What's a 'healthy diet' anyway?

A nutrition advisory panel is convened by the US Department of Agriculture every five years to review recent research in the field, make sense of it, and offer recommendations about what Americans should be eating for optimal health.  Those food pyramids, MyPlate, decades of advice to limit our cholesterol, saturated fat and salt intake?  All the work of these panels of experts who scoured the data and told us what it meant.  And as a result, from the 1960's onward, good, conscientious people reduced their cholesterol intake, took the salt shaker off the table and the whole milk and butter out of the refrigerator, cattle were bred to be leaner, eggs were banned from breakfast, low-salt and low-fat processed foods appeared on the shelves, and heart disease death rates ... continued to fall.

Deaths due to diseases of the heart (United States: 1900–2006). Circulation.2010; 121: e46-e215

Now, according to numerous news accounts, including here at the Washington Post, after more than 50 years of anti-cholesterol, anti-fat expert advice, the current advisory panel is reportedly poised to recommend that we need no longer need to limit the amount of cholesterol we eat, nor worry about our salt intake.  Bring on the shrimp, the lobster, the eggs, the meat, banish the guilt!

Oh, wait.  Hold on a sec.  Let's go back to those falling heart disease rates.  I remember one of the first lectures I heard as a new grad student at the University of Texas School of Public Health in the late 1970s, given by heart disease epidemiologist Reuel Stallones, Dean of the school.  His point was that rates had been falling since the 1960's and epidemiologists had no idea why.  He systematically destroyed every argument then (and now) current that might explain the rise and fall of heart disease death rates -- changing diet, decreased smoking, de/increased exercise.

In fact, he made the same case in 1980 in Scientific American in an article called "The Rise and Fall of Ischemic Heart Disease".  (The terms ischemic heart disease, coronary heart disease, and arteriosclerotic heart disease are more or less interchangeable, according to Stallones.)

In the U.S. the death rates attributed to heart attack and other results of the obstruction of the arteries that nourish the heart have fallen since the 1960's. Why they have is not understood.

Here's Stallones' graph of heart disease death rates, from 1900 to 1980.  I can't explain why deaths are still rising in the above graph in the 1950's, but falling in this graph; presumably this has to do with differing classifications of deaths due to heart disease.  Anyway, here rates rose rapidly starting in 1920 and then began to fall in the 1950's, steeply in the 1960's.

Stallones, Scientific American 354(5); 53-59

Here's another graph showing the decline more or less in line with Stallones' data, from a 2000 paper in Circulation.

"Death rates for major cardiovascular diseases in the United States from 1900 to 1997. *Rates are age-adjusted to 2000 standard." Source: Circulation, Cooper et al., 2000

As Stallones wrote, "Plainly a sustained decline in the death rate for ischemic heart disease commands attention and calls for explanation." And, he backs up to ask not only why the fall, but why it was that heart disease mortality began to rise so quickly in 1920, particularly among men.  Whatever explains the decrease must also explain the increase.

Smoking began to rise after World War 1, which fits the rise in heart disease mortality, and began to decrease from the mid-1960's or so, which fits the decrease.  But such an explanation would assume no latency period between beginning to smoke and its effects on heart disease.  And, middle-aged men quit smoking at higher rates than women, and this is not, as Stallones said, in concordance with the pattern of decline in heart disease mortality.  Treatment isn't an effective explanation either, because incidence rates -- new cases -- followed the same pattern as mortality.

He concluded,

In summary, four major variables are known to be associated with the risk of ischemic heart disease in individuals. Among the four, hypertension does not fit the trend of the mortality from ische­mic heart disease at all; physical activity fits only the rising curve, serum choles­terol fits only the falling curve and only cigarette smoking fits both. In no case is the fit as precise as one would like. This raises doubt that any of the factors is a fully satisfactory explanation for the variation in mortality.

So, in sum, as of 1980 epidemiology had no explanation for the rise and fall of heart disease mortality rates.

And epidemiology still can't tell us what causes heart disease, or predict who'll get it.  So, apparently we'll soon be told that we no longer have to monitor our cholesterol intake, and there's a lot of talk about fat consumption not being linked with heart disease anymore, and it's not clear whether obesity or hypertension are actually causal.  At least smoking is probably still a problem.

It's clear from the rise and fall of death rates through the 20th century that genes aren't going to be the major explanation because genes can't explain the spike in the 1920's and the fall 40 years later.  That experience also makes it clear that we can't predict environmental changes (or, often, even figure out what they were in hindsight) that might be associated with risk, and thus we aren't going to be able to predict the future, despite the claims of precision medicine advocates.

Stallones suggested that heart disease mortality data might indicate a single environmental cause to explain the rise and fall of death rates, but found reasons to argue against each of the most obvious ones.  Could the cause have been inflammatory?  If so, that would reinforce the idea that predicting future environments and causes is not going to be possible.

And, if there was a single cause, it's curious that our reductionist approaches, with large carefully designed samples and sophisticated statistical analysis, were unable to identify it, because that's what they are widely thought to be best at.  This makes it more likely that heart disease in populations has multiple causes.  And in fact every heart attack is unique, because no two people eat the same things, do the same amount of exercise, suffer the same infectious diseases, and so on. So maybe the very word 'cause', and the very approach (statistical), both of which assume some regular, replicability properties, are not being appropriately conceived.  This is a subject we'll discuss next time.....

"Experts" responding to the coming cholesterol recommendations have said that we still need to eat a healthy diet.  But when we still have no idea what's unhealthy, it's hard to know what is.

When good cholesterol isn't

First we were told to lower our cholesterol.  This was back in the 1960's, when the first results of the then major new epidemiological project, the Framingham Heart Study, were released.  If the Framingham Heart Study taught us anything, it was that high cholesterol was a major risk factor for heart disease.  So we all started eating oat bran and granola and eschewing beef.

And then,  in the 80's we were told that it's not all cholesterol we need to be concerned about, that there's a good and a bad cholesterol, and we should be raising one and lowering the other.  How?  Eat healthy -- no eggs, no butter, no red meat.

Egg in a spiral eggcup; Wikimedia

And then it turned out that the people living on the Mediterranean had known all along what eating healthy is -- everything in moderation, except for olive oil and red wine, two foods that we should all be consuming more of.  From the Mayo Clinic:

Key components of the Mediterranean diet

The Mediterranean diet emphasizes:

• Eating primarily plant-based foods, such as fruits and vegetables, whole grains, legumes and nuts
• Replacing butter with healthy fats, such as olive oil
• Using herbs and spices instead of salt to flavor foods
• Limiting red meat to no more than a few times a month
• Eating fish and poultry at least twice a week
• Drinking red wine in moderation (optional) [not clear which is optional here, the red wine or the moderation]

So, follow these new rules and live as long as the Italians do.  Somewhere along the line, though, eggs were taken off the list of forbidden foods, and the usual American replacement for butter, margarine, turned out to have transfats which are bad for you, and anyway, saturated fats -- the stuff that's hard at room temperature, like margarine -- aren't good for you in any form.

And it turns out it's hard to lower your bad cholesterol with diet.  So, maybe try doing it with drugs.  Statins are good.  Indeed, the more people taking statins the merrier.  But whether statins are lowering all the risky components of LDL is still open to question (e.g., this paper).  Statins are designed to control circulating lipids (fats), which confer heart-disease risk. They inhibit an enzyme called 'HMG-CoA reductase' which is expressed in liver cells as they produce cholesterol from raw ingredients and secrete it into the blood stream. Lower enzyme activity, lower circulating lipids. Whether this is what they are doing is still not entirely clear, however.  There is evidence that statins may be reducing inflammation in irritated arteries and veins, which may be what reduces risk of heart disease rather than any effect on cholesterol.  Perhaps heart disease is an inflammatory process more than one affected by cholesterol levels, after all.

Oh, but then a rather confusing study was published last year, showing that Australian men who switched polyunsaturated fat for the saturated fats in their diet did in fact lower their LDL, but they also were more likely to die of a heart attack than those who hadn't changed their diets.  Indeed, most people who have heart attacks don't have high LDL.

But ok, assuming the cholesterol model of heart disease, along with lowering LDL, it would make sense to also raise your HDL, the good cholesterol.  But now it turns out that it's possible to have too much of a good thing.  A new paper in Nature Medicine (paywall) reports that while HDL normally should keep arteries clear and protect against heart disease, in arterial walls, HDL acts quite differently from circulating HDL, and can lead to arterial blockage and heart attack.

The BBC reports that the authors say people should still "eat healthily".  But, what this means, when the definition of a healthy diet keeps changing, and today's healthy diet can be the cause of ill health, is not at all clear.

Everything in moderation seems good to go with.

Fruit and diabetes - a cocktail of results

Do you remember how much fresh fruit you ate last year?  Or, ok, in the last three months?  Or even last week?  What about differentiating between fruits; strawberries vs cantaloupe vs blueberries?  And how many??

We ask because a new study published in the British Medical Journal ("Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies," Muraki et al.), that's getting a lot of news play, reports that eating a serving of blueberries at least three times a week protects against type 2 diabetes (t2d).  Blueberries are best, but grapes and raisins are second best and apples and pears are third.  Cantaloupe, on the other hand, seems to be a risk factor, as does drinking your fruit as juice rather than eating it whole. 

The study looked at food questionnaire data from a ton of people; "66 105 women from the Nurses’ Health Study (1984-2008), 85 104 women from the Nurses’ Health Study II (1991-2009), and 36 173 men from the Health Professionals Follow-up Study (1986-2008)."  So the data must be robust--yes?

Food questionnaires are a well-established tool for eliciting dietary information, and they are used all the time.  But they are also notoriously unreliable, for reasons that are easy to understand; it's really hard, first, to think in terms of standardized portion sizes and, second, to remember how often you eat a food, particularly if it's seasonal.  And there's the subtle possibility of responder bias--knowing what the study is looking for.

An anecdote, for what it's worth.  My mother has been filling out food questionnaires as a subject in the Nurses' Health Study for decades.  I remember her reaction to the first one she was asked to complete because I was a graduate student in public health at the time, learning in epidemiology classes about state-of-the-art tools like diet surveys, so the fact that they might be seriously flawed was an eye opener.  Suffice it to say, she did a lot of guessing. It's not good science to extrapolate from a single case, I know, but the following, from the paper, suggests it might actually be valid in this instance.

The food frequency questionnaires were validated against diet records among 173 participants in the Nurses’ Health Study in 1980 and 127 participants in the Health Professionals Follow-up Study in 1986. Corrected correlation coefficients between food frequency questionnaire and diet record assessments of individual fruit consumption were 0.80 for apples, 0.79 for bananas, and 0.74 for oranges in women, and 0.67 for total whole fruits, 0.76 for fruit juice, 0.95 for bananas, 0.84 for grapefruit, 0.76 for oranges, 0.70 for apples and pears, 0.59 for raisins and grapes, and 0.38 for strawberries in men.

So portion size and frequency are hard to remember, and that's a problem.  But maybe there's something else influencing the results of this study.  We're betting it's a lot easier to remember when you consume something every day, like a glass of orange juice, or banana on your cereal, but harder to remember when you have something that is more likely to be only seasonally available, like plums, or apricots.  This could explain why there seems to be such variation in the accuracy with which people remember different fruits and juice.

But probably more significantly, we'd bet that people who are already at lower risk of t2d because they exercise, or watch their diets, are thinner and so forth, are the same people who include more fruits and vegetables in their diets.  So, blueberry consumption may be indicative of a low-risk lifestyle rather than nutritional components that protect against t2d.  And this is what was found.

In all three cohorts, total whole fruit consumption was positively correlated with age, physical activity, multivitamin use, total energy intake, fruit juice consumption, and the modified alternate health eating index score, and was inversely associated with body mass index and current smoking. Whole fruit consumption was associated with an increased probability of using post-menopausal hormones in the Nurses’ Health Study and with a reduced probability of using oral contraceptives in the Nurses’ Health Study II.

The investigators corrected for these correlations -- that is, essentially asked the question, "In the lower risk group in the study, are those who eat X fruit at even lower risk?".  These adjustments weakened the associations, which isn't surprising, and in fact adjusting for other things like gestational diabetes or cancer also attenuated the associations.  But they still found that blueberries, raisins, grapes, pears and apples were correlated with lower risk, and cantaloupe with higher.  Methodological questions aside, could blueberries really be protective against type 2 diabetes, but not cantaloupe?

The idea is that fruits are rich in fiber, antioxidants and phytochemicals, all of which are presumed to be protective.  But, some are sugary, which might instead be a risk factor.  Results of studies of the role of specific fruits in risk of t2d have varied, with different fruits sometimes implicated in risk and sometimes with protection. "In eight previous prospective studies, the association between total fruit consumption and risk of type 2 diabetes was examined, and the results were mixed."

And, the study found that association of risk with glycemic load was inconsistent, and varied by cohort; "...a significant, inverse association was found in the Nurses’ Health Study, but not in the other two cohorts."  Indeed, this wasn't the only outcome that varied by cohort.    

In the Nurses’ Health Study II and Health Professionals Follow-up Study, banana consumption was associated with a lower risk of type 2 diabetes, whereas in the Nurses’ Health Study a non-significant positive association was found. The association for strawberry consumption was significantly positive in the Health Professionals Follow-up Study but was non-significant and inverse in the Nurses’ Health Study.

The authors conclude about their findings that most, but not all, "were quite consistent among three cohorts." We would suggest, however, that despite the large cohort sizes, methodological issues, particularly recall issues with the food questionnaires, are significant enough that you shouldn't make your decisions about which fruit to put on your cereal based on these results.

The issues are mainly examples of data (recall) error, and confounding:  so many factors go together in this society, bombarded by health-advice 'news' (and 'scientific' reports like the blueberry study), that it is very difficult to disentangle them.  Usually, then each individual factor has low effect on its own.

You can make your own judgement about whether these kinds of study are worth reading, publishing, or funding.  You might, for example, classify them with GWAS and other 'Big Data' studies, and say that when many different factors are at play, with individually minor effects, and people know what the latest advice is and adjust their behavior (often subtly) accordingly, that we're just asking to be confounded when we ask about the wisdom of exposure to individual factors.

Unless, of course, you're from New England and you're partial to blueberries.  In that case: go ahead and dose up!  Otherwise, read something more worthwhile than massive, inconclusive, weak-factor studies.