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Charmed Substances
It’s been thirteen years this month since John Ioannidis published an article in PLoS Medicine entitled Why Most Published Research Findings Are False. Arguably, this article kicked off interest in the replication crisis. He’s back again, this time in JAMA, to warn us to be skeptical of nutrition research, as if we needed that warning. “The field needs radical reform.”
The majority of nutritional advice advocating the consumption or avoidance of specific foods (superfoods, killer foods) is based on epidemiological studies. Ioannidis notes that “…almost all foods revealed statistically significant associations with mortality risk.” Yet the causal connection is rarely established even as dietary recommendations are made based on such studies. Taken at face value, the results lead to unlikely conclusions that fail the sniff test:
Assuming the meta-analyzed evidence from cohort studies represents life span–long causal associations, for a baseline life expectancy of 80 years, eating 12 hazelnuts daily (1 oz) would prolong life by 12 years (ie, 1 year per hazelnut), drinking 3 cups of coffee daily would achieve a similar gain of 12 extra years, and eating a single mandarin orange daily (80 g) would add 5 years of life. Conversely, consuming 1 egg daily would reduce life expectancy by 6 years, and eating 2 slices of bacon (30 g) daily would shorten life by a decade, an effect worse than smoking. Could these results possibly be true?
One obvious logical error is that “much of the literature silently assumes disease risk is modulated by the most abundant substances; for example, carbohydrates or fats.” Since foods consist of dozens or hundreds of chemical constituents, this is naive. Even “seemingly similar foods vary in exact chemical signatures.”
Ioannidis observes that there is a precedent for such foolishness.
For decades, genome linkage scans struggled to link large chromosomal areas to disease risk. According to current knowledge, these previous efforts were doomed: each chromosomal area contains thousands of genetic variants. Linkage scans resulted in numerous articles, but limited useful information.
In short, the early work was bunk, and for similar reasons. There may be more wisdom about nutrition in a 45-year-old movie.
My favorite charmed substance is the egg. What are yours?
Published in Healthcare
The egg is mine too.
I laughed when you wrote the part about bacon and eggs shortening life span; my Dad is 94,and eats 2 eggs and 4 slices of bacon every single morning. He is sharp as knife and doing great; most days, my Mom cooks his breakfast for him, but this morning he cooked it himself because she slept in late :)
Bacon grease.
mmmmm Bacon Grease
If modern nutritionists were right, mankind wouldn’t have survived five minutes, let alone ice ages. Or in the desert. Or all the other conditions we’ve obviously survived.
And my Gamammy wouldn’t have lived to be 89 with all her mental faculties after eating bacon and biscuits with redeye gravy every day.
Just gonna leave this here…
My favorite charmed substance is alcohol.
My local news show reports on one of these nutritional “studies” almost every night. I pick and choose among those I want to believe. The other evening they reported on a study that concluded that any alcohol, even one drink a week, would shorten your life.
I choose not to believe that one.
My husband has lately tried intermittent fasting. He can bore you stupid on the rules – how long you go between dinner and your next meal blah blah blah.
(great results by the way – he looks fabulous)
I finally paid attention one day while he was explaining it to my sister. “So basically you’re skipping breakfast? I’ve been doing that since the Nixon administration.”
Anyway, there’s things I like and things I don’t. All the money in the world can’t get me to eat stuff I don’t like and I don’t have the self control to avoid the things I like. Lucky, I’m too lazy to cook the stuff I like.
My superfood around noon everyday is half a mug of half and half and a tablespoon or two of Kerry Gold butter. Nuke it for a couple of minutes, froth it and fill with coffee. It’s a white trash version of Bullet Proof coffee that my brainiac niece told me about years ago. I’m full till dinner, when I eat whatever someone else cooked.
Grew up on oleo because butter is bad for you. Now? No margarine in my house – lots of butter, though.
Could I be suicidal?
Only when you ate oleo!
Fasting is all the rage now. There may be something to it, given our hunter-gatherer roots. On the other hand, there’s been plenty of time for evolutionary adaptation since we were nomadic herdsmen, unless you’re Bakhtiari or something. I have no trouble going 20 hours without food.
I’m 59, overweight, and ride a bicycle for exercise.
In another 30 minutes or so (before 6 AM), I’m heading out for a nice 25 mile ride (accidentally did a 30 on Sunday morning).
Generally, when I’m riding, the only people who pass me are the guys on $3000 bikes, wearing spandex, in pelotons.
I eat… just like they tell me you shouldn’t.
Hmm, what is redeye gravy? Is that just another name for a Bloody Mary? I can go for some bacon and a bloody mary this morning.
I came to fasting halfassed and because of Lent. What I discovered even in my undoubtedly inefficient experience was that I was eating way too much food. The fasting actually turned out to be not much of a sacrifice after about a week of doing it (and not bothering about it on the weekends). I was able to get by with much less, and my cravings for bad stuff weren’t as frequent or as strong. Inches melted off and have mostly stayed off even when I’m not consciously fasting during Lent.
Now, I’m not sure what I’ll do next Lent since this clearly isn’t much of a sacrifice or penance anymore.
On January 1, for the past few years, I’ve started a three-day fast, drinking only water. Twice I’ve fasted for four days. I rarely feel hunger past the first eight hours or so.
I do it for the kicks.
I usually feel pretty good after a fast.
Butter.
I still remember a great Letterman bit from a long time ago. It was one of his Top 10 lists:
Top 10 Stories of 2005 (or whatever was 20 or 25 years in the future.)
#5: Oat Bran: The Silent Killer
The biggest food problem in half the world is the lack of it. In the other half it is too much of it.
When I lived in the San Francisco bay area, I never felt all that well. Then we moved up north to Lake County in late 2005.
Immediately I felt better. But why?
At the time, my spouse was told by Kaiser that he was fine and his medical problems were in his head. In actuality he was suffering from extremely high blood sugar levels and was not pleasant to live with. This remained the case until two months later when a Kaiser doctor realized that during the initial $ 4K worth of blood tests, his blood glucose levels had never been examined.
But despite all this craziness, I felt very good. I finally realized it was the air. Lake County was listed as having the second cleanest air in the country. All my years of periodically living on brown rice and of fasting and of trying this cleansing lifestyle or that one meant nothing and delivered nothing, because the problem was air quality.
Of course now our lovely Northern Calif rain forest has been plundered for the sake of the vineyards. This summer much of what remained has been burned up. So it may be we will need to leave the area as the air is not going to be anything like it once was. But it is interesting how in our search for good health we punish ourselves in terms of food when I imagine what many people need is oxygen and clean air.
I think it is also a mental health issue. A brain without sufficient circulation and oxygen is having a hard time functioning optimally. That’s why people with heart issues suffer depression and irritability so often.
Red Meat Consumption and Mortality: Results from 2 Prospective Cohort Studies.
Egg consumption and the risk of type 2 diabetes mellitus: a case-control study.
As the science of nutrition grew, our health started going backwards, heart attacks became common, cancer cases grew, and Diabetes and Alzheimer’s rates skyrocketed. All the while we grew fatter and fatter, trying one low fat low calorie diet after another. I see people 100 lbs overweight buying diet soda and low fat cookies, they’re listening to the “experts” after all, they should be thinning down like crazy. instead they get larger, the diseases start adding up, limbs are cut off, and eventually their body shuts down and they die. These are lawyers, engineers, educated people with families. This is not a matter of simple will-power and it’s insulting to these folks to say that. I don’t believe a word a nutritionist tells me. The lies put forth by Ancel Keys was responsible for the horror show that is the American food pyramid, thanks for the help big government!
If the nutrition industry is right, it should be easy to slim down and get healthy. But they’re wrong, dead wrong, which is why conventional diet advice has a 95% failure rate. What other thing in our lives fails 95% of the time and is still given any credence whatsoever? Here’s one question asked by a man much smarter than I am, a single question that really clarified things for me. Why are there fat doctors?
Nutrition research isn’t easy, and good research is unlikely to lead to patentable products.
Macronutrient choices have broad epigenetic effects. The ill advised low fat/high carb diet promoted for decades by the American Dietetic Association and American Heart Association has already caused massive mortality and morbidity and is likely to have repercussions for generations, most of them probably not good.
Some of the effect is due to macronutrient effects on the microbiome. This is an adaptive response: Our generation time is decades. Bacteria do it in seconds to minutes. Bacterial ecosystem change and, in response to long term macronutrient changes, microbial evolutionary change, gives us part of our adaptive response to dietary change.
Phytochemicals are another driver of epigenetic effects. Turmeric, and curcumin (one of its active components) is a trendy herb. Curcumin has been touted as an “antioxidant” with a “high ORAC value.” The real action takes place at the subcellular level. For example, curcumin has been shown to be neuroprotective in the case of injury to nerves. Here’s one of the mechanisms:
That’s one freaking activity of one freaking component of a complex plant part consumed fresh or dried (different activities) on a regular basis by many millions of people. So let’s figure out ways to dose curcumin to get really high blood levels. Right?
Well, not so fast. Basically, curcumin is one of a group of chemical compounds, Reactive Oxygen Species (ROS) and ROS initiators we don’t want running wild in our bodies though we use them as signalling compounds. Curcuma longa puts curcumin and its friends into its roots to keep critters from eating the roots before the plant has a chance to sexually reproduce, or to keep the roots alive long enough to send out new shoots and try sex again. Our GI tracts are set up to keep curcumin out. Sure, our gut microbiome seems to transform the root into compounds we can safely use, and we do absorb a little curcumin, package it for safe transportation and then allow it to be seen by the PERK system which, in appropriate circumstances it turns on the way a wild ROS running around from some acute damage would. Only it does it in a modulated fashion, and the Nrf2 response is hormetic, meaning a little, not much action, a sweet spot in the middle, and then downregulation from high doses.
And that’s one freaking activity of one freaking component…
We evolved eating whole foods. We should continue to do so. IMHO a lot (of the benefits of a gluten free diet in the early (before gluten free junk food days) was that the way to eat gluten free was to eat. real. food.
These are excellent examples of the kind of studies Ioannidis has in mind: correlation without causation and the presumption that the most abundant substance in a food modulates disease risk. The red meat study also suffers from low significance (hazard ratios 1.2 or below) while the egg study suffers from small-N (small number of subjects). Congratulations; both papers hit the Ioannidis trifecta.
Note how the smaller the study, the higher the hazard ratio/odds ratio. This goes to the replication issue: many effects decrease in size or disappear upon further scrutiny. From the PLoS paper:
But the beat goes on.
The experts never advised people to guzzle soda pop and eat crackers. They wanted people to consume a so-called “low-fat” diet (where fat calories are 30 percent or less as a percentage of total calories). But the government wanted people to achieve this by eating more whole fruits and whole vegetables, not a bunch of processed food.
So, now people are saying, “The experts made us fat” and are essentially giving up on being healthy.
It would be better if people studied the scientific literature on nutrition over at PubMed.com. There are thousands of scientific studies on nutrition. Some are short term and only look at bio-markers like fasting glucose and serum cholesterol. Others are long term and track disease and death rates.
Ignoring science isn’t a good idea. The law of gravity exists for the guy who jumps off a 20 story building even if he threw his physics textbook in the trash.
As for correlation doesn’t mean causation. This is certainly true.
However, as a doctor, I bet you advise your patients to not smoke cigarettes or to quit smoking if they currently smoke.
All of our scientific studies showing the harmful effects of smoking are observational studies. They are not double blind randomized intervention trials where we tell 50,000 people to smoke 3 packs of cigarettes each day and tell the other 50,000 people to not smoke.
You are a doctor. Are you telling your patients to just eat themselves into a coma? Of course not!
Dr. Lorentz,
I could, if I wanted to spend the time, post a hundred links to scientific studies on the link between dietary patterns and mortality/morbidity. And each of these scientific studies would be open to criticism in terms of study design, controlling for confounding variables and on an on.
But what an objective person should do is determine the weight of the evidence.
You can’t do that if you take the position up front that the all of the studies are flawed and therefore meaningless.