u/SerotoninSyndr0m3

The PURE study [1] is a observational cohort study involving 150k people across several countries which seems to strongly suggest higher protein and lower carb intake produced better health outcomes. Seems convincing, right?

Here's why your doctor is probably skeptical:

It's an observational, non-intervention study. No, I'm not using "correlation =/= causation" as hand waving. It's a serious fundamental weakness of the study design with clear evidence:

In PURE, high carbohydrate intake and low fat intake strongly correlate with poverty, particularly in low- and middle-income countries where refined carbs are the cheapest available calories.

Critics argue that the observed association reflects the broader health consequences of poverty, including reduced access to healthcare, clean water, sanitation, and medications, rather than a direct dietary effect.

The authors attempt to control for this effect by stratifying results by income, but they themselves admit "high consumption of carbohydrate and low consumption of animal products might simply reflect lower incomes; residual confounding as a potential reason for our results cannot be completely excluded."

PURE relied on country-specific food frequency questionnaires given at baseline only. This is a problem because:

Dietary intake was measured only once at baseline, and changes during the median 9.5-year follow-up could not be captured, likely weakening observed associations.

The study could not distinguish refined from whole-grain carbohydrates!!! we all know that cheap carbs are refined and have a horrible glycemic index, while you can eat expensive whole-grain carbs all day and hardly raise your blood sugar. The majority of carbs recorded in this study are refined, especially in low-middle income countries.

A systematic review of FFQ validity found median correlation coefficients of only 0.37–0.42 compared with reference methods, indicating substantial measurement imprecision. [2]

The study's findings on sodium are completely and demonstrably wrong. The study estimated sodium intake from a single fasting morning spot urine specimen using the Kawasaki formula, rather than the gold-standard multiple 24-hour urine collections.

The Kawasaki formula incorporates age, sex, body weight, and urinary creatinine. These variables themselves are independently associated with cardiovascular risk, confounding the sodium-CVD relationship.

A validation study using PURE China data concluded that "all formulae-led estimates from spot urine collections have high error rates: both random and systematic," and recommended studies not use spot urine samples to assess salt intake in association with health outcomes. [3]

A landmark 2022 NEJM study pooling six cohorts with multiple 24-hour urine collections (the gold standard) found a linear dose-response relationship between sodium intake and cardiovascular risk, with no J-shaped curve, directly contradicting PURE's findings. The authors concluded that the J-shaped association seen in PURE was "probably due to confounding variables that were used in the equations to estimate the 24-hour urinary sodium excretion from spot urine samples." [4]

There are several other reasons to be skeptical, but just know that the American Heart Associations consistent recommendations against excessive protein and saturated fat intake are based on RCTs, and PURE is an observational study, and therefore intrinsically less powerful, no matter how large the sample size is [5].

Bear in mind, there's some nuance to this if you keep digging. Such as that replacing saturated fats in already healthy individuals probably does not have a clinically significant effect size, but I'm running out of time here. I hope this give you all insight into why we in the medical community look at this kind of thing with a healthy dose of skepticism.

Why scientists and doctors largely ignore the PURE study