Dietary Intake of Major Minerals and Trace Elements in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: Implications for Dietary Intervention

Abstract

Introduction

An imbalanced diet is one of the leading causes of metabolic dysfunction-associated steatotic liver disease (MASLD) development. Diet modification remains the leading approach in the disease management. However, the role of minerals in MASLD development and treatment is poorly understood. In this retrospective study we compared minerals intake in patients with MASLD and age- and sex-matched controls, based on the data of a food frequency questionnaire.

Methods

A retrospective database search was performed to identify eligible data of the nutritional assessment with software based on a food frequency questionnaire. The institutional medical records of the obtained cohort were then searched for medical conditions in accordance with the inclusion/exclusion criteria. On the basis of the presence of MASLD, the subjects were allocated to either MASLD or the control group. Sex- and age-matched pairs were formed for the analysis. Consumption of major minerals and trace elements was compared using non-parametric statistics.

Results

Records of 15,862 subjects were screened, and the data of 226 sex- and age-matched pairs of patients with MASLD and controls were selected for the analysis. The absolute average daily intake of most of the minerals, except silicon, cobalt, molybdenum, nickel, and chromium, was greater in the MASLD group than in the control group. However, relative value (per 1000 kcal) analysis revealed that only boron intake was greater in the MASLD group (28.3 ± 38.5 vs 19.5 ± 24.7 μg/day, p = 0.013). Subjects with MASLD exceeded the recommended daily allowance (RDA) for sodium (241% of RDA), phosphorus (211%), vanadium (1576%), manganese (410%), and selenium (197%) intake, but consumed less than the recommended amounts of silicon (5% of the RDA), molybdenum (28%), fluorine (3%), zinc (91%), and chromium (37%).

Conclusion

Patients with MASLD consumed greater amounts of most minerals than did the control group due to overeating. When diet modification for patients with MASLD is planned, the intake of calcium, zinc, and boron needs to be controlled, and the diet may be modified with food supplements or specific foods rich in these minerals.

Key Summary Points

Why carry out the study?

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread disorder with the estimated average rate reaching 25% of the global population; in the absence of advanced treatment, low-calorie diet and physical activity remain the cornerstone approaches to disease management, but they may result in nutrient deficiencies.

The development of new specialized food products for patients with MASLD requires a better understanding of the role of the nutrients, especially minerals, in the disease development.

In this retrospective study we compared minerals intake in patients with MASLD and age- and sex-matched controls, based on the data of a food frequency questionnaire.

What was learned from the study?

Patients with MASLD consumed greater amounts of sodium (three times greater than the RDA), phosphorus (two times greater than the RDA), manganese, vanadium, and copper, but the consumption of zinc, chromium, silicon, molybdenum, and fluorine was lower than the RDA; consumption of boron was greater in patients than in controls, even after recalculation per 1000 kcal, but was generally lower than in food patterns associated with healthy eating.

If a low-calorie diet is planned for the treatment of MASLD, the intake of calcium, zinc, and boron needs to be controlled, and the diet may be modified with food supplements or specific foods rich in these minerals.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease, with the prevalence rising worldwide [1]. The condition is defined as the presence of excess triglyceride storage in the liver in the presence of at least one cardiometabolic risk factor [2]. A recently introduced definition of MASLD replaced the old term non-alcoholic fatty liver disease (NAFLD) and is embedded in the new consensus on steatotic liver disease (SLD) [1, 2]. However, on the basis of the studies showing nearly complete overlap between NAFLD and MASLD populations, with 99.8% accordance in the NAFLD cohort, while only 5.3% of individuals with NAFLD in the NHANES III database did not fulfil the MASLD criteria, the experts highlighted that the evidence on NAFLD may be transferred to the MASLD population and suggested the use of the term MASLD interchangeably [2]. The prevalence of MASLD varies widely, with the estimated average rate reaching 25% of the global population and has an increasing trend in parallel with the epidemic of obesity and diabetes [3, 4]. Currently, MASLD is the leading cause of end-stage liver disease and liver transplantation in developed countries [5, 6]. This is especially applicable for metabolic dysfunction-associated steatohepatitis (MASH), the progressive subtype of MASLD associated with inflammatory activity within the liver, progression of fibrosis, development of cirrhosis, and hepatocellular carcinoma [2, 6].

To date, only one drug has been approved for the treatment of MASH with fibrosis [7]; therefore, diet and lifestyle changes remain the cornerstone approaches to disease management in the majority of patients with MASLD, taking into account the cost of the drug, limited access to treatment, and the number of patients worldwide [8, 9]. Epidemiological studies have revealed that several dietary factors are involved in MASLD development and progression. Among them are excessive calorie intake and greater consumption of saturated fats, refined carbohydrates, fructose, and sugar-sweetened beverages [10]. These data serve as a basis for current recommendations on dietary interventions for MASLD, which are mostly restrictive [2, 11]. The recommended goal of calorie restriction should result in ≥ 10% overall body weight loss [12]. However, this strategy may lead to deficiencies in micronutrients, antioxidants, and anti-inflammatory factors in the long term. In real practice, patients do not adhere to a strict diet, and no more than 10% of them achieve the indicated weight loss, whereas half of them regain weight during the next 5 years [13]. Dietary interventions based on dietary pattern analyses have been used [14]. A Mediterranean diet, an isocaloric diet, or the use of functional food products enriched with vitamins, minerals, and other micronutrients may minimize the risks of deficiencies and have shown promising results in comparative trials [14–17]. The development of new specialized food products for patients with MASLD and the design of an optimal dietary plan require a better understanding of the role of these nutrients, especially minerals, in the disease development.

In the context of nutrition, a mineral is a chemical element that can be absorbed [18]. Minerals are one of the four groups of essential nutrients; the others are vitamins, essential fatty acids, and essential amino acids. According to the content in the human body and other mammals, the elements are divided into major minerals (≥ 0.01% of body weight) and trace elements (less than 0.01% of body weight). The five major minerals in the human body are calcium, phosphorus, potassium, sodium, and magnesium. The remaining minerals are called trace elements [19]. The generally accepted trace elements are iron, chlorine, cobalt, copper, zinc, manganese, molybdenum, iodine, selenium, and bromine; there is some evidence that there may be more. As minerals play critical roles in human health by regulating various physiological functions, the dietary focus on minerals derives from an interest in the support of the biochemical reactions of metabolism with the required elemental components [20, 21].

Unfortunately, only limited data on mineral consumption in patients with MASLD are available. Therefore, the aim of the present study was to compare the mineral intake of patients with MASLD and an age- and sex-matched control group according to the data obtained with the use of a food frequency questionnaire.

Methods

The data were obtained in a single-center retrospective study. The nutrition assessment software (Nutrilogic, Nutrilogic LLC, Moscow, Russia, registration No. 2018614588 on October 4, 2018) database was screened for eligible data according to the availability and accuracy of patients’ demographics and completeness of the nutritional assessment. The obtained cohort was later searched via institutional medical records for medical conditions in accordance with the inclusion/exclusion criteria. On the basis of the presence of MASLD, the subjects were allocated to either MASLD or the control group. The MASLD group was divided into metabolic dysfunction-associated steatotic liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH) groups on the basis of the new classification and criteria mentioned below [22]. We analyzed the consumption of minerals in paired groups matched by age and sex. The study design and subject allocation chart are shown in Fig. 1.

Fig. 1.

Study design and patient allocation chart. MASLD metabolic dysfunction-associated steatotic liver disease, MASL metabolic dysfunction-associated steatotic liver, MASH metabolic dysfunction-associated steatohepatitis, N number of subjects

Study Population

The records of subjects who were older than 18 years of age and who underwent nutritional assessment were considered eligible.

The exclusion criteria were incomplete nutritional assessment data; inaccurate values of energy intake (< 1000 or > 6000 kcal/day); presence of conditions or disorders that could significantly impact the results (including but not limited to food intolerance/allergy; history of chest or abdominal surgery, including bariatric procedures; major decompensated endocrine disorders; liver cirrhosis; heart failure stage I–IV by New York Heart Association (NYHA) class; chronic kidney disease that requires a special diet; any oncology, excluding skin carcinoma in situ; excessive alcohol intake (> 30 g/day for men, > 20 g/day for women); special diets and dietary supplements intake; viral and autoimmune liver diseases).

The diagnosis of MASLD was based on medical records, which were checked for supporting data: body mass index, waist circumference, pathomorphological assessment of a liver specimen(s) and/or the presence of excessive fat accumulation according to ultrasound, results of controlled attenuation parameter by FibroScan (Echosens, France), and blood chemistry data, including alanine and aspartate transaminase levels, glycated hemoglobin, high-density lipoprotein and plasma triglyceride concentrations. Subjects with chronic elevation of serum transaminases and in whom liver steatosis and liver fibrosis were confirmed by liver biopsy or transient elastography were considered patients with MASH. In the absence of steatohepatitis, subjects with MASLD were considered patients with MASL [22]. To establish MASLD we followed diagnostic algorithm proposed by European Association for the Study of the Liver (EASL)–European Association for the Study of Diabetes (EASD)–European Association for the Study of Obesity (EASO) Clinical Practice Guidelines [1]. We made all the efforts to exclude other conditions that could lead to excessive fat accumulation within the liver and excluded the data of subjects who were prescribed or used corticosteroids, amiodarone, methotrexate, tamoxifen, and active microsomal enzyme inhibitors.

Dietary Assessments

The records of dietary assessments were searched via Nutriliogic software (Nutrilogic LLC, Russia). This patented software is based on a food frequency questionnaire and is validated to obtain the values of the frequency and quantity of consumption of the relevant commonly used foods and products. The data are stored centrally and can be systematized using keyword queries. The software provides data on the intake of energy, nutrients, and food groups, covering 100 food items categorized into 16 major food groups: meat, fish, dairy, eggs, beverages, bread, grains, potatoes, vegetables, soups, fruits, nuts, confectionaries, fats and sauces, alcohol, and fast food. Qualified dieticians collected the data during routine clinical practice. For the purposes of this study, we included records obtained between 2019 and 2024.

Ethical Approval

As a result of the retrospective nature, study approval was waived by the Ethics Committee of the Federal Research Center of Nutrition and Biotechnology. The study was conducted in compliance with the ethical principles for medical research involving human subjects as stated in the Declaration of Helsinki of the World Medical Association. Patient consent was waived because of the retrospective nature of the study, and no personal information was retrieved or used during data mining and analysis. All the subjects gave informed consent for the use of their depersonalized data for scientific purposes according to local rules. No permission to access or use the nutrition assessment software database was necessary as the authors formed and own the database themselves. The use of the institutional medical records database was permitted under conditions of employment.

Statistical Analysis

Statistical analysis of the results was performed with Statistica 10 (StatSoft Inc., USA). Nonparametric statistics (Wilcoxon matched pairs analysis, Mann–Whitney U test) were used to compare the results between the studied groups. Differences were considered significant when the P value was < 0.05. For multiple comparisons, the Bonferroni correction was used.

Results

In total, records of 15,862 subjects were screened. The data of 452 patients were available for the final analysis after inclusion/exclusion criteria were applied (Fig. 1). The study population characteristics are shown in Table 1.

Table 1.

Study population demography and characteristics

	MASLD	Control	P
	n = 226	n = 226
Sex (M/F)	55/171 (24.3/75.5%)	55/171 (24.3/75.5%)	NA
BMI kg/m2	36.1 ± 8.8	25.8 ± 4.7	< 0.001
Weight, kg	101.2 ± 28.4	71.3 ± 14.9	< 0.001
Age, years	49.8 ± 14.2	49.5 ± 14.1	0.898
Mean daily nutrients intake
Energy, kcal/day	2251.7 ± 952.3	2008.5 ± 1006.2	0.001
Carbohydrates, g/day	242.4 ± 131.2	220.2 ± 130.7	0.035
Fats, g/day	99.5 ± 43.6	89.6 ± 49.8	0.006
Proteins, g/day	93.2 ± 38.3	81.6 ± 40.0	< 0.001
Dietary fiber, g/day	24.5 ± 12.8	22.1 ± 16.8	0.003

Data are presented as mean ± SD

MASLD metabolic dysfunction-associated steatotic liver disease, BMI body mass index, M male patients, F female patients, NA not applicable

Owing to the study design, there were no differences in age or sex distribution between patients with MASLD and controls. Patients with MASLD had a higher BMI and demonstrated greater consumption of energy per day (+ 250 kcal) because of increased consumption of all major macronutrients (proteins, fats, and carbohydrates). Notably, patients with MASLD consumed more carbohydrates per day (+ 24 g) than controls did. Patients with MASLD consumed more dietary fiber than those in the control group; however, in both groups the amount of dietary fiber consumption did not exceed the upper limit of the recommended daily allowance (25 g/day, according to recent national guidelines [23]).

Subgroup analysis revealed that patients with MASH were older and had higher BMI values than patients with MASL (Table 2). However, there was no difference in energy or macronutrient consumption between patients with MASH and controls.

Table 2.

Subgroups’ demographics and characteristics

	MASL	Control	P	MASH	Control	P
	n = 162	n = 162		n = 64	n = 64
Women, %	79.6%	79.6%	NA	65.6%	65.6%	NA
BMI, kg/m2	35.6 ± 9.4	25.5 ± 4.6	< 0.001	37.4 ± 6.8	26.4 ± 4.9	< 0.001
Weight, kg	98.9 ± 29.4	70.5 ± 14.7	< 0.001	107.3 ± 24.8	73.6 ± 15.3	< 0.001
Age, years	49.3 ± 14.4	49.0 ± 14.2	0.572	51.2 ± 13.7	50.9 ± 13.9	0.792
Liver fibrosis stage		NA			NA
F0	67.3%			48.4%
F1	6.8%			1.6%
F2	16.1%			26.6%
F3	8.6%			12.5%
F4	1.2%			10.9%
Liver stiffness, kPa	6.1 ± 2.5	NA		8.9 ± 6.5	NA	0.0001a
Mean daily nutrients intake
Energy, kcal/day	2215.5 ± 931.4	1976.0 ± 955.4	0.004	2343.4 ± 1005.1	2090.8 ± 1128.6	0.101
Carbohydrates, g/day	243.1 ± 133.2	133.2 ± 134.7	0.029	240.7 ± 126.8	225.9 ± 120.8	0.517
Fats, g/day	97.1 ± 88.2	42.8 ± 45.7	0.019	105.6 ± 45.4	93.3 ± 58.9	0.128
Proteins, g/day	90.8 ± 79.9	35.6 ± 37.3	0.002	99.4 ± 44.8	85.6 ± 46.2	0.128
Dietary fiber, g/day	24.0 ± 22.2	11.5 ± 18.4	0.004	25.9 ± 15.5	22.0 ± 12.1	0.242

Data are presented as mean ± SD

MASL metabolic dysfunction-associated steatotic liver, MASH metabolic dysfunction-associated steatohepatitis, N number of subjects, NA not applicable

^aMASL vs MASH

The data concerning the consumption of minerals by patients with MASLD and those in the control group are shown in Table 3.

Table 3.

Absolute and relative values of the consumption of major minerals and trace elements in the MASLD and control groups

	RDAa	Absolute values		P	Per 1000 kcal		P
		MASLD	Control		MASLD	Control
		Mean ± SD	Mean ± SD		Mean ± SD	Mean ± SD
Major minerals
Sodium (Na), mg/day	1300	3127.8 ± 2148.2	2648.2 ± 1847.8	0.001	1425.5 ± 784.7	1288.7 ± 453.1	0.112
Potassium (K), mg/day	3500	3648.3 ± 1445.3	3247.7 ± 2043.0	< 0.001	1954.4 ± 3642.7	1683.4 ± 620.6	0.410
Calcium (Ca), mg/day	1000b	956.0 ± 514.8	839.9 ± 466.7	0.011	438.8 ± 201.3	424.4 ± 130.6	0.953
Phosphorus (P), mg/day	700	1475.8 ± 598.3	1285.5 ± 591.0	< 0.001	685 ± 245.3	663.2 ± 142.2	0.228
Magnesium (Mg), mg/day	420	382.0 ± 156.0	343.6 ± 183.0	0.001	180.3 ± 69.2	178.3 ± 50	0.779
Sulfur (S), mg/day	NA	63.5 ± 54.0	53.8 ± 50.1	0.045	30.8 ± 31.1	27.6 ± 19.4	0.840
Trace elements
Iron (Fe), mg/day	M: 10; F: 18	19.8 ± 8.2	17.4 ± 9.6	< 0.001	9.2 ± 3.4	9.0 ± 2.7	0.801
Copper (Cu), mg/day	1	1.5 ± 0.6	1.3 ± 0.7	0.003	0.8 ± 1.5	0.7 ± 0.3	0.470
Cobalt (Co), μg/day	10	14.5 ± 10.5	13.6 ± 12.2	0.175	7.1 ± 5.7	7.5 ± 6	0.484
Silicon (Si), mg/day	30	1.5 ± 3.2	1.6 ± 6.9	0.297	0.7 ± 1.5	0.6 ± 1.7	0.349
Boron (B), μg/day	NA	56.4 ± 71.9	39.3 ± 52.7	0.002	28.3 ± 38.5	19.5 ± 24.7	0.013
Vanadium (V), μg/day	15	236.4 ± 182.4	199.7 ± 146.3	0.009	108.6 ± 68.8	105.8 ± 71.9	0.410
Iodine (I), μg/day	150	115.1 ± 71.6	99.9 ± 73.3	0.01	55.2 ± 35.3	55.6 ± 41.8	0.682
Manganese (Mn), mg/day	2	8.2 ± 6.4	6.9 ± 5.0	0.009	3.7 ± 2.2	3.6 ± 2.5	0.535
Molybdenum (Mo), μg/day	70	19.4 ± 14.5	20.4 ± 34.7	0.257	9.6 ± 7.6	11.6 ± 24.9	0.799
Nickel (Ni), μg/day	NA	42.9 ± 33.5	41.4 ± 51.0	0.177	21.1 ± 16.1	21.9 ± 19.3	0.867
Selenium (Se), μg/day	M: 70; F: 55	108.2 ± 49.0	91.3 ± 45.9	< 0.001	51 ± 19	48.9 ± 19.8	0.203
Fluorine (F), μg/day	4000	117.6 ± 85.7	106.8 ± 72.8	0.048	55.3 ± 32.9	56.8 ± 32.5	0.588
Chromium (Cr), μg/day	40	14.7 ± 10.4	13.8 ± 14.4	0.076	7.1 ± 5.1	7.4 ± 5.9	0.806
Zinc (Zn), mg/day	12	10.9 ± 4.8	9.6 ± 5.1	0.001	5.2 ± 2.2	5.1 ± 3.1	0.388

MASLD metabolic dysfunction-associated steatotic liver disease, RDA recommended daily allowance, M RDA for male patients, F RDA for female patients

^aAccording to [23]

^bFor subjects > 60 years old, 1200 mg/day

The absolute values of daily intake of all minerals, except silicon, cobalt, molybdenum, nickel, and chromium, were greater in the MASLD group. However, when relative values (per 1000 kcal/day) of consumption were evaluated, only boron intake was greater in patients with MASLD than in the control group (Table 3). Subjects with MASLD exceeded the recommended daily allowance (RDA) [23] for sodium (241% of the RDA), phosphorus (211%), vanadium (1576%), manganese (410%), and selenium (197%) intake, but consumed less than recommended amounts of silicon (5% of the RDA), molybdenum (28%), fluorine (3%), zinc (91%), and chromium (37%).

Subgroup analysis revealed that the absolute values of the daily intake of sodium, potassium, calcium, magnesium, phosphorus, iron, boron, vanadium, manganese, copper, selenium, and zinc were greater in the MASL group than in the control group. Nevertheless, analysis of relative values (per 1000 kcal/day) of consumption showed that only boron intake was greater in subjects with MASL, compared to the controls, whereas no significant difference was found for the rest of the minerals (Table 4).

Table 4.

Absolute and relative values of daily mineral consumption in the metabolic dysfunction-associated steatotic liver (MASL) and the control group

	Absolute values		P	Per 1000 kcal		P
	MASL	Control		MASL	Control
	Mean ± SD	Mean ± SD		Mean ± SD	Mean ± SD
Major minerals
Sodium (Na), mg/day	2980.3 ± 1542.4	2521.3 ± 1661.4	< 0.001	1378.4 ± 574.2	1263.4 ± 438.3	0.1
Potassium (K), mg/day	3574.19 ± 1433.3	3254.2 ± 2223.4	< 0.001	1699.6 ± 710.5	1691.6 ± 623.3	0.9
Calcium (Ca), mg/day	939.8 ± 484.4	833.9 ± 459.8	0.015	435.2 ± 204.0	427.5 ± 131.0	0.8
Magnesium (Mg), mg/day	376.4 ± 152.7	343.2 ± 193.0	0.004	178.8 ± 69.4	179.1 ± 50.2	0.5
Phosphorus (P), mg/day	1441.5 ± 573.0	1268.8 ± 556.3	0.001	669.7 ± 228.7	664.9 ± 138.4	0.7
Sulfur (S), mg/day	64.3 ± 55.4	55.2 ± 53.4	0.1	30.4 ± 26.2	28.5 ± 20.0	0.9
Trace elements
Iron (Fe), mg/day	19.7 ± 8.3	17.3 ± 9.9	< 0.001	9.2 ± 3.3	9.0 ± 2.7	0.9
Silicon (Si), mg/day	1.5 ± 3.1	1.91 ± 8.1	0.7	0.7 ± 1.3	0.7 ± 1.9	0.9
Boron (B), μg/day	56.4 ± 75.5	38.0 ± 50.0	0.003	28.4 ± 39.1	19.5 ± 25.0	0.03*
Vanadium (V), μg/day	236.2 ± 167.6	195.9 ± 149.7	0.002	109.7 ± 68.7	104.3 ± 71.6	0.3
Iodine (I), μg/day	113.6 ± 67.7	100.0 ± 72.5	0.06	54.7 ± 34.9	55.9 ± 40.1	0.8
Cobalt (Co), μg/day	14.3 ± 10.6	14.1 ± 13.5	0.6	6.9 ± 5.1	7.7 ± 6.0	0.2
Manganese (Mn), mg/day	8.1 ± 5.8	3.6 ± 2,1	0.024	6.7 ± 4.8	3.5 ± 2.3	0.4
Copper (Cu), mg/day	1.5 ± 0.6	1.3 ± 0.8	0.01	0.8 ± 1.8	0.7 ± 0.3	0.4
Molybdenum (Mo), μg/day	19.6 ± 14.9	21.9 ± 40.3	0.4	9.8 ± 7.9	12.5 ± 29.0	0.5
Nickel (Ni), μg/day	42.9 ± 33.6	43.14 ± 57.7	0.3	21.1 ± 16.6	22.7 ± 20.1	0.8
Selenium (Se), μg/day	107.33 ± 46.8	89.9 ± 44.7	< 0.001	50.6 ± 17.1	48.7 ± 19.2	0.3
Fluorine (F), μg/day	114.1 ± 63.5	109.0 ± 75.4	0.2	54.2 ± 29.5	58.4 ± 32.9	0.3
Chromium (Cr), μg/day	14.6 ± 10.4	14.2 ± 16.1	0.2	7 ± 4.9	7.6 ± 6.0	0.8
Zinc (Zn), mg/day	10.7 ± 4. 6	9.4 ± 4.9	0.009	5.1 ± 1.9	5.1 ± 2.8	0.7

MASL metabolic dysfunction-associated steatotic liver

*Statistically significant (P < 0.05)

Compared with those in the control group, the absolute mean daily intake of potassium and selenium in the MASH group was greater. There was no significant difference between the groups in terms of the consumption of other minerals (Table 5). The relative values of mineral consumption were similar between the MASH and control groups.

Table 5.

Absolute and relative values of daily mineral consumption in the MASH and control groups

	Absolute values		P	Per 1000 kcal		P
	MASH	Control		MASH	Control
	Mean ± SD	Mean ± SD		Mean ± SD	Mean ± SD
Major minerals
Sodium (Na), mg/day	3501.4 ± 3194.3	2969.4 ± 2234.8	0.3	1544.8 ± 1156.1	1352.7 ± 486.4	0.5
Potassium (K), mg/day	3836 ± 1470	3231.2 ± 1507.2	0.04*	2599.2 ± 6746.2	1662.6 ± 618.2	0.1
Calcium (Ca), mg/day	996.8 ± 587	855 ± 487.2	0.3	448 ± 195.7	416.6 ± 130.5	0.6
Magnesium (Mg), mg/day	396.4 ± 164.5	344.7 ± 155.9	0.1	184.2 ± 69.1	176.3 ± 49.8	0.6
Phosphorus (P), mg/day	1562.8 ± 654.9	1327.8 ± 673.6	0.1	723.7 ± 281.3	659 ± 152.6	0.1
Sulfur (S), mg/day	61.5 ± 50.6	50.1 ± 40.6	0.2	31.9 ± 41.1	25.2 ± 17.9	0.6
Trace elements
Iron (Fe), mg/day	19.9 ± 8.2	17.6 ± 8.6	0.1	9.3 ± 3.7	9 ± 2.6	0.7
Silicon (Si), mg/day	1.6 ± 3.6	0.8 ± 1.5	0.2	0.8 ± 1.9	0.4 ± 0.7	0.1
Boron (B), μg/day	56.5 ± 62.6	42.7 ± 59.2	0.2	27.9 ± 37.2	19.4 ± 24	0.2
Vanadium (V), μg/day	236.8 ± 216.8	209.3 ± 138.3	0.9	105.6 ± 69.6	109.5 ± 73.2	0.8
Iodine (I), μg/day	119.1 ± 81.1	99.5 ± 75.9	0.1	56.6 ± 36.6	55 ± 46.3	0.3
Cobalt (Co), μg/day	15.2 ± 10.4	12.4 ± 8	0.1	7.6 ± 6.9	6.8 ± 5.7	0.4
Manganese (Mn), mg/day	8.7 ± 7.7	7.4 ± 5.4	0.2	3.8 ± 2.3	3.9 ± 3	0.9
Copper (Cu), mg/day	1.5 ± 0.6	1.3 ± 0.6	0.1	0.7 ± 0.3	0.7 ± 0.3	0.9
Molybdenum (Mo), μg/day	18.8 ± 13.7	16.7 ± 11.4	0.5	9.3 ± 6.6	9.2 ± 7.9	0.6
Nickel (Ni), μg/day	42.8 ± 33.4	37 ± 27.4	0.4	21.1 ± 15.2	20 ± 17.2	0.4
Selenium (Se), μg/day	110.5 ± 54.6	94.9 ± 49.1	0.01*	52 ± 23.4	49.5 ± 21.4	0.4
Fluorine (F), μg/day	126.5 ± 125.7	101.3 ± 65.9	0.1	58.2 ± 40.5	52.7 ± 31.6	0.5
Chromium (Cr), μg/day	15 ± 10.6	12.7 ± 8.8	0.3	7.5 ± 5.6	6.9 ± 5.7	0.4
Zinc (Zn), mg/day	11.3 ± 5.3	9.9 ± 5.5	0.1	5.4 ± 2.8	5.2 ± 3.7	0.4

MASH metabolic dysfunction-associated steatohepatitis

*Statistically significant (P < 0.05)

Discussion

This study is the first to investigate the dietary intake of major minerals and trace elements in Russian patients with MASLD. We showed that patients with MASLD consumed more energy than controls did because they consumed more major macronutrients, which explains why the majority of them were obese or overweight (Table 1). The dietary intake of most of the minerals we studied was greater in patients with MASLD than in controls (Table 3), but recalculation of the consumption of minerals per 1000 kcal showed that the observed difference was the result of overeating. In other words, the dietary patterns of patients with MASLD and controls were similar, and the only difference was the amount of food consumed (Fig. 2).

Fig. 2.

Structure of energy sources in subjects with metabolic dysfunction-associated steatotic liver, and in the control group. MASL metabolic dysfunction-associated steatotic liver

A similar case–control study in Iran revealed decreased consumption of zinc and potassium in patients with NAFLD [24]; however, in that study, there were no differences in energy or macronutrient consumption between the NAFLD and control groups, and the mean energy intake for both groups was surprisingly low (less than 2000 kcal/day). Another study from Iran revealed increased energy intake by patients with NAFLD but no difference in the consumption of minerals when the daily intake per 1000 kcal was recalculated [25]. In a case–control study from Jordan [26], increased energy intake and increased calcium, iron, selenium, and zinc consumption were demonstrated in patients with NAFLD; however, the authors did not recalculate the consumption of minerals per 1000 kcal. For sure, local dietary habits specific for these Asian countries could influence the obtained results in energy and minerals consumption. However, a Canadian case–control study revealed that a typical Western diet increased the consumption of fats by patients with NAFLD, but it did not show any difference in the consumption of minerals between patients and controls, while sodium intake was increased in all studied groups [27]. A similar greater consumption of sodium was found in our study in both MASLD (three times higher than the RDA) and the control group (two times higher RDA), which reflects the similar dietary patterns in them (Fig. 2).

We found surprisingly lower amounts of silicon consumption in the MASLD and control groups than are recommended by national guidelines (Table 3) [23]. This can be partially explained by the low consumption of fruits and vegetables, which are the main sources of silicon in the diet. Another major source of silicon is grains; however, their processing to produce different types of bread, which is highly consumed by both studied groups, results in a dramatic decrease in the silicon content in the end product [28]. Of note, there is no evidence that decreased silicon consumption may influence the development of MASLD or any other liver disease.

Consumption of phosphorus at twofold greater than the RDA amounts was found in both groups in our study, which clearly reflects that they followed a Western-type diet. According to the NHANES, daily consumption of 1400–1700 mg/day of phosphorus was typical for middle-aged Americans at the end of the twentieth century [29]. In addition, a typical sign of this dietary pattern, which we found in both studied groups, was the combination of low or recommended consumption of calcium and twofold increased consumption of phosphorus, which can lead to bone metabolism imbalance [30].

Subjects of the MASLD and control groups in our study consumed greater amounts of vanadium than is recommended [23]; however, these levels were far below the safe upper limit for intake of this trace element [31]. The consumption of manganese in patients with MASLD and the controls was four times greater than is recommended by national or European RDAs for adults [32]; however, the dietary consumption of manganese is highly variable and can reach 11 mg/day with a typical Western diet [33].

The only mineral with increased daily intake in both absolute and relative (per 1000 kcal/day) values in our study in patients MASLD was boron (Table 3). We found a significant difference in the consumption of boron by patients with simple steatosis and participants in the control group (Table 4), but not in patients with MASH (Table 5). Boron is considered an essential mineral according to animal studies [34], but there are insufficient quantitative data to establish a definitive RDA. The average daily boron intake in the USA ranges from approximately 0.96 mg/day for women to 1.17 mg/day for men, with slightly greater consumption in vegetarians [35, 36]. Our study revealed that the level of boron consumption was twice as low even in patients with MASLD, which is not surprising because the major dietary sources of boron include nuts, dried fruits, legumes, fresh vegetables, and fruits [36, 37], which constitute less than 10% of the daily energy intake of the study participants (Fig. 2). Previous population-based study revealed that plasma boron concentrations were associated with dietary patterns, with higher boron levels linked to a healthier diet and lifestyle, including a lower BMI and favorable cardiometabolic profiles. Age, phosphate, and plasma lipid concentrations were directly associated with boron levels, whereas BMI, C-reactive protein (CRP), and plasma lipid concentrations were related inversely. The study identified a dietary pattern characterized by a high intake of fruits, nuts/seeds, tea, and wine and a low intake of bread, poultry, processed meat, and sweets associated with plasma boron concentrations [38]. These data were confirmed by a small clinical trial involving 13 healthy women who consumed a diet containing 10 mg more boron than their routine diet for 1 month. This increase was achieved by incorporating boron-rich foods such as dried fruits, avocado, and nuts into their diet, resulting in a significant decrease in BMI, body weight, and body fat mass despite similar energy and macronutrient consumption before and during the intervention [39]. After 1 month of intervention, the serum, saliva, and urine boron values increased 1.3-, 1.7-, and sixfold, respectively; however, a significant decrease in the serum concentrations of total cholesterol, triglycerides, and very low- and low-density lipoprotein cholesterol was detected. Boron supplementation at doses of 3 to 10 mg/day has been used in several studies of patients with osteoarthritis or postmenopausal women and has been shown to support bone health without exceeding the tolerable upper intake level, which is 20 mg/day for adults [40]. Thus, boron seems to be an important mineral for preventing or possibly treating MASLD in the future, as animal studies have clearly demonstrated the effects of boron on fat accumulation in the liver, insulin resistance, and its anti-inflammatory and antioxidative properties [41, 42].

The consumption of zinc was lower than that of RDA in both patients with MASLD and the controls; however, the difference in the consumption between groups was evidently related to overeating, as the recalculation of consumption of zinc per 1000 kcal showed no difference (Table 3). Zinc has been studied for its potential therapeutic effects on MASLD owing to its roles in metabolism, antioxidant defense, and inflammation. Patients with MASLD often have lower serum concentrations of zinc than healthy controls despite similar dietary zinc intakes, suggesting issues with absorption or greater requirements of the mineral in these patients [43]. Zinc supplementation has been shown to improve insulin resistance and oxidative stress in overweight patients with MASLD, although it does not significantly affect lipid profiles beyond the effects of a calorie-restricted diet [44]. In another study, zinc supplementation significantly reduced liver enzymes (alanine aminotransferase and γ-glutamyl transpeptidase) and waist circumference in overweight and obese patients with MASLD, indicating some improvement in liver function and metabolic health [45]. However, in both studies, the daily dose of zinc was 2.5 times higher than the RDA, and the dietary consumption of the mineral by both the patients and controls was similar and very close to the RDA. Unfortunately, liver steatosis was evaluated via abdominal ultrasound, which makes it difficult to differentiate the degree of steatosis and its changes during dietary intervention. However, in an animal model, zinc supplementation did not reverse established MASLD induced by a high-fat diet, suggesting that zinc may be more effective in prevention or early intervention than in reversing advanced stages of the disease [46].

The consumption of chromium was lower than that of RDA in both patients with MASLD and controls; however, there was no difference in consumption between the groups (Table 3). Animal studies indicate that chromium can reduce hepatic triglyceride accumulation, which is a key factor in the progression of NAFLD, and this reduction is associated with the elevation of hepatic lipid catabolic enzymes [47]. Interestingly, an independent negative correlation between blood chromium and hepatic steatosis in the American population was found, and the calculation revealed that an elevation of 1 μg/L in blood chromium corresponded to a decrease in the controlled attenuation parameter by − 5.62 (− 11.02, − 0.21) dB/m, suggesting that the effect of intervening with blood chromium may be a potential therapeutic strategy for MASLD [48]. The data of another population-based study suggest that patients with NAFLD are more likely to experience depression, whereas those with higher serum concentrations of chromium have lower odds of suffering from depression, and this association persists even after adjusting for other factors [49]. However, a placebo-controlled trial with chromium picolinate supplementation at a dose 10 times greater than the RDA over 3 months (400 µg/day) demonstrated a clear effect on triglycerides, insulin, HOMA-IR, fetuin-A, and some inflammatory markers, but not on fasting glucose, cholesterol, LDL, HDL, or liver steatosis [50, 51].

The consumption of copper in the MASLD group was 30% higher than the RDA (Table 3); however, it is three times lower than the recently established Acceptable Daily Intake for the EU at 0.07 mg/kg/day [32]. The data of some studies suggested that a low hepatic copper concentration is associated with NAFLD and its complications [52–54], but serum copper levels are not significantly associated with NAFLD, indicating that serum copper may not be a reliable marker for this disease [52, 55]. Indeed, the results of studies on serum copper and NAFLD risk are controversial. Thus, in one study, lower serum copper levels were associated with NAFLD only in men with metabolic syndrome, but not in women [56], whereas other research showed that excess serum copper is significantly associated with the risk of NAFLD, which is prominent in female patients, middle-aged individuals, and subjects with improved insulin resistance [57]. Other authors reported that certain genetic polymorphisms may be associated with different copper liver contents and disease phenotypes [54, 58]; therefore, it is difficult to determine the exact proportion of patients with NAFLD in whom copper exposure or metabolism is involved in disease risk or progression. Copper may also have an indirect effect on the risk and progression of NAFLD, as many polyphenolic compounds (curcumin, epigallocatechin-3-gallate, resveratrol, etc.) recognized as being effective against NAFLD have been demonstrated to bind copper to exert its antioxidant and chelating activities [59]. On the other hand, excessive copper consumption may be associated with significant liver toxicity which often exhibits liver steatosis [20, 60].

Despite the approval of the first drug for the treatment of MASH with fibrosis, the combination of diet and physical activity will remain the mainstream treatment for most patients with MASLD for many years. Achieving a weight loss of 7–10% from baseline is crucial for improving liver steatosis and reducing cardiovascular risk. Even modest weight loss (> 5%) can yield significant benefits according to high-quality studies and meta-analyses [61–64]. According to these data, professional societies of hepatologists recommend a hypocaloric diet combined with regular physical activity as first-line treatment for MASLD [2, 9, 65]. In addition to low adherence to hypocaloric diets in the long term, the risk of micronutrient deficiency is substantial [66]. Thus, 3-month use of a specially designed hypocaloric diet in subjects with obesity provided dietary reference intake of micronutrients and resulted in even lower levels of zinc, vitamin C, and lycopene than before the intervention [67]. A 3-month low-carbohydrate ketogenic diet in patients with obesity was associated with the intake of magnesium, calcium, iron, phosphorus, and potassium below the recommended values and a decrease in the calcium blood level [68]. Similarly, in another study, patients with obesity were prescribed a healthy diet, with increased consumption of fruits and vegetables and avoidance of high-energy dense food for 4 months; at the end of the dietary intervention, the consumption of calcium, magnesium, zinc, copper, and manganese decreased [69].

To achieve nutritional adequacy, supplementation with micronutrients (vitamins and minerals, such as K, Na, Mg, Ca, and omega-3 fatty acids) is recommended for patients on a very low-calorie diet [70]; however, these recommendations may not be universal. As shown in the study cited above, the consumption of sodium decreased during 4 months of dietetic intervention, but still exceeded the RDA [69]. Ethnic differences and local dietary patterns may also be important; thus, a 12-month intervention with different low-calorie diets in young women Asian with obesity showed that normal iron and zinc status can be maintained during 12 months of energy restriction, in contrast to studies with participation of subjects of European [71].

In our study, we observed inadequate consumption of several minerals, which may be worsened by the prescription of a low-calorie diet for the treatment of MASLD. Changing the calcium to phosphorus ratio to 2:1 is quite difficult, as in patients with MASLD, phosphorus intake is two times higher than the RDA, and the consumption of calcium is close to the recommended amounts (Table 3). According to studies of low-calorie diets, the decrease in the consumption of calcium is more profound than that of phosphorus [68, 69]; therefore, the increase of the consumption of calcium with supplements or foods enriched with calcium is necessary. The increased consumption of calcium up to 1400 mg/day using calcium supplements or three portions of skimmed milk during the 8-week low-calorie diet was safe and did not influence iron absorption and metabolism [72], which may be disturbed by increased calcium intake. Zinc is of potential concern if a low-calorie diet is prescribed to patients with MASLD because its consumption does not reach the RDA (Table 3), and a low-calorie diet can make it even worse [69]. According to an interventional study, zinc supplementation (30 mg/day) with a restricted-calorie diet diminished appetite, allowing for increased adherence to diet, and had favorable effects on the reduction of the levels of inflammatory markers and insulin resistance—key factors associated with the progression of MASLD [73]. It would be desirable to increase boron consumption, as it is very low in patients with MASLD as well as in controls (Table 3). The absence of RDA and studies using boron supplementation in patients with MASLD leave the possibility to increase its consumption by the introduction of boron-rich foods, with up to 10 mg of boron a day, as a study that used the same approach in women with obesity demonstrated favorable effects [39].

Our study had several limitations. First, we studied only consumption, but not the blood levels of minerals, whose absorption may differ between patients and controls. We used an age- and sex-matched paired study design, which allowed us to diminish the influence of the food habits between women and men, and those observed in different age groups on the results. We did not assess the menopausal status of women older than 50 years of age enrolled in the study, although some metabolic differences may exist between pre- and postmenopausal groups, which may to some extent affect the study results. It would be better to compare pairs with similar BMIs, but this is extremely difficult to perform, as the vast majority of patients with MASLD have excessive weight or obesity.

Conclusions

This study revealed that the intake of most minerals was greater in patients with MASLD than in controls because of overeating. Patients with MASLD consumed greater amounts of sodium (three times greater than the RDA), phosphorus (two times greater than the RDA), manganese, vanadium, and copper, but the consumption of zinc, chromium, silicon, molybdenum, and fluorine was lower than the RDA. The consumption of boron was greater in patients than in controls, even after recalculation per 1000 kcal, but was generally lower than in food patterns associated with healthy eating. If a low-calorie diet is planned for the treatment of MASLD, the intake of calcium, zinc, and boron needs to be controlled, and the diet may be modified with food supplements or specific foods rich in these minerals.

Author Contributions

Conceptualization—Vasily Isakov; methodology—Vasily Isakov, Sergey Morozov, Armida Sasunova and Alexei Goncharov; software—Alexei Goncharov; validation—Sergey Morozov; data analysis—Alexei Goncharov; resources—Vasily Isakov, Sergey Morozov; writing, original draft—Vasily Isakov, Sergey Morozov, Alexei Goncharov; writing, review & editing—Sergey Morozov and Vasily Isakov; supervision—Vasily Isakov. All authors have read and agreed to the published version of the manuscript.

Funding

The research was funded by the Russian Science Foundation (Project No. 19-76-30014). No funding or sponsorship was received for the publication of this article.

Data Availability

The data are presented in the paper. The raw data supporting the conclusions of this article may be shared upon reasonable request to the corresponding author.

Declarations

Conflict of Interest

Vasily Isakov, Armida Sasunova, Sergey Morozov and Alexei Goncharov have nothing to disclose.

Ethical Approval

As a result of the retrospective nature, study approval was waived by the Ethics Committee of the Federal Research Center of Nutrition and Biotechnology. The study was conducted in compliance with the ethical principles for medical research involving human subjects as stated in the Declaration of Helsinki of the World Medical Association. No permission to access or use the nutrition assessment software database was necessary as the authors formed and own the database themselves. The use of the institutional medical records database was permitted under conditions of employment. Patient consent was waived because of the retrospective nature of the study, and no personal information was retrieved or used during data mining and analysis. All the subjects gave informed consent for the use of their depersonalized data for scientific purposes according to local rules.