Tag: amino acids

Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats

Abstract:

Recent studies have reported that plasma levels of tricarboxylic acid (TCA) cycle metabolites and TCA cycle-related metabolite change in patients with chronic fatigue syndrome (CFS) and in healthy humans after exercise. Exogenous dietary citric acid has been reported to alleviate fatigue during daily activities and after exercise. However, it is unknown whether dietary citric acid affects the plasma levels of these metabolites. Therefore, the present study aimed to investigate the effects of exogenously administered citric acid on TCA cycle metabolites and TCA cycle-related metabolites in plasma.

Sprague-Dawley rats were divided into control and citric acid groups. We evaluated the effect of exogenous dietary citric acid on the plasma TCA cycle and TCA cycle-related metabolites by metabolome analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). TCA cycle metabolites, including plasma citrate, cis-aconitate, and isocitrate, were significantly elevated after exogenous administration of citric acid. Anaplerotic amino acids, which are converted to TCA cycle metabolites, such as serine, glycine, tryptophan, lysine, leucine, histidine, glutamine, arginine, isoleucine, methionine, valine, and phenylalanine, also showed significantly elevated levels.

Citric acid administration significantly increased the levels of initial TCA cycle metabolites in the plasma. This increase after administration of citric acid was shown to be opposite to the metabolic changes observed in patients with CFS. These results contribute novel insight into the fatigue alleviation mechanism of citric acid.

Source: Hara Y, Kume S, Kataoka Y, Watanabe N. Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats. Heliyon. 2021 Dec 4;7(12):e08501. doi: 10.1016/j.heliyon.2021.e08501. PMID: 34934832; PMCID: PMC8654791. https://pubmed.ncbi.nlm.nih.gov/34934832/

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome

Abstract:

Myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is a debilitating disease of unknown etiology, with hallmark symptoms including postexertional malaise and poor recovery. Metabolic dysfunction is a plausible contributing factor.

We hypothesized that changes in serum amino acids may disclose specific defects in energy metabolism in ME/CFS. Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients.

The amino acid pattern suggested functional impairment of pyruvate dehydrogenase (PDH), supported by increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPARδ in peripheral blood mononuclear cells from both sexes. Myoblasts grown in presence of serum from patients with severe ME/CFS showed metabolic adaptations, including increased mitochondrial respiration and excessive lactate secretion. The amino acid changes could not be explained by symptom severity, disease duration, age, BMI, or physical activity level among patients.

These findings are in agreement with the clinical disease presentation of ME/CFS, with inadequate ATP generation by oxidative phosphorylation and excessive lactate generation upon exertion.

 

Source: Fluge Ø, Mella O, Bruland O, Risa K, Dyrstad SE, Alme K, Rekeland IG, Sapkota D, Røsland GV, Fosså A, Ktoridou-Valen I, Lunde S, Sørland K, Lien K, Herder I, Thürmer H, Gotaas ME, Baranowska KA, Bohnen LM, Schäfer C, McCann A, Sommerfelt K, Helgeland L, Ueland PM, Dahl O, Tronstad KJ. Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome. JCI Insight. 2016 Dec 22;1(21):e89376. doi: 10.1172/jci.insight.89376. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161229/ (Full article)

 

Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome

Abstract:

A variety of dietary interventions has been used in the management of chronic fatigue syndrome (CFS), yet no therapeutic modality has demonstrated conclusive positive results in terms of effectiveness. The main aim of this study was to evaluate the effects of orally administered guanidinoacetic acid (GAA) on multidimensional fatigue inventory (MFI), musculoskeletal soreness, health-related quality of life, exercise performance, screening laboratory studies, and the occurrence of adverse events in women with CFS.

Twenty-one women (age 39.3 ± 8.8 years, weight 62.8 ± 8.5 kg, height 169.5 ± 5.8 cm) who fulfilled the 1994 Centers for Disease Control and Prevention criteria for CFS were randomized in a double-blind, cross-over design, from 1 September 2014 through 31 May 2015, to receive either GAA (2.4 grams per day) or placebo (cellulose) by oral administration for three months, with a two-month wash-out period.

No effects of intervention were found for the primary efficacy outcome (MFI score for general fatigue), and musculoskeletal pain at rest and during activity.

After three months of intervention, participants receiving GAA significantly increased muscular creatine levels compared with the placebo group (36.3% vs. 2.4%; p < 0.01). Furthermore, changes from baseline in muscular strength and aerobic power were significantly greater in the GAA group compared with placebo (p < 0.05). Results from this study indicated that supplemental GAA can positively affect creatine metabolism and work capacity in women with CFS, yet GAA had no effect on main clinical outcomes, such as general fatigue and musculoskeletal soreness.

 

Source: Ostojic SM, Stojanovic M, Drid P, Hoffman JR, Sekulic D, Zenic N. Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome. Nutrients. 2016 Jan 29;8(2):72. doi: 10.3390/nu8020072. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772036/ (Full article)

 

NMR metabolic profiling of serum identifies amino acid disturbances in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating multisystem disorder characterised by long-term fatigue with a variety of other symptoms including cognitive dysfunction, unrefreshing sleep, muscle pain, and post-exertional malaise. It is a poorly understood condition that occurs in ~5 in every 1000 individuals. We present here a preliminary study on the analysis of blood samples from 11 CFS and 10 control subjects through NMR metabolic profiling.

Identified metabolites that were found to be significantly altered between the groups were subjected to correlation analysis to potentially elucidate disturbed metabolic pathways. Our results showed a significant reduction of glutamine (P=0.002) and ornithine (P<0.05) in the blood of the CFS samples. Correlation analysis of glutamine and ornithine with other metabolites in the CFS sera showed relationships with glucogenic amino acids and metabolites that participate in the urea cycle. This indicates a possible disturbance to amino acid and nitrogen metabolism. It would be beneficial to identify any potential biomarkers of CFS for accurate diagnosis of the disorder.

Copyright © 2012 Elsevier B.V. All rights reserved.

 

Source: Armstrong CW, McGregor NR, Sheedy JR, Buttfield I, Butt HL, Gooley PR. NMR metabolic profiling of serum identifies amino acid disturbances in chronic fatigue syndrome. Clin Chim Acta. 2012 Oct 9;413(19-20):1525-31. doi: 10.1016/j.cca.2012.06.022. Epub 2012 Jun 21. https://www.ncbi.nlm.nih.gov/pubmed/22728138

 

Hematologic and urinary excretion anomalies in patients with chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) have a broad and variable spectrum of signs and symptoms with variable onsets. This report outlines the results of a single-blind, cross-sectional research project that extensively investigated a large cohort of 100 CFS patients and 82 non fatigued control subjects with the aim of performing a case-control evaluation of alterations in standard blood parameters and urinary amino and organic acid excretion profiles.

Blood biochemistry and full blood counts were unremarkable and fell within normal laboratory ranges. However, the case-control comparison of the blood cell data revealed that CFS patients had a significant decrease in red cell distribution width and increases in mean platelet volume, neutrophil counts, and the neutrophil-lymphocyte ratio.

Evaluation of the urine excretion parameters also revealed a number of anomalies. The overnight urine output and rate of amino acid excretion were both reduced in the CFS group (P < 0.01). Significant decreases in the urinary excretion of asparagine (P < 0.0001), phenylalanine (P < 0.003), the branch chain amino acids (P < 0.005), and succinic acid (P < 0.0001), as well as increases in 3-methylhistidine (P < 0.05) and tyrosine (P < 0.05) were observed.

It was concluded that the urinary excretion and blood parameters data supported the hypothesis that alterations in physiologic homeostasis exist in CFS patients.

 

Source: Niblett SH, King KE, Dunstan RH, Clifton-Bligh P, Hoskin LA, Roberts TK, Fulcher GR, McGregor NR, Dunsmore JC, Butt HL, Klineberg I, Rothkirch TB. Hematologic and urinary excretion anomalies in patients with chronic fatigue syndrome. Exp Biol Med (Maywood). 2007 Sep;232(8):1041-9. https://www.ncbi.nlm.nih.gov/pubmed/17720950

 

beta-Alanine and gamma-aminobutyric acid in chronic fatigue syndrome

Abstract:

BACKGROUND: Due to the occurrence of sleep disturbances and fatigue in chronic fatigue syndrome (CFS), an investigation was performed to examine if there is an abnormal excretion of gamma-aminobutyric acid (GABA) and/or its structural analogue beta-alanine in the urine from CFS patients. Both GABA and beta-alanine are inhibitory neurotransmitters in the mammalian central nervous system.

METHODS: The 24 h urine excretion of GABA and beta-alanine was determined by isotope dilution gas chromatography mass spectrometry in 33 CFS patients and 43 healthy controls. The degree of symptoms in both patients and controls was measured by grading of three typical CFS symptoms using a Visual Analogue Scale.

RESULTS: Men had a significantly higher excretion of both beta-alanine and GABA than women. Comparing CFS patients with healthy controls showed no significant difference in excretion of neither beta-alanine nor GABA. No correlation was found between the excretion of beta-alanine or GABA and any of the three characteristic CFS symptoms measured. However, two female and two male CFS patients excreted considerably higher amounts of beta-alanine in their 24 h urine samples than control subjects.

CONCLUSIONS: Increased excretion of beta-alanine was found in a subgroup of CFS patients, indicating that there may be a link between CFS and beta-alanine in some CFS patients.

 

Source: Hannestad U, Theodorsson E, Evengård B. beta-Alanine and gamma-aminobutyric acid in chronic fatigue syndrome. Clin Chim Acta. 2007 Feb;376(1-2):23-9. Epub 2006 Jul 14. https://www.ncbi.nlm.nih.gov/pubmed/16934791

 

Urinary and plasma organic acids and amino acids in chronic fatigue syndrome

Abstract:

Previous work by others have suggested the occurrence of one or more chemical or metabolic ‘markers’ for ME/CFS including specific amino acids and organic acids and a number of unidentified compounds (CFSUM1, CFSUM2). We have shown elsewhere that CFSUM1 is partially derivatised pyroglutamic acid and CFSUM2 partially derivatised serine and have suggested and demonstrated that the analytical methods used were unsuitable to identify or to accurately quantify urinary metabolites. We have now made a detailed analysis of plasma and urinary amino acids and of urinary organic acids from patients with ME/CFS and from three control groups.

Fasting blood plasma and timed urine samples were obtained from 31 patients with CFS, 31 age and sex-matched healthy controls, 15 patients with depression and 22 patients with rheumatoid arthritis. Plasma and urinary amino acids and urinary organic acids were determined using established and validated methods and data compared by statistical analysis. None of the previously reported abnormalities in urinary amino acids or of organic acids could be confirmed.

Results however provide some evidence in patients with ME/CFS for underlying inflammatory disease and for reduced intramuscular collagen with a lowered threshold for muscle micro-injury. These factors in combination may provide a basis for the fatigue and muscle pain that are the major symptoms in these patients.

 

Source: Jones MG, Cooper E, Amjad S, Goodwin CS, Barron JL, Chalmers RA. Urinary and plasma organic acids and amino acids in chronic fatigue syndrome. Clin Chim Acta. 2005 Nov;361(1-2):150-8. http://www.ncbi.nlm.nih.gov/pubmed/15992788