Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), ␤-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mildto-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight-and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed.

Background: Ketones are the brain's main alternative fuel to glucose. Dietary medium-chain triglyceride (MCT) supplements increase plasma ketones, but their ketogenic efficacy relative to coconut oil (CO) is not clear. Objective: The aim was to compare the acute ketogenic effects of the following test oils in healthy adults: coconut oil [CO; 3% tricaprylin (C8), 5% tricaprin (C10)], classical MCT oil (C8-C10; 55% C8, 35% C10), C8 (>95% C8), C10 (>95% C10), or CO mixed 50:50 with C8-C10 or C8. Methods: In a crossover design, 9 participants with mean ± SD ages 34 ± 12 y received two 20-mL doses of the test oils prepared as an emulsion in 250 mL lactose-free skim milk. During the control (CTL) test, participants received only the milk vehicle. The first test dose was taken with breakfast and the second was taken at noon but without lunch. Blood was sampled every 30 min over 8 h for plasma acetoacetate and β-hydroxybutyrate (β-HB) analysis. Results: C8 was the most ketogenic test oil with a day-long mean ± SEM of +295 ± 155 µmol/L above the CTL. C8 alone induced the highest plasma ketones expressed as the areas under the curve (AUCs) for 0–4 and 4–8 h (780 ± 426 µmol ⋅ h/L and 1876 ± 772 µmol ⋅ h/L, respectively); these values were 813% and 870% higher than CTL values (P < 0.01). CO plasma ketones peaked at +200 µmol/L, or 25% of the C8 ketone peak. The acetoacetate-to-β-HB ratio increased 56% more after CO than after C8 after both doses. Conclusions: In healthy adults, C8 alone had the highest net ketogenic effect over 8 h, but induced only half the increase in the acetoacetate-to-β-HB ratio compared with CO. Optimizing the type of MCT may help in developing ketogenic supplements designed to counteract deteriorating brain glucose uptake associated with aging. This trial was registered at clinicaltrials.gov as NCT 02679222.

No abstract

The results obtained from this study suggest the following: The concentration of total serum proteins in mice is changed very little under the various treatments, while protein fractions showed significant alterations.The concentrations of various serum proteins remain almost constant under normal conditions. Intraperitoneal administration of imidazole or benzimidazle at the mentioned doses induces rapid quantitative changes in the serum which are recovered in about 3 days after injection.Whole-body X-irradiation at 750 r creates slow but progressive and persisting serious changes in concentration of serum protein fractions which end in death of animals 8 -10 days after ir radiation.Whole-body X-irradiation of imidazole or benzimidazole protected animals results in quantitative rapid changes in concentration of serum protein fractions for about four days. There after a slow but steady restoration begins. The concentration approaches the normal levels towards the 10th day after irradiation.Imidazole and benzimidazole proved to be good radioprotectants against the effects of X-radiation on serum protein fractions. Benzimidazole seems to surpass imidazole.Because of the potential practical importance of certatin chemical compounds that exhibit a protec tive character against lethal effects of ionizing ra diation, excessive work has been done to identify the most effective non-toxic ones. Since P a t t et a l . 1 reported that the amino acid, cysteine, signicantly increased the survival of irradiated rats, thousands of agents have been tested, T h o m s o n 2. Repeated investigations have been also carried out to study the mechanism through which such compounds m ani fest their protective effects. It seems likely, however, that all those compounds exert their effects by in fluencing the production of reactive radicals by radiation. The protection of the vital cellular func tions is thus achieved either by production of hy poxia, i. e. reduction of oxygenation in tissues, or through reaction with the free radicals released by radiation to inactivate them. The biological diffi culty with the application of these compounds in general is that they appear to be effective only at close to toxic levels. Moreover, almost none of these agents has been shown to be of benefit when given after radiation exposure. Most of the experiments were carried out on mice. The increase in 30 day survival has been usually taken as a parameter to assume that the protectant is effective in changing