The effect of acute and 14-day exogenous ketone supplementation on glycemic control in adults with type 2 diabetes: two randomized controlled trials.

Acute ingestion of the exogenous ketone monoester supplement [(R)-3-hydroxybutyl-(R)-3-hydroxybutyrate] lowers blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, it is unknown how acute or repeated ingestion of exogenous ketones affects blood glucose control in individuals with type 2 diabetes (T2D). We conducted two randomized, counterbalanced, double-blind, placebo-controlled crossover trials to determine if 1) acute exogenous ketone monoester (0.3 g/kg body mass; N = 18) or 2) 14-day thrice daily premeal exogenous ketone monoester (15 g; N = 15) supplementation could lower blood glucose in individuals living with T2D. A single dose of the ketone monoester supplement elevated blood ß-OHB to ∼2 mM. There were no differences in the primary outcomes of plasma glucose concentration (acutely) or serum fructosamine (glycemic control across 14 days) between conditions. Ketone monoester ingestion acutely increased insulin and lowered nonesterified fatty acid concentrations; plasma metabolomics confirmed a reduction in multiple free fatty acids species and select gluconeogenic amino acids. In contrast, no changes were observed in fasting metabolic outcomes following 14 days of supplementation. In the context of these randomized controlled trials, acute or repeated ketone monoester ingestion in adults with T2D did not lower blood glucose when consumed acutely in a fasted state and did not improve glycemic control following thrice daily premeal ingestion across 14 days. Future studies exploring the mechanistic basis for the (lack of) glucose-lowering effect of exogenous ketone supplementation in T2D and other populations are warranted.NEW & NOTEWORTHY Exogenous ketone supplements can acutely lower blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, the effect of exogenous ketones on glucose metabolism in adults with type 2 diabetes has not been investigated in a controlled setting. In adults with type 2 diabetes, ketone monoester ingestion did not lower blood glucose acutely in a fasted state and did not improve glycemic control across thrice daily premeal ingestion across 14 days.

Impact of a Low-Carbohydrate Compared with Low-Fat Breakfast on Blood Glucose Control in Type 2 Diabetes: A Randomized Trial.

BACKGROUND: In type 2 diabetes (T2D), consuming carbohydrates results in a rapid and large increase in blood glucose, particularly in the morning when glucose intolerance is highest. OBJECTIVES: We investigated if a low-carbohydrate (LC) breakfast (∼465 kcal: 25 g protein, 8 g carbohydrates, and 37 g fat) could improve glucose control in people with T2D when compared with a low-fat control (CTL) breakfast (∼450 kcal:20 g protein, 56 g carbohydrates, and 15 g fat). METHODS: Participants with T2D (N = 121, 53% women, mean age 64 y) completed a remote 3-month parallel-group randomized controlled trial comparing a LC with standard low-fat guideline CTL breakfast. The change in HbA1c was the prespecified primary outcome. Continuous glucose monitoring, self-reported anthropometrics, and dietary information were collected for an intention-to-treat analysis. RESULTS: HbA1c was reduced (-0.3%; 95% CI: -0.4%, -0.1%) after 12 wks of a LC breakfast, but the between-group difference in HbA1c was of borderline statistical significance (-0.2; 95% CI: -0.4, 0.0; P = 0.06). Self-reported total daily energy (-242 kcal; 95% CI: -460, -24 kcal; P = 0.03) and carbohydrate (-73 g; 95% CI: -101, -44 g; P < 0.01) intake were lower in the LC group but the significance of this difference is unclear. Mean and maximum glucose, area under the curve, glycemic variability, standard deviation, and time above range were all significantly lower, and time in the range was significantly higher, in the LC group compared with CTL (all P < 0.05). CONCLUSIONS: Advice and guidance to consume a LC breakfast appears to be a simple dietary strategy to reduce overall energy and carbohydrate intake and improve several continuous glucose monitoring variables when compared with a CTL breakfast in persons living with T2D. The trial was registered at clinicaltrials.gov as NCT04550468.

Vitamin complex (ascorbic acid, alpha-tocopherol and beta-carotene) induces micronucleus formation in PBMNC unrelated to ROS production.

OBJECTIVES: To evaluate the correlation between reactive oxygen species (ROS) production and micronucleus formation induced by a vitamin complex in peripheral blood mononuclear cells from healthy people aged between 40 and 85 years old. METHODS: Peripheral blood mononuclear cells (PBMNCs) were purified utilizing ficoll-hypaque gradient. ROS production by PBMNCs was quantified by luminol-dependent chemiluminescence in the presence or in the absence of the vitamin complex. DNA damage in PBMNC by the vitamin complex was detected by the micronucleus technique. Statistical analyses were made with the Student's 't' test and the Pearson correlation. P < 0.05 was considered significant. RESULTS: The vitamin complex induced MN formation in PBMNC but did not augment ROS production. There was no correlation between ROS production and MN formation either in the presence or in the absence of the vitamin complex. DISCUSSION: There was no increase in the ROS production in the presence of the vitamin complex. The vitamin complex induced an augmentation in the MN formation. There was no correlation between ROS production and the induction of MN formation. Since no association could be detected between ROS production and MN formation, additional studies are required in order to investigate the possible mechanism of vitamin-induced MN formation.

The role of oxidative stress in the aging process.

The aging of organisms is characterized by a gradual functional decline of all organ systems. An appropriate theory must explain four main characteristics of aging: it is progressive, endogenous, irreversible, and deleterious for the individual. The aging of the immune system, or immunosenescence, is manifested by an increased susceptibility to infections with increased morbidity and mortality. Phagocytic capacity, synthesis of reactive oxygen intermediaries, and the intracellular killing efficiency of neutrophils are impaired in the elderly. Among all aging theories, the most updated one describes the free radicals. It implies that progressive aging is associated with higher levels of oxidative biomolecules reacted with free radicals. Although reactive oxygen species (ROS) are predominantly implicated in causing cell damage, they also play a major physiological role in several aspects of intracellular signaling and regulation. ROS include a number of chemically reactive molecules derived from oxygen. Not only oxygen, but also nitrogen can be deleterious species. The overproduction of reactive nitrogen species (RNS) is called nitrosative stress. ROS/RNS are known to play a dual role in biological systems since they can be either harmful or beneficial to living systems.