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Low-Carb Diets Won Tough Clinical Test
U.S. trial saw more calories burned on low-carb vs. low-fat diets 02/21/2019 By Craig Weatherby

A debate over the best weight-control diet — low-carb or low-fat — has lasted decades.

So, you’d think that by now, we’d have enough high-quality clinical evidence to end the argument.

In weight-control trials, low-carb diets have tended to modestly outperform high-carb diets — but the trials haven’t been large, long, or sufficiently rigorous to settle the question.

Further, recent evidence suggests that the proportions of whole versus processed foods in your diet may matter as much or more as its mix of fat, carbs, and protein: see Stunning Study Upsets a Big Diet Debate.

Ongoing uncertainty about the effects of low-carb versus high-carb diets explains the excitement elicited by a recent, tightly controlled clinical trial of substantial size and length.

Clinical trial tested the carbohydrate-insulin hypothesis of obesity
Most people on low-calorie diets regain lost pounds within one or two years — in part because the body adapts to lower calorie intake by slowing metabolism and storing rather than burning calories.

David S. Ludwig, M.D. — a co-lead author of the new trial — discussed the metabolic dangers of sugary diets in a University of California video that went viral.

He's ascribed to the Carbohydrate-Insulin hypothesis of obesity, which proposes that added sugars and the sugar-like starches in refined grains raise insulin levels, driving fat cells to store excessive calories.

With fewer calories available to the rest of the body, hunger grows and metabolism slows — which, as Dr. Ludwig says, is “a recipe for weight gain”.

Comparing carb levels head to head
The unusually rigorous clinical trial was led by Boston Children’s Hospital, in partnership with Framingham State University (Ebbeling CB et al. 2018).

In short, the Massachusetts-based researchers found that the people placed on a low-carb diet burned more calories daily, versus those assigned to a high-carb diet that provided the same number of calories.

The five-month clinical trial — called the Framingham State Food Study or (FS)2 — tightly controlled what people ate by providing them with fully prepared meals.

At the outset, each participant’s weight, insulin response to foods, metabolic hormones, and average calories burned was carefully measured.  

The scientists interviewed 1,685 potential participants by telephone to find the best candidates, and eventually enrolled 234 overweight adults (age 18 to 65, body mass index of 25 or higher).

During the first, 10-week phase of the trial, all the participants were assigned to eat a calorie-restricted diet that was designed to shed 10% to 14% of body weight.

Out of the 234 volunteers, 164 achieved that weight-loss goal and were randomly assigned to one of three diet groups for an additional five months:

  • High-carb diet: 60% of total calories from carbs
  • Moderate-carb diet: 40% of total calories from carbs
  • Low-carb diet: 20% of total calories from carbs

Most of the carbohydrate-rich foods provided to all three groups featured whole, unrefined grains and were low in added sugars.

During this second, five-month phase of the trial, each participants’ total calorie intake was adjusted to successfully maintain their weight loss.

The goal of the second phase was to measure calorie-burning among the three groups by providing them with “double-labeled” water — a method that's considered the best available.

By the end of the trial’s second phase, the low-carb diet group was burning more daily calories than the high-carb group.

Specifically, the people assigned to the low-carb diet burned about 250 more calories a day, versus those on the high-carb diet.

As the study’s co-lead author, Cara Ebbeling, Ph.D., said, “If this difference persists— and we saw no drop-off during the 20 weeks of our study — the effect would translate into about a 20-pound weight loss after three years, with no change in calorie intake.”

And — among the participants who displayed the highest insulin response to dietary carbs at the outset of the trial — the advantage for those in the low-carb group was even greater, at about 400 extra calories burned per day, versus the high-carb group.

In addition, average levels of ghrelin — a hormone linked to reduced calorie-burning — were significantly lower in the low-carb group, versus the high-carb diet group.

Taken together, those two characteristics of the low-carb group — more calories burned per day and lower average levels of ghrelin — lend strong support to the Carbohydrate-Insulin hypothesis of weight gain.

As Prof. Ebbeling said “Our observations challenge the belief that all calories are the same to the body. Our study did not measure hunger and satiety, but other studies suggest that low-carb diets also decrease hunger, which could help with weight loss in the long term.”

Most experts applaud the trial; questions remain
In an interview with The New York Times, famed nutrition-health researcher Dariush Mozaffarian, M.D., of Tufts University praised the trial’s quality and stressed its importance.

As he said, “This study confirms that, remarkably, diets higher in starch and sugar change the body’s burn rate after weight loss, lowering metabolism. The observed metabolic difference was large, more than enough to explain the yo-yo effect so often experienced by people trying to lose weight.”

Dr. Mozaffarian agreed that the findings undermine conventional wisdom on calorie counting: “It’s time to shift guidelines, government policy, and industry priorities away from calories and low-fat and toward better diet quality.”

Obesity expert Dr. Kevin Hall of the National Institute of Diabetes and Digestive and Kidney Diseases agreed that the Massachusetts-based trial was unusually well-designed and tightly controlled.

In his interview with The New York Times, Dr. Hall questioned the reliability of the method used to track calorie-burning — called double-labeled-water — in people on low-carb diets.

He based that skepticism on the results of a recent study by he and colleagues at Cold Spring Harbor Laboratory (Hall KD et al. 2018).

But the double-labeled-water method remains the current gold standard for measuring calorie expenditure, and Dr. Hall's study has not yet been peer-reviewed.


  • Ebbeling CB, Feldman HA, Klein GL, Wong JMW, Bielak L, Steltz SK, Luoto PK, Wolfe RR, Wong WW, Ludwig DS. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial. BMJ. 2018 Nov 14;363:k4583. doi: 10.1136/bmj.k4583.
  • Gardner CD, Trepanowski JF, Del Gobbo LC, Hauser ME, Rigdon J, Ioannidis JPA, Desai M, King AC. Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial. JAMA. 2018 Feb 20;319(7):667-679. doi: 10.1001/jama.2018.0245. Erratum in: JAMA. 2018 Apr 3;319(13):1386. JAMA. 2018 Apr 24;319(16):1728.
  • Hall KD et al. Methodologic Issues in Doubly Labeled Water Measurements of Energy Expenditure During Very Low-Carbohydrate Diets. October 23, 2018. bioRxiv