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. 2020 Feb 12;55(2):164–170. doi: 10.1093/alcalc/agaa001

Lower Serum Magnesium Concentrations are associated With Specific Heavy Drinking Markers, Pro-Inflammatory Response and Early-Stage Alcohol-associated Liver Injury§

Vatsalya Vatsalya 1,2,3,4,2,✉, Khushboo S Gala 1, Maithili Mishra 5, Melanie L Schwandt 6, John Umhau 6, Matthew C Cave 1,2,3,4,7, Dipendra Parajuli 1,2, Vijay A Ramchandani 6,3, Craig J McClain 1,2,3,4,7,3
PMCID: PMC7082490  PMID: 32047901

Abstract

Aim

Chronic heavy alcohol intake frequently causes liver inflammation/injury, and altered mineral metabolism may be involved in this liver pathology. In this study, we evaluated the association of heavy drinking, changes in serum magnesium levels and biochemical evidence of liver injury in alcohol-use-disorder (AUD) patients who had no clinical signs or symptoms of liver injury. We also aimed to identify any sex-based differences in patients with mild or no biochemical evidence of liver injury induced by heavy drinking.

Methods

114 heavy drinking alcohol-dependent (AD) female and male patients aged 21–65 years without clinical manifestations of liver injury, who were admitted to an alcohol treatment program, were grouped by alanine aminotransaminase (ALT) levels: ≤ 40 IU/L, as no liver injury (GR.1), and ALT>40 IU/L as mild liver injury (GR.2). Patients were actively drinking until the day of admission. Comprehensive metabolic biochemistry results, fatty acid panel, serum magnesium and drinking history data were collected at admission; and study-specific measures were evaluated.

Results

In all AD patients, lower magnesium was significantly associated with the heavy drinking marker and heavy drinking days past 90 days (HDD90). A lower serum magnesium concentration was observed in AD patients with mild liver injury. Females of both groups had mean levels of magnesium in the deficient range. A clinically significant drop in magnesium levels was observed only in the GR.2 (mild liver injury) male AD patients. Females showed a significant association between low magnesium levels and the ω6:ω3 polyunsaturated fatty acids (PUFAs) ratio.

Conclusions

Specific heavy drinking markers showed an association with lower magnesium levels. Low serum magnesium levels are common in subjects with AUD and appear to be associated with the onset of liver injury.

Lowered serum magnesium is associated with the development of liver injury and with heavy drinking markers in patients with AUD. At the onset of ALD, females showed a significant correlation between magnesium and pro-inflammatory PUFAs.

Introduction

Heavy alcohol drinking is responsible for several systemic and organ-level pathologies (Chalasani and Szabo, 2015; Vatsalya et al., 2016a). Alcohol intake leads to various electrolyte and mineral disturbances, and one of the most common disturbances is hypomagnesemia (Elisaf et al., 1995). With heavy alcohol intake, there can be a loss of magnesium from tissues and increased urinary loss (Pasqualetti et al., 1987; Shane and Flink, 1991). Chronic alcohol abuse has been reported to deplete the total body supply of magnesium (Vandemergel and Simon, 2015). Experimental data confirm that a single dose of alcohol, as well as chronic consumption can cause hypomagnesemia in rats (Papierkowski and Pasternak, 1998; Young et al., 2003; Romani, 2008).

Hypomagnesemia has been studied widely in subjects with alcoholic liver disease (ALD) (Wu and Kenny, 1996; Turecky et al., 2006). One study showed a decrease in serum magnesium levels with an increase in serum alcohol concentrations (Petroianu et al., 1991). In alcoholic cirrhosis (AC), the degree of magnesium depletion found on muscle biopsy correlated with increasing severity of liver injury (Aagaard et al., 2002). Another study showed that higher intake of magnesium may be associated with a reduced risk of mortality due to all types of liver disease, particularly among alcohol drinkers and those with hepatic steatosis (Wu et al., 2017). Patients with alcoholic hepatitis/cirrhosis frequently complain of muscle cramps, and magnesium supplements have been used to treat muscle cramps. However, there are gaps in our understanding of hypomagnesemia, including its clinical relevance and its development during the onset of alcohol-induced liver injury. Adverse effects of heavy alcohol drinking can have varied manifestations in the context of sex, age, nutritional status, etc. (Marsano et al., 2016), and there are very few publications that have addressed the role of these factors in alcohol use disorder (AUD)-associated (rather than alcohol-induced liver injury associated) hypomagnesemia.

The primary aim for this study was to identify what pattern(s) and amount of drinking were associated with low serum magnesium in this observational single-assessment clinical study. We further evaluated the association of lower serum magnesium with the onset of liver injury, and association of low magnesium with a pro-inflammatory marker associated with liver injury. Lastly, we investigated the modifying effects of demographic measures (primarily sex and age) in magnesium dysregulation.

Patients and Methods

Patient population and enrollment

This study was approved by the Institutional Review Board of National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda MD, under the larger protocol, 05-AA-0121, used for screening. The study has been indexed at the National Clinical Trial website (www.clinicaltrials.gov: NCT00001673). All study data and samples were collected after completion of the consent process; study was performed throughout the year and study participants were primarily from the states of Maryland, Washington DC and Virginia (It was open for all potential candidates from the USA.) Our study included 114 male and female subjects, aged 21–65 years (Table 1). None of the subjects had clinical manifestations of ALD (without a diagnosis of AC, hepatitis or hepatocellular carcinoma, which was an exclusion criteria in this study) (Marsano et al., 2016). All the assessments included in this study were collected at admission. Subjects were diagnosed with AUD according to DSM-IV, based on the alcohol-dependence module of the SCID I-interview and alcohol withdrawal for either: (a) clinically manifested significant alcohol withdrawal symptoms, as observed by Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) scores of ≥9, with or without detectable blood alcohol concentrations (BACs) or (b) in the absence of the above, current intoxication above 0.1 g/dl BAC, self-reported history of continuous alcohol use >1 month, and self-reported previous episodes of significantly distressful alcohol withdrawal symptoms. More information on patient participation and enrollment can be obtained in previous publications from the same cohort (Vatsalya et al., 2016b; Vatsalya et al., 2018).

Table 1.

Demographic, drinking history, liver injury measures (Vatsalya et al., 2016b) and serum magnesium levels of the alcohol-dependent patients without any liver injury and with mild ALD

Measures Group 1 (normal ALT, GR.1) Group 2 (elevated ALT, GR.2) Between group P—value
Males (34; 58.6%) Females (24; 41.4%) Total (58; 50.4%) Males (40; 70.2%) Females (16; 29.8%) Total (56; 49.6%)
Age (years) 37.6 ± 10.5 42.3 ± 10.6 39.6 ± 10.7 43.0 ± 10.3 43.1 ± 10.3 43.0 ± 10.2 0.080
BMI (kg/m2) 27.7 ± 4.2 25.7 ± 7.3 26.9 ± 5.7 25.7 ± 3.8 26.3 ± 5.0 25.9 ± 4.1 NS
Drinking history
TD90 957.2 ± 622.5 925.7 ± 735.1 946.1 ± 656.9 1186.7 ± 528.5 950.3 ± 411.3 1119.8 ± 505.9 NS
HDD90 62.1 ± 26.9 62.7 ± 20.8 62.3 ± 24.7 73.5 ± 20.7 76.8 ± 14.6 74.5 ± 19.1 0.007
AvgDPD90 13.9 ± 7.9 13.0 ± 7.7 13.6 ± 7.7 15.6 ± 5.9 12.1 ± 5.1 14.6 ± 5.8 NS
NDD90 67.4 ± 24.9 67.4 ± 21.0 67.4 ± 23.4 76.7 ± 17.9 78.2 ± 13.6 77.1 ± 16.7 0.017
NNDD90 22.4 ± 24.9 22.5 ± 21.1 22.4 ± 23.4 13.2 ± 17.9 11.8 ± 13.6 12.8 ± 16.7 0.019
Liver injury markers
ALT (IU/L) 28.9 ± 6.9 22.0 ± 8.3 26.0 ± 8.2 86.4 ± 35.3 111.9 ± 77.7 93.6 ± 51.6 NA
AST (IU/L) 27.4 ± 16.2 28.8 ± 15.1 28.0 ± 15.7 113.8 ± 79.5 181.4 ± 116.8 133.1 ± 95.7 ≤0.001
Mineral analysis
Magnesium (mmol/L) 0.913 ± 0.1 0.843 ± 0.09 0.884 ± 0.10 0.845 ± 0.11 0.805 ± 0.12 0.833 ± 0.11 0.013
Nutritional status
CONUT 0.97 ± 1.0 1.36 ± 1.4 1.13 ± 1.2 1.24 ± 1.2 0.93 ± 0.7 1.15 ± 1.1 NS
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BMI: Body mass index; TD90: total drinks in 90 days; HDD90: heavy drinking days in last 90 days; AvgDPD90: average drinks per drinking day in last 90 days; NDD90: number of drinking days in last 90 days; NNDD90: number of non-drinking days in last 90 days. NA: not applicable; NS: not significant.

Demographics, drinking and laboratory assessments

Demographics (age, sex, body mass index [BMI]) and recent drinking history information were also recorded at admission. Heavy drinking measures were collected from Time-line Follow-back questionnaire (Sobell et al., 2003). Measures were assessed for the past 90 days and included total drinks (TD90), number of drinking days (NDD90), number of non-drinking days (NNDD90), average drinking per drinking days (AvgDPD90) and heavy drinking days (HDD90). We also used the “Controlling Nutritional Status Test” (CONUT) test to establish nutritional status (Fukushima et al., 2011).

On the day of evaluation, blood samples were drawn for a serum chemistry panel, which includes tests for liver injury and the serum magnesium level (Table 1). The alanine aminotransaminase (ALT) level was used as a biomarker for early liver injury (Medline Plus-National Institutes of Health) based on the guideline provided until 2014, corresponding to the timeframe of the data collection. Normal ALT values were set at ≤ 40 IU/L, and patients were categorized as Group 1: those with normal ALT levels and Group 2: those with ALT > 40 IU/L, as indicative of mild liver injury. The reference normal range for serum magnesium is 0.85–1.10 mmol/L. Aspartate transaminase (AST), a liver injury marker (reference range—normal: 9–34; unit: U/L), was evaluated as well. Patients with serum magnesium < 0.85 mmol/L were considered as having magnesium deficiency. Comprehensive fatty acid panel was analyzed. More details on the assay for fatty acids are available in a previous publication (Vatsalya et al., 2016b). ω6:ω3 ratio was used as a proinflammatory indicator/marker (unit: ratio unit score: reference range—n = 1–4 is anticipated normal: n = ≥10 indicates adverse consequences) (Simopoulos, 2002). All laboratory assessments were conducted by the department of laboratory medicine, NIH, as per its guidelines until 2014 (https://medlineplus.gov/ency/article/003487.htm).

Statistical analysis

One-way ANOVA was used to evaluate demographic and drinking history measures. Univariate analysis of covariance (ANCOVA) was used to evaluate differences in the magnesium levels in both the groups and by sex within the liver injury groups. Drinking history and other demographic factors were tested as confounders of the extent and progression of liver injury. Regression analysis was used to characterize the association of liver injury markers and drinking history measures by sex. Linear regression analysis (as univariate- or multivariate-independent variable models) was used to assess the association of liver injury and serum magnesium. Log transform analyses were performed to accommodate variability in the data for all figures; and results only for non-representative changes were mentioned. SPSS 25.0 (IBM Chicago, IL) and Microsoft Excel 2016 (MS Corp, Redmond WA) were used for statistical analysis and data computation, respectively. Statistical significance was established at P ≤ 0.05. Data are expressed as mean ± standard deviation (M ± SD), unless otherwise noted.

Results

Demographics and drinking profile

There were no significant differences in the demographic measures of age and BMI between the cohorts in this study (Table 1); however, Group 2 was heavily weighted to males. The drinking measures, HDD90 and NDD90, were significantly higher in GR.2, and we found statistically significant lower serum magnesium levels in GR.2 (Table 1). There were no statistical differences in the nutritional status of the patients, either by group or by sex using the CONUT (Table 1).

Differences in serum magnesium between and within the groups

Serum magnesium levels were significantly lower in GR.2 subjects (Fig. 1a). Thirty-one of 56 GR.2 AUD (55.33%) patients exhibited low magnesium in comparison with 18 with low magnesium of the 58 subjects (31.03%) in GR.1. This finding was likely due to the low magnesium levels in the males in GR.2. Comparing the males of GR.1 and GR.2, this difference was larger and highly significant (Fig. 1b). Females of both the groups had serum magnesium levels in the deficient range, but mean magnesium levels in females between the two groups were not significantly different (Fig. 1c). Males in GR.1 showed normal mean serum magnesium level compared to the deficient level in the females of GR.1, and this was statistically significant (Fig. 1b and c). Both the males and females of GR.2 showed magnesium levels in the deficient range. Females showed lower magnesium levels compared to the males in GR.2, although there was no statistical difference.

Fig. 1.

Fig. 1.

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 Serum magnesium level in AUD patients. Fig. 1a: serum magnesium level in AUD patients without (GR.1) and with mild liver injury (GR.2). Fig. 1b: serum magnesium level in male AUD patients without (GR.1) and with mild liver injury (GR.2), Power was 0.771. Fig. 1c: serum magnesium level in female AUD patients without (GR.1) and with mild liver injury (GR.2). Power was 0.311. *P = 0.013; **P = 0.008. The reference normal range for serum magnesium is 0.75–1.00 mmol/L. Data are presented as M ± SD. Statistical significance was set at P < 0.05.

Association of serum magnesium and drinking markers

We found inverse associations between magnesium and both HDD90 (significant) and NDD90 drinking markers (non-significant) (Fig. 2a and b) in all AUD patients. Analysis on log-transformed data showed the same results as with the raw data. Lowering of magnesium values was associated with the heavy drinking markers (Fig. 2). We did not find any statistically significant association between serum magnesium and drinking markers within either of the two patient groups or by sex within each group or between the two groups (data not shown). However, all AUD females (with and without liver injury) in this study showed a significant association between serum magnesium and HDD90, P = 0.049 (Fig. 2c). These results remained unchanged with the addition of age as a covariate in the analysis.

Fig. 2.

Fig. 2.

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 Association of serum magnesium level and liver injury markers in AUD patients with mild liver injury (Group 2). Fig. 2a: association of serum magnesium and AST in all Group 2 AUD patients (with mild liver injury). Fig. 2b: association of serum magnesium level and AST in male AUD patients of GR.2. Fig. 2c: association of serum magnesium level and AST in female AUD patients of GR.2. Fig. 2a: association of serum magnesium and ALT in all AUD patients (with mild liver injury) of GR.2. Fig. 2b: association of serum magnesium level and ALT in male AUD patients of GR.2. Fig. 2c: association of serum magnesium level and ALT in female AUD patients of GR.2. Statistical significance was set at P < 0.05.

Association of serum magnesium and liver injury markers

Serum magnesium was significantly inversely associated with AST and ALT in the GR.2 AUD patients with mild liver injury (Fig. 3a–f). We did not find any such association between serum magnesium and liver injury markers in GR.1 AUD patients (who did not have elevated markers of liver injury). Among the GR.2 patients, this finding was driven by the associations seen in male patients: serum magnesium and ALT (P = 0.028), serum magnesium and AST (P = 0.018). Analysis on log-transformed data showed the same results as with the raw data.

Fig. 3.

Fig. 3.

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 Association of serum magnesium level and liver injury markers in AUD patients with mild liver injury (Group 2). Fig. 3a: association of serum magnesium and AST in all AUD patients with mild liver injury (GR.2). Fig. 3b: association of serum magnesium level and AST in male AUD patients of GR.2. Fig. 3c: association of serum magnesium level and AST in female AUD patients of GR.2. Fig. 3d: association of serum magnesium and ALT in all AUD patients (with mild liver injury) of GR.2. Fig. 3e: association of serum magnesium level and ALT in male AUD patients of GR.2. Fig. 3f: association of serum magnesium level and ALT in female AUD patients of GR.2. Statistical significance was set at P < 0.05.

Association of serum magnesium with markers of inflammation

Group 2 (mild liver injury) patients showed a significant inverse association between serum magnesium and the ω6:ω3 ratio, P = 0.026 (Fig. 4a). When we analyzed this association in context of sex in GR.2, we found that females showed a significant correlation between magnesium and the ω6:ω3 ratio, P = 0.014, while males did not (Fig. 4b and c). There was no such significant association found in GR.1 patients. Analysis on log-transformed data showed the same results as with the raw data.

Fig. 4.

Fig. 4.

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 Association of serum magnesium level and ω6:ω3 ratio in AUD patients with mild liver injury (Group 2). Fig. 4a: association of serum magnesium and ω6:ω3 ratio in all the AUD patients of GR.2. Fig. 4b: association of serum magnesium level and ω6:ω3 ratio in all the male AUD patients of GR.2. Fig. 4c: association of serum magnesium level and ω6:ω3 ratio in all the female AUD patients of GR.2. Statistical significance was set at P < 0.05. Correlational coefficients (r) are provided.

Discussion

Decreased magnesium levels have been reported in various studies on chronic alcohol dependence and in ALD (Mützell, 1988; Shane and Flink, 1991; Petroianu et al., 1991). A decreased serum magnesium level has been reported in severely intoxicated people (Rylander et al., 2001). Our study patients were not clinically overtly malnourished as assessed by the CONUT. We found lower serum magnesium levels in the heavy drinking AUD patients who exhibited mild liver injury (GR.2) compared to those with no biochemical evidence of liver injury (GR.1). This decrease was statistically significant in the GR.2 males compared to AUD males without any liver injury (Fig. 1b). Females from both groups showed similarly deficient mean serum magnesium levels (Fig. 1c). We also found male- and female-specific associations between magnesium and inflammatory markers in the context of liver injury (ALT, Group 2). Sex differences have previously been reported in various types of alcohol-induced organ injury (Vatsalya et al., 2016a). We found an association between inflammation, characterized by the ω6:ω3 ratio, and magnesium values in the GR.2 (elevated ALT) female AUD patients. It is possible that the females are more vulnerable to hypomagnesemia with increased inflammation.

Magnesium plays an important role in cellular energy metabolism, DNA transcription, protein synthesis and electrolyte balance (Musso, 2009). Recently, interest has focused on the pathophysiology and implications of early stages of magnesium deficiency. Subclinical magnesium deficiency has been postulated to be an important cause of chronic diseases and early mortality (DiNicolantonio et al., 2018). Our study detected decreases in magnesium levels in association with the onset of alcohol-associated liver injury (Fig. 3). One of the mechanisms for decreased magnesium in alcohol dependence could be poor diet in which the majority of calories is derived from alcohol, leading to several micronutrient deficiencies (McClain et al., 1991). Indeed, our study also showed an association between a heavy drinking marker (HDD90) and magnesium levels, regardless of the presence/absence of any liver injury in AUD patients (Fig. 2). One preclinical study has shown that chronic alcohol exposure using an alcohol fed rodent model leads to significant decreases in serum magnesium, and impaired magnesium homeostasis and transport in tissues (Dyer and Sampson, 1998).

Preclinical studies in alcohol-fed rats have shown that supplementation with magnesium partially attenuated oxidative stress and tissue damage, as evidenced by improved total antioxidant status in serum, activity of glutathione peroxidase, the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in the liver and tissue histopathological changes (Markiewicz-Górka et al., 2011). Moreover, oral administration of magnesium in animal models has also shown efficacy in improving hepatic encephalopathy that can occur with advanced liver disease (Li et al., 2017). In this study, glutamine synthetase regulation seemed to improve with magnesium supplementation.

Several human studies have reported hypomagnesemia in patients with ALD (Rink, 1986; Turecky et al., 2006). Magnesium supplementation has been suggested to have anti-fibrotic activity in the liver (El-Tantawy et al., 2017). One trial of magnesium supplementation in human chronic alcohol users in Finland showed that transaminase levels, specifically AST, were found to be lower among the magnesium-treated group compared to the placebo group (Poikolainen and Alho, 2008). In liver disease, magnesium deficiency has been suggested to play a role in muscle cramps and weakness, and in glucose intolerance (McClain et al., 2011). Indeed, muscle magnesium has been shown to be an independent risk factor for muscle weakness in AC (Aagaard et al., 2002). Studies have also correlated hypomagnesemia with the presence of liver steatosis and steatohepatitis on biopsy in patients with NAFLD (Eshraghian et al., 2018).

Our study had several limitations. There are several pathways that are potentially involved in magnesium deficiency. For example, increased urinary excretion is one likely cause of loss of magnesium (Rylander et al., 2001). Our study did not investigate any of the potential mechanisms of magnesium absorption, transport or excretion. Our study was an observation study and not an intervention trial, and we did not correlate hypomagnesaemia with symptoms, such as muscle cramps. Circulatory Mg represents only about 1% of total body Mg content, and we did not measure magnesium level from other bodily specimens. There is a gap in the literature concerning magnesium dysregulation at the onset of ALD; thus, our study has tried to cover only some aspects of this gap in knowledge, as described. This study was conducted as a proof of principle study, in which we examined subjects at the early stage of ALD. Thus, this study is only a snapshot of these subjects at admission to a treatment center. We only observed mild to moderate effect sizes in our study. One possible reason is that we are studying only AUD and early ALD, and we did not evaluate advanced ALD such as AC or alcoholic hepatitis. Studies of more advanced liver disease, for example acute alcoholic hepatitis, could further our knowledge of magnesium dysregulation and inflammatory markers in liver injury; this is an important direction of future studies.

In summary, our study supports previous reports of decreased serum micronutrient concentrations, including magnesium, in patients with AUD (Leevy and Moroianu, 2005; Dasarathy, 2016). Importantly, we show that patients with AUD who are transitioning to early ALD have even greater magnesium depletion. We recently reported similar findings concerning zinc deficiency in early ALD, and we postulate that deficiency of certain micronutrients may predispose to the development of alcohol-associated liver injury. Further prospective longitudinal studies are required to determine whether magnesium supplementation attenuates symptoms such as muscle cramps and whether magnesium supplemental decreases progression to early ALD. At this time, it would seem prudent to provide magnesium supplementation to patients with AUD who have low serum magnesium concentrations.

Authors’ contribution

V.V. is the project PI and designed the study. V.V. and M.L.S managed and processed clinical data. V.V. and M.M. analyzed data. V.V., C.J.M., K.S.G. and M.M. interpreted the outcomes. V.V., C.J.M., M.L.S. and K.S.G. wrote the manuscript. C.J.M., V.A.R., M.L.S., M.C.C., D.P., J.U. and V.V. contributed scientifically. All the authors have approved the submission version of this manuscript.

Financial/Grant Support

Study was supported by Z99-AA999999 (V.V.) and U01-AA026936–02, U01AA026980–2, and 1R01AA023681–05 (C.J.M.). Research reported in this publication was supported by an Institutional Development Award from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM113226 (C.J.M.) and the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under award number P50AA024337 (C.J.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research was also supported by the V.A. (1I01BX002996-01A2, C.J.M.).

Acknowledgments

We thank research/clinical staff of NIAAA and University of Louisville for their support. We thank Ms. Marion McClain for editing this manuscript.

Conflict of Interest statement

All authors declare no conflict of interest.

References

  1. Aagaard N, Andersen H, Vilstrup H, et al. (2002) Muscle strength, Na, K-pumps, magnesium and potassium in patients with alcoholic liver cirrhosis–relation to spironolactone. J Intern Med 252:56–63. [DOI] [PubMed] [Google Scholar]
  2. Chalasani N, Szabo G (2015) Alcoholic and Non-Alcoholic Fatty Liver Disease. Springer, Cham. [Google Scholar]
  3. Dasarathy S. (2016) Nutrition and alcoholic liver disease: effects of alcoholism on nutrition, effects of nutrition on alcoholic liver disease, and nutritional therapies for alcoholic liver disease. Clin Liver Dis 20:535–50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dinicolantonio JJ, O’keefe JH, Wilson W (2018) Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis. Open Heart 5:e000668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dyer SA, Sampson HW (1998) Magnesium levels in alcohol-treated rodents using different consumption paradigms. Alcohol 16(3):195–9. [DOI] [PubMed] [Google Scholar]
  6. El-Tantawy WH, Sabry D, Abd Al Haleem EN (2017) Comparative study of antifibrotic activity of some magnesium-containing supplements on experimental liver toxicity. Molecular study. Drug Chem Toxicol 40:47–56. [DOI] [PubMed] [Google Scholar]
  7. Elisaf M, Merkouropoulos M, Tsianos E, et al. (1995) Pathogenetic mechanisms of hypomagnesemia in alcoholic patients. J Trace Elem Med Biol 9:210–4. [DOI] [PubMed] [Google Scholar]
  8. Eshraghian A, Nikeghbalian S, Geramizadeh B, et al. (2018) Serum magnesium concentration is independently associated with non-alcoholic fatty liver and non-alcoholic steatohepatitis. United European Gastroenterol J 6:97–103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fukushima K, Ueno Y, Kawagishi N, et al. (2011) The nutritional index ‘CONUT’is useful for predicting long-term prognosis of patients with end-stage liver diseases. Tohoku J Exp Med 224:215–9. [DOI] [PubMed] [Google Scholar]
  10. Leevy CM, Moroianu ŞA (2005) Nutritional aspects of alcoholic liver disease. Clin Liver Dis 9:67–81. [DOI] [PubMed] [Google Scholar]
  11. Li Y, Ji CX, Mei LH, et al. (2017) Oral administration of trace element magnesium significantly improving the cognition and locomotion in hepatic encephalopathy rats. Sci Rep 7:1817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Markiewicz-Górka I, Zawadzki M, Januszewska L, et al. (2011) Influence of selenium and/or magnesium on alleviation alcohol induced oxidative stress in rats, normalization function of liver and changes in serum lipid parameters. Hum Exp Toxicol 30:1811–27. [DOI] [PubMed] [Google Scholar]
  13. Marsano LS, Vatsalya V, Hassan A, et al. (2016) Clinical features, disease modifiers, and natural history of alcoholic liver disease In Alcoholic and Non-Alcoholic Fatty Liver Disease. Springer, Cham. [Google Scholar]
  14. Mcclain CJ, Barve SS, Barve A, et al. (2011) Alcoholic liver disease and malnutrition. Alcohol Clin Exp Res 35:815–20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mcclain CJ, Marsano L, Burk RF, et al. (1991© 1991 by Thieme Medical Publishers, Inc.) Trace metals in liver disease. Semin Liver Dis 321–39. [DOI] [PubMed] [Google Scholar]
  16. Musso CG. (2009) Magnesium metabolism in health and disease. Int Urol Nephrol 41:357–62. [DOI] [PubMed] [Google Scholar]
  17. Mützell S. (1988) Cardiovascular and some biochemical effects of high alcohol consumption. Ups J Med Sci 93:277–88. [DOI] [PubMed] [Google Scholar]
  18. Papierkowski A, Pasternak K (1998) The effect of a single dose of morphine and ethanol on magnesium level in blood serum and tissues in mice. Magnes Res 11:85–9. [PubMed] [Google Scholar]
  19. Pasqualetti P, Casale R, Colantonio D, et al. (1987) Serum levels of magnesium in hepatic cirrhosis. Quaderni Sclavo di diagnostica clinica e di laboratorio 23:12–7. [PubMed] [Google Scholar]
  20. Petroianu A, Barquete J, De Almeida Plentz E, et al. (1991) Acute effects of alcohol ingestion on the human serum concentrations of calcium and magnesium. J Int Med Res 19:410–3. [DOI] [PubMed] [Google Scholar]
  21. Poikolainen K, Alho H (2008) Magnesium treatment in alcoholics: a randomized clinical trial. Subst Abuse Treat Prev Policy 3:1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rink EB. (1986) Magnesium deficiency in alcoholism. Alcohol Clin Exp Res 10:590–4. [DOI] [PubMed] [Google Scholar]
  23. Romani AM. (2008) Magnesium homeostasis and alcohol consumption. Magnes Res 21:197–204. [PubMed] [Google Scholar]
  24. Rylander R, Megevand Y, Lasserre B, et al. (2001) Moderate alcohol consumption and urinary excretion of magnesium and calcium. Scand J Clin Lab Invest 61:401–5. [DOI] [PubMed] [Google Scholar]
  25. Shane S, Flink E (1991) Magnesium deficiency in alcohol addiction and withdrawal. Magnes Trace Elem 10:263–8. [PubMed] [Google Scholar]
  26. Simopoulos AP. (2002) The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 56:365–79. [DOI] [PubMed] [Google Scholar]
  27. Sobell LC, Sobell MB, Connors GJ, et al. (2003) Assessing drinking outcomes in alcohol treatment efficacy studies: selecting a yardstick of success. Alcoholism: Clinical and Experimental Research 27(10):1661–1666. [DOI] [PubMed] [Google Scholar]
  28. Turecky L, Kupcova V, Szantova M, et al. (2006) Serum magnesium levels in patients with alcoholic and non-alcoholic fatty liver. Bratisl Lek Listy 107:58. [PubMed] [Google Scholar]
  29. Vandemergel X, Simon F (2015) Evolution of metabolic abnormalities in alcoholic patients during withdrawal. J Addict 2015:1–4 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vatsalya V, Bin Liaquat H, Ghosh K, et al. (2016a) A review on the sex differences in organ and system pathology with alcohol drinking. Curr Drug Abuse Rev 9:87–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Vatsalya V, Kong M, Cave MC, et al. (2018) Association of serum zinc with markers of liver injury in very heavy drinking alcohol dependent patients. J Nutr Biochem. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vatsalya V, Song M, Schwandt ML, et al. (2016b) Effects of sex, drinking history, and Omega-3 and Omega-6 fatty acids Dysregulation on the onset of liver injury in very heavy drinking alcohol-dependent patients. Alcohol Clin Exp Res 40:2085–93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wu C, Kenny M (1996) Circulating total and ionized magnesium after ethanol ingestion. Clin Chem 42:625–9. [PubMed] [Google Scholar]
  34. Wu L, Zhu X, Fan L, et al. (2017) Magnesium intake and mortality due to liver diseases: results from the third National Health and Nutrition Examination Survey Cohort. Sci Rep 7:17913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Young A, Cefaratti C, Romani A (2003) Chronic EtOH administration alters liver Mg2+ homeostasis. American J Physiol-Gastrointestinal and Liver Physiol 284:G57–67. [DOI] [PubMed] [Google Scholar]

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