The human brain is energetically expensive in adults but even more so during early development. Current models of human brain energy metabolism remain largely glucocentric, with ketone bodies, mainly acetoacetate and β-hydroxybutyrate, often framed as secondary fuels used during fasting, starvation, or metabolic stress in adults. However, this perspective underestimates their physiological importance during early brain development. Here we re-examine the role of ketone bodies in brain development, with emphasis on their contribution to both energy metabolism and lipid synthesis. We performed a narrative synthesis of historical and contemporary literature on ketone uptake, oxidation, and anabolic metabolism in the developing brain, with a focus on studies in humans and animals that are rarely cited today and often poorly accessible online. The available evidence indicates that ketones are a significant substrate for ATP production in the infant brain and an important carbon source for the endogenous synthesis of cholesterol and fatty acids required for brain lipid formation. Impaired ketone availability, transport, or utilization may represent an underrecognized contributor to altered neurodevelopment and vulnerability to neurological and psychiatric disorders. Nutritional ketosis should therefore not be viewed only as an emergency metabolic state, but as a physiological feature of human brain development with therapeutic relevance across neurological and psychiatric disease.
In the early 1990s it was first proposed that the long-chain omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may have therapeutic potential in depression. This suggestion was supported by observational studies reporting an association between low dietary omega-3 PUFA intake and increased risk of depression and lower omega-3 PUFA blood levels in those with depression. DHA, EPA, and their bioactive lipid mediators operate via multiple overlapping and independent mechanisms of action, and some of these mechanisms have the potential to improve depressive symptoms, such as enhancing neuroplasticity, modulating of the endocannabinoid system, and exerting anti-inflammatory and proresolving effects. However, although numerous clinical trials and their subsequent meta-analyses have investigated their efficacy, the results have been mixed and inconsistent. These inconsistencies likely stem from heterogeneity and limitations in the design of the clinical trials, including mixed study populations, small sample sizes, lack of appreciation of the differences between DHA and EPA, inappropriate placebo comparators, and a lack of applied standardized diagnostic criteria. This review explores the divergent effects of DHA and EPA on neuroplasticity and inflammation and identifies under which conditions long-chain omega-3 PUFAs may provide the greatest therapeutic effects in depression.
Glucosinolates (GSLs) from Brassica carinata press cake are of interest both as antinutritional factors to be removed from feed and as precursors of bioactive compounds for biocontrol, but their selective recovery must contend with the dual constraints of myrosinase activity and protein preservation. This study investigates hydro-ethanolic extraction and miscella concentration at laboratory and pilot scales on industrial-type press cakes and finely milled powders. At laboratory scale, when press cake was ground, fully dispersed in solvent and extracted after thermal myrosinase inactivation, GSL yields above 90% were achieved with low residual levels in the final meal, showing that neither diffusion nor thermal degradation is an intrinsic barrier. In contrast, pilot-scale percolation on intact cakes plateaued at about 70% overall recovery, with roughly 30% of initial GSLs remaining in spent cakes despite extended extraction times and high solvent-to-solid ratios, highlighting strong mass-transfer and percolation limitations. Incomplete myrosinase inactivation further caused substantial and variable GSL losses, particularly during miscella concentration, where up to 60–70% of solubilized GSLs could no longer be accounted for under some evaporation conditions. Clarification of extracts by centrifugation prior to evaporation allowed miscella concentration without measurable additional losses in selected trials. Overall, a carinata-based GSL “biorefinery brick” appears technically feasible only within a very narrow operating window and at a processing cost that is difficult to justify for bulk feed applications, unless high-value outlets for GSL-rich fractions can be secured.
Oil-in-water emulsions, emulgels, and bigels are options in the pharmaceutical and cosmetic fields for formulating highly valued vegetable oils, such as those extracted from sacha inchi. Nonetheless, the stability of these heterodisperse systems is an issue of particular attention to avoid concerns about the safety and efficacy of the final products. To provide a comparative view of the physical and primary oxidative stability of emulsions, emulgels, and bigels, this research was conducted, maintaining the same qualitative composition across all samples while varying the amounts of the starting materials and the preparation method. The obtained behaviors are analyzed in light of the systems’ microstructure, which is investigated by polarized light microscopy, conductivity measurements, IR spectroscopy, and theoretical analyses based on the Hansen solubility parameters and Karger parameters. The uniformity in emulsions' microstructure versus the formation of oily phase aggregates aleatorily dispersed in the aqueous phase in emulgels and bigels makes emulsions the least stable systems, exhibiting stability indices of 152 min against 9467 min and 11541 min for bigels and emulgels, respectively. Including glycerol in the aqueous phase promotes more organized microstructures, favoring stability indices of emulsions but not of emulgels and bigels. The reduction in water activity by 0.2 units when adding glycerol, compared with formulations without glycerol, does not seem to affect the primary oxidative stability during storage at 30 °C ± 2 °C and 40 °C ± 2 °C for 3 months. These findings contribute to understanding these kinds of heterodisperse systems, which is of great importance for their galenic development.
Stroke and dementia are among the leading causes of disability. They confer risks for each other and share some of the same, largely modifiable, risk and protective factors. This prompted international, expert-driven calls for the joint prevention of stroke and dementia. There is increasing evidence of the link between diet and brain aging. A large body of research has focused on omega-3 fatty acids, with a special interest in docosahexaenoic acid (DHA), a critical element of brain membranes. Preclinical research uncovered a myriad of effects of DHA and other omega-3 fatty acids that slow down the pathological continuum of stroke and dementia. However, there is still a gap with clinical research, mostly caused by the slow, silent evolution of both diseases. Advances in structural neuroimaging have fueled research on the topic by helping in detecting subtle brain changes that take place years (or even decades) before the clinical onset of stroke/dementia. A few randomized controlled trials tested whether dietary supplementation with omega-3 reduces brain vulnerability as assessed by magnetic resonance imaging. However, key challenges remain. Besides methodological heterogeneity, small sample sizes limit power, and follow-up durations may be too short to detect meaningful structural neuroanatomical changes. Leveraging well-powered, deep-phenotyped ( i.e ., extensively characterized with detailed clinical, biological, and/or lifestyle data) prospective longitudinal cohorts allows circumventing these caveats. This narrative review gathers the most relevant evidence on omega-3 biomarkers (which objectively reflect omega-3 dietary intake and metabolism) and structural neuroimaging, with emphasis on cerebrovascular and neurodegenerative phenotypes.
