Is low-carb the key to permanent weight loss?

Relation

Ebbeling CB, Feldman HA, Klein GL, et al. Effects of a low-carbohydrate diet on energy expenditure during weight loss: randomized trial. BMJ. 2018;363:k4583.

Draft

Randomized controlled trial with a weight loss run-in period.

Objective

Measuring the effects of diets with different carbohydrate-to-fat ratios on total energy expenditure.

Participant

A total of 164 adults ages 18 to 65 with a BMI of 25 or more participated in this study.

intervention

After a run-in period of 12% (10% to 14%) weight loss, participants were randomly assigned to either a low-carbohydrate (20% of calories), moderate-carbohydrate (40% of calories), or high-carbohydrate (60% of calories) diet for 20 weeks.

The diet was calorically adjusted to maintain weight loss within 2 kg during the 20-week intervention. Protein intake was a controlled amount at 20% of calorie intake. Fat accounted for the remaining 60%, 40%, or 20% of total calories for each participant. Meals were distributed to participants, who were required to weigh themselves daily at home and submit data electronically to the investigators.

Study parameters assessed

Assessments included (but were not limited to) body weight; energy intake; physical activity; Total energy expenditure calculated using estimated CO₂Production; Ghrelin, leptin and postprandial insulin secretion before weight loss.

Primary outcome measures

The primary endpoint was total energy expenditure and secondary endpoints included ghrelin and leptin levels.

Key insights

There was a linear trend toward increasing total energy expenditure (52 kcal/day) for every 10% decrease in the proportion of carbohydrate intake (P=0.002). Compared to the high-carbohydrate cohort, individuals in the moderate and low cohorts had higher total energy expenditure, averaging 91 kcal/d and 209 kcal/d.

This effect was greater in those who started with high insulin levels at baseline. Among those in the highest third of insulin secretion before weight loss, there was a difference of 308 kcal/d between the low- and high-carbohydrate diets in the intention-to-treat analysis and 478 kcal/d in the per-protocol analysis (P<0.004).

Both ghrelin and leptin were significantly lower in the low-carb group, with ghrelin showing a steeper decline than leptin.

Practice implications

This study is the largest and longest randomized trial published to evaluate the effects of a low-carbohydrate diet on weight loss. It suggests that not all calories are created equal and implies that the current obesity epidemic may not be due to fat intake or excess calories, but specifically excess carbohydrates.

The main strengths of this study are the study duration and the researchers' ability to control food intake. In a previous study comparing low-fat versus low-carbohydrate diets, Gardner et al. no significant difference in weight loss; However, this intervention only used health education without controlling for actual food intake.¹A recent meta-analysis by Hall and Guo showed no significant difference in energy expenditure between low-carb and high-fat diets.²This was likely because the studies included in this analysis were short-term, mostly lasting less than 2 weeks. The authors of the current study believe it may take at least 2 or 3 weeks to adjust to a low-carb, high-fat diet.

While the primary outcome of weight loss is interesting due to increased calorie burning, the secondary outcome (ghrelin and leptin) provides additional information about why a low-carbohydrate diet can result in weight loss, even if it is isocaloric.

It is also interesting that the low-carbohydrate cohort had a moderate increase in basal metabolic rate and increased physical activity, which contributes to the long-lasting effects of the low-carbohydrate diet in weight loss and maintenance of normal body weight.

While the primary outcome of weight loss is interesting due to increased calorie burning, the secondary outcome (ghrelin and leptin) provides additional information about why a low-carbohydrate diet can result in weight loss, even if it is isocaloric. Ghrelin is a hormone that helps regulate appetite and fat metabolism. When elevated, it increases hunger and food intake.³Ghrelin also plays a crucial role in insulin metabolism, with elevated levels contributing not only to obesity but also to metabolic syndrome and type 2 diabetes.⁴Leptin is also a hormone that regulates appetite and energy balance, and studies show that obese individuals have elevated leptin concentrations.⁵Both ghrelin and leptin were significantly lower in the low-carbohydrate cohort of the current study.

The ghrelin/leptin connection between low-carb diets and weight loss explains an important aspect of weight loss, namely appetite control. Increased satiety leads to lower calorie intake. Hu et al. showed that a low-carbohydrate diet increased peptide YY, a satiety signal, compared to a low-fat diet, showing that there was better appetite control in the low-carbohydrate group.⁶

Defining a low-carb diet can be difficult. An article published in the journal in 2013Current diabetes reportsdefines the carbohydrate spectrum this way (based on a 2,000 calorie diet):⁷

• Sehr niedrig = 21 bis 70 g/Tag (4,2 %-14 % der Kalorienaufnahme)
• Mäßig niedrig = 150 bis 200 g/Tag (30 % – 40 %)
• Moderat = 200 bis 325 g/Tag (40 % – 65 %)
• Hoch = >325 g/Tag (>65%)

A review published in theJournal of the American Osteopathic Associationmakes these distinctions:⁸

• Kohlenhydratarm/fettreich = 20 bis 100 g/Tag
• Ketogen = <50 g/Tag
• Atkins = Induktion < 20 g/Tag dann 80 bis 100 g/Tag
• Zone = 40 % der Gesamtkalorien

In the present study, carbohydrates accounted for the following percentage of total calories:

• Hoch = 60 %
• Moderat = 40 %
• Niedrig = 20 %

Because of the inconsistent definition associated with “low-carb,” it can be difficult to compare studies on the results of low-carb diets. Research on the ketogenic diet, which has the lowest carbohydrate intake, has increased, particularly in the fields of cardiology⁹and oncology.¹⁰Poor patient compliance and excessive consumption of unhealthy fats are problems associated with the ketogenic diet and other ultra-low carb diets. Poor food quality choices can bias the results of these studies and may not be reflected in the data unless specifically measured as a confounding factor. Tracking micronutrient intake, pro-inflammatory food consumption, processed foods, and macronutrient subtypes (i.e., fermentable vs. non-fermentable carbohydrates) would help analyze the data and lead to more rigorous conclusions. Right now, it is important for doctors to guide their patients away from consuming inflammatory foods and toward a healthy diet, regardless of their underlying diet.

While a low-carb diet has been shown to promote heart health,¹¹A recent observational study called this into question. The study was published this year inJournal of the American College of Cardiologyand followed 13,852 participants (mean age 54, 45% male) for a median of 22.4 years. They found that there is a correlation between a low-carbohydrate diet (<39% of calories) and an increase in atrial fibrillation.¹²However, there are several issues that make the results of this study questionable. First of all, 39% carbohydrates in the diet is not considered low-carb (as previously described). The study also used a food frequency questionnaire, which can be unreliable. Finally, there appeared to be a U-shaped curve where the group that consumed the most carbohydrates also had a 16% increased risk of atrial fibrillation. In addition, confounding factors such as high blood pressure, diabetes and other risks for atrial fibrillation were not taken into account.

Although this study received some media attention, further research in the form of randomized clinical trials is needed before counseling patients. In fact, other research has shown that a low-carb diet may help reduce the risk of conditions that increase the risk of atrial fibrillation, such as high blood pressure and diabetes.^13-15

Final thoughts

We agree with Ludwig and Ebbeling, who wrote: "Despite intensive research, the causes of the obesity epidemic remain incompletely understood and traditional calorie-restricted diets continue to lack long-term effectiveness... Pending definitive studies, the principles of a low glycemic load diet offer a practical alternative to the traditional focus on dietary fat and calorie restriction."¹⁶This latest study provides further evidence that the advice to simply eat less and burn more is outdated.

Integrative practitioners who use nutritional counseling as a key intervention will likely want to consider helping patients adopt a low-carbohydrate diet to achieve lasting weight loss while reducing the risk of chronic disease. According to the study reviewed here, patients with the highest insulin levels prior to weight loss may benefit the most from this (low-carb diet) as a lifestyle choice.