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Title:
Does a ketogenic diet lower a very high Lp(a)? A striking experiment in a male physician
Authors:
Scholl, Johannes Georg
Abstract:
The level of lipoprotein(a) (Lp(a)), an important cardiovascular risk factor, is considered to be genetically determined. I am a 55-year-old male physician specialised in preventive medicine and a hobby triathlete with a body mass index of 24.9 kg/m2 and a maximum oxygen consumption (VO2max) of ~50 mL/(kg×min), with an average of 7-10 hours of exercise per week. I discovered my own Lp(a) at 92-97 mg/dL in 2004 and measured a maximum Lp(a) of 108 mg/dL in 2013. Surprisingly, I observed a much lower Lp(a) of 65 mg/dL in 2018. This happened after I had adopted a very-low-carb ketogenic diet for long-term endurance exercise. My n=1 experiment in July 2020 demonstrated an increase in Lp(a) back to 101 mg/dL on a very high-carb diet within 2 weeks, and a drop back to 74 mg/dL after 3 weeks on the ketogenic diet afterwards. The observed large changes in my Lp(a) were thus reproducible by a change in carbohydrate consumption and might have clinical relevance for patients as well as researchers in the field of Lp(a).
Published:
2020-12
Title:
Effects of Ketogenic Dieting on Body Composition, Strength, Power, and Hormonal Profiles in Resistance Training Men
Authors:
Wilson, Jacob M.; Lowery, Ryan P.; Roberts, Michael D.; Sharp, Matthew H.; Joy, Jordan M.; Shields, Kevin A.; Partl, Jeremy M.; Volek, Jeff S.; D'Agostino, Dominic P.
Abstract:
Wilson, JM, Lowery, RP, Roberts, MD, Sharp, MH, Joy, JM, Shields, KA, Partl, JM, Volek, JS, and D'Agostino, DP. Effects of ketogenic dieting on body composition, strength, power, and hormonal profiles in resistance training men. J Strength Cond Res 34(12): 3463–3474, 2020—This study investigated the impact of an isocaloric and isonitrogenous ketogenic diet (KD) versus a traditional western diet (WD) on changes in body composition, performance, blood lipids, and hormonal profiles in resistance-trained athletes. Twenty-five college-aged men were divided into a KD or traditional WD from weeks 1 to 10, with a reintroduction of carbohydrates from weeks 10 to 11, while participating in a resistance training program. Body composition, strength, power, and blood lipid profiles were determined at weeks 0, 10, and 11. A comprehensive metabolic panel and testosterone levels were also measured at weeks 0 and 11. Lean body mass (LBM) increased in both the KD and WD groups (2.4% and 4.4%, p < 0.01) at week 10. However, only the KD group showed an increase in LBM between weeks 10 and 11 (4.8%, p
Published:
2020-12
Title:
Fossils from Mille-Logya, Afar, Ethiopia, elucidate the link between Pliocene environmental changes and Homo origins
Authors:
Alemseged, Zeresenay; Wynn, Jonathan G.; Geraads, Denis; Reed, Denne; Andrew Barr, W.; Bobe, René; McPherron, Shannon P.; Deino, Alan; Alene, Mulugeta; J. Sier, Mark; Roman, Diana; Mohan, Joseph
Abstract:
Published:
2020-12
Title:
Homo sapiens: The Superspreader of Plant Viral Diseases
Authors:
Ranawaka, Buddhini; Hayashi, Satomi; Waterhouse, Peter M.; de Felippes, Felipe F.
Abstract:
Plant viruses are commonly vectored by flying or crawling animals, such as aphids and beetles, and cause serious losses in major agricultural and horticultural crops. Controlling virus spread is often achieved by minimizing a crop’s exposure to the vector, or by reducing vector numbers with compounds such as insecticides. A major, but less obvious, factor not controlled by these measures is Homo sapiens. Here, we discuss the inconvenient truth of how humans have become superspreaders of plant viruses on both a local and a global scale.
Published:
2020-12
Title:
L-carnitine improves metabolic disorders and regulates apelin and apelin receptor genes expression in adipose tissue in diabetic rats
Authors:
Ranjbar Kohan, Neda; Tabandeh, Mohammad Reza; Nazifi, Saeed; Soleimani, Zahra
Abstract:
Apelin is a new adipocytokine that acts as an endogenous hormone in various tissues through its receptor (APJ). This study aimed to investigate the effects of oral administration of L-carnitine (LC) on the expression of Apelin and APJ in adipose tissue of experimentally induced insulin-resistant and type 2 diabetic rats. In this experimental study, 60 male rats fed with high fat/high carbohydrate (HF/HC) diet. After 50 mg/kg intraperitoneally injection of streptozotocin (STZ) and confirmation of diabetes (FBS higher than 126 mg/dl), the animals were daily treated with 300 mg/kg LC for 28 days. At days 7, 14, and 28 of posttreatment, the expression of apelin and APJ in adipose tissue were determined using qPCR in diabetic, diabetic + LC treated, control, and control + LC treated groups. Apelin, insulin, TNF-α, and IL1-β were measured by the ELISA method. Results demonstrated that the rats fed with the HF/HC diet for 5 weeks were hyperinsulinemic and normoglycemic, while after STZ injection, they showed hyperinsulinemia and hyperglycemia with higher levels of HOMA-IR. Apelin serum level, APJ and apelin gene expression in adipose tissue increased significantly with the development of diabetes compared to the control group. Treatment with LC for 14 days caused a reduction in apelin and APJ expressions in adipose tissue of diabetic rats. TNF-α and IL1-β levels were reduced in diabetic rats 14 days after their treatment with LC. The study results show that L-carnitine could act as a new regulator in apelin gene expression in adipose tissue, improving the metabolic disorders in diabetic patients.
Published:
2020-12
Title:
Multi-omics Approaches To Decipher the Impact of Diet and Host Physiology on the Mammalian Gut Microbiome
Authors:
Milani, Christian; Alessandri, Giulia; Mancabelli, Leonardo; Mangifesta, Marta; Lugli, Gabriele Andrea; Viappiani, Alice; Longhi, Giulia; Anzalone, Rosaria; Duranti, Sabrina; Turroni, Francesca; Ossiprandi, Maria Cristina; Sinderen, Douwe van; Ventura, Marco
Abstract:
In recent years, various studies have demonstrated that the gut microbiota influences host metabolism. However, these studies were focused primarily on a single or a limited range of host species, thus preventing a full exploration of possible taxonomic ...
Published:
2020-12
Title:
SUCCESSFUL REIMPLEMENTATION OF A VERY LOW CARBOHYDRATE KETOGENIC DIET AFTER SGLT2 INHIBITOR ASSOCIATED EUGLYCEMIC DIABETIC KETOACIDOSIS
Authors:
Fieger, Ethan I.; Fadel, Kristen M.; Modarres, Amir H.; Wickham, Edmond P.; Wolver, Susan E.
Abstract:
Objective: We report a case of a successful reimplementation of a very low carbohydrate ketogenic diet (VLCKD) after a case of euglycemic diabetic ketoacidosis (euDKA). Methods: A 42-year-old female with a history of type 2 diabetes mellitus on a self-administered VLCKD was prescribed a sodium-glucose co-transporter 2 (SGLT2) inhibitor. Two weeks after initiation, she presented with nausea and vomiting and was found to be in euDKA which was treated with fluid resuscitation, insulin infusion, and cessation of the SGLT2 inhibitor. She was discharged on insulin and instructed not to resume a VLCKD. Results: After discharge, the patient experienced rapid weight gain and deteriorating glycemic control and desired to resume a VLCKD. She was referred to a university-based medical weight loss clinic that specializes in a VLCKD. The patient was monitored with daily contact via the electronic health record's patient portal and serial laboratory testing while her carbohydrate intake was slowly reduced and her insulin titrated off. She has safely remained in ketosis for 2 years without a further episode of euDKA. Conclusion: As the clinical use of SGLT2 inhibitors and the VLCKD both become increasingly common, it is vital for practitioners to be aware that the combination can lead to euDKA. We present a case of successfully resuming a VLCKD after recovering from euDKA and cessation of SGLT2 inhibitor therapy.
Published:
2020-12
Title:
Insulin Treatment Is Associated with Increased Mortality in Patients with COVID-19 and Type 2 Diabetes
Authors:
Yu, Bo; Li, Chenze; Sun, Yang; Wang, Dao Wen
Abstract:
COVID-19 caused by SARS-COV-2 infection can lead to multi-organ injuries and significant mortality in severe and critical patients, especially among those individuals with type 2 diabetes (T2D) as a comorbidity. While attenuated mortality was observed with aggressive glucose control, it was unclear whether therapeutic regimens including insulin treatment were beneficial for patients with COVID-19 and T2D. This retrospective study investigated 689 patients with COVID-19 and T2D from a cohort of 3,305 cases from Wuhan, China. Unexpectedly, we found that insulin treatment for patients with COVID-19 and T2D was associated with a significant increase in mortality (27.2% versus 3.5%; adjusted HR, 5.38 [2.75–10.54]). Further analysis showed that insulin treatment was associated with enhanced systemic inflammation and aggravated injuries of vital organs. Therefore, insulin treatment for patients with COVID-19 and T2D should be used with caution.
Published:
2020-11
Title:
Milk and Dairy Products and Their Impact on Carbohydrate Metabolism and Fertility—A Potential Role in the Diet of Women with Polycystic Ovary Syndrome
Authors:
Janiszewska, Justyna; Ostrowska, Joanna; Szostak-Węgierek, Dorota
Abstract:
Milk and dairy products are considered an important component of healthy and balanced diet and are deemed to exert a positive effect on human health. They appear to play a role in the prevention and treatment of carbohydrate balance disturbances. The products include numerous valuable components with a potential hypoglycemic activity, such as calcium, vitamin D, magnesium and probiotics. Multiple authors suggested that the consumption of dairy products was negatively associated with the risk of type 2 diabetes mellitus, insulin resistance and ovulation disorders. However, there are still numerous ambiguities concerning both the presumed protective role of dairy products in carbohydrate metabolism disorders, and the advantage of consuming low-fat dairy products over high-fat ones, especially in women with the risk of ovulation disorders. Therefore, this literature review aims at the presentation of the current state of knowledge concerning the relationship between dairy product consumption and the risk of insulin resistance, type 2 diabetes mellitus in women, and the potential effect on the course of polycystic ovary syndrome.
Published:
2020-11
Title:
Plants Containing Urinary Tract, Gastrointestinal, or Miscellaneous Toxins that Affect Livestock
Authors:
Stegelmeier, Bryan L.; Davis, T. Zane; Clayton, Michael J.
Abstract:
Whether exposed by grazing toxic range or pasture plants or by eating contaminated feed, there are plant toxins that produce urinary tract disease, gastroenteritis, and other miscellaneous or multisystemic diseases. Diagnosis can be challenging and requires incorporation of field studies, clinical signs, gross and microscopic pathology, and chemical identification of plants, toxins, and metabolites in animal samples. The objectives of this review are to introduce poisonous plants that commonly poison livestock in North America; describe clinical and pathologic lesions they produce in livestock; and present current technology available to identify poisoning, treat affected animals, and minimize or avoid poisoning additional animals.
Published:
2020-11
Title:
[The impact on metabolic and reproductive diseases of low-carbohydrate and ketogenic diets]
Authors:
Moreno-Sepúlveda, José; Capponi, Magdalena
Abstract:
With low carbohydrate diets glucose becomes unavailable as a source of energy for our body, leading to the production of ketones from fatty acids in the liver. The increase in plasma ketones is known as nutritional ketosis. The available evidence from basic and clinical studies indicates that both low carbohydrate and high fat low carbohydrate diets are effective for weight loss and are better than non-intervention. However, low carbohydrate diet and ketogenic diets induce unique metabolic changes and consistently improve some markers of cardiovascular risk, lowering elevated blood glucose, insulin, triglycerides, ApoB and saturated fat concentrations, reducing small dense LDL particle numbers, glycated hemoglobin levels, blood pressure and body weight while increasing HDL-cholesterol concentrations and reversing non-alcoholic fatty liver disease. Low carbohydrate diets are an efficient strategy for the management of obesity and metabolic syndrome. They may also benefit patients with polycystic ovary syndrome. They must be prescribed by trained professionals to balance the risks and benefits for each individual patient. Future research is required to improve the knowledge about individual responses to dietary interventions, their safety, tolerance, efficacy and long-term effects.
Published:
2020-11
Title:
Global Dietary Patterns and Functional Gastrointestinal Disorders
Authors:
Axelrod, Cara Hannah; Saps, Miguel
Abstract:
Functional Gastrointestinal Disorders (FGIDs) are common. In the United States alone, approximately 25 million Americans are estimated to have at least one FGID. Nonpharmacological treatment options include psychological/behavioral approaches, and dietary interventions that can vary across countries. The aim of this review is to evaluate the available evidence for dietary interventions for the treatment of childhood FGIDs amongst various cultures and regions of the world. This review includes clinical trials of dietary therapies for the treatment of FGIDs in children posted on or before 13 July 2020 in PubMed. Overall, the consensus view suggests that the westernization of diets is linked to the development of FGIDs, and diets low in Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAPs) may reduce abdominal symptoms. However, more work is needed to confirm these findings.
Published:
2020-10
Title:
Is There Such a Thing as “Anti-Nutrients”? A Narrative Review of Perceived Problematic Plant Compounds
Authors:
Petroski, Weston; Minich, Deanna M.
Abstract:
Plant-based diets are associated with reduced risk of lifestyle-induced chronic diseases. The thousands of phytochemicals they contain are implicated in cellular-based mechanisms to promote antioxidant defense and reduce inflammation. While recommendations encourage the intake of fruits and vegetables, most people fall short of their target daily intake. Despite the need to increase plant-food consumption, there have been some concerns raised about whether they are beneficial because of the various ‘anti-nutrient’ compounds they contain. Some of these anti-nutrients that have been called into question included lectins, oxalates, goitrogens, phytoestrogens, phytates, and tannins. As a result, there may be select individuals with specific health conditions who elect to decrease their plant food intake despite potential benefits. The purpose of this narrative review is to examine the science of these ‘anti-nutrients’ and weigh the evidence of whether these compounds pose an actual health threat.
Published:
2020-10
Title:
Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing
Authors:
Cunnane, Stephen C.; Trushina, Eugenia; Morland, Cecilie; Prigione, Alessandro; Casadesus, Gemma; Andrews, Zane B.; Beal, M. Flint; Bergersen, Linda H.; Brinton, Roberta D.; de la Monte, Suzanne; Eckert, Anne; Harvey, Jenni; Jeggo, Ross; Jhamandas, Jack H.; Kann, Oliver; la Cour, Clothide Mannoury; Martin, William F.; Mithieux, Gilles; Moreira, Paula I.; Murphy, Michael P.; Nave, Klaus-Armin; Nuriel, Tal; Oliet, Stéphane H. R.; Saudou, Frédéric; Mattson, Mark P.; Swerdlow, Russell H.; Millan, Mark J.
Abstract:
The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes.
Published:
2020-09
Title:
Dietary Fructose Alters the Composition, Localization and Metabolism of Gut Microbiota in Association with Worsening Colitis
Authors:
Montrose, David C.; Nishiguchi, Ryohei; Basu, Srijani; Staab, Hannah A.; Zhou, Xi Kathy; Wang, Hanhan; Meng, Lingsong; Johncilla, Melanie; Cubillos-Ruiz, Juan R.; Morales, Diana K.; Wells, Martin T.; Simpson, Kenneth W.; Zhang, Shiying; Dogan, Belgin; Jiao, Chen; Fei, Zhangjun; Oka, Akihiko; Herzog, Jeremy W.; Sartor, R. Balfour; Dannenberg, Andrew J.
Abstract:
Published:
2020-09
Title:
Exercise, Dietary Protein, and Combined Effect on IGF-1
Authors:
Gulick, C. N.; Peddie, M. C.; Jowett, T.; Hackney, A. C.; Rehrer, N. J.
Abstract:
Insulin-like growth factor 1 (IGF-1) is a dichotomous hormone. While beneficial for growth/repair, and regulating muscle hypertrophy, high concentrations of IGF-1 are associated with increased risk of cancer and mortality. Factors thought to mediate IGF-1 include dietary protein and exercise. The purpose of this study was to analyze acute effects of dietary protein and/or exercise on plasma free IGF-1 and the time-course thereof to inform individuals who may benefit from increased IGF-1 (muscle growth/repair) or reduced IGF-1 (risk/diagnosis of cancer). Twenty-four participants (11 females, 24.9±4.6y) completed the three-way crossover study consisting of: (1)a high protein (42g) meal; (2)exercise (20min with four 30sec sprints); and (3)exercise followed by a high protein meal. Blood samples were collected fasted at rest, immediately after rest (or 5min after exercise), and at regular intervals throughout a 5h recovery. An additional fasted venipuncture was performed the morning following each condition (24h after baseline). Free IGF-1 was higher at immediately after exercise in the exercise condition (p=0.04). In the protein condition the 24h IGF-1 was 17.5% higher (p=0.02) than baseline. IGF-1 did not change over time in response to exercise with protein. The data gleaned from this study can enhance the knowledge of the time-course effects from protein and/or exercise on IGF-1. This study can provide a foundation for future research to investigate optimal timing and dosage to enhance muscle protein synthesis for athletes, as well as investigate whether consistent high protein meals may chronically elevate IGF-1 and increase the risk of deleterious health outcomes.
Published:
2020-09
Title:
The Importance of the Fatty Acid Transporter L-Carnitine in Non-Alcoholic Fatty Liver Disease (NAFLD)
Authors:
Savic, Dragana; Hodson, Leanne; Neubauer, Stefan; Pavlides, Michael
Abstract:
L-carnitine transports fatty acids into the mitochondria for oxidation and also buffers excess acetyl-CoA away from the mitochondria. Thus, L-carnitine may play a key role in maintaining liver function, by its effect on lipid metabolism. The importance of L-carnitine in liver health is supported by the observation that patients with primary carnitine deficiency (PCD) can present with fatty liver disease, which could be due to low levels of intrahepatic and serum levels of L-carnitine. Furthermore, studies suggest that supplementation with L-carnitine may reduce liver fat and the liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST) in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). L-carnitine has also been shown to improve insulin sensitivity and elevate pyruvate dehydrogenase (PDH) flux. Studies that show reduced intrahepatic fat and reduced liver enzymes after L-carnitine supplementation suggest that L-carnitine might be a promising supplement to improve or delay the progression of NAFLD.
Published:
2020-08
Title:
Baseline HOMA IR and Circulating FGF21 Levels Predict NAFLD Improvement in Patients Undergoing a Low Carbohydrate Dietary Intervention for Weight Loss: A Prospective Observational Pilot Study
Authors:
Watanabe, Mikiko; Risi, Renata; Camajani, Elisabetta; Contini, Savina; Persichetti, Agnese; Tuccinardi, Dario; Ernesti, Ilaria; Mariani, Stefania; Lubrano, Carla; Genco, Alfredo; Spera, Giovanni; Gnessi, Lucio; Basciani, Sabrina
Abstract:
Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease. Very low-calorie ketogenic diets (VLCKD) represent a feasible treatment as they induce profound weight loss and insulin resistance (IR) improvement. Despite the recognized benefits on NAFLD deriving from pharmacological administration of fibroblast growth factor 21 (FGF21), whose endogenous counterpart is a marker of liver injury, little is known about its physiology in humans. Aim: To identify predictors of NAFLD improvement as reflected by the reduction of the non-invasive screening tool hepatic steatosis index (HSI) in obese patients undergoing a weight loss program. Methods: Sixty-five obese patients underwent a 90-day dietary program consisting of a VLCKD followed by a hypocaloric low carbohydrate diet (LCD). Anthropometric parameters, body composition, and blood and urine chemistry were assessed. Results: Unlike most parameters improving mainly during the VLCKD, the deepest HSI change was observed after the LCD (p = 0.02 and p < 0.0001, respectively). Baseline HOMA-IR and serum FGF21 were found to be positive (R = 0.414, p = 0009) and negative (R = 0.364, p = 0.04) independent predictors of HSI reduction, respectively. Conclusions: We suggest that patients with IR and NAFLD derive greater benefit from a VLCKD, and we propose a possible role of human FGF21 in mediating NAFLD amelioration following nutritional manipulation.
Published:
2020-07
Title:
Most meat products have digestible indispensable amino acid scores that are greater than 100, but processing may increase or reduce protein quality
Authors:
Bailey, Hannah M.; Mathai, John K.; Berg, Eric P.; Stein, Hans H.
Abstract:
An experiment was conducted to test the hypothesis that meat products have digestible indispensable amino acid scores (DIAAS) >100 and that various processing methods will increase standardised ileal digestibility (SID) of amino acids (AA) and DIAAS. Nine ileal-cannulated gilts were randomly allotted to a 9 × 8 Youden square design with nine diets and eight 7-d periods. Values for SID of AA and DIAAS for two reference patterns were calculated for salami, bologna, beef jerky, raw ground beef, cooked ground beef and ribeye roast heated to 56, 64 or 72°C. The SID of most AA was not different among salami, bologna, beef jerky and cooked ground beef, but was less (P < 0·05) than the values for raw ground beef. The SID of AA for 56°C ribeye roast was not different from the values for raw ground beef and 72°C ribeye roast, but greater (P 100 and bologna and 64°C ribeye roast had the greatest (P 100 regardless of processing. However, overcooking meat may reduce AA digestibility and DIAAS.
Published:
2020-07
Title:
Most meat products have digestible indispensable amino acid scores that are greater than 100, but processing may increase or reduce protein quality
Authors:
Bailey, Hannah M.; Mathai, John K.; Berg, Eric P.; Stein, Hans H.
Abstract:
An experiment was conducted to test the hypothesis that meat products have digestible indispensable amino acid scores (DIAAS) >100 and that various processing methods will increase standardised ileal digestibility (SID) of amino acids (AA) and DIAAS. Nine ileal-cannulated gilts were randomly allotted to a 9 × 8 Youden square design with nine diets and eight 7-d periods. Values for SID of AA and DIAAS for two reference patterns were calculated for salami, bologna, beef jerky, raw ground beef, cooked ground beef and ribeye roast heated to 56, 64 or 72°C. The SID of most AA was not different among salami, bologna, beef jerky and cooked ground beef, but was less (P < 0·05) than the values for raw ground beef. The SID of AA for 56°C ribeye roast was not different from the values for raw ground beef and 72°C ribeye roast, but greater (P 100 and bologna and 64°C ribeye roast had the greatest (P 100 regardless of processing. However, overcooking meat may reduce AA digestibility and DIAAS.
Published:
2020-07
Title:
Serious adverse events and deaths in PCSK9 inhibitor trials reported on ClinicalTrials.gov: a systematic review
Authors:
van Bruggen, F. H.; Nijhuis, G. B. J.; Zuidema, S. U.; Luijendijk, Hendrika
Abstract:
BACKGROUND: Previous reviews of PCSK9 inhibitor trials are limited by a focus on composite cardiovascular outcomes. ClinicalTrials.gov provides trial results for individual clinical outcomes. Aim of this systematic review was to assess the effect of PCSK9 inhibitors on the risk of myocardial infarction, stroke/TIA, heart failure, diabetes mellitus, neurocognitive events, all-cause serious adverse events (SAE), and all-cause deaths as registered on ClinicalTrials.gov. METHODS: PubMed, regulatory reports, ClinicalTrials.gov, and company websites were used to search studies. Randomized trials comparing PCSK9 inhibitor with placebo in participants with hypercholesterolemia were eligible. Study characteristics, risk of bias, and numbers of participants with the outcomes of interest were collected. RESULTS: We identified 33 lipid-lowering and 4 clinical outcomes trials with results on ClinicalTrials.gov (n = 16,958 and n = 73,836, respectively). Risk of bias was generally high. PCSK9 inhibitors did not affect the risk of any of the investigated outcomes in either type of trial. However, in clinical outcomes studies, alirocumab decreased the risk of all-cause SAE (OR 0.92; 95% CI 0.86-0.98), and evolocumab probably increased the risk of mortality (OR 1.12; 95% CI 1.00-1.25). CONCLUSIONS: Our meta-analysis of clinical events registered on ClinicalTrials.gov did not show that PCSK9 inhibitors improve cardiovascular health. Evolocumab increased the risk of all-cause mortality.
Published:
2020-07
Title:
Health Effects of Coffee: Mechanism Unraveled?
Authors:
Kolb, Hubert; Kempf, Kerstin; Martin, Stephan
Abstract:
The association of habitual coffee consumption with a lower risk of diseases, like type 2 diabetes mellitus, chronic liver disease, certain cancer types, or with reduced all-cause mortality, has been confirmed in prospective cohort studies in many regions of the world. The molecular mechanism is still unresolved. The radical-scavenging and anti-inflammatory activity of coffee constituents is too weak to account for such effects. We argue here that coffee as a plant food has similar beneficial properties to many vegetables and fruits. Recent studies have identified a health promoting mechanism common to coffee, vegetables and fruits, i.e., the activation of an adaptive cellular response characterized by the upregulation of proteins involved in cell protection, notably antioxidant, detoxifying and repair enzymes. Key to this response is the activation of the Nrf2 (Nuclear factor erythroid 2-related factor-2) system by phenolic phytochemicals, which induces the expression of cell defense genes. Coffee plays a dominant role in that regard because it is the major dietary source of phenolic acids and polyphenols in the developed world. A possible supportive action may be the modulation of the gut microbiota by non-digested prebiotic constituents of coffee, but the available data are still scarce. We conclude that coffee employs similar pathways of promoting health as assumed for other vegetables and fruits. Coffee beans may be viewed as healthy vegetable food and a main supplier of dietary phenolic phytochemicals.
Published:
2020-06
Title:
Case report of nutritional rickets in an infant following a vegan diet
Authors:
Lemoine, A.; Giabicani, E.; Lockhart, V.; Grimprel, E.; Tounian, P.
Abstract:
We report the case of a 13-month-old infant who was referred to the pediatric emergency department because of psychomotor regression with four bone fractures due to nutritional rickets. The reason was prolonged breastfeeding from a vegetarian mother followed by a vegan diet for the infant after weaning. Rickets is one of the many nutritional deficiencies that could affect infants fed vegan or vegetarian diets. These diets are a public health concern requiring adapted information that suggests alternative formulas made from rice or soy proteins and adapted supplementation after weaning.
Published:
2020-05
Title:
The uneven weight distribution between predators and prey: Comparing gut fill between terrestrial herbivores and carnivores
Authors:
De Cuyper, Annelies; Meloro, Carlo; Abraham, Andrew J.; Müller, Dennis W. H.; Codron, Daryl; Janssens, Geert P. J.; Clauss, Marcus
Abstract:
The general observation that secondary consumers ingest highly digestible food and have simple short guts and small abdominal cavities intuitively results in the assumption that mammalian carnivores carry less digesta in their gut compared to herbivores. Due to logistic constraints, this assumption has not been tested quantitatively so far. In this contribution, we estimated the dry matter gut contents (DMC) for 25 species of the order Carnivora (including two strictly herbivorous ones, the giant and the red panda) using the physical 'Occupancy Principle', based on a literature data collection on dry matter intake (DMI), apparent dry matter digestibility (aD DM) and retention time (RT), and compared the results to an existing collection for herbivores. Scaling exponents with body mass (BM) for both carnivores and herbivores were in the same range with DMI ~ BM0.75; aD DM ~ BM0; RT ~ BM0.11 and DMC ~ BM0.88. The trophic level (carnivore vs herbivore) significantly affected all digestive physiology parameters except for RT. Numerically, the carnivore DMI level reached 77%, the RT 32% and DMC only 29% of the corresponding herbivore values, whereas the herbivore aD DM only reached 82% of that of carnivores. Thus, we quantitatively show that carnivores carry less inert mass or gut content compared to herbivores, which putatively benefits them in predator-prey interactions and might have contributed to the evolution towards unguligradism in herbivores. As expected, the two panda species appeared as outliers in the dataset with low aD DM and RT for a herbivore but extremely high DMI values, resulting in DMC in the lower part of the herbivore range. Whereas the difference in DMI and DMC scaling in herbivores might allow larger herbivores to compensate for lower diet quality by ingesting more, this difference may allow larger carnivores not to go for less digestible prey parts, but mainly to increase meal intervals, i.e. not having to hunt on a daily basis.
Published:
2020-05
Title:
Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer
Authors:
Liu, Xiaoguang; Olszewski, Kellen; Zhang, Yilei; Lim, Esther W.; Shi, Jiejun; Zhang, Xiaoshan; Zhang, Jie; Lee, Hyemin; Koppula, Pranavi; Lei, Guang; Zhuang, Li; You, M. James; Fang, Bingliang; Li, Wei; Metallo, Christian M.; Poyurovsky, Masha V.; Gan, Boyi
Abstract:
Liu et al. show that cancer cells with high levels of SLC7A11 have increased dependency on the pentose phosphate pathway and consequently accumulate disulfide, and can be therapeutically targeted by limiting glucose supply.
Published:
2020-04
Title:
mTOR at the nexus of nutrition, growth, ageing and disease
Authors:
Liu, Grace Y.; Sabatini, David M.
Abstract:
The mTOR pathway integrates a diverse set of environmental cues, such as growth factor signals and nutritional status, to direct eukaryotic cell growth. Over the past two and a half decades, mapping of the mTOR signalling landscape has revealed that mTOR controls biomass accumulation and metabolism by modulating key cellular processes, including protein synthesis and autophagy. Given the pathway’s central role in maintaining cellular and physiological homeostasis, dysregulation of mTOR signalling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing. In this Review, we highlight recent advances in our understanding of the complex regulation of the mTOR pathway and discuss its function in the context of physiology, human disease and pharmacological intervention.
Published:
2020-04
Title:
Effects of a four-week very low-carbohydrate high-fat diet on biomarkers of inflammation: Non-randomised parallel-group study
Authors:
Cipryan, Lukas; Maffetone, Phil B.; Plews, Daniel J.; Laursen, Paul B.
Abstract:
BACKGROUND: It is commonly assumed that increased dietary fat and/or caloric excess induces chronic inflammatory processes, since the association between obesity and chronic adipose tissue with systemic inflammation has been shown previously. As far as we know, the reported health benefits of a VLCHF or ketogenic diet have not adequately involved an evaluation of biomarkers of inflammation. AIM: This study investigated the effects of a four-week very low-carbohydrate high-fat (VLCHF) diet in healthy young individuals on biomarkers of inflammation. METHODS: Eighteen moderately trained males (age 23.8 ± 2.1 years) were assigned to two groups. One group switched to a non-standardised VLCHF diet for four weeks, while the second group remained consuming their normal habitual diet (HD). Biomarkers of inflammation (adiponectin, leptin, resistin and interleukin-6) and substrate metabolism (fasting glucose and triacylglyceride concentrations) were analysed from blood at baseline and after four weeks. RESULTS: There was moderate evidence for substantial changes in leptin serum concentrations in the VLCHF group, with small to large decreases compared to the HD group after four weeks (effect size = 0.78, 95% CI 0.42, 0.93, p = 0.008; Bayes Factor10 = 5.70). No substantial between-group change differences over time were found across any other biomarkers. CONCLUSIONS: A four-week period of consuming a VLCHF diet in healthy young men was not associated with any considerable changes in markers of inflammation but showed evidence for lowered serum leptin concentrations relative to the HD group.
Published:
2020-03
Title:
Higher cholesterol levels, not statin use, are associated with a lower risk of hepatocellular carcinoma
Authors:
Yi, Sang-Wook; Kim, Se Hwa; Han, Ki Jun; Yi, Jee-Jeon; Ohrr, Heechoul
Abstract:
We aimed to examine whether statin users have a lower risk of hepatocellular carcinoma (HCC) after careful consideration of prevalent statin use and cholesterol levels. During a mean prospective follow-up of 8.4 years in 400,318 Koreans, 1686 individuals were diagnosed with HCC. When prevalent users were included, HCC risk was reduced by >50% in statin users, regardless of adjustment for total cholesterol (TC). When prevalent users were excluded, new users who initiated statins within 6 months after baseline had a 40% lower risk of HCC (hazard ratio [HR] = 0.59) in a TC-unadjusted analysis. However, this relationship disappeared (HR = 1.16, 95% CI = 0.80-1.69) after adjusting for TC levels measured within 6 months before statin initiation. TC levels had strong inverse associations with HCC in each model. High cholesterol levels at statin initiation, not statin use, were associated with reduced risk of HCC. Our study suggests no protective effect of statins against HCC.
Published:
2020-03
Title:
Ketogenic, Hypocaloric Diet Improves Nonalcoholic Steatohepatitis
Authors:
Belopolsky, Yuliya; Khan, Mohammad Q.; Sonnenberg, Amnon; Davidson, David J.; Fimmel, Claus J.
Abstract:
Background and objectives: Nonalcoholic steatohepatitis (NASH) is strongly associated with obesity. A weight loss of ≥10% is necessary to improve NASH severity, but this goal has rarely been achieved in published studies using different diet protocols. The effect of a ketogenic, hypocaloric, commercial diet ("Ideal Protein," IP) on body weight, metabolic markers, and liver tests in a group of NASH patients is evaluated in this study. Daily calorie intake was tailored to achieve a weight loss of ≥10%. Methods: We analyzed 38 patients with NASH who were placed on the IP diet between 2014 and 2018 and compared their outcomes with 6 control patients who declined the diet. All patients were evaluated by a trained health coach in weekly intervals throughout the study period. Clinical and laboratory data obtained before and at 6.5 months after intervention were compared using paired t-testing. Results: The patients on the IP diet experienced a significant weight reduction (217 ± 8 lb vs. 194 ± 7 lb; mean ± S.E.M.), corresponding to an average weight loss of 9.7% ± 1.6%. Significant changes in systolic blood pressure (133 ± 3 mmHg vs. 123 ± 3 mmHg), triglycerides (200 ± 21 mmol/L vs. 132 ± 11 mmol/L), hemoglobin A1c (6.71% ± 0.29% vs. 5.74% ± 0.19%), SGPT (97.3 ± 11.1 IU/L vs. 44.2 ± 5.9 IU/L), SGOT (82.4 ± 10.5 IU/L vs. 32.8 ± 5.2 IU/L), and Fib-4 scores (2.25 ± 0.23 vs. 1.40 ± 0.13) were also observed (P
Published:
2020-03
Title:
Medium Chain Triglycerides induce mild ketosis and may improve cognition in Alzheimer's disease. A systematic review and meta-analysis of human studies
Authors:
Avgerinos, Konstantinos I.; Egan, Josephine M.; Mattson, Mark P.; Kapogiannis, Dimitrios
Abstract:
INTRODUCTION/AIM: The brain in Alzheimer's disease shows glucose hypometabolism but may utilize ketones for energy production. Ketone levels can potentially be boosted through oral intake of Medium Chain Triglycerides (MCTs). The aim of this meta-analysis is to investigate the effect of MCTs on peripheral ketone levels and cognitive performance in patients with mild cognitive impairment and Alzheimer's disease. METHODS: Medline, Scopus and Web of Science were searched for literature up to March 1, 2019. Meta-analyses were performed by implementing continuous random-effects models and outcomes were reported as weighted Mean Differences (MDs) or Standardized Mean Differences (SMDs). RESULTS: Twelve records (422 participants) were included. Meta-analysis of RCTs showed that, compared with placebo, MCTs elevated beta-hydroxybutyrate [MD = 0.355; 95 % CI (0.286, 0.424), I2 = 0 %], showed a trend towards cognitive improvement on ADAS-Cog [MD = -0.539; 95% CI (-1.239, -0.161), I2 = 0 %], and significantly improved cognition on a combined measure (ADAS-Cog with MMSE) [SMD = -0.289; 95 % CI (-0.551, -0.027), I2 = 0 %]. CONCLUSIONS: In this meta-analysis, we demonstrated that MCTs can induce mild ketosis and may improve cognition in patients with mild cognitive impairment and Alzheimer's disease. However, risk of bias of existing studies necessitates future trials.
Published:
2020-03
Title:
Potential of coconut oil and medium chain triglycerides in the prevention and treatment of Alzheimer's disease
Authors:
Chatterjee, Pratishtha; Fernando, Malika; Fernando, Binosha; Dias, Cintia B.; Shah, Tejal; Silva, Renuka; Williams, Shehan; Pedrini, Steve; Hillebrandt, Heidi; Goozee, Kathryn; Barin, Edward; Sohrabi, Hamid R.; Garg, Manohar; Cunnane, Stephen; Martins, Ralph N.
Abstract:
Alzheimer's disease (AD) is the most common form of dementia. Currently, there is no effective medication for the prevention or treatment of AD. This has led to the search for alternative therapeutic strategies. Coconut oil(CO) has a unique fatty acid composition that is rich in medium chain fatty acids(MCFA), a major portion of which directly reaches the liver via the portal vein, thereby bypassing the lymphatic system. Given that brain glucose hypometabolism is a major early hallmark of AD, detectable well before the onset of symptoms, ketone bodies from MCFA metabolism can potentially serve as an alternative energy source to compensate for lack of glucose utilisation in the brain. Additionally, neuroprotective antioxidant properties of CO have been attributed to its polyphenolic content. This review discusses how the metabolism of CO and MCFA may aid in compensating the glucose hypometabolism observed in the AD brain. Furthermore, we present the current evidence of the neuroprotective properties of CO on cognition, amyloid-β pathogenicity, inflammation and oxidative stress. The current review addresses the influence of CO/MCFA on other chronic disorders that are risk factors for AD, and addresses existing gaps in the literature regarding the use of CO/MCFA as a potential treatment for AD.
Published:
2020-03
Title:
The Relation of the Chronic Disease Epidemic to the Health Care Crisis
Authors:
Holman, Halsted R.
Abstract:
Currently, some 50% of the population has a chronic disease, creating an epidemic, and 86% of health care costs are attributable to chronic disease. The medical profession and its leadership did not recognize or respond appropriately to the rising prevalence ...
Published:
2020-03
Title:
The zooarchaeology and paleoecology of early hominin scavenging
Authors:
Pobiner, Briana L.
Abstract:
Questions about the timing, frequency, resource yield, and behavioral and biological implications of large animal carcass acquisition by early hominins have been a part of the "hunting-scavenging debate" for decades. This article presents a brief outline of this debate, reviews the zooarchaeological and modern ecological evidence for a possible scavenging niche among the earliest animal tissue-consuming hominins (pre-2.0 Ma), revisits some of the questions that this debate has generated, and outlines some ways to explore answers to those questions with evidence from the archaeological record.
Published:
2020-03
Title:
Are low-carbohydrate diets safe in diabetic and nondiabetic chronic kidney disease?
Authors:
Mitchell, Nia S.; Scialla, Julia J.; Yancy, William S.
Abstract:
Diabetes mellitus and obesity both contribute to chronic kidney disease (CKD) and diabetic kidney disease (DKD), and they can accelerate the loss of kidney function. Dietary intake can potentially have wide-reaching effects on the risk of CKD/DKD and their progression by reducing weight and blood pressure, improving glycemic control, reducing hyperfiltration, and modulating inflammation. Low-carbohydrate (LC) diets can reduce weight and improve glycemic control, but the relatively higher protein content also raises concern in CKD/DKD. Empiric evidence supporting the kidney-related benefits or risks of LC diets is needed to understand the balance of these potential harms and benefits for patients with DKD and is the subject of our review.
Published:
2020-02
Title:
Equivalent Reduction in Greenhouse Gas Emissions by Mahayana Buddhists Practicing Vegetarian Diets
Authors:
Tseng, Ampere A.
Abstract:
The equivalent reduction in greenhouse gas emissions (GHGEs) by Mahayana Buddhists with vegetarian diets is quantitatively evaluated. The Buddhists in seven Mahayana-dominated countries or regions, i.e., China, Japan, Vietnam, South Korea, Taiwan, Hong Kong, and Singapore, are studied. Assessments of the vegetarian population among these Mahayana-dominated countries or regions are performed. Correlation formulas based on data from a national survey are developed to quantify the GHGEs of various dietary groups by using the meat consumption as the only required input. To demonstrate its reliability, the prediction from the formulas developed is first compared with the results of a food production-and-consumption study using a different approach. Then, the formulas are used to assess the GHGE reduction due to Mahayana Buddhists with vegetarian diets. The assessment indicates that Mahayana Buddhists with vegetarian diets account for the equivalent GHGE reduction of 48.83 million metric tons of carbon dioxide equivalent, which is a huge amount and is equal to 11.3 or 8.9% of the GHGEs from France or the UK in 2012, respectively.
Published:
2020-02
Title:
The role of macrophages in obesity-associated islet inflammation and β-cell abnormalities
Authors:
Ying, Wei; Fu, Wenxian; Lee, Yun Sok; Olefsky, Jerrold M.
Abstract:
The dominant immune cell type causing pancreatic islet inflammation in individuals with obesity and/or type 2 diabetes mellitus is the macrophage. In this Review, we focus on the characteristics of inflammation in obese or type 2 diabetes mellitus islets and the consequences of this with respect to β-cell function.
Published:
2020-02
Title:
Very Low-Calorie Ketogenic Diet: A Safe and Effective Tool for Weight Loss in Patients with Obesity and Mild Kidney Failure
Authors:
Bruci, Adriano; Tuccinardi, Dario; Tozzi, Rossella; Balena, Angela; Santucci, Silvia; Frontani, Riccardo; Mariani, Stefania; Basciani, Sabrina; Spera, Giovanni; Gnessi, Lucio; Lubrano, Carla; Watanabe, Mikiko
Abstract:
Very low-calorie ketogenic diets (VLCKD) are an effective and increasingly used tool for weight loss. Traditionally considered high protein, ketogenic diets are often looked at with concern by clinicians due to the potential harm they pose to kidney function. We herein evaluated the efficacy and safety of a VLCKD in patients with obesity and mild kidney failure. A prospective observational real-life study was conducted on ninety-two patients following a VLCKD for approximately 3 months. Thirty-eight had mild kidney failure and fifty-four had no renal condition and were therefore designated as control. Anthropometric parameters, bioelectrical impedance and biochemistry data were collected before and at the end of the dietary intervention. The average weight loss was nearly 20% of initial weight, with a significant reduction in fat mass. We report an improvement of metabolic parameters and no clinically relevant variation regarding liver and kidney function. Upon stratification based on kidney function, no differences in the efficacy and safety outcomes were found. Interestingly, 27.7% of patients with mild renal failure reported normalization of glomerular filtrate after dietary intervention. We conclude that, when conducted under the supervision of healthcare professionals, a VLCKD is an effective and safe treatment for weight loss in patients with obesity, including those affected by mild kidney failure.
Published:
2020-02
Title:
Association between dietary insulin index and load and psychological disorders
Authors:
Anjom-Shoae, Javad; Keshteli, Ammar Hassanzadeh; Afshar, Hamid; Esmaillzadeh, Ahmad; Adibi, Peyman
Abstract:
The present study was carried out to determine whether the dietary insulin index (DII) and dietary insulin load (DIL) are related to psychological disorders in a cross-sectional study among adults. A total of 3172 Iranian adults (age range of 18–55 years) were included. Data on dietary intakes were collected using a validated dish-based 106-item semi-quantitative FFQ. DII and DIL were calculated using food insulin index values published earlier. To assess depression and anxiety, an Iranian validated version of the Hospital Anxiety and Depression Scale was used. Furthermore, psychological distress was examined using the General Health Questionnaire. Among women, a significant positive association was seen; such that women in the highest quartile of DIL had higher odds of depression than those in the lowest quartile (OR 1·84; 95 % CI 1·14, 2·96). In terms of DII, in the fully adjusted model, women in the top quartile of DII were more likely to be depressed compared with those in the bottom quartile (OR 1·65; 95 % CI 1·05, 2·58). In conclusion, we found a significant positive association between DIL and DII and odds of depression among women, but not in men. However, such findings were not seen for anxiety and psychological distress.
Published:
2020-01
Title:
Fasting reveals largely intact systemic lipid mobilization mechanisms in respiratory chain complex III deficient mice
Authors:
Tomašić, Nikica; Kotarsky, Heike; de Oliveira Figueiredo, Rejane; Hansson, Eva; Mörgelin, Matthias; Tomašić, Ivan; Kallijärvi, Jukka; Elmér, Eskil; Jauhiainen, Matti; Eklund, Erik A.; Fellman, Vineta
Abstract:
Mice homozygous for the human GRACILE syndrome mutation (Bcs1lc.A232G) display decreased respiratory chain complex III activity, liver dysfunction, hypoglycemia, rapid loss of white adipose tissue and early death. To assess the underlying mechanism of the lipodystrophy in homozygous mice (Bcs1lp.S78G), these and wild-type control mice were subjected to a short 4-hour fast. The homozygotes had low baseline blood glucose values, but a similar decrease in response to fasting as in wild-type mice, resulting in hypoglycemia in the majority. Despite the already depleted glycogen and increased triacylglycerol content in the mutant livers, the mice responded to fasting by further depletion and increase, respectively. Increased plasma free fatty acids (FAs) upon fasting suggested normal capacity for mobilization of lipids from white adipose tissue into circulation. Strikingly, however, serum glycerol concentration was not increased concomitantly with free FAs, suggesting its rapid uptake into the liver and utilization for fuel or gluconeogenesis in the mutants. The mutant hepatocyte mitochondria were capable of responding to fasting by appropriate morphological changes, as analyzed by electron microscopy, and by increasing respiration. Mutants showed increased hepatic gene expression of major metabolic controllers typically associated with fasting response (Ppargc1a, Fgf21, Cd36) already in the fed state, suggesting a chronic starvation-like metabolic condition. Despite this, the mutant mice responded largely normally to fasting by increasing hepatic respiration and switching to FA utilization, indicating that the mechanisms driving these adaptations are not compromised by the CIII dysfunction. Summary statement: Bcs1l mutant mice with severe CIII deficiency, energy deprivation and post-weaning lipolysis respond to fasting similarly to wild-type mice, suggesting largely normal systemic lipid mobilization and utilization mechanisms.
Published:
2020-01
Title:
Ketogenesis-generated β-hydroxybutyrate is an epigenetic regulator of CD8+ T-cell memory development
Authors:
Zhang, Huafeng; Tang, Ke; Ma, Jingwei; Zhou, Li; Liu, Jincheng; Zeng, Liping; Zhu, Liyan; Xu, Pingwei; Chen, Jie; Wei, Keke; Liang, Xiaoyu; Lv, Jiadi; Xie, Jing; Liu, Yuying; Wan, Yonghong; Huang, Bo
Abstract:
Glycogen has long been considered to have a function in energy metabolism. However, our recent study indicated that glycogen metabolism, directed by cytosolic phosphoenolpyruvate carboxykinase Pck1, controls the formation and maintenance of CD8+ memory T (Tmem) cells by regulating redox homeostasis1. This unusual metabolic program raises the question of how Pck1 is upregulated in CD8+ Tmem cells. Here, we show that mitochondrial acetyl coenzyme A is diverted to the ketogenesis pathway, which indirectly regulates Pck1 expression. Mechanistically, ketogenesis-derived β-hydroxybutyrate is present in CD8+ Tmem cells; β-hydroxybutyrate epigenetically modifies Lys 9 of histone H3 (H3K9) of Foxo1 and Ppargc1a (which encodes PGC-1α) with β-hydroxybutyrylation, upregulating the expression of these genes. As a result, FoxO1 and PGC-1α cooperatively upregulate Pck1 expression, therefore directing the carbon flow along the gluconeogenic pathway to glycogen and the pentose phosphate pathway. These results reveal that ketogenesis acts as an unusual metabolic pathway in CD8+ Tmem cells, linking epigenetic modification required for memory development.
Published:
2020-01
Title:
Low-Carbohydrate Diets in the Management of Obesity and Type 2 Diabetes: A Review from Clinicians using the Approach in Practice
Authors:
Kelly, Tara; Unwin, David; Finucane, Francis
Abstract:
Low-carbohydrate diets are increasingly used to help patients with obesity and type 2 diabetes. We sought to provide an overview of the evidence for this treatment approach, considering the epidemiology and pathophysiology of obesity and diabetes in terms of carbohydrate excess. We describe the mechanistic basis for the clinical benefits associated with nutritional ketosis and identify areas of practice where the evidence base could be improved. We summarize the key principles which inform our approach to treating patients with low-carbohydrate diets. The scientific controversy relating to these diets is real but is consistent with the known challenges of any dietary interventions and also the limitations of nutritional epidemiology. Secondly, notwithstanding any controversy, international guidelines now recognize the validity and endorse the use of these diets as a therapeutic nutritional approach, in appropriate patients. Thirdly, we have found that early de-prescription of diabetes medications is essential, in particular insulin, sulphonylureas, and sodium-glucose cotransporter (SGLT2) inhibitors. Fourthly, we encourage patients to eat ad libitum to satiety, rather than calorie counting per se. Furthermore, we monitor cardiovascular risk factors frequently, as with all patients with obesity or diabetes, but we do not necessarily consider an increase in low-density lipoprotein (LDL)-cholesterol as an absolute indication to stop these diets, as this is usually related to large LDL particles, which are not associated with increased cardiovascular risk. In the absence of large randomized controlled trials with cardiovascular and other hard endpoints, adopting a low-carbohydrate diet is a legitimate and potentially effective treatment option for patients with diabetes or obesity.
Published:
2020-01
Title:
Modular biogenesis of mitochondrial respiratory complexes
Authors:
Barros, Mario H.; McStay, Gavin P.
Abstract:
Mitochondrial function relies on the activity of oxidative phosphorylation to synthesise ATP and generate an electrochemical gradient across the inner mitochondrial membrane. These coupled processes are mediated by five multi-subunit complexes that reside in this inner membrane. These complexes are the product of both nuclear and mitochondrial gene products. Defects in the function or assembly of these complexes can lead to mitochondrial diseases due to deficits in energy production and mitochondrial functions. Appropriate biogenesis and function are mediated by a complex number of assembly factors that promote maturation of specific complex subunits to form the active oxidative phosphorylation complex. The understanding of the biogenesis of each complex has been informed by studies in both simple eukaryotes such as Saccharomyces cerevisiae and human patients with mitochondrial diseases. These studies reveal each complex assembles through a pathway using specific subunits and assembly factors to form kinetically distinct but related assembly modules. The current understanding of these complexes has embraced the revolutions in genomics and proteomics to further our knowledge on the impact of mitochondrial biology in genetics, medicine, and evolution.
Published:
2020-01
Title:
The basic machineries for mitochondrial protein quality control
Authors:
Vazquez-Calvo, Carmela; Suhm, Tamara; Büttner, Sabrina; Ott, Martin
Abstract:
Mitochondria play pivotal roles in cellular energy metabolism, the synthesis of essential biomolecules and the regulation of cell death and aging. The proper folding, unfolding and degradation of the many proteins active within mitochondria is surveyed by the mitochondrial quality control machineries. Here, we describe the principal components of the mitochondrial quality control system and recent developments in the elucidation of the molecular mechanisms maintaining a functional mitochondrial proteome.
Published:
2020-01
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