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Post-op metabolites

Levels of kynurenine metabolites substantially decreased post-op

The researchers report that none of the kynurenines were correlated to fasting glucose, whereas neopterin was strongly, positively correlated to both fasting glucose and HbA1c

Plasma levels of the kynurenine (3-hydroxykynurenine and 3-hydroxyanthranilic acid) metabolites were substantially decreased, along with a metabolic improvement one year after bariatric surgery, according to a study published by researchers from Norway. The stated that their study examining the role of kynurenine metabolites in the pathophysiologic pathways leading to metabolic impairment in individuals with obesity warrants further investigation.

In the paper, ‘Inflammatory markers, the tryptophan-kynurenine pathway, and vitamin B status after bariatric surgery’, published in PlosOne, the investigators noted that plasma levels of 3-hydroxykynurenine and 3-hydroxyanthranilic acid seemed to be positively correlated to impaired glucose tolerance. Therefore, the study authors from University of Bergen, Haukeland University Hospital, Affiliation Bevital AS, Bergen, Førde Hospital Trust, Førde and Voss Hospital, Bergen Health Trust, Voss, Norway, investigated circulating tryptophan, kynurenine and its metabolites, neopterin, B-vitamins, CRP, and HbA1c in individuals with obesity before, three and 12 months after bariatric surgery.

It is known that obesity leads to low-grade chronic inflammation and is associated with increased risk of metabolic diseases. Therefore, inflammatory markers may be useful as a diagnostic tool to identify subjects with obesity at high risk of developing metabolic diseases. In their longitudinal study, the researchers included 37 patients with severe obesity, scheduled to undergo bariatric surgery - either laparoscopic sleeve gastrectomy (LSG) or biliopancreatic diversion with duodenal switch (BPD-DS). Clinical examination and blood sampling were performed two days before surgery and repeated after three and 12 months.


At inclusion, 38% had diabetes, of which one patient had type 1 diabetes mellitus, 17% hypertension and 12% hypercholesterolemia. LSG was performed on 25 patients (68%) whereas 12 underwent BPD-DS. Patients selected for BPD-DS were older than the LSG patients and more frequently used anti-diabetic drugs. This subset also had higher levels of HbA1c, tryptophan and 3-hydroxyanthranilic acid.

The researchers report that none of the kynurenines were correlated to fasting glucose, whereas neopterin was strongly, positively correlated to both fasting glucose and HbA1c. Both 3-hydroxykynurenine and 3-hydroxyanthranilic acid showed strong positive associations to HbA1c, whereas 3-hydroxykynurenine was also correlated positively to the TG:HDL-ratio. At inclusion, BMI was positively correlated to CRP (p<0.05), but they did not find correlations to any of the other markers measured in the study.

Reduction of body weight was higher in the BPD-DS group (%EBMIL 109% (85.7–114)) than in the LSG group (%EBMIL 84.7% (70.0–91.4), p<0.005). Fasting glucose (17%), HbA1c (13%) and triglycerides (39%) decreased while HDL-cholesterol (23%) increased, indicating a more favourable metabolic profile one year after surgery.

Before surgery, 13 patients were diagnosed with diabetes, 10 of these used oral anti-diabetic drugs or insulin. After surgery none of the patients with T2D used insulin and only one patient used oral anti-diabetic medication.

They noted decreased plasma levels of tryptophan and all the kynurenine pathway metabolites, except for anthranilic acid. However,anthranilic acid was unchanged at three months, but significantly increased after one year. The KTR and CRP decreased after surgery, while levels of neopterin were unchanged (Figure 1).

Figure 1: Inflammatory markers after bariatric surgery. Samples were measured at baseline, 3 months and after one year in 37 patients undergoing bariatric surgery. P values for trend over time are estimated with a random intercept mixed model, adjusted for type of operation and vitamin B supplementation. Data are given as median (25th to 27th percentile).

Analysing the LSG and BPD-DS groups separately showed the same results as in the combined group regarding CRP, neopterin, and the B vitamins measured, as well as the kynurenine metabolites, except for anthranilic acid, which was increased in the BPD-DS group but not significantly changed in the LSG group.

To examine whether baseline metabolite levels could predict surgical outcomes, thye analysed whether BMI, HbA1c, fasting glucose, and the TG:HDL-ratio after surgery were related to plasma kynurenines, inflammatory markers and B vitamins at baseline. Changes in BMI one year after surgery did not correlate with the metabolite levels at baseline, but they observed a positive association with changes in tryptophan (p=0.07) and kynurenine (p=0.014). Changes in HbA1c one year after surgery were positively correlated with baseline levels of 3-hydroxyanthranilic acid (p=0.041) and tryptophan (p=0.027). In addition, changes in 3-hydroxykynurenine one year after surgery were positively correlated to the changes in both HbA1c (p=0.029) and the TG:HDL-ratio (p=0.024). The analyses were adjusted for age, gender, eGFR, and operation method.

The researchers acknowledged that patients in this study received multi-vitamin supplements containing vitamin B2, B3 and B6 after surgery, making it difficult to evaluate the effect of reduced inflammation vs. supplements or impaired vitamin uptake on measured levels of vitamin B3 and B6. They also added that the type of bariatric surgery performed could play a role regarding weight loss, metabolic improvement and decreased inflammation. However, due to the small sample size the study was not designed to evaluate differences in the surgical procedures.

“Strong correlations between HbA1c and the kynurenine metabolites 3-hydroxykynurenine and 3-hydroxyanthranilic acid were observed in patients with obesity scheduled for bariatric surgery,” the authors conclude. “Following surgery, vitamin B6 levels increased whereas KTR and CRP decreased, indicating down-regulated inflammation after profound weight loss. The role of kynurenine metabolites in the pathophysiologic pathways leading to metabolic impairment in individuals with obesity needs further evaluation.”

To access this paper, please click here

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