Trial reportJournal of Alzheimer's disease : JAD2020
Ca:Mg Ratio, APOE Cytosine Modifications, and Cognitive Function: Results from a Randomized Trial.
Trial report in Journal of Alzheimer's disease : JAD, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 17 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Magnesium Treatment on Vitamin D Resistance
Ca:Mg Ratio and Cognitive Function in the Personalized Prevention of Colorectal Cancer Trial
Methylomic Biomarkers, Magnesium Deficiency and Colon Neoplasia Prevention
Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Magnesium and Cognitive Health in Adults: A Systematic Review and Meta-Analysis.Advances in nutrition (Bethesda, Md.) · 2024Pooled it
- Pooled it
- Ca:Mg ratio, medium-chain fatty acids, and the gut microbiome.Clinical nutrition (Edinburgh, Scotland) · 2022Trial
- Magnesium treatment on methylation changes of transmembrane serine protease 2 (TMPRSS2).Nutrition (Burbank, Los Angeles County, Calif.) · 2021Trial
- Associations between Traditional Chinese Medicine Body Constitution and Cardiovascular Disease Risk in a White population.Aging and health research · 2025Article
- The Role of Magnesium in Depression, Migraine, Alzheimer's Disease, and Cognitive Health: A Comprehensive Review.Nutrients · 2025Review
- Roles of Necroptosis, Apoptosis, and Inflammation in Colorectal Carcinogenesis: A Longitudinal Human Study.Cancer prevention research (Philadelphia, Pa.) · 2025Article
- Nutritional strategies against dementia in rural populations.Frontiers in nutrition · 2025Review
- The Concurrent Association of Magnesium and Calcium Deficiencies with Cognitive Function in Older Hospitalized Adults.Nutrients · 2024Article
- Associations between traditional Chinese medicine body constitution and obesity risk among US adults.Longhua Chinese medicine · 2023Article
- Diet in the Prevention of Alzheimer's Disease: Current Knowledge and Future Research Requirements.Nutrients · 2022Review
- Pre-diagnostic dietary consumption of calcium and magnesium and calcium-to-magnesium intake ratio and ovarian cancer mortality: results from the ovarian cancer follow-up study (OOPS).European journal of nutrition · 2022Article
- Magnesium Status and Calcium/Magnesium Ratios in a Series of Cystic Fibrosis Patients.Nutrients · 2022Article
- N6-methyladenine-modified DNA was decreased in Alzheimer's disease patients.World journal of clinical cases · 2022Article
- Dietary calcium and magnesium intake and risk for incident dementia: The Shanghai Aging Study.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- Perspective: Characterization of Dietary Supplements Containing Calcium and Magnesium and Their Respective Ratio-Is a Rising Ratio a Cause for Concern?Advances in nutrition (Bethesda, Md.) · 2021Article
- A meta-analysis of Alzheimer's disease's relationship with human ApoE gene variants.American journal of translational research · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundDeterioration of ionized calcium (Ca2+) handling in neurons could lead to neurodegenerative disease. Magnesium (Mg) antagonizes Ca during many physiologic activities, including energy metabolism and catalyzation of demethylation from 5-methylcytosine(5-mC) to 5-hydroxymethylcytosine(5-hmC).
objectiveTo test the hypothesis that actively reducing the Ca:Mg intake ratio in the diet through Mg supplementation improves cognitive function, and to test whether this effect is partially mediated by modified cytosines in Apolipoprotein E (APOE).
methodsThis study is nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), a double-blind 2×2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center. Target doses for both Mg and placebo arms were personalized.
resultsAmong those aged > 65 years old who consumed a high Ca:Mg ratio diet, we found that reducing the Ca:Mg ratio to around 2.3 by personalized Mg supplementation significantly improved cognitive function by 9.1% (p = 0.03). We also found that reducing the Ca:Mg ratio significantly reduced 5-mC at the cg13496662 and cg06750524 sites only among those aged > 65 years old (p values = 0.02 and 0.03, respectively). Furthermore, the beneficial effect of reducing the Ca:Mg ratio on cognitive function in those aged over 65 years was partially mediated by reductions in 5-mC levels (i.e., cg13496662 and cg06750524) in APOE (p for indirect effect = 0.05).
conclusionOur findings suggest that, among those age 65 and over with a high dietary Ca:Mg ratio, optimal Mg status may improve cognitive function partially through modifications in APOE methylation. These findings, if confirmed, have significant implications for the prevention of cognitive aging and Alzheimer's disease.Clinical Trial Registry number and website: #100106 https://clinicaltrials.gov/ct2/show/NCT03265483.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.