Objective: A eucaloric very low-carbohydrate ketogenic diet (euVLCK;<50 g per day) induces ketosis and reduces portal insulin concentrations, which down-regulate GH receptors in the liver and reduce IGF-I synthesis. Somatostatin receptor ligands (SRLs) reduce GH secretion by the pituitary tumor, resulting in normalization of IGF-I in about 45% of acromegaly patients. Remaining patients should switch to (or add) the expensive drug pegvisomant (PEGV). Our concept is that in acromegaly a euVLCK diet exerts insulin-induced IGF-I normalization without the unwanted increase in GH, as the GH-inhibiting SRL therapy is continued.

Method: We performed a proof-of-concept study (n=11, 6 females) to determine whether a 2-week euVLCK diet (~35 g carbohydrate, 155 g fat and 115 g protein per day, no restriction in kcal) as adjuvant to first-generation SRLs reduces IGF-I concentrations in uncontrolled acromegaly patients.

Results: During the euVLCK diet, mean carbohydrate intake decreased from 194.4 [SD 143.1] grams to 32.6 [14.7]. IGF-I concentrations decreased significantly (median 0.83 [IQR 0.62-0.91] ULN vs 1.10 [1.02-1.25], p=0.014) and normalized in all but one patient, without the concomitant increase in GH (median 1.9 [IQR 0.4-3.7] µg/l vs 2.0[0.7-3.6], p=1.00). The patient without a decrease in IGF-I after the euVLCK diet had the highest degree of insulin resistance at baseline. Overall, the diet was well tolerated and all patients completed the study. Interestingly, IGF-I concentrations remained suppressed in six patients who continued a low-carbohydrate diet (80 g per day; median 0.83 [IQR 0.75-1.01] ULN after median 3.0 months) and warranted SRL dose reduction in three patients.

Conclusion: This proof-of-concept study illustrates the ability of an adjuvant euVLCK diet to achieve control of IGF-I without affecting GH concentrations in acromegaly patients uncontrolled with first-generation SRLs. Our results could affect the clinical management of acromegaly as a euVLCK diet might