## Thursday, November 21, 2013

### Nuts and longevity: correlation isn't causation

For most people, their death is an unfortunate career move. It's been observed that children are born at most 10 months after their fathers' death and the IRS only collects the taxes for about 12 months after the death. Richard Feynman pointed out that he wouldn't like to die twice because it's so boring.

The eternal president and the dear leader in the representative halls of North Korea.

But there are exceptions. Kim Il Sung (1912-1994) was kind of promised to become an eternal president after he dies; the law was adopted in 1998. However, the Korean leader still liked some old-fashioned benchmarks to measure when the life ends, too. We just learned that he ordered his doctors to prolong his life to 120 years. They failed but 82 years isn't bad.

Maybe the doctors should tell him to eat nuts every day. According to a Harvard study in New England Journal of Medicine,
Association of Nut Consumption with Total and Cause-Specific Mortality (Ying Bao et al.)
(see also a NEJM quick take animation), the probability of a heart disease-related death during a 30-year-long period dropped by 29 percent and the probability of a cancer death dropped by 11 percent among those who were eating nuts more or less every day – leading to something like a 20-percent average from these two causes.

It seems to me that this difference is huge, given the large sample – 119,000 people were tracked. Up to nonlinearities (and the neglected other causes of death than these two), you could say that the "rate of death" was lower by 20 percent as well which may mean that the life of nut eaters should be almost 15 years longer. This is a vastly higher difference than the statistical fluctuation you expect from such a large sample.

Purely numerically, by a mindless calculation, I would bet that the statistical significance of this finding is much greater than 5 standard deviations. Nuts are probably good for you. But I still think that there is a potential catch:
Correlation isn't causation.
Well, more precisely, a statistically significant correlation almost certainly proves "some kind of causation" but it may be a different causation than one naively expects. As far as I understand, the people were not made to change their habits. Why is there this correlation between the reduced death rate and the consumption of nuts?

Nuts are probably healthy.

But I believe that there is an alternative explanation that was arguably not given a sufficient attention:
Healthier people love to eat nuts more than the less healthy people do.
This hypothetical relationship may be interpreted as a categorization of people's DNAs that affects their whole lives; but it may also be interpreted as a time-dependent quantity. In the first case, the "genetically more long-lived" people just have the tastes that attract them to nuts. In the second case, it doesn't even have to be about genetics, but it may be that when the people lose their attraction to nuts, it is a symptom of their getting ill or less immune which makes an early death more likely.

Moreover, I have a feeling that this concern applies to much of the medical research. The actual causal relationship may often be the opposite one to the causal relationship that is being immediately extracted. In some cases, the right explanation of the correlation between A and B may be more complex – there may be another factor, C, that causes both A and B (or makes them more likely) which is also enough for a correlation between A and B.

There are TRF readers who are close to medicine or life sciences. Let me ask you: Do the researchers actually realize this potential loophole? Is this loophole being ruled out in much of the research that uses a correlation to prove a causal relationship?

Thanks.

How Jim Parsons would behave if he were not expected to resemble a string theorist.

Along with biases and a lower required statistical significance, this is one of the major reasons why I intuitively tend to find much of the medical research saying "XY is good or bad for you" somewhat untrustworthy but maybe I should be more welcoming.

1. In my average long life I have seen medical "fads" come and go so I am always dubious about medical claims of goodness.

The one that has stuck with me was the high cholesterol of anything back when they found the correlation of heart disease and cholesterol. Then ten years after my father died they came up with the good cholesterol that could clean up after the bad cholesterol :(. I still regret my rationing him the clams I gathered from the sea, because the doctor had said it was bad for him. Now they say all sea food has good cholesterol!

2. Hm, eating too many nuts only increases my coupling constant with the second Higgs that is lurking somewhere, and the resulting effects are not exactly what doctors would call healthy ... :-/

So what is going wrong here ...?

3. The medicine research had to be really primitive and useless when they were not paying attention to the "types" of the cholesterol. I hope that they have it right now but if it were deeply incomplete once, it can be deeply incomplete again.

4. LOL, not sure whether this is serious but the nuts generally tend to bring some "good fats" only.

5. I would guess the benefit comes from what the nut-eaters were NOT eating. It's unlikely they were sitting down to a meal of nuts - much more likely nuts were being used for snacks, replacing chips, crisps, crackers, etc. That means protein and fat were being substituted for carbohydrates, which (contrary to almost all 'official' advice) has a demonstrated health benefit. Partial evidence for this is presented in the surprisingly good NEJM animated segment, which noted that "compared to non-nut eaters, they were health nuts", i.e., exercising more, weighing less, etc. (Interestingly, the nut-eaters drank more alcohol than the non-nut eaters.)

I agree that it is very hard to tease out the exact causation in such studies. Was it the exercise, and those who exercise are more interested in losing weight, and therefore eliminated the junk food snacks? Perhaps, but conventional wisdom would advise those who are exercising more to fuel their exercise with carbohydrates. Food for thought ;-)

6. ANY nut consumption had this claimed effect, including peanuts that are in fact legumes. Identify the common causality - more studies are needed (forever if it is confounded variables). Zajc, below, has it nailed. Hydrogen cyanide ruins the taste of tobacco, a classic trace detection tactic. What about nuts?

7. Lubos, being that chemistry is a very well understood subject, shouldn't we try to demonstrate these kinds of hypotheses without statistical studies? Can't we just say that if you put food X in your body it will cause reaction Y, which is good for body part Z? EX: nuts have linoleic acid and many other things that are good for your heart for chemical reasons.

8. Chemistry is relatively well understood, but biology isn't when it comes to subtle effects of diet, environment and genetics!

9. My understand is that generally an effect of less than a factor of 1/2 less or 2 more are generally considered unimpressive. The "medical" literature is literally teeming with stuff like this, almost all of which is wrong just from inconsistency.

10. Even without the cigarettes smokers as a group would,be less healthy than non-smokers because emotionally and physically unsound individuals are more apt to smoke cigarettes. Nonetheless, evidence shows that starting to smoke is harmful and quitting is beneficial even if smoking is less harmful than pure longevity/smoking correlations would suggest.

Of course these correlations are generally unconvincing but I, too, am astonished at the quantitative result of the nuts-consumption study. I cannot easily conceive of any dietary preference that would fully account for the magnitude of the result. I do like nuts and intend to eat more of them.

11. I too am suspicious about what ELSE you are eating (and drinking) besides nuts! ;-)