Tag: acylcarnitine deficiency

Comparison of serum acylcarnitine levels in patients with myalgic encephalomyelitis/chronic fatigue syndrome and healthy controls: a systematic review and meta-analysis

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease (ME/CFS/SEID) is a condition diagnosed primarily based on clinical symptoms, including prolonged fatigue and post-exertional malaise; however, there is no specific test for the disease. Additionally, diagnosis can be challenging since healthcare professionals may lack sufficient knowledge about the disease. Prior studies have shown that patients with ME/CFS/SEID have low serum acylcarnitine levels, which may serve as a surrogate test for patients suspected of having this disease. This systematic review and meta-analysis aimed to investigate the differences in serum acylcarnitine levels between patients with ME/CFS/SEID and healthy controls.

Methods: This systematic review was conducted using PubMed and Ichushi-Web databases. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we included all studies from the databases’ inception until February 17, 2023, that evaluated blood tests in both patients with ME/CFS/SEID and healthy control groups. The primary endpoint was the difference in serum acylcarnitine levels between the two groups.

Results: The electronic search identified 276 studies. Among them, seven met the eligibility criteria. The serum acylcarnitine levels were analyzed in 403 patients with ME/CFS/SEID. The patient group had significantly lower serum acylcarnitine levels when compared with the control group, and the statistical heterogeneity was high.

Conclusion: The patient group had significantly lower serum acylcarnitine levels when compared with the control group. In the future, the measurement of serum acylcarnitine levels, in addition to clinical symptoms, may prove to be a valuable diagnostic tool for this condition.

Source: Jinushi R, Masuda S, Tanisaka Y, Nishiguchi S, Shionoya K, Sato R, Sugimoto K, Shin T, Shiomi R, Fujita A, Mizuide M, Ryozawa S. Comparison of serum acylcarnitine levels in patients with myalgic encephalomyelitis/chronic fatigue syndrome and healthy controls: a systematic review and meta-analysis. J Transl Med. 2023 Jun 19;21(1):398. doi: 10.1186/s12967-023-04226-z. PMID: 37337273; PMCID: PMC10280864. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280864/ (Full text)

A case of post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome characterized by post-exertional malaise and low serum acylcarnitine level

Abstract:

COVID-19 afflicts patients with acute symptoms and longer term sequelae. One of the sequelae is myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is often difficult to diagnose, having no established tests. In this article, we synthesize information from literature reviews on patients with ME/CSF that developed after recovery from COVID-19.

Source: Jinushi R, Nishiguchi S, Masuda S, Sasaki A, Koizumi K, Ryozawa S. A case of post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome characterized by post-exertional malaise and low serum acylcarnitine level. Clin Case Rep. 2023 Feb 10;11(2):e6930. doi: 10.1002/ccr3.6930. PMID: 36789311; PMCID: PMC9913186. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913186/ (Full text)

A multi-omics based anti-inflammatory immune signature characterizes Long COVID Syndrome

Abstract:

To investigate Long COVID Syndrome (LCS) pathophysiology, we performed an exploratory study with blood plasma derived from three groups: 1) healthy vaccinated individuals without SARS-CoV-2 exposure; 2) asymptomatic recovered patients at least three months after SARS-CoV-2 infection and; 3) symptomatic patients at least 3 months after SARS-CoV-2 infection with chronic fatigue syndrome or similar symptoms, here designated as Long COVID Syndrome (LCS) patients.

Multiplex cytokine profiling indicated slightly elevated pro-inflammatory cytokine levels in recovered individuals in contrast to LCS patients. Plasma proteomics demonstrated low levels of acute phase proteins and macrophage-derived secreted proteins in LCS. High levels of anti-inflammatory oxylipins including omega-3 fatty acids in LCS were detected by eicosadomics, whereas targeted metabolic profiling indicated high levels of anti-inflammatory osmolytes taurine and hypaphorine, but low amino acid and triglyceride levels and deregulated acylcarnithines. A model considering alternatively polarized macrophages as a major contributor for these molecular alterations is presented.

Source: Kovarik JJ, Bileck A, Hagn G, Meier-Menches SM, Frey T, Kaempf A, Hollenstein M, Shoumariyeh T, Skos L, Reiter B, Gerner MC, Spannbauer A, Hasimbegovic E, Schmidl D, Garhöfer G, Gyöngyösi M, Schmetterer KG, Gerner C. A multi-omics based anti-inflammatory immune signature characterizes Long COVID Syndrome. iScience. 2022 Dec 5:105717. doi: 10.1016/j.isci.2022.105717. Epub ahead of print. PMID: 36507225; PMCID: PMC9719844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719844/ (Full text)

Plasma and Urinary Carnitine and Acylcarnitines in Chronic Fatigue Syndrome

Abstract:

Contradictory reports have suggested that serum free carnitine and acylcarnitine concentrations are decreased in patients with chronic fatigue syndrome (CFS) and that this is a cause of the muscle fatigue observed in these patients. Others have shown normal serum free carnitine and acylcarnitines in similar patients. We report here studies on free, total and esterified (acyl) carnitines in urine and blood plasma from UK patients with CFS and three control groups.

Plasma and timed urine samples were obtained from 31 patients with CFS, 31 healthy controls, 15 patients with depression and 22 patients with rheumatoid arthritis. Samples were analysed using an established radioenzymatic procedure for total, free and esterified (acyl) carnitine.

There were no significant differences in plasma or urinary total, free or esterified (acyl) carnitine between UK patients with CFS and the control groups or in renal excretion rates of these compounds. The data presented here show that, in the CFS patients studied, there are no significant abnormalities of free or esterified (acyl) carnitine. It is thus unlikely that abnormalities in carnitine homeostasis have any significant role in the aetiology of their chronic fatigue.

Source: Jones MG, Goodwin CS, Amjad S, Chalmers RA. Plasma and urinary carnitine and acylcarnitines in chronic fatigue syndrome. Clin Chim Acta. 2005 Oct;360(1-2):173-7. doi: 10.1016/j.cccn.2005.04.029. PMID: 15967423. https://pubmed.ncbi.nlm.nih.gov/15967423/

Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome. Potential involvement of altered carnitine palmitoyltransferase-I activity

Abstract:

OBJECTIVE: The underlying aetiology of chronic fatigue syndrome is currently unknown; however, in the light of carnitine’s critical role in mitochondrial energy production, it has been suggested that chronic fatigue syndrome may be associated with altered carnitine homeostasis. This study was conducted to comparatively examine full endogenous carnitine profiles in patients with chronic fatigue syndrome and healthy controls.

DESIGN: A cross-sectional, observational study.

SETTING AND SUBJECTS: Forty-four patients with chronic fatigue syndrome and 49 age- and gender-matched healthy controls were recruited from the community and studied at the School of Pharmacy & Medical Sciences, University of South Australia.

MAIN OUTCOME MEASURES: All participants completed a fatigue severity scale questionnaire and had a single fasting blood sample collected which was analysed for l-carnitine and 35 individual acylcarnitine concentrations in plasma by LC-MS/MS.

RESULTS: Patients with chronic fatigue syndrome exhibited significantly altered concentrations of C8:1, C12DC, C14, C16:1, C18, C18:1, C18:2 and C18:1-OH acylcarnitines; of particular note, oleyl-L-carnitine (C18:1) and linoleyl-L-carnitine (C18:2) were, on average, 30-40% lower in patients than controls (P < 0.0001). Significant correlations between acylcarnitine concentrations and clinical symptomology were also demonstrated.

CONCLUSIONS: It is proposed that this disturbance in carnitine homeostasis is reflective of a reduction in carnitine palmitoyltransferase-I (CPT-I) activity, possibly a result of the accumulation of omega-6 fatty acids previously observed in this patient population. It is hypothesized that the administration of omega-3 fatty acids in combination with l-carnitine would increase CPT-I activity and improve chronic fatigue syndrome symptomology.

© 2011 The Association for the Publication of the Journal of Internal Medicine.

 

Source: Reuter SE, Evans AM. Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome. Potential involvement of altered carnitine palmitoyltransferase-I activity. J Intern Med. 2011 Jul;270(1):76-84. doi: 10.1111/j.1365-2796.2010.02341.x. Epub 2011 Jan 19. https://www.ncbi.nlm.nih.gov/pubmed/21205027

 

Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases

Abstract:

Recently, we found a serum acylcarnitine (ACR) deficiency in Japanese patients with chronic fatigue syndrome (CFS). To clarify whether this ACR abnormality is a characteristic of CFS or not, we also studied the levels of serum carnitine in Swedish subjects.

Both serum ACR and free carnitine (FCR) levels in normal healthy subjects were quite different between Japanese (n=131) and Swedish people (n=46) (p<0.001). However, it is confirmed that Swedish patients with CFS (n=57) also had serum ACR deficiency (p<0.001). When we studied the levels of serum ACR and FCR in Japanese patients with various kinds of diseases (CFS, hematological malignancies, chronic pancreatitis, hypertension, diabetes mellitus, chronic hepatitis type C, psychiatric diseases), a significant decrease in the levels of serum ACR was only found in patients with CFS and chronic hepatitis type C (p<0.001).

Therefore, we concluded that ACR deficiency in serum might be a characteristic abnormality in only certain types of diseases.

 

Source: Kuratsune H, Yamaguti K, Lindh G, Evengard B, Takahashi M, Machii T, Matsumura K, Takaishi J, Kawata S, Långström B, Kanakura Y, Kitani T, Watanabe Y. Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases. Int J Mol Med. 1998 Jul;2(1):51-6. http://www.ncbi.nlm.nih.gov/pubmed/9854142

 

Serum levels of carnitine in chronic fatigue syndrome: clinical correlates

Abstract:

Carnitine is essential for mitochondrial energy production. Disturbance in mitochondrial function may contribute to or cause the fatigue seen in chronic fatigue syndrome (CFS) patients. One previous investigation has reported decreased acylcarnitine levels in 38 CFS patients.

We investigated 35 CFS patients (27 females and 8 males); our results indicate that CFS patients have statistically significantly lower serum total carnitine, free carnitine and acylcarnitine levels, not only lower acylcarnitine levels as previously reported. We also found a statistically significant correlation between serum levels of total and free carnitine and clinical symptomatology. Higher serum carnitine levels correlated with better functional capacity.

These findings may be indicative of mitochondrial dysfunction, which may contribute to or cause symptoms of fatigue in CFS patients.

 

Source: Plioplys AV, Plioplys S. Serum levels of carnitine in chronic fatigue syndrome: clinical correlates. Neuropsychobiology. 1995;32(3):132-8. http://www.ncbi.nlm.nih.gov/pubmed/8544970

 

Acylcarnitine deficiency in chronic fatigue syndrome

Abstract:

One of the characteristic complaints of patients with chronic fatigue syndrome (CFS) is the skeletal muscle-related symptom. However, the abnormalities in the skeletal muscle that explain the symptom are not clear.

Herein, we show that our patients with CFS had a deficiency of serum acylcarnitine. As carnitine has an important role in energy production and modulation of the intramitochondrial coenzyme A (CoA)/acyl-CoA ratio in the skeletal muscle, this deficiency might induce an energy deficit and/or abnormality of the intramitochondrial condition in the skeletal muscle, thus resulting in general fatigue, myalgia, muscle weakness, and postexertional malaise in patients with CFS.

Furthermore, the concentration of serum acylcarnitine in patients with CFS tended to increase to the normal level with the recovery of general fatigue. Therefore, the measurement of acylcarnitine would be a useful tool for the diagnosis and assessment of the degree of clinical manifestation in patients with CFS.

 

Source: Kuratsune H, Yamaguti K, Takahashi M, Misaki H, Tagawa S, Kitani T. Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S62-7. http://www.ncbi.nlm.nih.gov/pubmed/8148455

 

Symptoms, signs and laboratory findings in patients with chronic fatigue syndrome

Abstract:

This review summarizes the symptoms, signs and laboratory abnormalities seen in 59 patients with chronic fatigue syndrome (CFS), 2 patients with post-infectious CFS and in 26 patients with possible CFS whose illnesses fulfill the criteria proposed by the study group of the Ministry of Welfare, Japan.

The characteristic symptoms and signs of CFS are prolonged generalized fatigue following exercise, headache, neuropsychological symptoms, sleep disturbance and mild fever. In possible CFS patients, the frequency of mild fever, muscle weakness, myalgia and headache is low.

Our standard hematologic and laboratory tests revealed a few abnormality in patients with CFS. The characteristic abnormality in CFS patients is the low values of 17-Ketosteroid-Sulfates/creatinine in morning urine and the acylcarnitine deficiency. It seems likely that this deficiency of acylcarnitine induces an energy deficit in the skeletal muscle, resulting in general fatigue, myalgia, muscle weakness and postexertional malaise in CFS patients. Virologic studies revealed no evidence of retrovirus infection with HTLV-1, HTLV-2 and HIV, but the reactivation of HHV-6 infection was apparent.

 

Source: Kuratsune H, Yamaguti K, Hattori H, Tazawa H, Takahashi M, Yamanishi K, Kitani T. Symptoms, signs and laboratory findings in patients with chronic fatigue syndrome. Nihon Rinsho. 1992 Nov;50(11):2665-72. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337562