Twenty adults without diabetes lived four continuous weeks in the NIH Clinical Center’s Metabolic Clinical Research Unit in Bethesda, Maryland. The 2-week crossover feeding study had no washout period and rotated participants between a plant-based, low-fat diet and an animal-based, low-carbohydrate diet. Nick Norwitz argued that carryover effects were so large that the trial’s headline calorie gap could not hold up. Walter C. Willett agreed the original paper was misleading, yet the 2021 study led by Kevin D. Hall still has not been retracted.
The Nature Medicine paper reported that participants ate 550 to 700 fewer calories per day on the low-fat plan and lost more body fat.
The reanalysis, published in The Journal of Nutrition on December 19, 2023, used publicly available data from 16 of the 20 original participants and found a very different pattern. Energy intake on the low-carbohydrate diet was 1,164 kcal/day lower when that diet came first than when it came second, while the low-fat diet showed the opposite pattern at 924 kcal/day. The carry-over effect was significant, with a P interaction value of 0.0004, while the net dietary effect was not significant at P = 0.4. The reanalysis also found that body fat fell when the low-carbohydrate diet came first and rose when it came second, then concluded that the short trial design and the missing washout period blocked any causal claim about chronic macronutrient effects.
In 2025, David S. Ludwig, Walter C. Willett, and Mary E. Putt published a Nature Medicine commentary cautioning that short-term dietary crossover trials can be invalidated by carry-over effects, and they singled out the Hall study as a prime example. In a secondary analysis in the American Journal of Clinical Nutrition, the original investigative group said diet order significantly affects energy balance in randomized crossover feeding studies, and in their reply they put the apparent advantage of the low-fat diet down to an enormous carry-over effect of about 2,000 kcal/day.
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