Journal of Medical and Biomedical Discoveries (ISSN: 2688-8718)

Article / research article

"Association of Intake of Dietary Vitamin C and Vegetables with Non-Alcoholic Fatty Liver Disease (NAFLD) In Middle-Aged Japanese Men"

Shiori Sugawara1,2 and Ikuyo Tsukamoto1,3*

1Department of Food Science and Nutrition, Nara Women’s University, Kitauoya-nishimachi, Nara, Japan

2Department of Health and Nutrition, Sendai Shirayuri Women’s College, Honda-Cho, Izumi-ku, Sendai, Japan

3Faculty of Clinical Nutrition, Hiroshima International University, Hirokoshingai, Kure, Hiroshima, Japan

*Corresponding author: Ikuyo Tsukamoto, Faculty of Clinical Nutrition, Hiroshima International University, Hirokoshingai, Kure, Hiroshima, Japan. Tel: +81823738254; E-mail: itsuka@cc.nara-wu.ac.jp

Received Date: 16 February, 2019; Accepted Date: 05 March, 2019; Published Date: 13 March, 2019

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common causes of liver disease world-wide and has been recognized as a major health burden. The aim of the present study was to determine the associations of plasma Vitamin C (VitC) levels and intake of dietary VitC and vegetables with ultrasound-diagnosed non-alcoholic fatty liver disease (NAFLD) in Japanese men. The plasma VitC levels and the intake of dietary VitC and vegetables decreased with the severity of fatty liver. After adjustment for the age, body mass index (BMI), physical activity, and smoking status, higher intake of dietary VitC and vegetables was significantly associated with a lower prevalence of NAFLD. The odds ratio (OR) for the highest quartile (Q4) versus the lowest quartile (Q1) of the intake of dietary VitC was 0.27 (P=0.045) and the OR for Q4 versus Q1 of vegetable intake was 0.29 (P=0.035). These results suggest that increases in the intake of dietary VitC and vegetables prevent NAFLD independently of BMI.

Keywords: Dietary Vitamin C Intake; NAFLD; Plasma Vitamin C; Vegetable Intake

Abbreviations: BMI: Body Mass Index

                             BP: Blood Pressure

                             NAFLD: Non-Alcoholic Fatty Liver Disease

                             OR: Odds Ratio

                             ROS: Reactive Oxygen Species

                             VitC: Vitamin C

                             VitE: Vitamin E

                             WC: Waist Circumference

Introduction

Non-alcoholic Fatty Liver Disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by relatively benign hepatic steatosis to Non-Alcoholic Steatohepatitis (NASH), severe cirrhosis and fibrosis.  NAFLD has become one of the most common causes of liver disease world-wide and has been recognized as a major health burden. Currently, there is still no specific treatment for NAFLD except lifestyle modification involving exercise and dietary adjustment. NAFLD is strongly linked to obesity, with a reported prevalence as high as 80% in obese patients and only16% in individuals with a normal BMI and without metabolic risk factors [1,2]. Obesity is a state of chronic low-grade inflammation [3]. Oxidative stress is considered to cause the metabolic disturbances in obesity. In agreement with a putative role of oxidative stress in the etiology of NAFLD, the antioxidant nutrient, Vitamin C (VitC), but not Vitamin E (VitE), has been reported to reduce oxidative stress and inhibit the development of experimental liver steatosis in rats [4]. VitC is a water-soluble, chain-breaking antioxidant that scavenges essentially all physiologically relevant free radicals [5]. VitC deficiency is defined as plasma levels below 23 μM [6]. The deficiency of VitC potentially enhances susceptibility to oxidative stress and disease [7]. VitC status inversely correlates with BMI and is significantly decreased in obese compared with lean individuals [8-11]. Thus, the association of NAFLD with obesity and oxidative stress suggests an important role of VitC in NAFLD progression. Some studies showed correlations of NAFLD progression with dietary VitC intake, while others did not [12]. Furthermore, dietary VitC intake is not necessarily correlated with plasma VitC levels [13]. The results of the studies examining VitC plasma levels in NAFLD [14-16] are inconclusive and do not allow a definitive conclusion regarding plasma VitC levels as well as VitC intake in NAFLD [12]. Thus, there is a need for further study to elucidate the effects of plasma VitC levels and dietary intakes of VitC on NAFLD. In this study, to clarify the role of VitC in the development and progression of NAFLD, we investigated the association of the plasma VitC levels and intake of dietary VitC and vegetables with NAFLD in Japanese men.

Subjects and Methods

Subjects

The subjects were 198 Japanese men who participated in a health examination conducted in 2007, 2008, 2009, 2011, and 2013 at Nara Health Promotion Center. All participants who had present and past medical treatment and medication use, evidence of other liver diseases (viral hepatitis B or C, primary biliary cirrhosis, sclerosing cholangitis, autoimmune hepatitis hemochromatosis, or drug-induced liver disease), or more than 20 grams per day of alcohol consumption were excluded. The study was designed in accordance with the principles of the Declaration of Helsinki of the World Medical Association and approved by the Ethics Committee of Nara Women’s University, Japan. At the time of enrolment, written informed consent was obtained from each participant.

Measurement

The participants underwent routine health examinations, anthropometric and blood pressure (BP) measurements, and the collection of fasting blood samples. A face-to-face interview was conducted by trained interviewers using questionnaires about the medical condition, medication use, lifestyle of physical activity (more than 30 min of exercise or 1 hour of walking per day), current smoking, and alcohol drinking (20 grams of ethanol per day), and a previously validated food frequency questionnaire [17].

Ultrasonography of The Liver

Diagnosis of NAFLD in this study was based on sonographic evidence of a fatty liver and negative test results of HBsAg and anti-HCV antibody. Abdominal ultrasonography was performed by clinical hepato-gastroenterologists using Ultrasound GE LOGIQ7 (General Electric Co., CT, USA). The results of ultrasonography were divided into mild, moderate, and severe stages according to the criteria described by Saverymuttu et al. [18].

Anthropometry

The Body Mass Index (BMI) was calculated as the body weight (kilogram) divided by the square of the height (meter). The Waist Circumference (WC) was measured using an anthropometric measuring tape at a horizontal plane midway between the lowest rib and iliac crest. Blood pressure (BP) was measured in triplicate with a validated semi-automatic sphygmomanometer.

Laboratory Measurements

All serum and plasma samples were obtained in a fasting state. The biochemical parameters such as Alanine Transaminase Activity (ALT), Aspartate Transaminase Activity (AST), Triacylglycerol (TG), total cholesterol, LDL-cholesterol, HDL-cholesterol, fasting blood glucose, fasting insulin, HbA1c, adiponectin, VitC, and VitE were measured by Osaka Kessei Research Laboratories Inc. (Osaka, Japan). The insulin resistance index was calculated using Homeostasis Model Assessment (HOMA-IR) (HOMA-IR=fasting insulin (μU/millilitre) × fasting glucose (milligram/decilitre)/405).

Statistical analysis

Statistical analyses were performed using SPSS software version 23.0 (IBM Inc., Armonk, NY, USA). All statistical tests were 2-sided and P<0.05 was considered significant. The distribution of continuous variables was examined for normality by Shapiro-Wilk’s test. Continuous and categorical data are expressed as the mean ± Standard Deviation (SD) and as a proportion (%), respectively. Differences between groups was examined by the Jonckheere-Terpstra test or the Chi-square test. Spearman’s correlation coefficients were calculated to assess possible relationships between variables. Logistic regression analysis calculating the odds ratios (OR) and 95% Confidence Intervals (CI) was performed to examine the associations between NAFLD across quartiles of variables considering the lowest quartile as the reference.

Results

Subjects characteristics

The subjects participating in this study were 36 to 77 years old (those in their thirties, forties, fifties, sixties, and seventies were 8, 71, 98, 18, and 3 men, respectively). Of the total population, 63.6 and 54.5 % subjects were with NAFLD and overweight/obese (BMI ≥ 25), respectively. The subjects were divided into 4 groups based on the results of ultrasonography: normal (n=72), mild-(n=40), moderate-(n=63), and severe-NAFLD (n=23). Their characteristics are shown in (Table 1). As the severity of fatty liver increased, there were higher BMI, WC, BP, AST, ALT, TG, fasting glucose, insulin, HbA1c, and HOMA-IR and lower levels of HDL-cholesterol, adiponectin, and VitC. No significant trend was found in age, life style factors, total cholesterol, LDL-cholesterol, or VitE among the 4 groups.  The presence of metabolic disturbance among 4 groups is shown in (Table 2). There were significant increased proportions of subjects with overweight/obese, abdominal obesity, insulin resistance, abnormality for ALT or AST, and deficiency of VitC as the severity of fatty liver increased, although no significant difference was observed in hypertension, dyslipidaemia, or diabetes. The proportions of subjects with overweight/obese and deficiency of VitC were 83 and 22% in moderate NAFLD group, and 96 and 91 % in severe NAFLD group, respectively. These results suggested that more than 90% of the subjects with severe NAFLD were obese and VitC deficient.

Dietary intake

Intake of energy, nutrients, and food groups is shown in (Table 3). A significant decreased trend was only shown in the intake of dietary VitC and vegetables by Jonckheere-Terpstra test. The intake of vegetables in NAFLD group (mild + moderate + severe) was significantly different from that in the normal (the mean intake of vegetables in normal, 210.3 gram and NAFLD group, 165.9 gram; p=0.008 by Mann-Whitney’s test).

Relation Between Plasma VitC Level and Clinical Markers and Dietary Intake

The relationships between plasma VitC level and clinical markers and intake of dietary VitC and vegetables are shown in (Table 4). The levels of plasma VitC significantly correlated with BMI, WC, BP, ALT, insulin, HOMA-IR, and adiponectin, while no correlation was observed in the intake of VitC or vegetables. Neither intake of dietary VitC nor vegetables was correlated with these clinical factors including the plasma VitC levels. However, a significant correlation between intake of VitC and vegetables was observed (r=0.507, p<0.001).

Association Between NAFLD and BMI, Plasma VitC Levels, and Intake of Dietary VitC and Vegetables

To determine the associations between the prevalence of NAFLD (mild+moderate+severe) across quartiles of BMI, plasma VitC levels, intake of dietary VitC and vegetables, considering the lowest quartile as the reference, logistic regression analysis was performed. The OR for NAFLD by quartiles of the variables is shown in (Table 5). A higher BMI was associated with a higher prevalence of NAFLD. The analysis indicated that the increase in median levels of BMI (from 22.6 to 29.1) increased the OR for NAFLD to 27.8-times. Conversely, a higher quartile of the levels of plasma VitC and intake of vegetables was associated with a decreased OR for NAFLD in a crude regression model. The increase in median levels of plasma VitC from 13.6 to 35.6, 45.9, and 61.7 μM decreased the OR to 0.38, 0.32, and 0.17, respectively. The increase in median intake of vegetable from 96 to 272 gram decreased the OR to 0.37. Following adjustment for age, BMI, physical activity and smoking, a higher quartile of intake of dietary VitC and vegetables associated with a decreased prevalence of NAFLD, although the significant association disappeared in plasma VitC level. The adjusted model demonstrated that the increase in the median intake of dietary VitC (from 48 to 127 milligram) and vegetables (from 96 to 272 gram) decreased the OR for NAFLD to 0.27 and 0.29, respectively.

Discussion

This study showed that the level of plasma VitC, and intake of dietary VitC and vegetables decreased as the severity of fatty liver increased. The lower plasma VitC levels was considered to be caused by the increase in oxidative stress and/or the decrease of the intake of dietary VitC and its main source, vegetables.  The plasma VitC levels were found to inversely correlate with BMI and WC. In agreement with these results, epidemiological studies also showed that VitC status inversely correlated with BMI and significantly decreased in obese compared with lean individuals [8-11, 19]. The increase in BMI and WC resulted from fat accumulation. Fat-accumulated adipose tissue generates oxidative stress (Fat reactive oxygen species (ROS)) [20]. The association of oxidative stress with fat accumulation (obesity; increase in BMI and WC) is well known [21-23]. Indeed, patients with NAFLD showed the increase in oxidative stress as well as BMI [24,25]. Recently, the study using a transgenic mouse model has reported that augmented adipose oxidative stress (Fat ROS) inhibits healthy adipose expansion with ectopic lipid accumulation, such as fatty liver [20], indicating that there is no fat accumulation in the liver, if there is no ROS production. These suggest that NAFLD associates with ROS production which is prevented by VitC.

The VitC status (plasma VitC level) is a result of the balance between oxidative stress and the intake of VitC. The plasma VitC level did not correlate with the intake of VitC and its main source, vegetables, in this study. The intake of dietary VitC decreased as the severity of fatty liver increased. The intake of vegetables also decreased in NAFLD groups. These suggests that a lower level of plasma VitC in NAFLD observed in this study is caused by both the increased oxidative stress by the increased BMI and the decreased intake of dietary antioxidant nutrient, VitC and vegetables.

Logistic regression analysis demonstrated that higher quartiles of plasma VitC levels were associated with a lower OR for NAFLD. The 4.5-fold increase in the median of plasma VitC decreased OR for NAFLD to 0.17 in a crude model. However, the significant association disappeared in the adjusted model, suggesting that the plasma VitC level was dependent on BMI. The intakes of dietary VitC and vegetables were inversely associated with the prevalence of NAFLD. The increases in the median of the intake of VitC from 48 to 127 mg (about 2.6-fold increase) and vegetables from 96 to 272g (about 2.8-fold increase) decreased the OR to 0.27 and 0.29 in the adjusted model, respectively. These results suggest that the increase in the intake of VitC and vegetables prevents NAFLD independently of BMI. In agreement with our results, an inverse association of the intake of vegetables and dietary VitC with NAFLD was reported in the study using proton-magnetic resonance spectroscopy in China [26]. The inverse association between dietary VitC intake and NAFLD was also found in Chinese middle-aged and older adults [27]. However, plasma VitC and VitC intakes in Canadian patients with simple steatosis or NASH were reported to be similar to those in healthy controls [16]. This discrepancy may be explained by the difference between Western diet and Japanese or Chinese diet. Indeed, all Canadian participants of three groups in the study were described to follow a similar Western diet [16].

Vitamin E is a lipophilic molecule with antioxidant activity that prevents membrane damage by ROS. In this study, no significant difference between normal and NAFLD groups was observed in the plasma VitE levels. The supplementation of VitE for patients with NASH resulted in clinical improvement [28, 29], but no beneficial effect was observed in other paper [30-33]. The daily supplementation of VitE was suggested to increase the risk of prostate cancer [21]. It is known that vitamin C functions in vivo to repair the membrane-bound oxidized vitamin E by the interaction at the membrane-cytosol interface [34], suggesting the decrease of VitE level may not occur if VitC status is sufficient to regenerate VitE.

Our study had a number of limitations. First, the ultrasonography has some limitations for diagnosis of NAFLD, although it is widely used as a first-line investigation for hepatic steatosis of subjects in a health examination as this study. It can accurately determine moderate and severe fatty infiltration, but the finding of a normal liver on ultrasonography cannot rule out mild fatty infiltration of the liver. It cannot distinguish between steatosis alone and NASH. The liver histology by biopsy is needed to determine the stage of NAFLD, although it is not possible in a health examination. Second, because the participants were limited to Japanese men, our findings may not be generalized to other populations. Third, because of the relatively small sample size, it is possible that associations between other nutrients and NAFLD might have been detectable in a larger population. Fourth, although we controlled for the confounding variables, we cannot rule out the possibility that unknown or unmeasured confounders account for the observed associations. Finally, the cross-sectional design of our investigation mandates that inferences about causality should be made with caution.

In conclusion, the plasma VitC levels and the intake of dietary VitC and vegetables decreased as the severity of fatty liver increased. The higher intake of dietary VitC and vegetables was associated with a lower prevalence of NAFLD independently of BMI. The dietary intake of VitC and vegetables may be important in the prevention of NAFLD.

Acknowledgments

We gratefully acknowledge the clinical support of Dr. Takemi Akahane and Dr. Kennichi Fukui of Nara Health Promotion Center.


Normal

NAFLD

 

 

Mild

Moderate

Severe

P

Age (y)

51.6

±

7.1

54.2

±

6.3

50.7

±

7.1

51.1

±

8.4

0.389

Life style factors

 Physical activity (%yes)

35.6

40.5

32.2

40.0

0.847

Current smoking (%yes)

16.9

29.7

20.3

13.3

0.415

Anthropometry indicators

BMI (kilogram/m2)

23.6

±

2.3

25.3

±

1.9

26.9

±

2.4

29.4

±

3.4

<0.001

WC (centimetre)

85.8

±

6.8

89.7

±

5.2

93.2

±

6.9

98.2

±

7.3

<0.001

SBP (mmHg)

124.6

±

12.9

126.6

±

14.1

132.7

±

13.5

133.4

±

12.1

<0.001

DBP (mmHg)

78.7

±

9.0

81.9

±

9.8

83.5

±

10.8

86.3

±

8.9

0.001

Biochemical parameters

AST (IU/Litre)

20.2

±

5.1

21.2

±

5.2

29.8

±

15.1

33.3

±

10.9

<0.001

ALT (IU/ Litre)

20.9

±

8.8

24.7

±

10.5

45.9

±

28.2

60.7

±

26.3

<0.001

TG (milligram/decilitre)

130.5

±

123.0

150.3

±

74.9

155.3

±

83.0

140.1

±

74.5

0.020

Total cholesterol (milligram/ decilitre)

212.8

±

31.1

201.5

±

28.0

213.5

±

31.5

201.2

±

31.9

0.549

HDL-cholesterol (milligram / decilitre)

55.3

±

14.1

48.9

±

9.1

49.6

±

9.6

45.7

±

8.4

<0.001

LDL-cholesterol (milligram / decilitre)

132.1

±

28.9

127.6

±

24.6

137.5

±

30.7

133.1

±

30.8

0.326

Glucose (milligram / decilitre)

98.9

±

13.8

99.1

±

8.7

105.0

±

11.9

110.5

±

15.4

<0.001

Insulin (μU/millilitre)

6.3

±

3.2

8.1

±

3.1

12.0

±

7.8

16.4

±

9.1

<0.001

HbA1c (%)

5.2

±

0.4

5.2

±

0.3

5.4

±

0.4

5.6

±

0.4

<0.001

HOMA-IR

1.55

±

0.92

1.99

±

0.80

3.16

±

2.23

4.60

±

2.91

<0.001

Adiponectin (μ gram/millilitre)

8.1

±

2.9

6.1

±

2.5

5.6

±

2.6

4.4

±

1.1

<0.001

Vitamin C (μmols/Litre)

45.7

±

17.4

41.2

±

13.6

38.2

±

18.6

14.3

±

4.6

<0.001

Vitamin E (milligram/decilitre)

1.14

±

0.48

0.96

±

0.33

1.16

±

0.40

0.92

±

0.28

0.719

Data are expressed as the mean ± standard deviation or proportion (%).


Table 1: Characteristics of Subjects.


Normal

 

NAFLD 

 

 

 

Mild

Moderate

Severe

P

Overweight/obese

26.4

62.5

82.5

95.7

<0.001

Abdominal obesity

55.6

82.5

88.9

100.0

<0.001

Hypertension

15.3

25.0

27.0

30.4

0.281

Dyslipidemia

56.9

52.5

69.8

65.2

0.266

Diabetes

4.2

2.5

9.5

17.4

0.090

Insulin Resistance

11.3

27.5

60.3

69.6

<0.001

Abnormal ALT or AST value

2.8

7.5

41.3

82.6

<0.001

VitC deficiency

12.5 

12.5

21.7

90.9

<0.001

Data are expressed as yes%.

Overweight/Obese: BMI >=25, Abdominal Obesity: WC>=85centimetre, Hypertension: SBP>=140 or DBP>=90, Dyslipidemia: TG>=150, LDL-Cholesterol>=140, or HDL-Cholesterol<40milligram /deciliter, Diabetes: Glucose>=126milligram/deciliter or HbA1c>=6.5, Insulin Resistance: HOMA-IR>=2.5, Abnormal Value of ALT or AST: ALT>40 or AST>37, VitC Deficiency: VitC< 23μM. P, Chai-square Test.


Table 2: Presence of Metabolic Disturbance.


 

Per day

Normal

NAFLD

Mild

Moderate

Severe

P

Energy

kilocalorie

2151

±

426

2170

±

462

2215

±

405

2123

±

581

0.931

 

Protein

gram

68.6

±

14.6

67.8

±

14.0

69.9

±

13.6

69.4

±

19.3

0.561

 

Fat

gram

62.1

±

19.4

65.2

±

20.6

66.4

±

16.1

59.9

±

25.4

0.637

 

Carbohydrate

gram

311.0

±

72.9

305.1

±

75.4

316.9

±

69.7

313.8

±

84.5

0.663

 

Na

milligram

3535

±

1326

3626

±

1120

3687

±

1203

2909

±

810

0.303

 

K

milligram

2275

±

590

2132

±

421

2262

±

620

2034

±

612

0.152

 

Ca

milligram

543

±

229

515

±

135

512

±

177

460

±

224

0.167

 

Mg

milligram

245

±

62

233

±

46

244

±

60

221

±

60

0.465

 

Fe

milligram

7.2

±

3.1

6.7

±

1.6

6.9

±

1.4

6.7

±

2.1

0.642

 

Zn

milligram

8.9

±

2.0

8.6

±

1.9

8.8

±

2.1

8.5

±

2.4

0.725

 

Vitamin A

mg

519

±

206

458

±

135

458

±

147

443

±

180

0.056

 

Vitamin D

mg

8.1

±

5.9

7.2

±

3.0

7.0

±

3.3

8.3

±

5.6

0.800

 

Vitamin E

milligram

6.5

±

1.9

6.2

±

1.5

6.5

±

1.6

6.1

±

2.2

0.528

 

Vitamin K

mg

187

±

69

175

±

58

176

±

62

171

±

107

0.076

 

Vitamin B1

milligram

0.95

±

0.34

0.90

±

0.27

0.92

±

0.21

0.99

±

0.40

0.754

 

Vitamin B2

milligram

1.07

±

0.33

1.04

±

0.26

1.04

±

0.26

1.09

±

0.37

0.657

 

Vitamin B6

milligram

1.14

±

0.30

1.06

±

0.23

1.08

±

0.26

1.03

±

0.33

0.112

 

Vitamin B12

mg

7.14

±

3.83

0.94

±

2.71

6.64

±

2.64

7.42

±

3.83

0.697

 

Vitamin C

milligram

93.8

±

46.9

82.2

±

30.9

82.7

±

47.4

76.1

±

30.8

0.033

 

cholesterol

milligram

318

±

120

314

±

118

340

±

107

341

±

114

0.130

 

Fiber

gram

12.7

±

3.6

11.7

±

2.7

11.8

±

2.92

11.2

±

3.42

0.058

 

Food group

Cereals

gram

536.0

±

153.6

517.4

±

176.0

540.1

±

150.0

583.2

±

159.0

0.217

 

Fats and oils

gram

15.1

±

8.6

14.9

±

7.8

15.4

±

8.9

12.2

±

4.7

0.571

 

Legumes

gram

45.5

±

31.7

44.8

±

28.7

45.1

±

26.0

37.4

±

41.4

0.380

 

Fruits

gram

93.7

±

89.5

95.8

±

73.6

73.9

±

79.5

70.9

±

78.8

0.058

 

Vegetables

gram

210.3

±

108.5

165.4

±

67.2

174.0

±

89.0

165.9

±

92.7

0.012

 

Fish and shellfish

gram

66.8

±

41.1

65.0

±

29.5

66.2

±

30.3

76.3

±

56.1

0.388

 

Meat and poultry

gram

75.0

±

49.9

82.6

±

59.1

86.7

±

45.5

82.3

±

55.2

0.091

 

Eggs

gram

33.2

±

23.1

31.9

±

19.7

35.9

±

21.0

37.6

±

29.2

0.351

 

Milk and
dairy products

gram

146.3

±

117.1

144.9

±

96.5

135.2

±

126.0

106.5

±

130.1

0.071

 

Data are expressed as the mean ± standard deviation. P, Jonckheere-Terpstra test.


Table 3: Intake of Energy, Nutrients, and Food groups.


 

Plasma VitC

r

p

BMI

-0.379

<0.001

WC

-0.327

0.002

SBP

-0.224

0.034

DBP

-0.224

0.034

ALT

-0.323

0.002

Insulin

-0.357

0.001

HOMA-IR

-0.366

<0.001

Adiponectin

0.304

0.007

Intake of dietary VitC

0.157

0.143

Intake of vegetables

0.113

0.289

r, correlation coefficient.


Table 4: Correlation of plasma VitC level with clinical markers and the intake of VitC and vegetables.


 

Quartiles of variable

P

Q1 (Lowest)

Q2

Q3

Q4 (Highest)

BMI

Median (kilogram/meter2)

22.6

24.7

26.3

29.1

N of NAFLD (%)

24.4

59.1

80.0

90.0

Unadjusted OR (95%CI)

1

(reference)

4.47

(1.88-10.62)

12.33

(4.77-31.92)

27.75

(8.96-85.93)

<0.001

Adjusted OR (95%CI)

1

(reference)

4.75

(1.83-12.32)

10.73

(3.90-29.55)

37.36

(9.36-149.13)

<0.001

plasma Vitamin C

Median (μmols/Liter)

13.6

35.6

45.9

61.7

N of NAFLD (%)

77.3

56.5

52.2

36.4

Unadjusted OR (95%CI)

1

(reference)

0.38

(0.11-1.39)

0.32

(0.09-1.17)

0.17

(0.05-0.63)

0.008

Adjusted OR (95%CI)

1

(reference)

1.13

(0.23-5.59)

1.62

(0.31-8.55)

0.81

(0.15-4.42)

0.842

Intake of Vitamin C

Median (milligram/day)

48

67

91

127

N of NAFLD (%)

75.5

58.3

66.6

55.1

Unadjusted OR (95%CI)

1

(reference)

0.45

(0.19- 1.08)

0.65

(0.27- 1.55)

0.40

(0.17-0.94)

0.093

Adjusted OR (95%CI)

1

(reference)

0.54

(0.17- 1.77)

0.53

(0.16- 1.78)

0.27

(0.08- 0.93)

0.045


Intake of Vegetables

Median

(gram/day)

96

147

195

272

N of NAFLD (%)

72.0

66.7

66.7

49.0

Unadjusted OR (95%CI)

1

(reference)

0.78

(0.33-1.84)

0.78

(0.33-1.82)

0.37

(0.16-0.86)

0.019

Adjusted OR (95%CI)

1

(reference)

0.70

(0.23-2.20)

0.74

(0.23-2.33)

0.29

(0.09-0.91)

0.035

NAFLD represents NAFLD group (mild + moderate + severe).

Adjusted for age, BMI (excluded in the case of BMI), physical activity, and smoking.


Table 5: Odds ratio (95% CI) for NAFLD by quartile of variables.

  1. Bellentani S, Saccoccio G, Masutti F, Crocè LS, Brandi G, et al. (2000) Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 132: 112-117.
  2. Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, et al. (2011) Prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 140: 124-131.
  3. Polimeni L, Del Ben M, Baratta F, Perri L, Albanese F, et al. (2015) Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis. World journal of hepatology 7: 1325-1336.
  4. Oliveira CP, Gayotto LC, Tatai C, Della NBI, Lima ES, et al. (2003) Vitamin C and vitamin E in prevention of Nonalcoholic Fatty Liver Disease (NAFLD) in choline deficient diet fed rats. Nutrition journal 2: 9.
  5. Buettner GR (1993) The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Archives of biochemistry and biophysics 300: 535-543.
  6. Smith JL, Hodges RE (1987) Serum levels of vitamin C in relation to dietary and supplemental intake of vitamin C in smokers and nonsmokers. Annals of the New York Academy of Sciences 498: 144-152.
  7. Tveden-Nyborg P, Lykkesfeldt J (2013) Does vitamin C deficiency increase lifestyle-associated vascular disease progression? Evidence based on experimental and clinical studies. Antioxid Redox Signal 19: 2084-2104.
  8. Canoy D, Wareham N, Welch A, Bingham S, Luben R, et al. (2005) Plasma ascorbic acid concentrations and fat distribution in 19,068 British men and women in the European Prospective Investigation into Cancer and Nutrition Norfolk cohort study. The American journal of clinical nutrition 82: 1203-1209.
  9. Johnston CS, Beezhold BL, Mostow B, Swan PD (2007) Plasma vitamin C is inversely related to body mass index and waist circumference but not to plasma adiponectin in non-smoking adults. J Nutr 137: 1757-1762.
  10. Mah E, Matos MD, Kawiecki D, Ballard K, Guo Y, et al. (2011) Vitamin C status is related to pro inflammatory responses and impaired vascular endothelial function in healthy, college-aged lean and obese men. J Am Diet Assoc 111: 737-743.
  11. da Silva VR, Moreira EA, Wilhelm-Filho D, de Miranda JX, Benincá JP, et al. (2012) Proinflammatory and oxidative stress markers in patients submitted to Roux-en-Y gastric bypass after 1 year of follow-up. European journal of clinical nutrition 66: 891-899.
  12. Ipsen DH, Tveden-Nyborg P, Lykkesfeldt J (2014) Does vitamin C deficiency promote fatty liver disease development? Nutrients 6: 5473-5499.
  13. Dehghan M, Akhtar-Danesh N, McMillan CR, Thabane L (2007) Is plasma vitamin C an appropriate biomarker of vitamin C intake? A systematic review and meta-analysis. Nutrition journal 6: 41.
  14. Madan K, Bhardwaj P, Thareja S, Gupta SD, Saraya A (2006) Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD). Journal of clinical gastroenterology 40: 930-935.
  15. Canbakan B, Senturk H, Tahan V, Hatemi I, Balci H, et al. (2007) Clinical, biochemical and histological correlations in a group of non-drinker subjects with non-alcoholic fatty liver disease. Acta gastro-enterologica Belgica 70: 277-284.
  16. Da Silva HE, Arendt BM, Noureldin SA, Therapondos G, Guindi M, et al. (2014) A cross-sectional study assessing dietary intake and physical activity in Canadian patients with non-alcoholic fatty liver disease vs healthy controls. J Acad Nutr Diet 114: 1181-1194.
  17. Kawashima A, Sugawara S, Okita M, Akahane T, Fukui K, et al. (2009) Plasma fatty acid composition, estimated desaturase activities, and intakes of energy and nutrient in Japanese men with abdominal obesity or metabolic syndrome. Journal of nutritional science and vitaminology 55: 400-406.
  18. Saverymuttu SH, Joseph AE, Maxwell JD (1986) Ultrasound scanning in the detection of hepatic fibrosis and steatosis. British medical journal 292: 13-15.
  19. Aasheim ET, Hofso D, Hjelmesaeth J, Birkeland KI, Bohmer T, et al. (2008) Vitamin status in morbidly obese patients: a cross-sectional study. The American journal of clinical nutrition 87: 362-369.
  20. Okuno Y, Fukuhara A, Hashimoto E, Kobayashi H, Kobayashi S, et al. (2018) Oxidative Stress Inhibits Healthy Adipose Expansion Through Suppression of SREBF1-Mediated Lipogenic Pathway. Diabetes 67: 1113-1127.
  21. Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, et al. (2011) Vitamin E and the risk of prostate cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 306: 1549-1556.
  22. Fujita K, Nishizawa H, Funahashi T, Shimomura I, Shimabukuro M (2006) Systemic oxidative stress is associated with visceral fat accumulation and the metabolic syndrome. Circ J 70: 1437-1442.
  23. Okauchi Y, Kishida K, Funahashi T, Noguchi M, Ogawa T, et al. (2011) Cross-sectional and longitudinal study of association between circulating thiobarbituric acid-reacting substance levels and clinicobiochemical parameters in 1,178 middle-aged Japanese men - the Amagasaki Visceral Fat Study. Nutr Metab (Lond) 8: 82.
  24. Kenneally S, Sier JH, Moore JB (2017) Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review. BMJ open gastroenterology 4: e000139.
  25. Del Ben M, Polimeni L, Carnevale R, Bartimoccia S, Nocella C, et al. (2014) NOX2-generated oxidative stress is associated with severity of ultrasound liver steatosis in patients with non-alcoholic fatty liver disease. BMC gastroenterology 14: 81.
  26. Chan R, Wong VW, Chu WC, Wong GL, Li LS, et al. (2015) Diet-Quality Scores and Prevalence of Nonalcoholic Fatty Liver Disease: A Population Study Using Proton-Magnetic Resonance Spectroscopy. PloS one 10: e0139310.
  27. Wei J, Lei GH, Fu L, Zeng C, Yang T, et al. (2016) Association between Dietary Vitamin C Intake and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study among Middle-Aged and Older Adults. PloS one 11: e0147985.
  28. Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, et al. (2010) Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 362: 1675-1685.
  29. Hoofnagle JH, Van Natta ML, Kleiner DE, Clark JM, Kowdley KV, et al. (2013) Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis. Alimentary pharmacology & therapeutics 38: 134-143.
  30. Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S (2003) Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 98: 2485-2490.
  31. Kawanaka M, Nishino K, Nakamura J, Mitsuhiko S, Daisuke G, e t al. (2013) Treatment of nonalcoholic steatohepatitis with vitamins E and C: a pilot study. Hepat Med 5: 11-16.
  32. Ersoz G, Gunsar F, Karasu Z, Akay S, Batur Y, et al. (2005) Management of fatty liver disease with vitamin E and C compared to ursodeoxycholic acid treatment. Turk J Gastroenterol 16: 124-128.
  33. Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, et al. (2011) Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA 305: 1659-1668.
  34. Chan AC (1993) Partners in defense, vitamin E and vitamin C. Canadian journal of physiology and pharmacology 71: 725-731.

Citation: Sugawara S and Tsukamoto I (2019) Association of Intake of Dietary Vitamin C and Vegetables with Non-Alcoholic Fatty Liver Disease (NAFLD) In Middle-Aged Japanese Men. J Med Biomed Discoveries 2: 111. DOI: 10.29011/JMBD-111.1000011

free instagram followers instagram takipçi hilesi