Fung et al. (2010) Low-carbohydrate diets and all-cause and cause-specific mortality: two cohort studies

by Fung, T. T., van Dam, R. M., Hankinson, S. E., Stampfer, M., Willett, W. C., & Hu, F. B.
Annals of Internal Medicine, 153(5), 289-98.

» Abstract «
BACKGROUND: Data on the long-term association between low-carbohydrate diets and mortality are sparse. OBJECTIVE: To examine the association of low-carbohydrate diets with mortality during 26 years of follow-up in women and 20 years in men. DESIGN: Prospective cohort study of women and men who were followed from 1980 (women) or 1986 (men) until 2006. Low-carbohydrate diets, either animal-based (emphasizing animal sources of fat and protein) or vegetable-based (emphasizing vegetable sources of fat and protein), were computed from several validated food-frequency questionnaires assessed during follow-up. SETTING: Nurses’ Health Study and Health Professionals’ Follow-up Study. PARTICIPANTS: 85 168 women (aged 34 to 59 years at baseline) and 44 548 men (aged 40 to 75 years at baseline) without heart disease, cancer, or diabetes. MEASUREMENTS: Investigators documented 12 555 deaths (2458 cardiovascular-related and 5780 cancer-related) in women and 8678 deaths (2746 cardiovascular-related and 2960 cancer-related) in men. RESULTS: The overall low-carbohydrate score was associated with a modest increase in overall mortality in a pooled analysis (hazard ratio [HR] comparing extreme deciles, 1.12 [95% CI, 1.01 to 1.24]; P for trend = 0.136). The animal low-carbohydrate score was associated with higher all-cause mortality (pooled HR comparing extreme deciles, 1.23 [CI, 1.11 to 1.37]; P for trend = 0.051), cardiovascular mortality (corresponding HR, 1.14 [CI, 1.01 to 1.29]; P for trend = 0.029), and cancer mortality (corresponding HR, 1.28 [CI, 1.02 to 1.60]; P for trend = 0.089). In contrast, a higher vegetable low-carbohydrate score was associated with lower all-cause mortality (HR, 0.80 [CI, 0.75 to 0.85]; P for trend < 0.001). LIMITATIONS: Diet and lifestyle characteristics were assessed with some degree of error. Sensitivity analyses indicated that results were probably not substantively affected by residual confounding or an unmeasured confounder. Participants were not a representative sample of the U.S. population. CONCLUSION: 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. PRIMARY FUNDING SOURCE: National Institutes of Health. [italics & bold added]

» Highlights & Notes «
Weight-loss trials lasting 6 months to 2 years … (pp. 289)
“Weight-loss trials lasting 6 months to 2 years have found low-carbohydrate diets to be as effective (3, 4) or more effective (5, 6) than diets with higher carbohydrate content …. these diets can be high in red meat and low in fruits, vegetables, and whole grains, which has been shown to increase risk for chronic diseases (10 -12).”

We found that women with higher low-carbohydrate diet … (pp. 289)
“We found that women with higher low-carbohydrate diet scores did not have greater risk for type 2 diabetes and coronary heart disease, and a low-carbohydrate dietary pattern that emphasized vegetable sources of fat and protein was associated with a lower risk for both diseases (15, 16).”

Context The relative effects of animal-based and vegetable-based low-carbohydrate … (pp. 290)
Context. The relative effects of animal-based and vegetable-based low-carbohydrate diets on mortality are uncertain.”

Contribution Two large, long-term cohort studies examined the relationship … (pp. 290)
Contribution. Two large, long-term cohort studies examined the relationships of animal-based and vegetable-based low-carbohydrate diets with mortality. Diets that emphasized animal sources of fat and protein were associated with higher all-cause, cardiovascular, and cancer mortality, whereas diets that emphasized vegetable sources of fat and protein were associated with lower all-cause and cardiovascular mortality.”

Implication A vegetable-based low-carbohydrate diet is probably healthier than … (pp. 290)
Implication. A vegetable-based low-carbohydrate diet is probably healthier than an animal-based low-carbohydrate diet.”

we prospectively examined the relationship between different types … (pp. 290)
we prospectively examined the relationship between different types of low-carbohydrate diets and all-cause and cause-specific mortality in 2 large cohorts in the United States.

The NHS (Nurses’ Health Study) is a cohort … (pp. 290)
“The NHS (Nurses’ Health Study) is a cohort study of 121 700 female nurses aged 30 to 55 years living in 11 U.S. states in 1976 (Figure, top). Questionnaires are sent biennially to collect medical, lifestyle, and other health-related information (19).”

The HPFS (Health Professionals’ Follow-up Study) was established … (pp. 290)
“The HPFS (Health Professionals’ Follow-up Study) was established in 1986 and included 51 529 male podiatrists, optometrists, pharmacists, dentists, and veterinarians aged 40 to 75 years (Figure, bottom).”

Both men and women who had higher overall … (pp. 294)
“Both men and women who had higher overall and animal low-carbohydrate scores had higher BMI and were more likely to be current smokers but had lower intakes of fruits and vegetables (Table 1). Conversely, those with higher vegetable low-carbohydrate score tended to have higher alcohol and whole grain intake.”

we observed a modest but statistically higher … (pp. 294)
“we observed a modest but statistically higher risk for all-cause mortality with the animal low-carbohydrate score”

A direct association was observed between the animal … (pp. 295)
“A direct association was observed between the animal low-carbohydrate score and colorectal cancer death when data were combined”

the overall and animal low-carbohydrate scores were posi- … (pp. 295)
“the overall and animal low-carbohydrate scores were positively associated with lung cancer mortality”

The vegetable low-carbohydrate score was not associated … (pp. 295)
“The vegetable low- carbohydrate score was not associated with lung cancer deaths.”

none of the low-carbohydrate scores was associated with … (pp. 295)
“none of the low-carbohydrate scores was associated with breast cancer or prostate cancer death.”

In our 2 cohorts of U.S. men and … (pp. 296)
“In our 2 cohorts of U.S. men and women who were followed for 20 to 26 years, we observed that the overall low-carbohydrate diet score was only weakly associated with all-cause mortality. However, a higher animal low-carbohydrate diet score was associated with higher all-cause and cancer mortality, whereas a higher vegetable low-carbohydrate score was associated with lower mortality, particularly CVD mortality.”

We observed stronger direct associations with mortality with … (pp. 296)
“We observed stronger direct associations with mortality with the animal but not with the vegetable low-carbohydrate score, suggesting that animal- and plant-based foods have a differential effect on mortality.”

Consistent with our results, higher intake of vegetable … (pp. 296)
“Consistent with our results, higher intake of vegetable protein, but not animal protein, was associated with a lower risk for coronary heart disease mortality in the Iowa Women’s Health Study (30). The lower CVD mortality observed with higher vegetable low-carbohydrate score in our study is probably due in part to the established benefit of unsaturated fats, dietary fiber, and micronutrients, such as magnesium and potassium, as well as other bioactive compounds, including vitamins, minerals, and phytochemicals (31).”

We found a positive association between animal and … (pp. 296)
“We found a positive association between animal and low-carbohydrate score and cancer mortality.”

Low-carbohydrate diets from animal and vegetable sources may … (pp. 296)
“Low-carbohydrate diets from animal and vegetable sources may have similar major macronutrient content, but the source of the macronutrients can result in large differences in dietary components that may affect mortality, such as specific fatty acids, protein, fiber, vitamins and minerals, and phytochemicals. Therefore, the associations that we observed are more likely to be mediated by these bioactive components rather the carbohydrate content.”

In conclusion, consumption of a vegetable-based low-carbohydrate … (pp. 297)
“In conclusion, consumption of a vegetable-based low- carbohydrate diet were associated with a lower risk for all- cause and CVD mortality, whereas high scores for the animal-based low-carbohydrate diet were associated with a higher risk for overall mortality. These results suggest that the health effects of a low-carbohydrate diet may depend on the type of protein and fat, and a diet that includes mostly vegetable sources of protein and fat is preferable to a diet with mostly animal sources of protein and fat.”

» Citation «
Fung, T. T., van Dam, R. M., Hankinson, S. E., Stampfer, M., Willett, W. C., & Hu, F. B. (2010). Low-Carbohydrate diets and all-cause and cause-specific mortality: Two cohort studies. Annals of internal medicine, 153(5), 289-98. doi:10.1059/0003-4819-153-5-201009070-00003

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