A Pilot Study of a Ketogenic Diet in Bipolar Disorder: Clinical, Metabolomic and Magnetic Resonance Spectroscopy Outcomes
Iain H. CampbellNicole NeedhamHelen GrossiIvana KamenskáShane SheehanGerard ThompsonMichael J. ThrippletonMelissa C. GibbsJoana LeitaoTessa MosesKarl BurgessBen MeadowcroftBenjamin P. RigbySharon SimpsonEmma McIntoshRachel BrownMaja Mitchell-GrigorjevaFrances CreasyJohn NorrieAilsa McLellanCheryl FisherTomasz ZielińskiGiulia GaggioniSaturnino LuzHarry CampbellDaniel J. Smıth
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Abstract Background Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder. Aims To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and brain magnetic resonance spectroscopy (MRS) outcomes. Method Euthymic individuals with bipolar disorder (N=27) were recruited to a 6-8 week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention. Results Of 27 recruited participants, 26 began and 20 completed the ketogenic diet for 6-8 weeks. For participants completing the intervention, mean body weight fell by 4.2kg (p<0.001), mean BMI fell by 1.5kg/m 2 (p<0.001) and mean systolic blood pressure fell by 7.4 mmHg (p<0.041). All participants had baseline and follow up assessments consistent with them being in the euthymic range with no statistically significant changes in symptoms (assessed by the Affective Lability Scale-18, Beck’s Depression Inventory and Young Mania Rating Scale). In some participants (those providing reliable daily ecological momentary assessment data; n=14) there was a positive correlation between daily ketone levels and self-rated mood (r=0.21, p<0.001) and energy (r=0.19 p<0.001), and an inverse correlation between ketone levels and both impulsivity (r =-.30, p<0.001) and anxiety (r=-0.19, p<0.001). From the MRS measurements, brain Glx (glutamate plus glutamine concentration) decreased by 11.6% in the anterior cingulate cortex ACC (p=0.025) and fell by 13.6% in the posterior cingulate cortex (PCC) (p=<0.001). Conclusions These preliminary findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted. Study Registration Number ISRCTN61613198Keywords:
Ketogenic Diet
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetermination of the Three-Dimensional Structure of Margatoxin by 1H, 13C, 15N Triple-Resonance Nuclear Magnetic Resonance SpectroscopyBruce A. Johnson, Scott P. Stevens, and Joanne M. WilliamsonCite this: Biochemistry 1994, 33, 50, 15061–15070Publication Date (Print):December 1, 1994Publication History Published online1 May 2002Published inissue 1 December 1994https://pubs.acs.org/doi/10.1021/bi00254a015https://doi.org/10.1021/bi00254a015research-articleACS PublicationsRequest reuse permissionsArticle Views167Altmetric-Citations61LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
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Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful analytical tool that has significantly advanced the understanding of cattle metabolism. Nuclear Magnetic Resonance (NMR) spectroscopy plays a pivotal role in the study of cattle metabolism, offering distinct advantages over other spectrometric methods. NMR spectroscopy is a powerful analytical tool that provides detailed molecular insights by exploiting the magnetic properties of atomic nuclei. Unlike mass spectrometry and infrared spectroscopy, NMR does not require extensive sample preparation or destruction, preserving the integrity of biological samples. This non-invasive nature is particularly beneficial for longitudinal studies in cattle, where metabolic changes over time are of interest. One of the key strengths of NMR spectroscopy is its ability to simultaneously detect and quantify a broad range of metabolites in complex biological matrices, such as blood, urine, and tissue extracts. This comprehensive metabolic profiling is crucial for understanding the biochemical pathways and physiological states in cattle. NMR's high reproducibility and quantitative accuracy further enhance its suitability for metabolic studies, enabling precise monitoring of metabolic fluctuations in response to dietary changes, environmental stressors, or disease conditions. NMR spectroscopy also offers unique advantages in elucidating structural information about metabolites. Through multidimensional NMR techniques, researchers can determine the molecular structure and conformation of metabolites, providing deeper insights into metabolic functions and interactions. This structural elucidation is often challenging with other spectrometric methods, which may lack the resolution or require derivatization of samples. Moreover, NMR spectroscopy's non-destructive nature allows for the analysis of living tissues and in vivo studies, facilitating real-time monitoring of metabolic processes. This capability is instrumental in studying dynamic metabolic responses and adaptations in cattle under different physiological states. Additionally, the development of advanced NMR techniques, such as high-resolution magic angle spinning (HR-MAS) and hyperpolarization, has further expanded the scope of NMR applications in metabolic research. NMR spectroscopy stands out as a superior method for studying cattle metabolism due to its non-destructive approach, comprehensive metabolic profiling, structural elucidation capabilities, and potential for in vivo analysis. These advantages make NMR an indispensable tool in advancing our understanding of cattle metabolism and improving livestock health and productivity. Keywords: Nuclear Magnetic Resonance (NMR), Cattles, Metabolomics.
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Abstract The ability of water and solutes to move through the cartilage matrix is important to the normal function of cartilage and is presumed to be altered in degenerative diseases of cartilage such as osteoarthritis and rheumatoid arthritis. Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) techniques were used to measure a self diffusion coefficient (D) for small solutes in samples of explanted cartilage for diffusion times ranging from 13 ms to 2s. With a diffusion time of 13 ms, the intratissue diffusivity of several small solutes (water, Na + , Li + , and CF 3 CO 2 − ) was found consistently to be about 60% of the diffusivity of the same species in free solution. Equilibration of the samples at low pH (which titrates the charge groups so that the net matrix charge of −300 m M at pH 8 becomes approximately −50 m M at pH 2) did not affect the diffusivity of water or Na + . These data, and the similarity between the D in cartilage relative to free solution for water, anions, and cations, are consistent with the view that charge is not an important determinant of the intratissue diffusivity of small solutes in cartilage. With 35% compression, the diffusivity of water and Li + dropped by 19 and 39%, respectively. In contrast, the diffusivity of water increased by 20% after treatment with trypsin (to remove the proteoglycans and noncollagenous proteins). These data and the lack of an effect of charge on diffusivity are consistent with D being dependent on the composition and density of the solid tissue matrix. A series of diffusion‐weighted proton images demonstrated that D could be measured on a localized basis and that changes in D associated with an enzymatically depleted matrix could be clearly observed. Finally, evidence of restriction to diffusion within the tissue was found with studies in which D was measured as a function of diffusion time. The measured D for water in cartilage decreased with diffusion times ranging from 25 ms to 2 s, at which point the measured D was roughly 40% of the diffusivity in free solution. Although changes in matrix density by compression or digestion with trypsin led to a decrease or increase, respectively, in the measured D, the functional change in measured diffusivity with diffusion time remained essentially unchanged. In a different type of study, in which bulk transport could be observed over long periods of time, cartilage was submerged in 99% D 2 O and MRI studies were performed to demonstrate the bulk movement of water out of the cartilage matrix. These studies yielded a diffusivity estimated to be approximately 40% of the diffusivity of water in solution, which is in agreement with the value obtained for the diffusivity at a diffusion time of 2 s. These NMR measurements of diffusion can be totally noninvasive; thus, the results reported here can be extended to in vivo situations.
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Structure of carzinophilin. IV. Structure elucidation by nuclear magnetic resonance spectroscopy. 2.
The molecular formula of carzinophilin has been decided as C31H33N3O12. A structure for carzinophilin is proposed on the basis of the nuclear magnetic resonance data obtained.
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Abbreviations: MR, magnetic resonance; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; 1 H MRS, proton magnetic resonance spectroscopy; 31 P MRS, phosphorus magnetic resonance spectroscopy; CE-MRI, contrast-enhanced magnetic resonance imaging; VOI, volume of interest; CSI, chemical shift imaging; MRSI, magnetic resonance spectroscopic imaging; STEAM, stimulated echo acquisition mode; PRESS, point resolved spectroscopy; CHESS, chemical shift selective; W–F, water-to-fat ratio; PME, phosphomonoester; PDE, phosphodiester; PCr, phosphocreatine; SV, single-voxel.
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Metabolomics is an emerging technology that promises the extensive analyses of small molecules in the biological specimen. Metabolomics is recognized as an imperative tool in several distinct areas such as infectious disease research, mapping cellular metabolic processes, investigating tumor metabolism, and environmental and nutritional research such as in phytochemistry, foodomics, and toxicology. Tools such as mass spectroscopy and nuclear magnetic resonance (NMR) spectroscopy are widely utilized for studying metabolomics. However, NMR has been proven to be more robust owing to its high-throughput and sensitive assessment of metabolic profiles. NMR-based metabolomics involve a sequence of steps starting from sample preparation to data analysis in order to unravel information with respect to both quality and quantity of metabolites. The current chapter elucidates the basic protocol used to perform both the qualitative and quantitative analysis of metabolites in complex biological samples using NMR spectroscopy.
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1H nuclear magnetic resonance (1H NMR) spectroscopy has found widespread applications in tumour studies. Several complementary NMR techniques have provided valuable information concerning tumours, including in vivo localized 1H NMR spectroscopy, ex vivo high-resolution 1H NMR spectroscopy of extracts of intact tissue biopsy samples, high-resolution magic angle spinning 1H NMR spectroscopy of intact tissue biopsy samples, and in vitro high-resolution 1H NMR spectroscopy of body fluids. On the basis of the combination of NMR measurements with multivariate data analysis, 1H NMR-based metabonomics has become a promisingly novel approach in the studies of tumour early diagnosis, processes and prognosis estimate.
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