Mineral Nutrition and the Risk of Chronic Diseases: A Mendelian Randomization Study

Cheng, Wenwen; Zhu, Qiang; Zhang, Hongyu

doi:10.3390/nu11020378

Cited by 53 publications

(49 citation statements)

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“…Magnesium is a crucial element that is required for the regulation of cellular and metabolic reactions. Alternations in magnesium content or its distribution within the body are associated with several agerelated diseases, such as diabetes [5,6]. Moreover, the effect of magnesium on cellular aging may be related to its interactions with telomere homeostasis [7].…”

Section: Introductionmentioning

confidence: 99%

Dietary Magnesium Intake and Leukocyte Telomere Attrition in Adults: The Regulatory Role of Serum Tumor Necrosis Factor α

Liu

et al. 2020

Mediators of Inflammation

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Objectives. In this study, we assessed the effects of dietary magnesium on leukocyte telomere length (LTL). Designs. The current cross-sectional analysis was based on data collected within a type 2 diabetes project. Settings. Dietary magnesium intake is associated with peripheral blood leukocyte telomere length (LTL). However, few epidemiological studies have evaluated the effects of magnesium on LTL in the clinical setting. Participants. This cross-sectional analysis included 467 participants (34.8% men). Measurements. Serum blood lipid profile, HbA1c, oxidative stress, and proinflammatory mediator levels were measured. Detailed dietary data were obtained using a 24 h food recall. LTL was assessed using a real-time PCR assay. Regression models and simple regulatory models were used for data analysis. Results. There was an inverse relationship between dietary magnesium and LTL (P<0.001), with a between-extreme-quarter difference of -0.55. Conversely, there was a positive relationship between dietary magnesium and serum tumor necrosis factor (TNF) α, with an interquarter difference of 3.79 pmol/mL (P for trend=0.006). Multivariate regression analysis revealed that the odds ratios (ORs) for shorter LTL and higher serum TNFα increased with magnesium intake, and the ORs of the differences between extreme quartiles were 2.60 (95% confidence interval (CI): 1.31–5.36; P=0.003) and 1.98 (95% CI: 1.09–3.59; P=0.008). There was a direct negative effect of dietary magnesium intake on LTL (B=−0.002; P=0.001), which appeared to be indirectly influenced by TNFα (-0.002 to -0.0005). Conclusions. Dietary magnesium intake may be a critical component of the cellular aging process, and its effect could be partly mediated by TNFα.

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Section: Introductionmentioning

confidence: 99%

Dietary Magnesium Intake and Leukocyte Telomere Attrition in Adults: The Regulatory Role of Serum Tumor Necrosis Factor α

Liu

et al. 2020

Mediators of Inflammation

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“…PheWAS-MR has been conducted on iron, but not copper [ 21 ]. Most importantly, few existing studies simultaneously examine multiple blood minerals at a phenome-wide scale to disentangle their confounded clinical effects [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

The Causal Effects of Blood Iron and Copper on Lipid Metabolism Diseases: Evidence from Phenome-Wide Mendelian Randomization Study

et al. 2020

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Blood levels of iron and copper, even within their normal ranges, have been associated with a wide range of clinical outcomes. The available epidemiological evidence for these associations is often inconsistent and suffers from confounding and reverse causation. This study aims to examine the causal clinical effects of blood iron and copper with Mendelian randomization (MR) analyses. Genetic instruments for the blood levels of iron and copper were curated from existing genome-wide association studies. Candidate clinical outcomes were identified based on a phenome-wide association study (PheWAS) between these genetic instruments and a wide range of phenotypes in 310,999 unrelated individuals of European ancestry from the UK Biobank. All signals passing stringent correction for multiple testing were followed by MR analyses, with replication in independent data sources where possible. We found that genetically predicted higher blood levels of iron and copper are both associated with lower risks of iron deficiency anemia (odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.67–0.85, p = 1.90 × 10−6 for iron; OR = 0.88, 95% CI: 0.78–0.98, p = 0.032 for copper), lipid metabolism disorders, and its two subcategories, hyperlipidemia (OR = 0.90, 95% CI: 0.85–0.96, p = 6.44 × 10−4; OR = 0.92, 95% CI: 0.87–0.98, p = 5.51 × 10−3) and hypercholesterolemia (OR = 0.90, 95% CI: 0.84–0.95, p = 5.34 × 10−4; OR = 0.93, 95% CI: 0.89–0.99, p = 0.022). Consistently, they are also associated with lower blood levels of total cholesterol and low-density lipoprotein cholesterol. Multiple sensitivity tests were applied to assess the presence of pleiotropy and the robustness of causal estimates. Regardless of the approaches, consistent evidence was obtained. Moreover, the unique clinical effects of each blood mineral were identified. Notably, genetically predicated higher blood iron is associated with an enhanced risk of varicose veins (OR = 1.28, 95% CI: 1.15–1.42, p = 4.34 × 10−6), while blood copper is positively associated with the risk of osteoarthrosis (OR = 1.07, 95% CI: 1.02–1.13, p = 0.010). Sex-stratified MR analysis further revealed some degree of sex differences in their clinical effects. Our comparative PheWAS-MR study of iron and copper comprehensively characterized their shared and unique clinical effects, highlighting their potential causal roles in hyperlipidemia and hypercholesterolemia. Given the modifiable nature of blood mineral status and the potential for clinical intervention, these findings warrant further investigation.

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“…13 14 Therefore, there are reasons to suspect the role of dietary magnesium intake in women with RA. Research on the relationship between magnesium and RA is limited and controversial, [15][16][17][18] with even fewer studies on women. According to a Pakistani study, women with RA had lower levels of magnesium in their blood, serum and hair.…”

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confidence: 99%

Relationship between dietary magnesium intake and rheumatoid arthritis in US women: a cross-sectional study

Zhu

Liu

et al. 2020

BMJ Open

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ObjectivesDiet has been shown to be associated with rheumatoid arthritis (RA), and magnesium has been shown to inhibit inflammatory responses, but research on the relationship between dietary magnesium and RA is limited and controversial. In this study, we aimed to explore the non-linear relationship between dietary magnesium intake and RA in US women.DesignCross-sectional survey.SettingNational Health and Nutrition Examination Survey (NHANES).Primary and secondary outcome measuresNon-linear relationship between dietary magnesium intake and prevalence of RA.ParticipantsA total of 13 324 women aged 18–80 years (RA n=12 306, non-RA n=1018) were included in this study.ResultsOverall, the absolute risk (AR) of RA was 7.24% in all participants. In the multivariable logistic regression analysis, we found a negative correlation between dietary magnesium intake and RA (OR=0.84, 95% CI 0.75 to 0.95, p=0.006). When we converted dietary magnesium intake into a categorical variable (tertiles), the ARs of the low group, the middle group and the high group were 9%, 7.1% and 4.9%, respectively. We noticed that the ORs between the three groups were not equidistant; then, we detected a U-shaped linking by smooth curve fitting and obtained inflection points at 181 and 446 mg/day. The prevalence of RA decreased when dietary magnesium intake was <181 mg/day (OR=0.7, 95% CI 0.5 to 0.8, p<0.001) and increased when it was >446 mg/day (OR=2.8, 95% CI 1.2 to 6.6, p=0.020), remaining at a minimum when it was between 181 and 446 mg/day (OR=1.0, 95% CI 0.7 to 1.2, p=0.700).ConclusionThere was a U-shaped relationship between dietary magnesium and RA in women, and our study highlights the importance of moderate dietary magnesium intake in possibly exerting a protective role in women with RA.

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Mineral Nutrition and the Risk of Chronic Diseases: A Mendelian Randomization Study

Cited by 53 publications

References 48 publications

Dietary Magnesium Intake and Leukocyte Telomere Attrition in Adults: The Regulatory Role of Serum Tumor Necrosis Factor α

Dietary Magnesium Intake and Leukocyte Telomere Attrition in Adults: The Regulatory Role of Serum Tumor Necrosis Factor α

The Causal Effects of Blood Iron and Copper on Lipid Metabolism Diseases: Evidence from Phenome-Wide Mendelian Randomization Study

Relationship between dietary magnesium intake and rheumatoid arthritis in US women: a cross-sectional study

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