scholarly journals Octanoic acid a major component of widely consumed medium-chain triglyceride ketogenic diet is detrimental to bone

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shreshta Jain ◽  
Reena Rai ◽  
Divya Singh ◽  
Divya Vohora
Keyword(s):  
Bone Loss ◽  
Ketogenic Diet ◽  
Octanoic Acid ◽  
Bone Microarchitecture ◽  
Medium Chain Triglyceride ◽  
Decanoic Acid ◽  
Clinical Findings ◽  
Micro Computed Tomography ◽  
Negative Effects ◽  
Treatment Groups

AbstractOctanoic acid is a medium-chained saturated fatty acid found abundantly in the ketogenic dietary supplements containing medium chained triglycerides (MCT) along with decanoic acid. The MCT ketogenic diet is commonly consumed for weight loss but has also showcased neuroprotective potential against neurodegenerative disorders. However, recent clinical findings have reported a critical disadvantage with the long-term consumption of ketogenic diet i.e. bone loss. The following study was employed to investigate whether the two major components of MCT diet also possess bone loss potential as observed with classical ketogenic diet. Swiss albino mice aged between 10 and 12 weeks, were divided into 3 treatment groups that were administered with oral suspensions of octanoic acid, decanoic acid and a combination of both for 4 weeks. Bone specific markers, microarchitectural parameters, using micro computed tomography, and biomechanical strength were analyzed. Remarkably deleterious alterations in the trabecular bone microarchitecture, and on bone markers were observed in the octanoic acid treated groups. Our results suggest significant negative effects on bone health by octanoic acid. These findings require further investigation and validation in order to provide significant clinically relevant data to possibly modify dietary composition of the MCT ketogenic diet.

scholarly journals Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium-chain triglyceride ketogenic diet

Epilepsia ◽  
2017 ◽  
Vol 58 (8) ◽  
pp. 1423-1429 ◽  
Author(s):  
Aziza Khabbush ◽  
Michael Orford ◽  
Yi-Chen Tsai ◽  
Tricia Rutherford ◽  
Maura O'Donnell ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Octanoic Acid ◽  
Medium Chain Triglyceride ◽  
Decanoic Acid ◽  
Acid Oxidation ◽  
Medium Chain ◽  
Mechanistic Insight ◽  
Insight Into

scholarly journals Decanoic Acid Stimulates Autophagy in D. discoideum

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2946
Author(s):  
Eleanor C. Warren ◽  
Pavol Kramár ◽  
Katie Lloyd-Jones ◽  
Robin S. B. Williams
Keyword(s):  
Octanoic Acid ◽  
Medium Chain Triglyceride ◽  
Decanoic Acid ◽  
Autophagic Flux ◽  
Therapeutic Effects ◽  
Autophagosome Formation ◽  
Control Activity ◽  
Medium Chain ◽  
Ketogenic Diets ◽  
Autophagy Induction

Ketogenic diets, used in epilepsy treatment, are considered to work through reduced glucose and ketone generation to regulate a range of cellular process including autophagy induction. Recent studies into the medium-chain triglyceride (MCT) ketogenic diet have suggested that medium-chain fatty acids (MCFAs) provided in the diet, decanoic acid and octanoic acid, cause specific therapeutic effects independent of glucose reduction, although a role in autophagy has not been investigated. Both autophagy and MCFAs have been widely studied in Dictyostelium, with findings providing important advances in the study of autophagy-related pathologies such as neurodegenerative diseases. Here, we utilize this model to analyze a role for MCFAs in regulating autophagy. We show that treatment with decanoic acid but not octanoic acid induces autophagosome formation and modulates autophagic flux in high glucose conditions. To investigate this effect, decanoic acid, but not octanoic acid, was found to induce the expression of autophagy-inducing proteins (Atg1 and Atg8), providing a mechanism for this effect. Finally, we demonstrate a range of related fatty acid derivatives with seizure control activity, 4BCCA, 4EOA, and Epilim (valproic acid), also function to induce autophagosome formation in this model. Thus, our data suggest that decanoic acid and related compounds may provide a less-restrictive therapeutic approach to activate autophagy.

Identifying the Molecular Mechanism of the Medium Chain Triglyceride (Ketogenic) Diet

2016 ◽  
Author(s):  
Matthew C. Walker ◽  
Robin S.B. Williams
Keyword(s):  
Ketogenic Diet ◽  
Seizure Control ◽  
Medium Chain Triglyceride ◽  
Decanoic Acid ◽  
In Vivo Models ◽  
Principal Mechanism ◽  
Excitatory Neurotransmitter ◽  
Medium Chain

The medium chain triglyceride (MCT) ketogenic diet provides a highly effective and commonly used approach for treating drug-resistant epilepsy. It is associated with elevated levels of two MCT-derived fatty acids, decanoioc and octanoic acids. Researchers have identified a role for decanoic acid and a range of novel related chemicals in seizure control in multiple acute in vitro and in vivo models. A principal mechanism of decanoic acid is direct inhibition of AMPA receptors, key excitatory neurotransmitter receptors widely recognized as a target for seizure control. These data suggest a therapeutic mechanism of the MCT ketogenic diet through a direct fatty acid–dependent mechanism, independent of ketosis. This discovery will enable the development of an improved and, potentially, better-tolerated diet and the generation of a corresponding pharmaceutical approach. The diet should be termed the MCT diet, as the consequent ketosis may not be necessary for seizure control.

scholarly journals The Role of Alcohol, LPS Toxicity, and ALDH2 in Dental Bony Defects

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 651
Author(s):  
Hsiao-Cheng Tsai ◽  
Che-Hong Chen ◽  
Daria Mochly-Rosen ◽  
Yi-Chen Ethan Li ◽  
Min-Huey Chen
Keyword(s):  
Bone Loss ◽  
Bacterial Infection ◽  
Bone Regeneration ◽  
Alcohol Drinking ◽  
Bacterial Species ◽  
Dominant Negative ◽  
Enzyme Inactivation ◽  
Wild Type ◽  
Micro Computed Tomography ◽  
Dominant Negative Mutation

It is estimated that 560 million people carry an East Asian-specific ALDH2*2 dominant-negative mutation which leads to enzyme inactivation. This common ALDH2 polymorphism has a significant association with osteoporosis. We hypothesized that the ALDH2*2 mutation in conjunction with periodontal Porphyromonas gingivalis bacterial infection and alcohol drinking had an inhibitory effect on osteoblasts and bone regeneration. We examined the prospective association of ALDH2 activity with the proliferation and mineralization potential of human osteoblasts in vitro. The ALDH2 knockdown experiments showed that the ALDH2 knockdown osteoblasts lost their proliferation and mineralization capability. To mimic dental bacterial infection, we compared the dental bony defects in wild-type mice and ALDH2*2 knockin mice after injection with purified lipopolysaccharides (LPS), derived from P. gingivalis which is a bacterial species known to cause periodontitis. Micro-computed tomography (micro-CT) scan results indicated that bone regeneration was significantly affected in the ALDH2*2 knockin mice with about 20% more dental bony defects after LPS injection than the wild-type mice. Moreover, the ALDH2*2 knockin mutant mice had decreased osteoblast growth and more dental bone loss in the upper left jaw region after LPS injection. In conclusion, these results indicated that the ALDH2*2 mutation with alcohol drinking and chronic exposure to dental bacterial-derived toxin increased the risk of dental bone loss.

Diagnosis and management of hook of hamate fractures

2017 ◽  
Vol 43 (5) ◽  
pp. 539-545 ◽  
Author(s):  
Assaf Kadar ◽  
Allen T. Bishop ◽  
Marissa A. Suchyta ◽  
Steven L. Moran
Keyword(s):  
Case Series ◽  
Clinical Results ◽  
Clinical Findings ◽  
Advanced Imaging ◽  
Level Of Evidence ◽  
Historical Case ◽  
Treatment Groups ◽  
Diagnosis And Management ◽  
Time To Diagnosis ◽  
Hook Of Hamate

The purpose of this study was to evaluate the time to diagnosis and management of hook of hamate fractures in an era of advanced imaging. We performed a retrospective study of 51 patients treated for hook of hamate fractures. Patients were sent a quickDASH questionnaire regarding the outcomes of their treatment. Hook of hamate fractures were diagnosed with advanced imaging at a median of 27 days. Clinical findings of hook of hamate tenderness had better sensitivity than carpal tunnel-view radiographs. Nonunion occurred in 24% of patients with non-operative treatment and did not occur in the operative group. Both treatment groups achieved good clinical results, with a grip strength of 80% compared with the non-injured hand and a median quickDASH score of 2. Advanced imaging improved the time to diagnosis and treatment compared to historical case series. Nonunion is common in patients treated non-operatively. Level of evidence: IV

scholarly journals Quality and Findings of Bitewing Radiographs among Twenty-Year-Old Conscripts in Finland

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Miika Hyvönen ◽  
Arttu Jaakkola ◽  
Tarja Tanner ◽  
Jari Päkkilä ◽  
Antti Kämppi ◽  
...  
Keyword(s):  
Bone Loss ◽  
Clinical Status ◽  
Tooth Wear ◽  
Cross Sectional Study ◽  
Clinical Findings ◽  
Caries Detection ◽  
Marginal Bone Loss ◽  
Cross Sectional ◽  
Caries Diagnostics

Objectives. Bitewing radiographs are mainly used to confirm clinical findings in caries diagnostics. The objective here was to investigate the quality of bitewing radiographs after short brush-up training and additional findings besides caries in a low-caries population. Methods. The material of this cross-sectional study comprised 377 pairs of bitewing radiographs of 19- to 20-year-olds taken by dentists. Radiography was considered indicated if one dentinal caries lesion was present on clinical examination. A senior oral radiologist evaluated quality and diagnosed the findings afterwards unaware of clinical status. The association between variables was analysed using cross tabulation and chi-squared testing. Results. Almost half of the images were of compromised quality (44.1%). Dentinal caries lesions were detected in 82.3% and enamel lesions in 73.5% of the subjects. On average, the subjects had 1.7 (SD 0.52) dentinal lesions. Fillings were found in 81.8%, fractures/cracks in 11.7%, and attrition in 7.4% of the subjects. Signs of excessive bite force were recorded in 19.4%, whereas marginal bone loss was detected in 6.4%. No significant correlation was detected between fractures, attrition, and excessive bite forces. Conclusions. Effort must be taken to ensure high quality of bitewing radiographs. In addition to caries detection, bitewing radiographs offer additional value, such as detecting excessive bite forces, tooth wear, and marginal bone loss among young adults.

scholarly journals Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study

2019 ◽  
Vol 11 ◽  
pp. 175883591985395 ◽  
Author(s):  
Elles J. T. M. van der Louw ◽  
Joanne F. Olieman ◽  
Patricia M. L. A. van den Bemt ◽  
Jacoline E. C. Bromberg ◽  
Esther Oomen-de Hoop ◽  
...  
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Ketogenic Diet ◽  
Standard Treatment ◽  
Medium Chain Triglyceride ◽  
High Grade Glioma ◽  
Future Research ◽  
Clinical Trial Registration ◽  
Beneficial Effects ◽  
Neurological Functioning

Background: High-grade glioma cells consume mainly glucose and cannot compensate for glucose restriction. Apoptosis may potentially occur under carbohydrate restriction by a ketogenic diet (KD). We explored the feasibility and safety of KD during standard treatment of chemoradiation in patients with glioblastoma multiforme. Methods: A full liquid KD induced ketosis within 2 weeks before start of chemoradiation. After 6 weeks, the KD was modified with solid foods and medium-chain-triglyceride emulsions and used for an additional 6 weeks while maintaining ketosis. During the total study period (14 weeks), feasibility, safety, coping (both patient and partner), quality of life (QoL), neurological functioning and impairment were measured. Overall survival was analyzed with actuarial estimates. Results: Eleven patients started the study protocol, nine reached ketosis and six (67%) completed the study. Severe adverse effects did not occur. The majority of coping scores ranged from 3 to 6 on a 10-point scale at all timepoints; QoL, neurological functioning, and impairment did not essentially change over time; overall survival ranged between 9.8 and 19.0 months. Conclusion: KD was feasible and safe as an adjuvant to standard chemoradiation treatment of glioblastoma multiforme. A supportive partner and intensive counseling were essential for coping. Future research should identify possible beneficial effects on overall survival. Clinical trial registration: Netherlands Trial Registry: NTR5167 (registration date 29-01-2015), http://www.trialregister.nl/trialreg/index.asp

scholarly journals Intragraft donor-specific anti-HLA antibodies in phenotypes of chronic lung allograft dysfunction

2019 ◽  
Vol 54 (5) ◽  
pp. 1900847 ◽  
Author(s):  
Annelore Sacreas ◽  
Jean-Luc Taupin ◽  
Marie-Paule Emonds ◽  
Liesbeth Daniëls ◽  
Dirk E. Van Raemdonck ◽  
...  
Keyword(s):  
Human Leukocyte ◽  
Hla Class I ◽  
Bronchiolitis Obliterans Syndrome ◽  
Clinical Findings ◽  
Micro Computed Tomography ◽  
Serum Samples ◽  
Chronic Lung Allograft Dysfunction ◽  
Leukocyte Antigen ◽  
Allograft Dysfunction ◽  
Restrictive Allograft Syndrome

IntroductionCirculating anti-human leukocyte antigen (HLA) serum donor-specific antibodies (sDSAs) increase the risk of chronic lung allograft dysfunction (CLAD) and mortality. Discrepancies between serological and pathological/clinical findings are common. Therefore, we aimed to assess the presence of tissue-bound graft DSAs (gDSAs) in CLAD explant tissue compared with sDSAs.MethodsTissue cores, obtained from explant lungs of unused donors (n=10) and patients with bronchiolitis obliterans syndrome (BOS; n=18) and restrictive allograft syndrome (RAS; n=18), were scanned with micro-computed tomography before elution of antibodies. Total IgG levels were measured via ELISA. Anti-HLA class I and II IgG gDSAs were identified using Luminex single antigen beads and compared with DSAs found in serum samples.ResultsOverall, mean fluorescence intensity was higher in RAS eluates compared with BOS and controls (p<0.0001). In BOS, two patients were sDSA+/gDSA+ and two patients were sDSA−/gDSA+. In RAS, four patients were sDSA+/gDSA+, one patient was sDSA+/gDSA− and five patients were sDSA−/gDSA+. Serum and graft results combined, DSAs were more prevalent in RAS compared with BOS (56% versus 22%; p=0.04). There was spatial variability in gDSA detection in one BOS patient and three RAS patients, who were all sDSA−. Total graft IgG levels were higher in RAS than BOS (p<0.0001) and in gDSA+versus gDSA− (p=0.0008), but not in sDSA+versus sDSA− (p=0.33). In RAS, total IgG levels correlated with fibrosis (r= −0.39; p=0.02).ConclusionsThis study underlines the potential of gDSA assessment as complementary information to sDSA findings. The relevance and applications of gDSAs need further investigation.

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