruits and dietary fiber, with typical intake being about half of the recommended levels.” Maybe the problem is we’re just telling people about the long-term benefits of fruit intake for chronic disease prevention, rather than the near-immediate improvements in well-being. Maybe we should be advertising the “happiness’ gains.” Perhaps, but we first need to make sure they’re real.

We’ve been talking about associations. Yes, “a healthy diet may reduce the risk of future depression or anxiety, but being diagnosed with depression or anxiety today could also lead to lower fruit and vegetable intake in the future.” Now, in these studies, we can indeed show that the increase in fruit and vegetable consumption came first, and not the other way around, but as the great enlightenment philosopher David Hume pointed out, just because the rooster crows before the dawn doesn’t mean the rooster caused the sun to rise.

To prove cause and effect, we need to put it to the test with an interventional study. Unfortunately, to date, many studies have compared fruit to chocolate and chips, for instance. Indeed, study participants randomized to eat fruit showed significant improvements in anxiety, depression, fatigue, and emotional distress, which is amazing, but that was compared to chocolate and potato chips, as you can see below and at 4:26 in my video. Apples, clementines, and bananas making people feel better than assorted potato chips and chunky chocolate wafers is not exactly a revelation.

This is the kind of study I’ve been waiting for: a randomized controlled trial in which young adults were randomized to one of three groups—a diet-as-usual group, a group encouraged to eat more fruits and vegetables, or a third group given two servings of fruits and vegetables a day to eat in addition to their regular diet. Those in the third group “showed improvements to their psychological well-being with increases in vitality, flourishing, and motivation” within just two weeks. However, simply educating people to eat their fruits and vegetables may not be enough to reap the full rewards, so perhaps greater emphasis needs to be placed on providing people with fresh produce—for example, offering free fruit for people when they shop. I know that would certainly make me happy!

How can we use sensory-specific satiety to our advantage?

When we eat the same foods over and over, we become habituated to them and end up liking them less. That’s why the “10th bite of chocolate, for example, is desired less than the first bite.” We have a built-in biological drive to keep changing up our foods so we’ll be more likely to hit all our nutritional requirements. The drive is so powerful that even “imagined consumption reduces actual consumption.” When study participants imagined again and again that they were eating cheese and were then given actual cheese, they ate less of it than those who repeatedly imagined eating that food fewer times, imagined eating a different food (such as candy), or did not imagine eating the food at all.

Ironically, habituation may be one of the reasons fad “mono diets,” like the cabbage soup diet, the oatmeal diet, or meal replacement shakes, can actually result in better adherence and lower hunger ratings compared to less restrictive diets.

In the landmark study “A Satiety Index of Common Foods,” in which dozens of foods were put to the test, boiled potatoes were found to be the most satiating food. Two hundred and forty calories of boiled potatoes were found to be more satisfying in terms of quelling hunger than the same number of calories of any other food tested. In fact, no other food even came close, as you can see below and at 1:14 in my video Exploiting Sensory-Specific Satiety for Weight Loss.

No doubt the low calorie density of potatoes plays a role. In order to consume 240 calories, nearly one pound of potatoes must be eaten, compared to just a few cookies, and even more apples, grapes, and oranges must be consumed. Each fruit was about 40 percent less satiating than potatoes, though, as shown here and at 1:45 in my video. So, an all-potato diet would probably take the gold—the Yukon gold—for the most bland, monotonous, and satiating diet.

A mono diet, where only one food is eaten, is the poster child for unsustainability—and thank goodness for that. Over time, they can lead to serious nutrient deficiencies, such as blindness from vitamin A deficiency in the case of white potatoes.

The satiating power of potatoes can still be brought to bear, though. Boiled potatoes beat out rice and pasta in terms of a satiating side dish, cutting as many as about 200 calories of intake off a meal. Compared to boiled and mashed potatoes, fried french fries or even baked fries do not appear to have the same satiating impact.

To exploit habituation for weight loss while maintaining nutrient abundance, we could limit the variety of unhealthy foods we eat while expanding the variety of healthy foods. In that way, we can simultaneously take advantage of the appetite-suppressing effects of monotony while diversifying our fruit and vegetable portfolio. Studies have shown that a greater variety of calorie-dense foods, like sweets and snacks, is associated with excess body fat, but a greater variety of vegetables appears protective. When presented with a greater variety of fruit, offered a greater variety of vegetables, or given a greater variety of vegetable seasonings, people may consume a greater quantity, crowding out less healthy options.

The first 20 years of the official Dietary Guidelines for Americans recommended generally eating “a variety of foods.” In the new millennium, they started getting more precise, specifying a diversity of healthier foods, as seen below and at 3:30 in my video. 

A pair of Harvard and New York University dietitians concluded in their paper “Dietary Variety: An Overlooked Strategy for Obesity and Chronic Disease Control”: “Choose and prepare a greater variety of plant-based foods,” recognizing that a greater variety of less healthy options could be counterproductive.

So, how can we respond to industry attempts to lure us into temptation by turning our natural biological drives against us? Should we never eat really delicious food? No, but it may help to recognize the effects hyperpalatable foods can have on hijacking our appetites and undermining our body’s better judgment. We can also use some of those same primitive impulses to our advantage by minimizing our choices of the bad and diversifying our choices of the good. In How Not to Diet, I call this “Meatball Monotony and Veggie Variety.” Try picking out a new fruit or vegetable every time you shop.

In my own family’s home, we always have a wide array of healthy snacks on hand to entice the finickiest of tastes. The contrasting collage of colors and shapes in fruit baskets and vegetable platters beat out boring bowls of a single fruit because they make you want to mix it up and try a little of each. And with different healthy dipping sauces, the possibilities are endless.