Acute and prolonged ketosis lower serum IGF-I levels in human subjects

Objective

Metabolic health and longevity are influenced by numerous factors including the growth hormone (GH) – insulin-like growth factor I (IGFI) axis and ketone bodies (KB). However, data on the impact of KB exposure on GH and IGF-I levels are few.

Design and patients

To investigate the effect of acute and chronic KB exposure on GH and IGF-I levels in human subjects. GH and IGF-I levels were measured in three human studies: i) After a single oral ingestion of KB (36.5 g of Na-D/L-βOHB) vs. placebo in six healthy individuals; ii): after a three-week isocaloric ketogenic diet (KD) compared to a standard diet (SD) in 11 overweight individuals; and iii) in a genetic predisposition study using the specific genetic variants in the SCOT gene (rs7712274 and rs7728482), which is associated with ketonuria.

Results

A single oral KB ingestion significantly lowered serum IGF-I with 33 ng/ml (KB ingestion) vs 15 ng/ml (placebo), P = 0.01. Ketogenic diet significantly lowered serum IGF-I levels 111 ng/ml (KD) vs 125 ng/ml (SD), P = 0.01 in combination with a two-fold increase in serum GH 0.9 ng/ml to 1.8 ng/ml (KD) compared to 0.9 ng/ml to 0.4 ng/ml (SD), P = 0.03. Individuals with genetic predisposition to ketonuria had lower levels of IGF-I (β = −0.0068, SE = 0.0029, P = 0.02).

Conclusions

KB exposure is associated with reduced serum IGF-I levels in the presence of non-suppressed or elevated GH levels. This observation points to a suppressive effect of KB on hepatic IGF-I production. The association between genetic predisposition to ketonuria and increased body size is unexpected and deserves further investigations.