Low-Carb Diets Linked to Higher All-Cause Mortality

Marlene Busko

September 18, 2018

MUNICH — In an observational study that used a one-time snapshot of carbohydrate intake, middle-aged Americans who consumed the least amount of carbohydrates were more likely to die from any cause, heart disease, or cancer during the subsequent decade than their peers who had the highest carbohydrate intake.

In a second part of the study, these findings were replicated in a meta-analysis of seven studies with cohorts from Greece, Japan, Sweden, and the United States that included people followed for almost 2 decades.

"Given the fact that low-carbohydrate diets may be unsafe, it would be preferable not to currently recommend these diets," senior study author Maciej Banach, MD, PhD, Medical University of Lodz, Poland, said during a press conference here at the European Society of Cardiology Congress 2018.

But, he conceded, "probably for a short time" — 6 or 12 months — low-carb diets might be useful for weight loss and good for parameters such as glucose and lipids.

It is impossible to draw conclusions about causation from an observational study, cautioned Michelle L. O'Donoghue, MD, Harvard Medical School, Boston, when asked for comment by theheart.org | Medscape Cardiology.

"One strength of the study is that it represents a large, well-characterized US population, and then it was validated in a meta-analysis of seven cohorts," she noted.

However, it also "highlights some of the perils of conducting this type of dietary research," she added. In "the past year, we have seen reports that differ markedly in their conclusions as to whether carbohydrate intake is helpful or hurtful."

Moreover, not all carbs are equal. "One can consume a diet rich in healthy whole-grain carbohydrates," she noted, or a diet full of "highly processed or junk foods." But the current study did not distinguish between types of carb or provide information on whether people in the low-carb group were replacing carbs with unhealthy foods.

Data such as those from the Blue Zone studies suggest that "the healthiest diets appear to have a carbohydrate base with a rich intake of vegetables and limited animal protein consumption," O'Donoghue explained.

"A predominantly plant-based diet," she said, "is what I personally recommend to friends and patients."

Low-Carb Controversy

"There is some controversy surrounding the long-term safety of consuming a low-carb diet, and studies have suggested that low-carb diets may increase the risk of cardiovascular disease and cancer-specific morbidity and mortality," Banach said.

"However," he added, "there are also opposite results suggesting no association in different populations."

To investigate this question, the researchers analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2000 cohort of 24,825 participants who were followed for a mean of 6.5 years. Mean age was 47.6 years, and 48.6% of the participants were men.

The cohort was divided into four quartiles on the basis of carbohydrate intake. The mean percentage of calories from carbohydrates was 66%, 57%, 49%, and 39%, for patients in quartiles 1, 2, 3, and 4, respectively.

To put this in context, the Dietary Guidelines for Americans recommends that carbohydrates make up 45% to 65% of total daily calories (page 97).

The researchers compared outcomes in participants with a lower carb intake (quartiles 2, 3, and 4) with those with the highest carb intake (quartile 1).

In the fully adjusted model, they corrected for between-group differences in age, sex, education, marital status, poverty-to-income ratio, total energy intake, physical activity, smoking, alcohol consumption, body mass index (BMI), hypertension, serum total cholesterol, and diabetes.

In this model, compared with the participants with the highest intake of carbs (quartile 1), participants with the lowest intake (quartile 4) had a "significant 32% increase in total mortality, 35% increase in cancer mortality, and 51% and 50% increases of coronary artery disease and stroke mortality, respectively," Banach reported.

Table. Mortality Risk for Highest (Quartile 4) vs Lowest (Quartile 1) Carbohydrate Intake
Cause of Death Hazard Ratio (95% Confidence Interval) P Value
Any 1.32 (1.14–2.01) <.001
Cancer 1.35 (1.06–1.69) <.001
Coronary heart disease 1.51 (1.19–1.91) <.001
Cerebrovascular disease 1.50 (1.12–2.31) <.001


This increased risk was much more evident in people who were not obese (BMI <30 kg/m²) than those who were obese, and in people 55 years and older than in younger people.

Results were similar, although slightly weaker, in the meta-analysis of almost 500,000 participants who were followed for a mean of 16 years.

During the follow-up period, the risk for all-cause mortality was 15% higher for participants with the lowest intake of carbs (quartile 4) than for those with the highest intake (quartile 1), the risk for cardiovascular disease mortality was 13% higher, and the risk for cancer mortality was 8% higher.

There was a step-wise increase in all-cause and cause-specific mortality as the intake of carbs decreased. Patients in quartiles 1, 2, 3, and 4 consumed 367, 245, 205, and 214 g/day of carbs, respectively.

"We might say we should be careful with the average level of carbohydrates less than 200 g/day...or 39% of energy," Banach told theheart.org | Medscape Cardiology.

Banach has disclosed no relevant financial relationships. O'Donoghue has received research grants from GlaxoSmithKline, Eisai, and AstraZeneca, and honoraria from diaDEXUS

European Society of Cardiology (ESC) Congress 2018: Poster P5409. Presented August 28, 2018. Abstract, Poster

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