Effect of a Ketogenic Diet on Metabolic Dysfunction‐Associated Steatotic Liver Disease (MASLD) Progression: A Randomized Controlled Trial

ABSTRACT

Background

Despite the popularity of a ketogenic diet, no randomized, controlled trials have evaluated its efficacy on metabolic dysfunction‐associated steatotic liver disease (MASLD) progression.

Methods

We conducted an 8‐week, open‐label, randomized controlled trial involving 24 patients with MASLD who were randomly assigned to either the home delivery ketogenic diet or a nutrition education program on adherence to the DASH diet. The primary outcome was a reduction in hepatic steatosis as measured by transient elastography.

Results

There were no significant differences between groups in liver stiffness and steatosis measurement after interventions. Subjects on a ketogenic diet had lost more weight than subjects in the control group at 8 weeks (mean change [95% CI], −6.16 [−7.22, −5.10] vs. −2.14 [−4.49, 0.21] kg; p = 0.001). The decrease in waist circumference, systolic blood pressure, fat mass, and visceral fat area was significantly greater among subjects on a ketogenic diet than among those in the control group. Laboratory parameters, including AST, triglyceride, and HDL were also significantly decreased among subjects on a ketogenic diet than among those in the control group.

Conclusions

A ketogenic diet produced a significantly greater weight loss (absolute difference, approximately 4%) than did the general lifestyle advice intervention for the first 8 weeks. A ketogenic diet was associated with a greater improvement in some risk factors for coronary heart disease and MASLD. However, a ketogenic diet did not reduce steatosis nor worsen MASLD progression. Longer and larger studies are required to determine the long‐term safety and efficacy of the ketogenic diet.

Trial Registration: TCTR20220426005

Metabolic dysfunction‐associate steatotic liver disease (MASLD) is the term for a range of liver disease conditions caused by an accumulation of fat in the liver. MASLD affects approximately 25% of the world's population and is closely associated with obesity and metabolic syndrome [1]. MASLD can lead to serious liver damage, including cirrhosis and liver cancer [2].

MASLD is caused by several mechanisms that induce inflammation and the death of liver cells, leading to liver fibrosis stimulation [3]. Nonetheless, insulin resistance is believed to be a main cause, with no current treatment for clear benefits. Thus, treatment potentially focuses on behavioral changes, such as aerobic exercise and controlling or avoiding foods that promote steatotic liver disease [4, 5].

A ketogenic diet is a dietary approach to building ketone bodies. It was initially developed to alleviate the symptoms of epilepsy by mimicking the involved metabolic mechanisms while fasting [6]. A ketogenic diet is a low‐carbohydrate diet to help reduce ghrelin and insulin secretion, causing a decrease in appetite, possible weight loss, and better control of blood sugar levels in people with type 2 diabetes due to insulin resistance [7, 8]. Hence, it has been hypothesized that the ketogenic diet can be beneficial for patients with steatotic liver disease as well. In recent years, many studies have shown the beneficial effects of a ketogenic diet on weight loss and intrahepatic fat reduction in patients with MASLD [9, 10, 11, 12]. However, some studies found that a ketogenic diet has demonstrated increase in cholesterol and inflammatory markers [13]. The effect of a ketogenic diet on MASLD is unclear. The aim of this study was to evaluate the comparative treatments for MASLD with a ketogenic diet, and general lifestyle advice from registered dietitians using an 8‐week randomized controlled trial.

1. Methods

1.1. Subjects

A total of 24 MASLD patients (16 women and 8 men) participated in the study. After scheduling for the first time, two participants in the control group asked to withdraw from the study (Table 1). Participants were recruited from the outpatient clinic at the Department of Gastroenterology and Hepatology, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand. Inclusion criteria were any one of either: (1) MASLD diagnosed by radiologic assessment (ultrasound, computed tomography [CT], or magnetic resonance imaging), or (2) Fibroscan (Echosens, Paris, France) with a controlled attenuation parameter (CAP) more than 200 dB/m. Potential subjects were excluded if they had chronic liver disease other than MASLD, type 1 and type 2 diabetes or patients taking Sodium‐glucose cotransporter 2 inhibitors (SGLT2i), had history of liver transplantation, had body mass index (BMI) < 25 kg/m [2], were unstable body weight (more than 10% change in the past 3 months, were performed weight loss surgery or usage of weight loss pills within the past 3 months), consumed alcohol > 210 g/week in men and > 140 g/week in women, had unstable cardiovascular disease, chronic kidney disease of stage G3a and above (GFR < 45 mL/min/1.73 m [2]), history of urinary tract stones, HIV infection, active malignancy within the past 5 years, were taking lipid‐lowering medications, were pregnant or lactating, or were taking medications that affect body weight. No participant was exposed to silymarin, vitamin E, or steatogenic medications such as steroids. This study was conducted in accordance with the guidelines of the Declaration of Helsinki and Consolidated Standards of Reporting Trials (CONSORT). All subjects provided written informed consent, and the protocol was approved by the Institutional Review Board, Royal Thai Army Medical Department (R129h/63) and registered at the Thai Clinical Trials Registry (TCTR20220426005). All authors had access to the study data and reviewed and approved the final manuscript.

TABLE 1.

Baseline characteristics of subjects.

Characteristics	Ketogenic diet (n = 12)	General lifestyle advice (n = 10)	p
Age (years)	37.42 ± 7.49	40.2 ± 7.57	0.398
Sex
Female	8 (66.7%)	8 (80%)	0.484
Male	4 (33.3%)	2 (20%)
Body weight (kg)	82.99 ± 11.12	78.33 ± 12.66	0.369
Height (cm)	161 ± 7.65	159.7 ± 6.95	0.684
Body mass index (kg/m2)	31.93 ± 2.7	31.16 ± 3.93	0.594
Waist circumference (cm)	102.44 ± 9.67	96.83 ± 12.95	0.272
Hip circumference (cm)	108.55 ± 8.34	108.44 ± 10.96	0.979
Underlying disease
Asthma	0 (0%)	1 (10%)	0.262
Dyslipidemia	0 (0%)	2 (20%)	0.104
Hypertension	0 (0%)	1 (10%)	0.262
No underlying disease	12 (100%)	7 (70%)	0.041

Abbreviation: N/A = not available.

1.2. Study Protocol

Subjects entered an 8‐week intervention program with either a ketogenic diet (low‐carbohydrate, high‐protein, and high‐fat), or general lifestyle advice counseling DASH (low‐fat, rich in vegetables/ fruits, and whole grains) diet from registered dietitians. Subjects, according to the inclusion criteria, received a detailed explanation of this study. All participants or their relatives were allowed to ask questions regarding the details of the study, prior to giving their signed written informed consent. The subjects were randomly assigned with the use of a random number generator, to follow either a ketogenic diet or general lifestyle advice from registered dietitians. A comprehensive nutrition education and physical assessment were undertaken after randomization. All subjects were advised on matters of food and nutrition and their impacts on health. Subjects were asked to assess their physical activity (min/week) and were instructed not to start any dietary supplements during the study. Subjects in both groups were instructed and met with a registered dietitian for 15–30 min at screening, 4, and 8 weeks to review dietary issues and physical activity assessments. After the end of their treatment, telephone follow up was performed after Day 7 to monitor any adverse events.

1.3. Ketogenic Diet

The 12 subjects who were assigned to a ketogenic diet met individually with a registered dietitian before beginning the program to review the features of the ketogenic diet protocol, which involves limiting carbohydrate intake without restricting consumption of fat and protein. Subjects were explained by a physician and a registered dietitian, as well as details on a ketogenic diet, including severe complications or side effects that could occur from a ketogenic diet and how to handle any adverse reactions. Ketogenic diets (1500 kcal per day, with approximately 5% of calories from carbohydrate, 70% from fat, and 25% from protein) were prepared with home delivery to subjects according to the specified address during the study period. Each subject was given a ketogenic diet food list and advised not to allow additional foods outside of what was provided. All patients are advised to keep food diaries which can be used to identify those at risk of undernutrition and monitor those on nutritional support.

1.4. Nutrition Education Program and General Lifestyle Advice (Control Group)

The 12 subjects who were assigned to the standard of care as a control group also met with a registered dietitian before beginning the study to review the components of the Dietary Approaches to Stop Hypertension (DASH) diet. A DASH diet includes foods that are rich in potassium, calcium, and magnesium (1500 kcal per day, with approximately 60% of calories from carbohydrate, 25% from fat, and 15% from protein) and receives instructions about counting calories. Each subject was counseled not to allow additional foods outside in addition to the DASH diet pattern and an energy restriction of 1500 kcal per day. The nutritional program was consistent with the dietary recommendations to reduce the intake of foods high in salt, sodium, saturated fat, total fat, and cholesterol while increasing the intake of fiber, protein, calcium, and minerals such as potassium, magnesium, and so on.

1.5. Outcomes

Primary outcomes of the study were differences in controlled attenuation parameter (CAP) and liver fibrosis measurement by transient elastography (TE) between the ketogenic diet group and the control group in 8 weeks. Secondary outcomes were differences in blood pressure, weight, BMI, waist and hip circumference, liver enzymes (alanine aminotransferase [ALT] and aspartate transaminase [AST]), fasting plasma glucose (FPG), lipid profile (cholesterol, high‐density lipoprotein [HDL], low‐density lipoprotein [LDL], and Triglycerides [TG]), and body composition (muscle mass, fat mass, and visceral fat area).

All subjects received a history taking as well as a physical examination and recorded weight, height, BMI, waist circumference, and hip circumference. To measure the results of this study, comparative data were collected within the same group and between the two groups, including the controlled attenuation parameter (CAP), liver stiffness (transient elastography [TE]), blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), body weight, BMI, waist and hip circumference, liver enzymes (ALT and AST), FPG, lipid profile (cholesterol, HDL, LDL, and TG), and body composition (muscle mass, fat mass, and visceral fat area) by body composition analyzer (InBody) before and after participating in the study in both study groups during a period of 8 weeks. The study period was 8 weeks, with data collection by transient elastography (Fibroscan) intervals. The 8‐week period was proper because changes in the CAP and liver fibrosis (TE) severity could be clearly observed. For the diets of both groups, there were doctors and nutritionists who controlled and monitored the food menus for each meal, in line with the required energy and nutrients in every subject.

To monitor whether the subjects were able to eat according to the researcher's planned diets, all participants must take photos of their daily food menus and send them to the researcher via the personal application every day until the end of the study. All food photos were analyzed, and dietary intake assessments were done by nutritionists throughout the study. To support adherence to the respective diet, subjects were also followed up by phone every week, and a visit to the dietitian was scheduled at Weeks 4 and 8.

1.6. Statistical Analysis

Data were validated and recorded as a data file with the STATA/MP 12 program, then analyzed using the following statistics:

1. Descriptive statistics, such as number, percentage, mean, standard deviation, minimum, and maximum values, were used to show general data about participants.

2. Chi‐square test or Fischer's exact test statistic was applied to compare the characteristics of group baseline data, and independent t‐test or Mann–Whitney U test was used for the continuous data.

3. Intergroup data was analyzed using a t‐test. A repeated measures analysis of variance (ANOVA) was tested to measure the difference between primary and secondary outcomes. They were considered statistically significant only when p < 0.05.

2. Results

2.1. Attrition

This study enrolled 24 participants with metabolic dysfunction‐associated steatotic liver disease who attended the outpatient department of Phramongkutklao Hospital, Bangkok, from September 1, 2021, to January 31, 2022. After scheduling for the first time, two participants in the control group asked to withdraw from the study due to the change in their daily job duties. Thus, they were unable to continue with their follow‐up appointment. This then left a total of 10 participants in the control group (Figure 1). The treatment group was provided with a home delivery ketogenic diet intervention that comprised a total of 12 patients. Whereas there were only 10 patients in the control group with the DASH Diet meal plan who were educated by doctors and nutritionists. The baseline characteristics of the subjects were summarized in Table 1. There were no adverse events reported in both groups.

FIGURE 1.

Flow chart depicting patient enrollment.

2.2. Liver Stiffness and Steatosis Measurement

Changes in the levels of transient elastography and controlled attenuation parameter scores are reported in Table 2. There were no significant differences between groups in liver stiffness or steatosis measurement. The group on a ketogenic diet had a relatively lower controlled attenuation parameter score than the control group.

TABLE 2.

Percent changes in weight, blood pressure, serum blood chemistry, liver stiffness, and steatosis measurement.

Variables	Ketogenic diet	General lifestyle advice	p
	Mean change (95% CI)	Mean change (95% CI)
Systolic blood pressure (mmHg)	−9.4 (−12.9, −5.8)	4.4 (−1.8, 10.6)	< 0.001
Diastolic blood pressure (mmHg)	−4.8 (−9.2, −0.4)	−1.9 (−8.25, 4.45)	0.39
Body weight (kg)	−6.1 (−7.2, −5.1)	−2.14 (−4.49, 0.21)	0.001
Body Mass Index (kg/m2)	−2.4 (−2.9, −2)	−1.52 (−2.91, −0.13)	0.17
Waist circumference (cm)	−9.6 (−13.2, −6.02)	−4.22 (−7.27, −1.17)	0.019
Hip circumference (cm)	−6.8 (−9.1, −4.4)	−4.1 (−6.87, −1.33)	0.11
Muscle mass (kg)	−0.8 (−1.3, −0.3)	−0.37 (−1.02, 0.28)	0.17
Fat mass (kg)	−4.8 (−5.9, −3.7)	−1.42 (−3.58, 0.74)	0.007
Visceral fat area (cm2)	−28.03 (−48.5, −7.5)	−3.73 (−8.7, 1.24)	0.03
Transient elastography (kPa)	−0.6 (−1.8, 0.5)	−0.67 (−1.51, 0.17)	0.97
Controlled attenuation parameter (dB/m)	−43.5 (−66.1, −21.03)	−13.3 (−36.82, 10.22)	0.053
AST (U/L)	−6.5 (−12.6, −0.5)	0.2 (−2.56, 2.96)	0.040
ALT (U/L)	−15.4 (−29.5, −1.2)	−1.2 (−5.24, 2.84)	0.053
Fasting plasma glucose (mg/dL)	−4.7 (−14.1, 4.6)	0.02 (−5.54, 5.58)	0.36
Cholesterol (mg/dL)	−9.2 (−33.9, 15.4)	0.5 (−13.15, 14.15)	0.47
Triglyceride (mg/dL)	−53.5 (−80.5, −26.4)	−14.5 (−43.34, 14.34)	0.041
LDL (mg/dL)	−3.4 (−26.9, 20.1)	−3.5 (−16.26, 9.26)	0.99
HDL (mg/dL)	−5.08 (−9.6, −0.5)	1.2 (−0.95, 3.35)	0.018

2.3. Weight

In the analysis, the group on a ketogenic diet had lost significantly more weight than the control group at 8 weeks (p = 0.001). The mean body weight decrease was 6.16 kg in the ketogenic diet group and 2.14 kg in the control group. Subjects on a ketogenic diet also lost significantly more waist circumference, fat mass, and visceral fat area than the control group at 8 weeks (Table 2). The effects of the diets on body compositions are shown in Figure 2.

FIGURE 2.

Mean (±SE) percent change in body weight (A), waist circumference (B), fat mass (C), and visceral fat area (D) among subjects on the ketogenic diet and those on general lifestyle advice counseling DASH (low‐fat, rich in vegetables/fruits, and whole grains) diet.

2.4. Blood Pressure

Systolic blood pressure decreased significantly in a ketogenic diet group (−9.42 mmHg, p < 0.001) but did not change significantly in the control group (Table 2). Diastolic pressure decreased in both groups, but there was no significant difference between groups.

2.5. Blood Chemistry

The effects of diets on blood chemistry, including aminotransferase enzyme, fasting plasma glucose, and lipid profiles are shown in Tables 2 and 3. There were no significant differences between groups in the blood biochemistry, except the significant decrease in serum triglyceride, serum HDL and AST concentrations were greater in the group on a ketogenic diet. However, the effects of the ketogenic diets significantly improved metabolic parameters over time during the investigatory period (Table 4).

TABLE 3.

Follow‐up of participant groups at the beginning and 8 weeks.

Variables	Week 0			Week 8
	Ketogenic diet	General lifestyle advice	p	Ketogenic diet	General lifestyle advice	p
Systolic blood pressure (mmHg)	132.3 ± 12.2	130.8 ± 15.8	0.80	122.9 ± 11.2	135.2 ± 14.07	0.034
Diastolic blood pressure (mmHg)	84.1 ± 11.9	85.8 ± 10.6	0.74	79.3 ± 11.06	83.9 ± 13.3	0.38
Body weight (kg)	82.9 ± 11.1	78.3 ± 12.6	0.36	76.8 ± 11.4	76.1 ± 12.1	0.90
Body mass index (kg/m2)	31.9 ± 2.7	31.1 ± 3.9	0.59	29.4 ± 2.9	29.6 ± 3.2	0.89
Waist circumference (cm)	102.4 ± 9.6	96.8 ± 12.9	0.27	93.5 ± 5.5	92.6 ± 10.9	0.81
Hip circumference (cm)	108.5 ± 8.3	108.4 ± 10.9	0.97	101.6 ± 6.7	104.3 ± 8.4	0.43
Muscle mass (kg)	27.09 ± 4.9	25.6 ± 5.3	0.51	26.2 ± 5.03	25.2 ± 5.3	0.66
Fat mass (kg)	34.2 ± 5.8	31.4 ± 8.1	0.37	29.3 ± 6.6	30.07 ± 7.2	0.81
Visceral fat area (cm2)	138.5 ± 18.5	124.04 ± 26.3	0.14	110.5 ± 32.7	120.3 ± 23.3	0.43
Transient elastography (kPa)	5.9 ± 3.1	5.01 ± 1.2	0.39	5.2 ± 1.7	4.3 ± 0.7	0.12
Controlled attenuation parameter (dB/m)	283.6 ± 43.1	262.1 ± 54.7	0.31	240.08 ± 30.2	248.8 ± 44.2	0.59
AST (U/L)	29.2 ± 11.6	19.8 ± 6.1	0.032	22.6 ± 4.8	20 ± 4.5	0.202
ALT (U/L)	44.08 ± 21.3	24.3 ± 10.3	0.012	28.6 ± 12.1	23.1 ± 8.7	0.24
FPG (mg/dL)	98.9 ± 18.7	92.5 ± 10.3	0.35	94.1 ± 9.4	92.6 ± 11.3	0.72
Cholesterol (mg/dL)	213.1 ± 50.2	197.8 ± 30.4	0.38	203.9 ± 36.9	198.3 ± 41.01	0.73
Triglyceride (mg/dL)	136.3 ± 76.5	132 ± 61.1	0.88	82.8 ± 44.6	117.5 ± 70.8	0.17
LDL (mg/dL)	138.9 ± 39.5	128.3 ± 33.1	0.508	135.5 ± 31.04	124.8 ± 43.5	0.509
HDL (mg/dL)	55 ± 12.3	54.9 ± 13.5	0.98	49.9 ± 10.2	56.1 ± 13.09	0.22

TABLE 4.

Follow‐up of participant groups over time.

Variables	Ketogenic diet			General lifestyle advice
	Week 0	Week 8	p	Week 0	Week 8	p
Systolic blood pressure (mmHg)	132.3 ± 12.2	122.9 ± 11.2	0.06	130.8 ± 15.8	135.2 ± 14.07	0.43
Diastolic blood pressure (mmHg)	84.1 ± 11.9	79.3 ± 11.06	0.30	85.8 ± 10.6	83.9 ± 13.3	0.68
Body weight (kg)	82.9 ± 11.1	76.8 ± 11.4	0.21	78.3 ± 12.6	76.1 ± 12.1	0.70
Body mass index (kg/m2)	31.9 ± 2.7	29.4 ± 2.9	0.03	31.1 ± 3.9	29.6 ± 3.2	0.13
Waist circumference (cm)	102.4 ± 9.6	93.5 ± 5.5	0.01	96.8 ± 12.9	92.6 ± 10.9	0.41
Hip circumference (cm)	108.5 ± 8.3	101.6 ± 6.7	0.04	108.4 ± 10.9	104.3 ± 8.4	0.31
Muscle mass (kg)	27.09 ± 4.9	26.2 ± 5.03	0.64	25.6 ± 5.3	25.2 ± 5.3	0.99
Fat mass (kg)	34.2 ± 5.8	29.3 ± 6.6	0.04	31.4 ± 8.1	30.07 ± 7.2	0.76
Visceral fat area (cm2)	138.5 ± 18.5	110.5 ± 32.7	0.01	124.04 ± 26.3	120.3 ± 23.3	0.70
Transient elastography (kPa)	5.9 ± 3.1	5.2 ± 1.7	0.48	5.01 ± 1.2	4.3 ± 0.7	0.03
Controlled attenuation parameter (dB/m)	283.6 ± 43.1	240.08 ± 30.2	0.01	262.1 ± 54.7	248.8 ± 44.2	0.51
AST (U/L)	29.2 ± 11.6	22.6 ± 4.8	0.07	19.8 ± 6.1	20 ± 4.5	0.66
ALT (U/L)	44.08 ± 21.3	28.6 ± 12.1	0.012	24.3 ± 10.3	23.1 ± 8.7	0.80
FPG (mg/dL)	98.9 ± 18.7	94.1 ± 9.4	0.53	92.5 ± 10.3	92.6 ± 11.3	0.98
Cholesterol (mg/dL)	213.1 ± 50.2	203.9 ± 36.9	0.60	197.8 ± 30.4	198.3 ± 41.01	0.82
Triglyceride (mg/dL)	136.3 ± 76.5	82.8 ± 44.6	0.06	132 ± 61.1	117.5 ± 70.8	0.003
LDL (mg/dL)	138.9 ± 39.5	135.5 ± 31.04	0.84	128.3 ± 33.1	124.8 ± 43.5	0.807
HDL (mg/dL)	55 ± 12.3	49.9 ± 10.2	0.22	54.9 ± 13.5	56.1 ± 13.09	0.72

2.6. Serum Ketone

During the first 4 weeks, patients in a ketogenic diet group were achieving light nutritional ketosis, defined as blood ketone levels of 0.5–3 mmol/L. However, there were no significant differences in serum ketone between the groups (0.73 ± 0.94 vs. 0.26 ± 0.13, p = 0.116).

3. Discussion

This pilot open‐label, randomized controlled trial demonstrates that the home delivery ketogenic diet produces greater weight loss than the control group with a nutrition education program and general lifestyle advice counseling for 8 weeks, with an absolute difference of approximately 4 kg. These also demonstrated greater loss of waist circumference, body weight and visceral fat mass, including relatively decreased liver steatosis measured by controlled attenuation parameters in a ketogenic diet group. These differences demonstrate a greater energy deficit from carbohydrate restriction in a ketogenic diet group. There is clear evidence that a ketogenic diet is an effective therapy for weight loss, but the mechanism to explain it remains unclear [10]. In our study, all subjects achieved only mild ketosis. It may be explained by the fact that subjects may consume little extra carbohydrate beyond the provided meal, which is why all participants in a ketogenic diet group reported excellent compliance. Our data suggested that ketosis was not an important predictor that affected weight loss benefits, since we did not find any relationship between ketosis and weight loss. Additionally, these findings indicate that long‐term adherence to a therapeutic ketogenic diet may be more achievable with a flexible approach, which allows for occasional, slight carbohydrate intake, as opposed to a strict, rigid approach focused on severe carbohydrate restriction. This flexibility may enhance sustainability and make the ketogenic diet a more practical option for long‐term use.

The difference in weight loss between the two groups demonstrates an overall greater energy deficit in the ketogenic diet group, despite the calorie deficit mainly from restricted carbohydrate intake in this group. The possible mechanism in charge of the decreased energy intake may explain the reduction in appetite due to the higher satiety effect of proteins since we provided the ketogenic diet with unrestricted protein and fat intake. Evidence of ketogenic diet exposure effects on MASLD outcomes has scientific rationales and clinical evidence of improving liver outcomes in patients with MASLD and not worsening hepatic steatosis, including metabolic parameters.

Although significant improvements were observed in metabolic markers, including weight loss, waist circumference, and lipid profiles, liver stiffness and steatosis did not show significant changes. One potential explanation for this could be the relatively short duration of the study (8 weeks), as MASLD is a chronic condition that may require a longer intervention period to observe meaningful changes in liver fat and stiffness. Furthermore, the mild level of ketosis achieved in this study may not have been sufficient to induce more pronounced effects on liver outcomes, suggesting that a more intense or prolonged ketogenic diet might be necessary to elicit significant changes in hepatic parameters.

High‐fat diets could contribute to MASLD, and high‐fat diet‐associated obesity is common in patients with MASLD. In animal models, long‐term high‐fat diet loading can induce obesity, insulin resistance, and MASH [11]. Poor eating habits with high fat intake and perhaps a fad diet such as the ketogenic diet, which emphasizes eating lots of fats while restricting carbohydrate, could lead to MASLD progression. However, in our study, there were no differences in serum cholesterol, liver stiffness, and steatosis measurement by transient elastography.

The overall effect of a ketogenic diet in compared to general lifestyle advise and a DASH diet meal plan on cardiovascular disease risk in our subjects remains uncertain. While the ketogenic diet was associated with improvements in certain cardiovascular risk factors (blood pressure, visceral fat, and serum triglycerides), it did not affect all parameters, and a decrease in serum HDL concentration was observed. The long‐term effects of the ketogenic diet, particularly regarding HDL cholesterol, warrant further investigation, as prolonged use could potentially increase cardiovascular risk due to high saturated fat intake and the limited consumption of fruits and vegetables. To better understand the long‐term safety and efficacy, future studies should involve larger cohorts with extended follow‐up periods to assess the sustainability of weight loss, improvements in metabolic markers, and their impact on liver health and cardiovascular outcomes. Furthermore, ketogenic diets are contraindicated in individuals with certain conditions, such as chronic kidney disease, type 1 diabetes, or a history of severe cardiovascular disease. Monitoring for complications, including electrolyte imbalances, gastrointestinal distress, and elevated inflammatory markers, is essential during implementation. These considerations highlight the need for individualized medical oversight when prescribing a ketogenic diet, particularly for MASLD patients.

Our study had several limitations. This was a pilot open‐label, randomized controlled trial study, and subjects were provided a home delivery diet only in a ketogenic diet group. Possible non‐adherence to a DASH diet meal plan could occur in the control group. However, we tried to minimize this by closely monitoring the dietary approach and performing a food diary for adherence assessment by registered dieticians. In addition, nutritional ketosis demonstrated light nutritional ketosis in the ketogenic diet group, but not much different with a DASH diet meal plan. Possible non‐adherence with little carbohydrate consumption could also occur in the ketogenic diet group. The control group in this study may be difficult to compare to the intervention, as it was education only rather than the provision of food. Therefore, this result may not only look at the effect of a ketogenic diet but also examine the differences between an intervention group with food provision (which likely increases adherence) and a control group with education only. This disparity likely affected adherence, contributing to the greater weight loss and metabolic improvements observed in the ketogenic diet group. Our study was also a nonblinded, small sample randomized controlled trial that could lead to bias due to a decrease in statistical power and the creation of type II error. This concern should be considered when interpreting the results. Moreover, this study also focused on only anthropometric effect, some cardiovascular risks, and liver‐related outcomes. We did not fully evaluate the effect of the ketogenic diet on other important outcomes, such as inflammatory markers, kidney function, and patients' health‐related quality of life. Moreover, our findings may not be generalized to MASH or MASH cirrhotic subjects or to obese subjects with serious obesity‐related complications, such as subjects with diabetes or with coronary disease. Finally, we did not perform a liver biopsy to diagnose subjects with MASLD and did not evaluate inflammatory markers.

4. Conclusion

In our pilot, open‐label, randomized controlled trial, we demonstrated the beneficial effects of a ketogenic diet on some cardiovascular parameters without worsening MASLD progression. However, at the present time, there is not enough information to determine whether the long‐term beneficial effects of a ketogenic diet outweigh its potential adverse outcomes on cardiovascular risk in MASLD patients. Additional long‐term and larger sample size studies are needed in these MASLD populations to evaluate the safety and efficacy of a ketogenic diet.

Ethics Statement

All subjects were properly instructed and consented to participate in this trial by signing the informed consent regulation provided by the Institutional Review Board of the Royal Thai Army Medical Department Committee (IRB number R129h/63) and registered at www . clinicaltrials . in.th (TCTR20220426005). The Institutional Review Board of the Royal Thai Army Medical Department Committee uses the World Medical Association: Delcaration of Helsinki, Guidelines For Good Clinical Practice: ICH Harmonized Tripartite Guideline, Council for International Organizations of Medical Sciences (CIOMS), Code of Federal Regulations: Title 45 Public Welfare; Part 46 Protection of Human Subjects and the Belmont Report to regulate the ethics concerns in publications.

Consent

Informed consent was obtained by signature of all participants and from all subjects to provide all the information regarding publication.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The datasets used during the current study are available from the corresponding author on reasonable request.