The calcium to magnesium ratio plus adequate vitamin D greatly determine success or not in the immune battle against pathogens and cancer, not to mention cardiovascular disease. Ionized calcium and magnesium in normal, healthy individuals can be calculated and a ratio determined from serum levels. Using widely accepted laboratory reference range values and NHANES data, the recommended daily allowances from the Institute of Medicine of the National Academy of Sciences for calcium, magnesium, and

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... D3 (cholecalciferol) are objectively refuted mathematically and physiologically. Midrange values for both cations, despite RDA sufficiency, are shown to be unattainable without secondary hyperparathyroidism (high parathormone (PTH), low D) or hypoparathyroidism (low PTH, high iCa:iMg) at the officially designated level of 25(OH)D sufficiency (30 ng/mL). Calcium and magnesium utilize the same calcium sensing receptor (CaSR) not only on cell membranes but also on organelle membranes. Intra-mitochondrial hydroxylation of cholecalciferol can become compromised. An imbalanced intake of calcium and magnesium can impact the efficacy of vitamin D supplementation. Several pertinent articles underscoring these conclusions are analyzed in detail. The impact of an imbalanced Ca:Mg ratio on Covid-19, Long Covid and vaccination is also discussed.