Animal-Based Low-Carbohydrate Diet Linked to Higher All-Cause Mortality Rates

Laurie Barclay, MD

September 07, 2010

September 7, 2010 — An animal-based, low-carbohydrate diet is associated with higher all-cause mortality rates, whereas a vegetable-based low-carbohydrate diet is associated with lower all-cause and cardiovascular disease mortality rates, according to the results of 2 prospective cohort studies reported in the September 7 issue of the Annals of Internal Medicine.

"Data on the long-term association between low-carbohydrate diets and mortality are sparse," write Teresa T. Fung, ScD, from the Department of Nutrition at Simmons College, Boston, Massachusetts, and colleagues. "Low-carbohydrate diets have been claimed to promote weight loss and improve blood cholesterol levels and blood pressure."

The goal of the study was to determine the association of low-carbohydrate diets with mortality during 26 years of follow-up in women (from 1980 to 2006) and 20 years in men (from 1986 to 2006). In the Nurses' Health Study and Health Professionals' Follow-up Study, diets were determined from several validated food frequency questionnaires administered during follow-up. Low-carbohydrate diets were characterized as animal based or vegetable based, depending on whether they emphasized animal or vegetable sources of fat and protein.

The study cohorts consisted of 85,168 women, aged 34 to 59 years at baseline, and 44,548 men, aged 40 to 75 years at baseline, with no known heart disease, cancer, or diabetes at baseline. During follow-up, there were 12,555 deaths in women, including 2458 related to cardiovascular disease and 5780 related to cancer. In men, there were 8678 deaths, including 2746 related to cardiovascular causes and 2960 related to cancer.

In a pooled analysis comparing the lowest vs the highest deciles, overall low-carbohydrate score was associated with a slight increase in overall mortality rates (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.01 - 1.24; P for trend = .136). Higher animal-based low-carbohydrate score was associated with higher all-cause mortality rates (pooled HR, 1.23; 95% CI, 1.11 - 1.37; P for trend = .051), cardiovascular deaths (corresponding HR, 1.14; 95% CI, 1.01 - 1.29; P for trend = .029), and cancer-related deaths (corresponding HR, 1.28; 95% CI, 1.02 - 1.60; P for trend = .089).

In contrast, higher vegetable-based low-carbohydrate score was linked to reduced all-cause mortality rates (HR, 0.80; 95% CI, 0.75 - 0.85; P for trend ≤ .001) and cardiovascular deaths (HR, 0.77; 95% CI, 0.68 - 0.87; P for trend < .001).

Limitations of this study include error inherent in measurement of diet and lifestyle characteristics and lack of generalizability to other populations. Residual and unmeasured confounding were not likely to significantly affect the results, according to the results of sensitivity analyses.

"A low-carbohydrate diet based on animal sources was associated with higher all-cause mortality in both men and women, whereas a vegetable-based low-carbohydrate diet was associated with lower all-cause and cardiovascular disease mortality rates," the study authors write.

In an accompanying editorial, William S. Yancy Jr, MD, MHS, from Veterans Affairs Medical Center and Duke University Medical Center in Durham, North Carolina, and colleagues describe various study limitations including dietary assessment and classification issues.

"[T]his well-written study addresses a critical, unresolved public health question of diet but cannot satisfy us with a definitive answer," Dr. Yancy and colleagues write. "The goal of our assessment is not to refute the utility of observational studies but to clarify the need for a large-scale clinical trial to provide a more definitive answer to the largest public health crisis in the United States: the effect of diet on obesity, chronic disease, and mortality. The current state of the evidence is such that no one can legitimately claim that a low-carbohydrate diet is either harmful or safe with any degree of certainty until a large-scale, randomized study with meaningful clinical end points is done."

The National Institutes of Health supported this study. The study authors have disclosed no relevant financial relationships. Dr. Yancy has received research grants from the Robert C. Atkins Foundation. The editorialists' other disclosures can be viewed online with the original journal article and editorial.

Ann Intern Med. 2010;153:289-298, 337-339.

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