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Reduced glomerular filtration or kidney reserve Dehydration or inconsistent fluid intake Low bicarbonate or limited buffering capacity High dietary acid load with low vegetable intake Sleep apnea or impaired nighttime oxygenation Sedentary lifestyle and low aerobic conditioning Gut fermentation and dysbiosis Alcohol, diuretics, stimulants and selected medications Elevated SAH and low SAM:SAH ratio Elevated homocysteine Low serum carbon dioxide or bicarbonate Creatinine, cystatin C and estimated GFR Urinalysis and urine albumin Uric acid, electrolytes and phosphorus Adenosine and expanded methylation analytes when available The clinical question is not simply Is the patient acidic? The more useful question is whether filtration, hydration, buffering, enzyme efficiency and downstream disposal are adequate to keep SAH, homocysteine, adenosine and other metabolites moving through the pathway