Presence of kynurenic acid in alcoholic beverages - Is this good news, or bad news?

Kynurenic acid (KYNA) is a metabolite of tryptophan formed enzymatically along kynurenine pathway in bacteria, fungi, plants and animals. It was suggested that yeast may produce KYNA during the fermentation process. Since KYNA was found to interact with alcohol metabolism by inhibition of aldehyde dehydrogenase activity the aim of this study was to measure the content of KYNA in selected alcoholic beverages of various type, beer, wine, mead and spirits. Moreover, the absorption and elimination rate of KYNA administered as a beverage was investigated in humans. Twelve healthy volunteers (6 female and 6 male) were studied. Fifty six samples of alcoholic beverages were of commercial origin. KYNA was determined by means of high-performance liquid chromatography method with fluorometric detection. KYNA was identified in all studied beverages. The amounts of KYNA found in various types of beverages differed significantly: mead 9.4-38.1 µg/100 ml, wine 1.4-10.9 µg/100 ml, beer 0.1-5.2 µg/100 ml, spirits 0.01-0.1 µg/100 ml. In human, it was found that KYNA is rapidly absorbed from digestive tract reaching its maximal concentration in blood 30 min after administration. Thus, the potential interaction between KYNA and alcohol occurring in human body after ingestion of alcoholic beverages was proven.

Fate and distribution of kynurenic acid administered as beverage.

BACKGROUND: Kynurenic acid (KYNA) is a biologically active metabolite of tryptophan exerting action on several receptors located in the brain and periphery. KYNA can be synthesized endogenously or supplied in the diet. It was documented that KYNA is present in various types of food. However, its presence in beverages was not yet investigated. Here, we measured content of KYNA in tea and coffee as well as analyzed distribution and fate of intragastrically administered labelled KYNA in mice. METHODS: 16 and 13 studied samples of tea and coffee, respectively were of commercial origin. Tea and coffee infusions were prepared according to the producers' guidelines. KYNA content in beverages was measured by means of HPLC detection. Adult male mice were used for analysis of fate of intragastrically administered labelled KYNA and collected samples were analyzed using liquid scintillation counter. RESULTS: KYNA was identified in all studied beverages. Amounts of KYNA found in various types of beverages differed significantly. The highest content of KYNA in tea and coffee was 8.7 µg/100 ml and 0.63 µg/100 ml, respectively. It was found that KYNA administered intragastrically as a liquid is absorbed from the digestive system and readily excreted in urine. The atypical kinetics of KYNA distribution were found in intestinal content of cecum, where it appeared later and persisted longer than in other tissues. CONCLUSIONS: Our data show that tea and coffee intake may contribute to KYNA content in the human organism. The distribution pattern of KYNA delivered as a liquid suggests that it either directly affects digestive system's functioning and intestinal microbiome composition, or participates in the whole body pool of KYNA.

On the toxicity of kynurenic acid in vivo and in vitro.

BACKGROUND: Kynurenic acid (KYNA), a tryptophan metabolite is an antagonist of ionotropic glutamate receptors and alpha-7 nicotinic receptor. Moreover, it is an agonist of G-protein receptor GPR35. Its neuroprotective, anticonvulsant, anti-inflammatory and antioxidant activity was documented. KYNA is present in food and herbal medicines. However, the data on effects induced by a long-lasting treatment with KYNA is lacking. The aim of the study was the assessment of toxicity of a prolonged administration of KYNA in rodents. The cytotoxicity of KYNA in vitro was also examined. METHODS: Adult mice and rats were used. KYNA was administered in the drinking water in concentrations of 25 or 250mg/L for 3-21 days. The following cells were cultured in an in vitro study: mouse fibroblast (NIH/3T3), green monkey kidney cells and primary chick embryo cells (CECC). Cell viability was determined with methyl thiazol tetrazolium reduction assay, neutral red uptake assay and lactate dehydrogenase leakage assay. RESULTS: KYNA affected neither body gain nor body composition. Blood counts were also unaffected. The viability of cells in the culture was lowered at high millimolar concentrations of KYNA. An elevated viability of GMK and CECC cells was detected in the presence of KYNA in micromolar concentrations. CONCLUSIONS: The obtained results showed that a long-term application of KYNA in the drinking water is well-tolerated by rodents. No evidence of a toxic response was recorded. Achieved results indicate that diets containing a high amount of KYNA or enriched with KYNA should not cause any risk to the human health.

Kynurenic Acid in the digestive system-new facts, new challenges.

This review provides information on the most recent findings concerning presence, origin, and role of kynurenic acid (KYNA), a tryptophan metabolite, in the digestive system. KYNA is an antagonist of both the ionotropic glutamate receptors and the alpha7 nicotinic acetylcholine receptor, as well as an agonist of G-protein coupled GPR35 receptor. Since the GPR35 receptor is mainly present in the gastrointestinal tract, researchers have concentrated on the digestive system in recent years. They have found that KYNA content increases gradually and significantly along the gastrointestinal tract. Interestingly, the concentration of KYNA in the lumen is much higher than in the wall of intestine. It has been documented that KYNA may have a positive influence on the number of pathologies in the gastrointestinal tract, in particular ulcers, colon obstruction, or colitis. Future studies might determine whether it is advisable to supplement KYNA to a human organism.

Potato- an important source of nutritional kynurenic acid.

Kynurenic acid (KYNA) is a metabolite of tryptophan which is formed along the kynurenine pathway. KYNA may possess neuroprotective, anti-inflammatory, antioxidant and antiproliferative properties. This study measured the concentration of KYNA in various varieties of potatoes and products made from potatoes. KYNA content was determined by means of the high-performance liquid chromatography with fluorescence detection. KYNA was found in all 16 studied varieties of potato tubers in amounts varying from 0.239 to 3.240 µg/g dry weight. The content of KYNA in potato tubers declined during long-term storage. The content of KYNA in French fries varied from 0.100 to 0.646 µg/g dry weight. KYNA content in potato crisps was 0.478 and 0.576 µg/g dry weight. Hence, all in all, we concluded that the amount of KYNA potentially delivered to the human body in potatoes and various foods produced from potatoes is high and might be compared to the amount of KYNA present in a maximum daily dose of popular herbs and herbal medicines.

Distribution, synthesis, and absorption of kynurenic acid in plants.

Kynurenic acid (KYNA) is an endogenous antagonist of the ionotropic glutamate receptors and the α7 nicotinic acetylcholine receptor as well as an agonist of the G-protein-coupled receptor GPR35. In this study, KYNA distribution and synthesis in plants as well as its absorption was researched. KYNA level was determined by means of the high-performance liquid chromatography with fluorescence detection. KYNA was found in leaves, flowers, and roots of tested medicinal herbs: dandelion (Taraxacum officinale), common nettle (Urtica dioica), and greater celandine (Chelidoniummajus). The highest concentration of this compound was detected in leaves of dandelion--a mean value of 0.49 µg/g wet weight. It was shown that KYNA can be synthesized enzymatically in plants from its precursor, L-kynurenine, or absorbed by plants from the soil. Finally, the content of KYNA was investigated in 21 herbal tablets, herbal tea, herbs in sachets, and single herbs in bags. The highest content of KYNA in a maximum daily dose of herbal medicines appeared in St. John's wort--33.75 µg (tablets) or 32.60 µg (sachets). The pharmacological properties of KYNA and its presence in high concentrations in medicinal herbs may suggest that it possesses therapeutic potential, especially in the digestive system and should be considered a new valuable dietary supplement.

Presence of kynurenic acid in food and honeybee products.

Kynurenic acid (KYNA) is an endogenous antagonist of ionotropic glutamate receptors and the alpha 7 nicotinic acetylcholine receptor, showing anticonvulsant and neuroprotective activity. In this study, the presence of KYNA in food and honeybee products was investigated. KYNA was found in all 37 tested samples of food and honeybee products. The highest concentration of KYNA was obtained from honeybee products' samples, propolis (9.6 nmol/g), honey (1.0-4.8 nmol/g) and bee pollen (3.4 nmol/g). A high concentration was detected in fresh broccoli (2.2 nmol/g) and potato (0.7 nmol/g). Only traces of KYNA were found in some commercial baby products. KYNA administered intragastrically in rats was absorbed from the intestine into the blood stream and transported to the liver and to the kidney. In conclusion, we provide evidence that KYNA is a constituent of food and that it can be easily absorbed from the digestive system.