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Intramyocellular Lipids, Insulin Resistance, and Functional Performance in Patients with Severe Obstructive Sleep Apnea.
Chien, MY, Lee, PL, Yu, CW, Wei, SY, Shih, TT
Nature and science of sleep. 2020;12:69-78
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Obstructive sleep apnoea syndrome (OSA) is characterized by repeated occlusion of the upper airway during sleep, resulting in periods of intermittent hypoxemia [low level of oxygen in blood]. The aim of this study was to (a) investigate the intramyocellular lipids (IMCL) and extramyocellular lipids (EMCL), biochemical data, and functional performance in patients with severe OSA versus controls, and (b) examine the correlations between intra-muscular lipid contents and biochemical and performance variables. This study is a clinical trial that recruited 20 patients with OSA and body mass index(BMI)-matched controls. Results demonstrate that patients with OSA had significantly lower IMCL and EMCL values when compared with their age-, and BMI-matched controls without OSA. Furthermore, compared with controls, patients with OSA had significantly reduced functional performance and exhibited abnormal biochemical data, including glucose and insulin levels and lipid profiles. Authors conclude that additional large-scale clinical trials are required to further explore the complex mechanism between OSA, muscle metabolism, and insulin action.
Abstract
PURPOSE An increasing number of studies have linked the severity of obstructive sleep apnea (OSA) with metabolic dysfunction. However, little is known about the lipid compartments (intramyocellular [IMCL] and extramyocellular [EMCL] lipids) inside the musculature in these patients. The present study was designed to investigate the IMCL and EMCL, biochemical data, and functional performance in patients with severe OSA, and to examine the correlations between intramuscular lipid contents and test variables. PARTICIPANTS AND METHODS Twenty patients with severe OSA (apnea-hypopnea index [AHI]: ≥30/h; body mass index [BMI]: 26.05±2.92) and 20 age- and BMI-matched controls (AHI <5/h) were enrolled. Proton magnetic resonance spectroscopy was used to measure the IMCL and EMCL of the right vastus lateralis muscle. Biochemical data, including levels of fasting plasma glucose, insulin, lipid profiles, and high-sensitivity C-reactive protein (hsCRP), were measured. Insulin resistance index (IR) was calculated using the homeostasis model assessment method. Performance tests included a cardiopulmonary exercise test and knee extension strength and endurance measurements. RESULTS Patients with severe OSA had significantly (P<0.05) lower values of IMCL (14.1±5.4 AU) and EMCL (10.3±5.8 AU) compared to the control group (25.2±17.6 AU and 14.3±11.1 AU, respectively). Patients with severe OSA had significantly higher hsCRP, IR, and dyslipidemia compared with controls (all P<0.05). Furthermore, IMCL was negatively correlated with AHI, cumulative time with nocturnal pulse oximetric saturation lower than 90% (TSpO2<90%) (ρ=-0.35, P<0.05), IR (ρ=-0.40, P<0.05), glucose (ρ=-0.33, P<0.05), and insulin (ρ=-0.36, P<0.05), and positively correlated with lowest oximetric saturation (ρ=0.33, P<0.01). CONCLUSION Skeletal muscle dysfunction and metabolic abnormalities were observed in patients with OSA that did not have obesity. IMCL was positively correlated with aerobic capacity and muscular performance, but negatively correlated with AHI and IR. Large-scale clinical trials are required to explore the complicated mechanism among OSA, intramuscular metabolism, and insulin action. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00813852.
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Significant Impact of the Ketogenic Diet on Low-Density Lipoprotein Cholesterol Levels.
Salas Noain, J, Minupuri, A, Kulkarni, A, Zheng, S
Cureus. 2020;12(7):e9418
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Ketogenic diet includes food with a very low-carbohydrate and high-fat content that aims to drastically reduce carbohydrate intake and replace it with fat, hence inducing ketosis. This study is a case report which presents a case of a rapid increase, followed by a rapid correction of low-density lipoprotein cholesterol (LDL-C) in a patient following a ketogenic diet. The patient is a 56-year-old Hispanic female who showed a rapid increase in LDL-C and total cholesterol after only 30-40 days of following a ketogenic diet. She was directed to follow a balanced diet and take statin medication. Results showed that the patient's BMI, four weeks after the discontinuation of ketogenic diet, did not change despite a marked improvement in her LDL-C. Authors conclude that due to the unpredictable response of LDL-C levels to a ketogenic diet, close monitoring of patients with a high risk of cardiovascular disease should be considered.
Abstract
It is well known, based on the previous research, that a ketogenic diet leads to an improvement in the lipid profile and decreases cardiovascular risk factors such as hypertension. However, recent studies have also reported increased levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) as a result of this diet. It has been postulated that this elevation in LDL-C would not likely increase cardiovascular complications due to the large LDL-C particle size. In this case report, we present a case of a rapid increase, followed by a rapid correction of LDL-C, in a patient following a ketogenic diet. A 56-year-old Hispanic female with a past medical history of hypertension and fibromyalgia presented to the outpatient clinic for evaluation of fatigue. She reported that she had been following a strict ketogenic diet along with daily regular exercise for approximately 30-40 days prior to this visit. Her diet consisted of low-carbohydrate vegetables, seafood, avocados, eggs, and coconut oil. The patient's physical exam was unremarkable. At the time of the visit, her BMI was calculated at 28 kg/m2, with a weight loss of approximately six to seven pounds since starting the ketogenic diet. Her fasting lipid profile showed a total cholesterol of 283 mg/dl, LDL-C of 199 mg/dl, high-density lipoprotein cholesterol (HDL-C) of 59 mg/dl, and triglycerides levels of 124 mg/dl. She was instructed to stop the ketogenic diet and to incorporate a balanced diet, which includes a higher amount of carbohydrates and lower fat. She was also started on high-intensity atorvastatin. However, she reported experiencing myalgias soon after initiating atorvastatin; therefore, the medication was switched to rosuvastatin 10 mg at bedtime. During her follow-up appointment, she reported not having consistently taken rosuvastatin due to the concern of worsening myalgias. Her lipid profile, after four weeks of ketogenic diet discontinuation and inconsistent use of statins, showed significant improvement resulting in a total cholesterol level of 190 mg/dl and LDL-C of 106 mg/dl. Statin therapy was discontinued, and the patient maintained optimal LDL-C levels on subsequent testing. This patient showed a rapid increase in LDL-C and total cholesterol after only 30-40 days of the ketogenic diet. Her drastic elevation in LDL-C could also be explained due to the rapid weight loss, as cholesterol in the adipose tissue is known to mobilize as the fat cells shrink. Interestingly, her BMI four weeks after the discontinuation of the ketogenic diet did not change despite a marked improvement in her LDL-C. Therefore, we believe the acute onset and resolution of hyperlipidemia was secondary to the ketogenic diet itself. This study helps to better understand expectations when recommending a ketogenic diet to patients and its consequences. There is currently no statistically significant study that proves this elevation of LDL-C would not increase cardiovascular risks. Furthermore, the necessity for statin therapy in a ketogenic diet-induced hyperlipidemia remains unknown.
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Inhalational Alzheimer's disease: an unrecognized - and treatable - epidemic.
Bredesen, DE
Aging. 2016;8(2):304-13
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Alzheimer’s disease (AD) is the third leading cause of death in the USA, with around 5.2 million Americans diagnosed with AD. Effective treatment with medications has yet to be found. A recent multiple therapy programme (originally known as MEND, now called ReCODE) proposed by Professor Bredesen and team, has shown some promising anecdotal results. Identifying sub-types of AD has been proposed as a means to develop targeted protocols for treatment. Recently, 3 sub-types of AD have been described: Type 1 (inflammatory), Type 2 (non-inflammatory or decreasing brain size) and Type 3 (damage to the outer layer of the cerebrum). This report describes 7 patients with Type 3 AD. Type 3 AD is characterised by exposure to specific toxins (usually inhaled) and is often associated with Chronic Inflammatory Response Syndrome (CIRS). The report provides the symptoms, signs and laboratory values representative of Type 3 AD and could be used by Nutrition Practitioners to help with implementation of appropriate nutrition protocols when working with clients with AD.
Abstract
Alzheimer's disease is one of the most significant healthcare problems today, with a dire need for effective treatment. Identifying subtypes of Alzheimer's disease may aid in the development of therapeutics, and recently three different subtypes have been described: type 1 (inflammatory), type 2 (non-inflammatory or atrophic), and type 3 (cortical). Here I report that type 3 Alzheimer's disease is the result of exposure to specific toxins, and is most commonly inhalational (IAD), a phenotypic manifestation of chronic inflammatory response syndrome (CIRS), due to biotoxins such as mycotoxins. The appropriate recognition of IAD as a potentially important pathogenetic condition in patients with cognitive decline offers the opportunity for successful treatment of a large number of patients whose current prognoses, in the absence of accurate diagnosis, are grave.
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Metabolic profiling distinguishes three subtypes of Alzheimer's disease.
Bredesen, DE
Aging. 2015;7(8):595-600
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The causes of Alzheimer’s Disease (AD) remain incompletely defined and there are currently no truly effective drug therapies available. However, there is growing evidence that disordered blood glucose management and hormonal changes and deficiencies, amongst other things, are implicated in symptom onset. Optimising these various metabolic processes, therefore, may be used as a comprehensive way to avoid cognitive decline or achieve cognitive improvements in symptomatic individuals. This report provides the metabolic results of 3 case studies and suggests 3 different types of AD classification, depending on the individual metabolic profile. Further studies are required to elaborate on the metabolic profiles suggested in this report, however Nutrition Practitioners working with cognitive decline, can use this report as a basis for individualised nutrition protocols to optimise metabolic processes in clients with cognitive decline.
Abstract
The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report that metabolic profiling reveals three Alzheimer's disease subtypes. The first is inflammatory, in which markers such as hs-CRP and globulin:albumin ratio are increased. The second type is non-inflammatory, in which these markers are not increased, but other metabolic abnormalities are present. The third type is a very distinctive clinical entity that affects relatively young individuals, extends beyond the typical Alzheimer's disease initial distribution to affect the cortex widely, is characterized by early non-amnestic features such as dyscalculia and aphasia, is often misdiagnosed or labeled atypical Alzheimer's disease, typically affects ApoE4-negative individuals, and is associated with striking zinc deficiency. Given the involvement of zinc in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling, this syndrome of Alzheimer's-plus with low zinc (APLZ) warrants further metabolic, genetic, and epigenetic characterization.