Table 1: Summary of observed disease stages, the corresponding key events, expected markers, presumed pathophysiology and distinct clinical diagnoses of chronic fatiguing illnesses.


Corresponding key stage events

Expected markers

Presumed pathophysiologic changes

Correlated clinical diagnosis


Lack of sunlight. 

Low calcium diet.
High phosphate diet.

25OHD3 low.
Pi/Crea and Ca2+/Crea ratio dependent on diet and 25OHD3? 

Calcium and/or phosphate deficiency,
according to underlying cause.

Phosphate toxicity due to high phosphate diet. 

Idiopathic fatigue


Calcium body stores low, but serum Ca2+ and Pi normal due to accelerated bone loss.

1,25(OH2D3) high, though 25(OH)D3 low.
Pi/Crea ratio very low or variable?
Ca2+/Crea ratio variable dependent on diet, PTHi and bone loss. 
PTHi low in magnesium deficiency.

FGF23 low due to low calcium x phosphate product and due to low 25OHD3?

αKL low due to low 25OHD3?
CaSR gene induction reduced due to low 25OHD3?

CaSR activity variable due to bone loss and diet.

Chronic fatigue syndrome


Calcium body stores very low.
Extracellular Ca2+ low normal.
Yet paradoxical hypercalciuria.
Global renal and bone mineral loss.

PTHi inappropriate to serum and urine Ca2+?

Pi/Crea- and Ca2+/Crea-ratio inappropriate to serum levels?  

αKL very low?
Ca2+ low normal due to  set-point change of Ca2+/PTHi curve?
Hypercalciuria due to set-point change or hyperactive CaSR?

Vitamin D3-resistant chronic fatigue syndrome
Resistance reversible by multi-minerals and phosphate?


Ca x Pi body stores extremely low.
Multiple mineral deficits variably and intermittently measurable.
Ca2+/Pi deposits at unwanted location.

Obviously elevated Pi/Crea and Ca2+/Crea ratio?
CaSR activity activated by other agonists? 

Unsuspected laboratory results? Truncated FGF23 and PTH?

Tubular epithelial damage with multi-mineral depletion?

Reduced renal NH4+excretion??
Global channelopathy?
Hormone resistance against CaSR, FGF23/
At least osteoporosis as clinical hint to the disorder.

Myalgic encephalopathy (younger patients).

Fibromyalgia (older patients).

Somatic irreversible secondary diseases.


















Abbreviations: 25OHD3: 25-hydroxyvitamin D3, 1,25(OH)2D3: 1,25-dihydroxyvitamin D3, αKl: α-Klotho, Ca2+: calcium, CaSR: Calcium sensing receptor, FGF23: Fibroblast Growth Factor-23, Pi: Phosphate,  PTHi: Parathormone intact