Mads Svart , Alisa D. Kjaergaard , Thien Vinh Luong , Lars C. Gormsen , Niels Møller , Jens Otto L. Jørgensen , Esben Søndergaard
{"title":"Acute and prolonged ketosis lower serum IGF-I levels in human subjects","authors":"Mads Svart , Alisa D. Kjaergaard , Thien Vinh Luong , Lars C. Gormsen , Niels Møller , Jens Otto L. Jørgensen , Esben Søndergaard","doi":"10.1016/j.endmts.2024.100207","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Metabolic health and longevity are influenced by numerous factors including the growth hormone (GH) – insulin-like growth factor I (IGF<img>I) axis and ketone bodies (KB). However, data on the impact of KB exposure on GH and IGF-I levels are few.</div></div><div><h3>Design and patients</h3><div>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.</div></div><div><h3>Results</h3><div>A single oral KB ingestion significantly lowered serum IGF-I with 33 ng/ml (KB ingestion) vs 15 ng/ml (placebo), <em>P</em> = 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), <em>P</em> = 0.03. Individuals with genetic predisposition to ketonuria had lower levels of IGF-I (β = −0.0068, SE = 0.0029, <em>P</em> = 0.02).</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":34427,"journal":{"name":"Endocrine and Metabolic Science","volume":"16 ","pages":"Article 100207"},"PeriodicalIF":0.0000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine and Metabolic Science","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666396124000517","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
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.