Abstract
A ketogenic diet is a potential adjuvant cancer therapy that limits glucose availability to tumours while fuelling normal tissues with ketone bodies. We examined the effect of a low carbohydrate ketogenic diet (LCKD) (80% kcal from fat, ketogenic ratio 1.75:1, w/w) compared to a general hospital diet (GD) on serum metabolic profiles in patients (n = 18, ≥ 19 years old) who underwent pancreatectomy for pancreatobiliary cancer. Serum samples collected preoperatively (week 0) and after the dietary intervention (week 2) were analysed with a nontargeted metabolomics approach using liquid chromatography–tandem mass spectrometry. Serum β-hydroxybutyrate and total ketone levels significantly increased after 2 weeks of LCKD compared to GD (p < 0.05). Principal component analysis score plots and orthogonal partial least squares discriminant analysis also showed significant differences between groups at week 2, with strong validation. In all, 240 metabolites differed between LCKD and GD. Pathways including glycerophospholipid and sphingolipid metabolisms were significantly enriched in the LCKD samples. LCKD decreased C22:1-ceramide levels, which are reported to be high in pancreatic cancer, while increasing lysophosphatidylcholine (18:2), uric acid, citrulline, and inosine levels, which are generally low in pancreatic cancer. Postoperative LCKD might beneficially modulate pancreatic cancer-related metabolites in patients with pancreatobiliary cancer.
Highlights
A ketogenic diet is a potential adjuvant cancer therapy that limits glucose availability to tumours while fuelling normal tissues with ketone bodies
Shukla et al reported that the ketone bodies β-hydroxybutyrate and acetoacetate were associated with inhibited cell growth, reduced glucose uptake, and decreased glutamine and glutamate levels in pancreatic cancer cells; these ketone bodies were associated with decreased measures of cachexia in patients[10]
The Patient-Generated Subjective Global Assessment (PG-SGA) score indicated that patients were in a poorer nutrition state after surgery, but this was alleviated at week 4 in both groups, and there were no significant differences between groups (Fig. 1e)
Summary
A ketogenic diet is a potential adjuvant cancer therapy that limits glucose availability to tumours while fuelling normal tissues with ketone bodies. La Torre et al reported that after surgical tumour resection, 88% of patients with pancreatic cancer had a medium-high www.nature.com/scientificreports risk of malnutrition[6] These patients had significantly longer recovery times and increased morbidity rates when compared to patients who were at a low risk of malnutrition[6]. To the best our knowledge, there are no metabolomics studies on the impact of a ketogenic diet in patients who have undergone pancreatectomy for pancreatobiliary cancer The purpose of this pilot study was to examine the postoperative effects of a low-carbohydrate ketogenic diet (LCKD) on the serum metabolic profiles in patients who underwent pancreatectomy for pancreatobiliary cancer, compared to a general hospital diet (GD)
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