Can the incidence and mortality of chronic diseases be explained by dietary patterns?

From the ancient period to the current day, each cultural area has had their distinctive dietary pattern (combinations of dietary components, such as food or nutrients, to summarize a total diet) to adapt to their lifestyle and environments, such as a Western style diet (American style), Mediterranean diet and Asian diet (Japanese style). In recent years, chronic diseases such as diabetes, obesity, atherosclerosis, cardiovascular disease, and hypertension incidence and prevalence rate, have rapidly increased and have become a burden of public health management. Because lifestyle modification is the only confirmed preventive method for the rapid increase of these patients, several methods are recommended, such as nutritional modification and diverse exercise without drug therapy.

In these lifestyle modification methods, dietary modification is extremely important for chronic disease prevention and management. So many dietary recommendations released by the international scientific committees and organizations state that a diet should be moderately low in caloric content, low in fat and carbohydrate content, and high in protein and fiber. These diets emphasize the reduction of carbohydrate intake and thereby encourage high protein intake, given that, in Western countries, high fat diets are also generally avoided. Many diets are low in carbohydrates and high in protein, such as the Atkins diet. Very low‐carbohydrate diets typically contain <10% carbohydrates, 25–35% proteins and 55–65% lipids. For comparison, the average American diet contains 50% carbohydrates (275 g/day), 15% protein (83 g/day) and 35% lipids (85 g/day). In the UK, the mean intake, as a percentage of total energy, is approximately 48% carbohydrates, 17% protein and 35% lipids. Hession et al. suggest that low‐carbohydrate, high‐protein diets were associated with a slightly greater increase in high‐density lipoprotein cholesterol and to a slightly greater decrease in triglycerides. In contrast, these diets were associated with a slightly greater increase in low‐density lipoprotein cholesterol.

Recently, low‐carbohydrate and high‐protein diets have become extremely popular with consumers and patients. However, concerns have been expressed about the health effects of low‐carbohydrate and high‐protein diets, even though little documented information exists about the long‐term health consequences of low‐carbohydrate and high‐protein diets. Also these methods have not been fully confirmed for their benefit and usefulness by long‐term, large, randomized clinical trials, but have only been found by short‐term, small, randomized clinical trials and meta‐analysis.

Last year in Annals of Internal Medicine, Fung et al. published a very interesting article about all cause and cause‐specific mortality in a Nurses’ Health Study and Health Professionals’ Follow‐up Study cohort. They examined the relationships of animal based or vegetable based fat and protein mixed low‐carbohydrate diets with cardiovascular and cancer mortality over 20‐years prospective follow up in two cohorts. They used a low‐carbohydrate score, which was based on the percentage of energy as carbohydrate, fat and protein. They concluded that a low‐carbohydrate diet based on animal sources was associated with higher all‐cause cardiovascular and cancer mortality in both men and women, whereas a vegetable‐based low‐carbohydrate diet was associated with lower all‐cause and cardiovascular disease mortality rates. Another three long‐term observational studies on the effects of a long‐term low‐carbohydrate diet on mortality were carried out. In a long‐term cohort study of Swedish women, decreasing carbohydrate or increasing protein intake by one decile were associated with an increase in total mortality by 6% (95% CI 0, 12) and 2% (95% CI −1, 5), respectively. So, they concluded that low carbohydrate and high protein intake was associated with increased total and, particularly, cardiovascular mortality amongst women. During 10 years of follow up in Greek participants of the European Prospective Investigation Cancer and Nutrition study, higher intake of carbohydrates was associated with a significant reduction of total mortality, whereas higher intake of protein was associated with a non‐significant increase of total mortality. Positive associations of low‐carbohydrate and high‐protein score were noted with respect to both cardiovascular and cancer mortality. Therefore, they suggested that prolonged consumption of diets low in carbohydrates and high in protein is associated with an increase in total mortality. In an elderly Swedish cohort study for 10.2‐year median follow up, adjusted hazard ratios for the Mediterranean diet score were 0.71 (95% CI 0.55, 0.92) for all‐cause mortality and 0.63 (95% CI 0.42, 0.96) for cardiovascular mortality, and the carbohydrate restricted diet scores were 1.19 (95% CI 0.97, 1.45) for all‐cause mortality and 1.44 (95% CI 1.03, 2.02) for cardiovascular mortality. They concluded that adherence to a Mediterranean dietary pattern decreased mortality, but adherence to a carbohydrate‐restricted dietary pattern increased mortality in elderly Swedish men. Another Asian population‐based cohort study was divided into three major dietary patterns (vegetable‐rich, fruit‐rich and meat‐rich) and followed up for 5.7 years. They reported that the meat‐rich diet was associated with increased risk of diabetes (HR = 1.18; 95% CI 0.98, 1.42) and a slightly elevated risk of total mortality, whereas the fruit‐rich diet lowered mortality. From the aforementioned four studies’ results, low‐carbohydrate and high‐protein diets didn’t show favorable effects for cardiovascular and cancer mortality.

On the contrary, adverse effects have not been reported for the long‐term consumption of Mediterranean‐type diets, low‐glycemic index/glycemic load diets or low‐carbohydrate, high vegetable protein diets. Are all kinds of low‐carbohydrate high‐protein diets sustainable and safe for very long periods? Are all low‐carbohydrate high‐protein from vegetable origin diets really beneficial to specific disease mortality? No definitive answer exists. Future studies will need to address the long‐term safety of low carbohydrate high‐vegetable protein diets.

How did we interpret and understand these results? All forms of low‐carbohydrate and high‐protein diets did not have adverse long‐term effects. Therefore, frequently recommended dietary patterns that indiscriminately focus on low intake of carbohydrates and high intake of proteins in general, should be considered for effectiveness. However, large population‐based, long‐term intervention studies analyzing the impact of specific dietary patterns on the mortality of specific diseases are not feasible. The results of the study by Fung et al. must be confirmed by well‐designed, large, population‐based, long‐term interventional studies.

Until now, observational trials remain a major source of evidence for differential effects of the quantity and quality of carbohydrates and protein on the risk and mortality of specific diseases. In observational studies for dietary pattern, many researchers use exploratory and hypothesis‐oriented approaches (Table 1).

Table 1

 Approach to define dietary pattern in observational studies

1. Exploratory approach (use of study specific data)

A. Factor analysis

B. Cluster analysis

2. Hypothesis‐oriented approach (use of prior information)

A. Dietary recommendation, food pyramid use

B. Reduced rank regression (RRR)

C. Indexes and score

Therefore, these epidemiological observation studies have many limitations, such as the selective under‐reporting of nutritional intake possibly being related to specific diseases and the conscious awareness of the relationship between food intake and specific diseases. These limitations are of particular concern for cross‐sectional studies and less pertinent for prospective studies addressing disease outcomes, such as cardiovascular disease and cancer. So, simultaneous consideration for the prospective epidemiological evidence linking diet to the subsequent development of outcome was very important.

In conclusion, each dietary pattern reflects the specific traditional cultures and environments where the population lives. Therefore, frequently recommended dietary pattern modification to prevent specific disease development and adverse outcomes should be considered seriously before being applied to the whole population. Dietary pattern modification must be evaluated for its efficacy and adverse effects, not by an observational study, but a prospective epidemiological intervention study.