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Sunday, 25 September 2016

Animal Protein vs Plant Protein - the illusion of scale in diet epidemiology.

This graph appeared in Jason Fung's excellent Intensive Dietary Management blog here. I don't really want to disagree with Jason's statement that animal protein raises insulin more than plant protein, as I haven't looked into the evidence for that or what it means - I merely want to point out that this graph, and the paper it comes from, do not by themselves provide evidence that eating animal protein is associated with a higher risk of developing type 2 diabetes than eating plant protein.

The paper, by Sluijs et al, is titled "Dietary Intake of Total, Animal, and Vegetable Protein and Risk of Type 2 Diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL Study" and states
"During 10 years of follow-up, 918 incident cases of diabetes were documented. Diabetes risk increased with higher total protein (hazard ratio 2.15 [95% CI 1.77–2.60] highest vs. lowest quartile) and animal protein (2.18 [1.80–2.63]) intake. Adjustment for confounders did not materially change these results. Further adjustment for adiposity measures attenuated the associations. Vegetable protein was not related to diabetes. Consuming 5 energy % from total or animal protein at the expense of 5 energy % from carbohydrates or fat increased diabetes risk.
Diets high in animal protein are associated with an increased diabetes risk. Our findings also suggest a similar association for total protein itself instead of only animal sources. Consumption of energy from protein at the expense of energy from either carbohydrates or fat may similarly increase diabetes risk. This finding indicates that accounting for protein content in dietary recommendations for diabetes prevention may be useful."

Leaving aside the implausibility of the finding for the moment, there's an inconsistency in this abstract. If vegetable protein isn't "related to" diabetes, why is total protein a problem?

I knew from reading Song et al recently that the quartiles for vegetable protein actually represent quite small amounts. In the graph above, the upper quartile of vegetable protein is eating 33g/day, while the lower quartile of animal protein is eating 35g/day. So if you want to compare similar amounts of these proteins, you need to compare upper quartile vege with lower quartile animal, and they have exactly the same association with diabetes. And total protein (meat and vege combined) actually had a stronger association with diabetes than animal protein (1.67 in model 3, vs 1.58 for animal protein).

In real life, most people were eating both sorts of protein. Across the animal protein quartiles in Table 1, vegetable protein stayed very constant (people ate much the same amount of wheat). Unfortunately, there is no baseline data that tells us how much animal protein the quartiles of vegetable protein ate.

But let's take a common-sense approach to this data. Model 3, which I cited earlier, isn't adjusted for BMI and waist circumference. The highest protein quartile reports eating fewer total calories than the others, but has significantly greater BMI and waist circumference. And when these are adjusted for (Model 4, Table 2), voila, the association between protein and diabetes disappears from the quartile calculations; only the per 10g association remains. And this, though small, is greater for total protein (1.16) than for animal protein (1.13).
Amount of total protein across quartiles is 64g, 72g, 79g, and 88g. This range hardly seems excessive. Why it would be associated with diabetes at all is, frankly, a mystery. And what would happen if this population ate 64g, 72g, 79g, or 88g of plant protein is completely unknowable.

EDIT: some afterthoughts

The abstract of this paper only reports the completely unadjusted HRs. That is, not even age or sex adjusted. "Attenuated" really means "Disappeared".

The upper protein quartile ate fewer calories, were more active, and had significantly higher BMI (2 points) and waist circumference (4cm).
In other words, either this study breaks the sacred rules of diet thermodynamics, or diet was not reported accurately.
The quartile who ate least vegetable protein had to have eaten more animal protein than the others, just to survive. So why is their risk of diabetes so low?


John Velden said...

Good stuff.

I am certain you could find a great number of body builders who have much higher protein intakes and virtually no chance of developing T2DM compared to comparative BMI population.

Key difference being small waist to height/weight = low visceral fat and higher lean mass.

Are you aware of visfatin?

George Henderson said...

Thanks John,

as far as I know, though I haven't looked at the data for a while, RCTs where protein is increased and CHO reduced (or rather feeding studies, because it's almost impossible to significantly boost protein for long in RCTs) don't predict any harm.

I think a missing variable in EPIC is height. Whether someone's protein intake is right or whether it's possibly high because they're overeating in general is surely easier to guess if you know an individual's height.

I'm guessing that visfatin is mostly a fasting state regulator, hence is suppressed by both insulin and somatostatin?