An Alternative Enzymatic Route to the Ergogenic Ketone Body Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate

The oral administration of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, allows inducing a beneficial level of blood ketone bodies without the adverse effects due to the adhesion to a ketogenic diet. Several studies documented the therapeutic effectiveness of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in treating neurodegenerative diseases as well as its boosting activity of athletic and cognitive performances during prolonged physical exercises. Further studies considering this ketone body ester for therapy of other pathologies are also underway. In the present work, we describe the synthesis of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate through the enantioselective transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol catalyzed by immobilized Candida antarctica lipase B (CAL-B). The enantiopure (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate by CAL-B catalyzed acetylation with vinyl acetate. The economy of the synthetic procedure has been improved by recycling the unreacted (S) enantiomers of the ethyl 3-hydroxybutyrate and 1,3-buatnediol after stereochemical inversion achieved by tosylation and SN2 with ammonium acetate. The overall procedure allows to incorporate up to 70% of the starting racemic reagents into the final product.

Blood Ketone Bodies and Breath Acetone Analysis and Their Correlations in Type 2 Diabetes Mellitus

Analysis of volatile organic compounds in the breath for disease detection and monitoring has gained momentum and clinical significance due to its rapid test results and non-invasiveness, especially for diabetes mellitus (DM). Studies have suggested that breath gases, including acetone, may be related to simultaneous blood glucose (BG) and blood ketone levels in adults with types 2 and 1 diabetes. Detecting altered concentrations of ketones in the breath, blood and urine may be crucial for the diagnosis and monitoring of diabetes mellitus. This study assesses the efficacy of a simple breath test as a non-invasive means of diabetes monitoring in adults with type 2 diabetes mellitus. Human breath samples were collected in Tedlar™ bags and analyzed by headspace solid-phase microextraction and gas chromatography-mass spectrometry (HS-SPME/GC-MS). The measurements were compared with capillary BG and blood ketone levels (β-hydroxybutyrate and acetoacetate) taken at the same time on a single visit to a routine hospital clinic in 30 subjects with type 2 diabetes and 28 control volunteers. Ketone bodies of diabetic subjects showed a significant increase when compared to the control subjects; however, the ketone levels were was controlled in both diabetic and non-diabetic volunteers. Worthy of note, a statistically significant relationship was found between breath acetone and blood acetoacetate (R = 0.89) and between breath acetone and β-hydroxybutyrate (R = 0.82).

Two-Week Exclusive Supplementation of Modified Ketogenic Nutrition Drink Reserves Lean Body Mass and Improves Blood Lipid Profile in Obese Adults: A Randomized Clinical Trial

The ketogenic diet has long been recommended in patients with neurological disorders, and its protective effects on the cardiovascular system are of growing research interest. This study aimed to investigate the effects of two-week of low-calorie ketogenic nutrition drinks in obese adults. Subjects were randomized to consume drinks either a ketone-to-non-ketone ratio of 4:1 (KD 4:1), a drink partially complemented with protein at 1.7:1 (KD 1.7:1), or a balanced nutrition drink (BD). Changes in body weight, body composition, blood lipid profile, and blood ketone bodies were investigated. Blood ketone bodies were induced and maintained in the group that consumed both 4:1 and 1.7:1 ketogenic drinks (p < 0.001). Body weight and body fat mass significantly declined in all groups between 0 and 1 week and between 1 and 2 weeks (p < 0.05), while skeletal muscle mass remained unchanged only in the KD 1.7:1 group (p > 0.05). The blood lipid profile improved, appetite was reduced, and fullness was maintained in the two ketogenic drink groups. This study indicates the possibility for the development of obesity treatments based on ketogenic nutrition drinks even with a moderate ketogenic ratio of 1.7:1, as well as adjuvant therapies based on ketosis induction and maintenance for the treatment of other diseases and health conditions.

Metabolism-Based Treatments to Counter Cancer

Accumulating evidence indicates that cancer is a type of mitochondrial metabolic disease. Chronic damage to mitochondria causes a gradual shift in cellular energy metabolism from respiration to fermentation. Consequently, fermentable metabolites become the drivers of cancer. Mitochondrial injury can explain the long-standing “oncogenic paradox,” and all major hallmarks of cancer including genomic instability. Restriction of fermentable fuels therefore becomes a viable therapeutic strategy for cancer management. The ketogenic diet (KD) is a metabolic therapy that lowers blood glucose and elevates blood ketone bodies. Ketone bodies are a “super fuel” for functional mitochondria, but cannot be metabolized efficiently by tumor mitochondria. The efficacy of KDs for cancer management can be enhanced when used together with drugs and procedures (such as hyperbaric oxygen therapy) (that further target fermentation. Therapeutic ketosis can represent an alternative, nontoxic strategy for managing and preventing a broad range of cancers while reducing healthcare costs.

The effect of thyroxin on hepatic redox equilibrium and lipid metabolism in rats treated with doxorubicin

The main side effects of the administration of doxorubicin, a widely used anticancer drug, is the generation of a reactive oxygen species (ROS) in normal cells. As a result, redox disorders and secondary oxidative stress are developed. Doxorubicin ROS generation is attributed to enzymes that are produced abundantly in hepatocytes. Oxidative stress has been a well-known risk factor of doxorubicin-related toxicity. However, in addition, according to the data collected in the last decade, changes in thyroxin status can propagate ROS generation, and, thus, initiate the doxorubicin hepatic effect. Moreover, both compounds have an impact on the cell metabolism. The aim of the study was to verify the thesis that thyroxin can modulate the effect of doxorubicin with regard to redox status and lipid metabolism disorders. In our work, we determined the ratio of NADP+/ NADPH and NAD+/NADH in liver homogenates, blood ketone bodies and triglycerides in the liver and blood in rats treated with doxorubicin and thyroxin. Our results indicate that thyroxin has an insignificant effect on NAD+/NADH, NADP+/NADPH ratios and on hepatic and blood triglycerides. Moreover, thyroxin administration normalized the level of blood ketone bodies that was disturbed by doxorubicin.