Brianna Stubbs

Buck Institute for Research on Aging

Ketosis, the metabolic response to energy crisis, is a mechanism to sustain life by altering oxidative fuel selection. Often overlooked for its metabolic potential, ketosis is poorly understood outside of starvation or diabetic crisis. Thus, we studied the biochemical advantages of ketosis in humans using a ketone ester-based form of nutrition with...

Objective: The ketones d-β-hydroxybutyrate (BHB) and acetoacetate are elevated during prolonged fasting or during a "ketogenic" diet. Although weight loss on a ketogenic diet may be associated with decreased appetite and altered gut hormone levels, it is unknown whether such changes are caused by elevated blood ketones. This study investigated the...

Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate “ketogenic” diet, but adherence to such diets can be difficult. An alternative way to increase blood D-β-hydroxybutyrat...

Introduction Bis-octanoyl (R)-1,3-butanediol (BO-BD) is a novel, palatable ketone ester that, when consumed, is hydrolyzed in the gastrointestinal tract into octanoic acid (OCT) and (R)-1,3-butanediol (BDO) which are subsequently metabolized into beta-hydroxybutyrate (BHB). Metabolism of BO-BD is hypothesized to be similar to bis-hexanoyl (R)-1,3-b...

Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). Here, we identify β-hydroxybutyrate (βHB), a ketone body, as a regulator of protein solubility in the aging brain. βHB is a small molecule metabolite which primarily provides an oxidative substrate for ATP during hypoglycemic conditions, and also regulates other cellular proces...

Introduction: Bis-hexanoyl (R)-1,3-butanediol (BH-BD) is a novel ketone ester that, when consumed, is hydrolyzed into hexanoic acid (HEX) and (R)-1,3-butanediol (BDO) which are subsequently metabolized into beta-hydroxybutyrate (BHB). Methods: We undertook a randomized, parallel, open-label study in healthy adults ( n = 33) to elucidate blood BHB,...

In heart, glucose and glycolysis are important for anaplerosis and potentially therefore for d-beta-hydroxybutyrate (βHB) oxidation. As a glucose store, glycogen may also furnish anaplerosis. We determined the effects of glycogen content on βHB oxidation and glycolytic rates, and their downstream effects on energetics, in the isolated rat heart. Hi...

Objective: Growing interest in the metabolic state of ketosis has driven development of exogenous ketone products to induce ketosis without dietary changes. Bis hexanoyl (R)-1,3-butanediol (BH-BD) is a novel ketone ester which, when consumed, increases blood beta-hydroxybutyrate (BHB) concentrations. BH-BD is formulated as a powder or ready-to-drin...

Sports nutrition science seeks to determine optimal dietary protocols for athletes pushing the limits of human physiology in power, endurance, and skill. Traditionally, dietary interventions aimed to stimulate performance have focused on strategic intake of carbohydrates, protein, and fat. However, recent development of oral ketone supplements has...

Background: Ketosis has been reported to benefit healthspan and resilience, which has driven considerable interest in development of exogenous ketones to induce ketosis without dietary changes. Bis hexanoyl (R)-1,3-butanediol (BH-BD) is a novel ketone di-ester that can be used as a food ingredient that increases hepatic ketogenesis and blood beta-...

Ketogenic diets have been treating epilepsy for over 100 years, and in recent decades the awareness and applications of ketogenic therapies have expanded dramatically. The second edition of Ketogenic Diets and Metabolic Therapies: Expanded Roles in Health and Disease honors the major milestone of entering the second century of metabolic therapies....

Purpose: In this study, we determined ketone oxidation rates in athletes under metabolic conditions of high and low carbohydrate (CHO) and fat availability. Methods: Six healthy male athletes completed 1 h of bicycle ergometer exercise at 75% maximal power (WMax) on three occasions. Prior to exercise, participants consumed 573 mg·kg bw ⁻¹ of a keto...

Chronic Obstructive Pulmonary Disease (COPD) is a debilitating inflammatory respiratory condition that presents with worsening breathing difficulties and it is assumed to be progressive and incurable. As an inflammatory disease, COPD is associated with recruitment of immune cells to lung tissue and increased levels of pro-inflammatory cytokines, in...

BACKGROUND: During hypoxia an operators cognitive performance may decline. This decline is linked to altered brain metabolism, resulting in decreased adenosine triphosphate (ATP) production. Ketone bodies are an alternative substrate to glucose for brain metabolic requirements; previous studies have shown that the presence of elevated ketone bodies...

Nutritional ketosis is a state of mildly elevated blood ketone concentrations resulting from dietary changes (e.g., fasting or reduced carbohydrate intake) or exogenous ketone consumption. In this study, we determined the tolerability and safety of a novel exogenous ketone diester, bis-hexanoyl-(R)-1,3-butanediol (BH-BD), in a 28-day, randomized, d...

A series of studies was conducted to assess the genetic toxicity of a novel ketone ester, bis hexanoyl (R)-1,3-butanediol (herein referred to as BH-BD), according to Organization for Economic Co-operation and Development testing guidelines under the standards of Good Laboratory Practices. In bacterial reverse mutation tests, there was no evidence o...

Bis-hexanoyl (R)-1,3-butanediol (BH-BD) is novel ketone ester undergoing development as a food ingredient to achieve nutritional ketosis in humans. Male and female Crl:CD(SD) rats were administered BH-BD twice daily at 9,000, 12,000 or 15,000 mg/kg/day, by oral gavage in a 90-day toxicity study with 28-day recovery period; and an interim 28-day pha...

A novel ketone ester, bis hexanoyl (R)-1,3-butanediol (BH-BD), has been developed as a means to elevate blood ketones, for use as an energy substrate and a signaling metabolite. The metabolism of BH-BD and its effects on blood beta-hydroxybutyrate (BHB) levels was evaluated in various in vitro matrices and through analysis of plasma collected from...

Ketone bodies are endogenous metabolites that are linked to multiple mechanisms of aging and resilience. They are produced by the body when glucose availability is low, including during fasting and dietary carbohydrate restriction, but also can be consumed as exogenous ketone compounds. Along with supplying energy to peripheral tissues such as brai...

Respiratory viral infections remain a scourge, with seasonal influenza infecting millions and killing many thousands annually and viral pandemics, such as COVID-19, recurring every decade. Age, cardiovascular disease, and diabetes mellitus are risk factors for severe disease and death from viral infection. Immunometabolic therapies for these popula...

A new study in mice reveals time-dependent effects of a ketogenic diet on resident immune cells in visceral adipose tissue, which have consequences for whole-body metabolic homeostasis.

Ketone bodies are a promising area of neuroprotection research that may be ideally suited to the injured newborn. During normal development, the human infant is in significant ketosis for at least the first week of life. Ketone uptake and metabolism is upregulated in the both the fetus and neonate, with ketone bodies providing at least 10% of cereb...

Exogenous ketone drinks may improve athletic performance and recovery, but information on their gastrointestinal tolerability is limited. Studies to date have used a simplistic reporting methodology that inadequately represents symptom type, frequency, and severity. Herein, gastrointestinal symptoms were recorded during three studies of exogenous k...

Apart from acting as an alternative energy source in oxidative tissues, including muscle, ketone bodies regulate the metabolism of other substrates, but are cataplerotic. Glycogen can be mobilised for anaplerosis, regenerating Krebs cycle intermediates, thus glycogen availability may affect the hearts’ ability to oxidise ketone bodies. We hypothesi...

Rationale The oxidation of ketone bodies plus glucose improves the efficiency of the working rat heart by ~30% compared to glucose alone.¹ However, perfusions of hearts with ketones alone led to gradual functional decline with reduced flux through α-ketoglutarate dehydrogenase.² We have shown that that the rate of d-β-hydroxybutyrate (βHB) oxidatio...