Moreover, the impact of carbohydrate overconsumption on intrahepatic lipid deposition has gained much attention. Recent studies report that a low‐carbohydrate diet is more effective than a low‐fat diet in improving obesity. Hession et al. systematically reviewed the impacts of low‐carbohydrate vs. low‐fat/low‐calorie diets in achieving weight control and found that the low‐carbohydrate diet is more effective than the low‐fat/low‐calorie diet. 5 Haufe et al. also compared the effects of low‐carbohydrate and low‐fat diets in a randomized control study and found that both the low‐carbohydrate and low‐fat diets effectively reduced intrahepatic fat content. 6

The composition of the macronutrients ratio is significantly different according to geographic and ethnic settings. The energy percentage of carbohydrate is very high in Asian compared to non‐Asian populations. Carbohydrate energy percentage, rather than fat proportion, in total energy intake is reportedly associated with aminotransferase activity, prevalence of hypertension, and diabetes in Korean. 4

Non‐alcoholic fatty liver disease (NAFLD) has become a serious health burden all over the world. The pathophysiology of NAFLD is similar to that of obesity, diabetes, and dyslipidemia in many aspects. Lifestyle modification, including diet and exercise, is fundamental to treating NAFLD. Unfortunately, there is no specialized diet program or diet recommendation for NAFLD. Most physicians have followed anti‐obesity or anti‐dyslipidemic diet programs for NAFLD patients. 1 Because most diet recommendations for obesity, hypertension, and hypercholesterol emphasize reducing fat and total energy intake, NAFLD patients also usually follow that strategy. 2 , 3 Diet education programs for obesity or dyslipidemia mainly focusing on reducing fat consumption have been used for NAFLD patients in Korea. However, the ratio of fat energy consumption is less than 20% in most Asian cultures; therefore, for Korean NAFLD patients, the conventional low‐fat diet education might be both unrealistic and ineffective.

Calculation of sample size and a statistical analysis plan were finalized before patient enrollment. Sample size was calculated as follows: (i) low‐fat education group, estimated normalization of ALT rate at week 8 approximately 15%; and (ii) low‐carbohydrate education group, expected normalization rate of ALT in 35%. 7 With a two‐sided α‐value of 0.05 and power of 80% (β = 0.20), the total number of patients required was calculated as 104. The primary end‐point of this study was the ALT normalization rate. The ALT normalization rate was analyzed using the χ 2 ‐test. The body fat distribution changes and liver HU were analyzed using the paired t ‐test. All statistical analyses were carried out using spss version 18 (SPSS, IBM, Chicago, IL, USA). P ‐values less than 0.05 were considered statistically significant, unless stated otherwise. All authors had access to the study data and reviewed and approved the final manuscript.

The height, weight, waist circumference, and levels of ALT, aspartate aminotransferase, total cholesterol, triglyceride, insulin, and fasting glucose of patients were measured at baseline and week 8. Intrahepatic fat content was also examined through the visceral fat CT at baseline and the end of the study. Liver and spleen Hounsfield units (HU) were measured on pre‐enhanced CT images. The CT scanner used in this study was a 32‐channel multidetector CT, and liver and spleen's HU were obtained by measuring the HU of 12 regions of interest then calculating the average. A fatty liver was diagnosed if the liver/spleen HU was less than 1.0.

An 8‐week low‐fat or low‐carbohydrate diet education was provided to each subject according to their group allocation. After 4, 6, and 8 weeks of dietary education, the levels of perceived difficulty of the dietary regimen and perceived compliance were measured. Questionnaires were provided from The Korea National Health and Nutrition Examination Survey. The perceived difficulty level was scored on a scale of 1 to 6 as follows: 1, very difficult; 2, difficult; 3, slightly difficult; 4, fairly easy; 5, easy; and 6, very easy. The perceived compliance to the diet education was also scored on a scale of 1 to 6 as follows: 1, never followed; 2, not followed; 3, seldom followed; 4, followed; 5, quite followed; and 6, fairly followed. The change in physical activity was assessed based on the following criteria: grade 1, <20 min; grade 2, 20–30 min; grade 3, 30–40 min; grade 4, 40–50 min; grade 5, 50–60 min; and grade 6, ≥60 min.

The individual diet education program included a face‐to‐face education session and three telephone education sessions. The first face‐to‐face session took approximately 40 min per subject and a booklet with information on calorie intake, macronutrient composition, and specific food group consumption patterns was used. Subsequently, three telephone education sessions were undertaken every second week with pre‐mailed brief handout materials on simple behavioral tips. The dietary criteria for the low‐carbohydrate diet group were: taking approximately 25 kcal/kg of ideal body weight to reduce weight and consuming 50–60% carbohydrate, 20–25% proteins, and 20–25% fats. The dietary criteria for the low‐fat diet group were: taking approximately 25 kcal/kg according to ideal body weight to reduce weight and consuming 60–70% carbohydrates, 15–20% proteins, and 15–20% fats. Guidelines about planning menus and recipes were provided according to each group's dietary criteria. A total of five dietitians were engaged in this study. All education sessions for participants were taken by the same dietitian to ensure the education's continuity and individualization. A 5‐day diet diary was collected from all participants twice before and after completion of the 8‐week diet education period. The 5‐day diet diary included weekday as well as weekend dietary information within a 2‐week period. Nutrient intakes were calculated using CAN‐Pro (version 4.0; The Korean Nutrition Society, Seoul, South Korea).

The primary end‐point was the rate of ALT normalization after 8 weeks. Secondary end‐points included: (i) normalization of liver / spleen ratio on computed tomography (CT) scan at week 8; (ii) changes in visceral fat area; (iii) changes in triglyceride and cholesterol levels; (iv) changes in body weight; and (v) compliance with diet education.

The study participants were randomly allocated into two groups, a low‐carbohydrate diet education group and a low‐fat diet education group, through a computer‐based 1:1 allocation system and the block size was four. Randomization was stratified according to body mass index (BMI) (cut‐off value of BMI was 25). The allocation process was concealed from clinicians.

The exclusion criteria were as follows: patients who took drugs which might cause fatty liver, such as herbal medicines, steroids, or amiodarone, within 1 month, patients with positive serological tests for hepatitis B or C as well as autoimmune hepatitis, and patients who had undergone any nutritional education program for diabetes and/or blood pressure.

Patients with fatty liver, newly diagnosed by sonography, and abnormal liver chemistry who visited one of five tertiary hospitals were enrolled for the study. Sonographic fatty liver was defined as the abdominal ultrasonic examination showing intrahepatic vessel blurring as well as increased liver parenchyma echogenicity compared to right renal cortex among the patients with less than 140 g (male) and 70 g (female) alcohol consumption per week. All subjects had abnormal alanine transaminase (ALT) levels. Elevated liver enzyme was defined as serum ALT >40 IU/L.

This study was a parallel group randomized trial. The reporting form followed the guidelines of the CONSORT statement. A schematic flow of the study is shown in Figure 1 . Dietary intervention was carried out for 8 weeks. All participants gave their signed written consent and the study was approved by the ethics committees of the institutional review boards of participating hospitals (2012–02–003‐005). This clinical trial was registered with the Korea Clinical Research Information Service (KCT0000970, https://cris.nih.go.kr/cris/index.jsp ).

At the end of the 8‐week dietary education period, there was no difference in physical activity indicators between the low‐fat and low‐carbohydrate diet education groups (Table 4 ). The subjective difficulty level in relation to understanding the dietary education regimen was assessed at 4, 6, and 8 weeks. The 4‐week evaluation showed that participants had a slightly higher difficulty in understanding the low‐carbohydrate diet education compared to the low‐fat diet education; however, the difficulty level assessed at 6 and 8 weeks showed no difference. Moreover, on average, the compliance levels of both education groups were high and the two groups showed no difference in the level of compliance.

Both the education programs decreased the total energy intake. The low‐fat diet group decreased the total energy intake from 1906 kcal to 1787 kcal ( P = 0.066) while the low‐carbohydrate diet group significantly decreased the total energy intake from 1974 kcal to 1648 kcal ( P = 0.0001) (Fig. 2 ). Compared to the low‐fat diet education group, both the carbohydrate and fat intakes were lowered only in the low‐carbohydrate education group; however, they showed no statistical difference at the end of study.

At the end of the study, both the liver HU and liver / spleen HU ratio increased only in the low‐carbohydrate education group from the baseline (Table 3 ). Moreover, levels of both total abdominal fat and subcutaneous fat were significantly reduced in the low‐carbohydrate group. However, no significant difference in total abdominal fat, visceral fat, or subcutaneous fat was observed in the low‐fat group.

The ALT normalization rate of the low‐carbohydrate education group (38.5%) was significantly higher than that of the low‐fat education group (16.7%) (Table 2 ). Compared to the baseline, the mean ALT levels decreased in 80.8% of the low‐carbohydrate diet group and in 57.4% of the low‐fat diet group. The average decrement in ALT of the low‐fat diet education group was 7.3 U/L and that of the low‐carbohydrate education group was 30.3 U/L, which showed a significant decrease in the low‐carbohydrate education group.

In both low‐carbohydrate and low‐fat diet education groups, weight, waist circumference, and BMI significantly decreased (Table 1 ). However, in the low‐carbohydrate diet education group alone, not only the systolic and diastolic blood pressures but also low‐density lipoprotein cholesterol concentrations decreased significantly. In contrast, in the low‐fat diet group, fasting glucose and cholesterol levels showed no significant changes.

Among 120 enrolled patients, 110 patients met the study criteria. Four participants withdrew informed consent due to difficulty in following diet education program. Out of 106 participants, 54 (50.9%) and 52 (49.1%) patients were allocated to the low‐fat and low‐carbohydrate diet groups, respectively. There was no difference in age, clinical parameters, and body fat distribution between the low‐fat and low‐carbohydrate diet groups (Tables S1 – S3 ).

Discussion

In our study, a low‐carbohydrate education program was more effective and realistic in Korean NAFLD patients. It indicated that the low‐carbohydrate education strategy was more effective in not only reducing body weight but also improving metabolic parameters among Koreans, a population in which, generally, carbohydrates make up a large proportion of total energy intake.

The National Cholesterol Education Program (Adult Treatment Panel III) recommended a low‐fat diet of <30% or a low‐carbohydrate diet of <50%.3 However, it is arguable whether the same strategy can be applied to Asian countries where rice is a staple food. According to the Korea National Health and Nutrition Examination Survey, carbohydrate makes up more than 60% of energy intake in 83% of the Korean population.8 These data showed that the mean carbohydrate and fat proportions are approximately 67.7% and 17.4% of total energy intake, respectively. Japan also shared a similar average carbohydrate energy intake (61.6%).9

Even though fat constitutes less than 30% of the total calorie intake in the majority of Asian people, most education programs focus on reducing fat intake. In our study, the total calorie intake, as well as amount of fat intake, decreased more in the low‐carbohydrate group compared to the low‐fat group. Although our study originally aimed to compare the efficacy of low‐carbohydrate and low‐fat diet education, direct efficacy comparison between the two diet regimens was not feasible due to the difference in total calorie intake. However, we believe that a low‐carbohydrate diet tends to reduce overall intake in high carbohydrate intake cultures, and part of the differences between outcomes in the low‐carbohydrate group is likely related to calorie restriction rather than macronutrient restriction. It means that improvement of fatty liver in the low‐carbohydrate diet group is more attributable to the reduction in total energy intake rather than changes in macronutrient composition. It also means that low‐carbohydrate diet education, rather than low‐fat diet education, reduced the total energy intake of participants effectively. As a result, it can be concluded that low‐carbohydrate diet education is more effective for reducing total calorie intake compared to low‐fat diet education among NAFLD patients with a dietary pattern of high carbohydrate consumption.

However, there are several unsolved issues related to low‐carbohydrate diets in clinical trials. First, the optimal carbohydrate proportion is still unclear. According to researchers and ethics, a wide variation exists. Some studies defined a low‐carbohydrate diet as <40% of total energy intake, whereas others defined it as <60%. Moreover, despite the same macronutrient compositions, one was defined as a low‐carbohydrate diet and the other as a low‐fat diet.10, 11 Second, depending on the ethnic and cultural setting, macronutrient compositions vary widely. There are no data to evaluate whether the influence of carbohydrate composition is the same between a high carbohydrate‐consuming country and a high fat‐consuming country. Third, the impact of a low‐carbohydrate diet on obesity was different in three previous studies.10, 11 A low‐carbohydrate diet was effective in reducing body weight in patients with insulin resistance; however, the effect disappeared in normal insulin resistance subjects.12-14 This study showed that total energy restriction clearly decreased serum aminotransferase activity as well as intrahepatic fat deposition. The low‐carbohydrate education program was a more effective and realistic approach compared to the low‐fat diet program to reduce energy intake in Korea. The impact of macronutrition might be different depending on country/region‐specific cultural settings in patients with NAFLD. Therefore, the best approach to establishing the optimal education program is to understand which type of education program is more appropriate for reduction in total energy consumption in a particular setting.

There are some limitations of this study. First, our dietary intervention relied solely on education. Not all participants followed their macronutrient intake recommendation. Some low‐carbohydrate education participants did not decrease their amount of carbohydrate intake or carbohydrate energy percent. A total diet intervention trial could suggest more concrete data about the effects of carbohydrate composition in patients with fatty liver disease. Second, patients did not ingest a true low carbohydrate ketogenic diet (i.e., Atkins diet). The average carbohydrate energy intake is 67% in the Korean population. A true low carbohydrate ketogenic diet, with <40% of carbohydrate energy percent, is not realistic in this setting. We therefore recommend using “reduced carbohydrate” rather than “low carbohydrate”, as applied in non‐Asian countries. Finally, intrahepatic fat deposition was assessed by CT in this study. The gold standard method to assess intrahepatic fat is liver biopsy. Although the unenhanced CT scan showed good performance in qualitative diagnosis of fatty liver, there is still argument regarding the quantitative assessment of steatosis.15