Published Science

DR. JOHN RAE, F.R.S., whose death we announced last week, was perhaps the most persevering and successful of the Arctic travellers by land whose journeys called forth the admiration of the world forty years ago. He was a native of Orkney, born in 1813, and studied medicine at Edinburgh, where he qualified in 1833. Rae was early brought face to face with his life-work, his first engagement on leaving college being as surgeon to the Hudson Bay Company's ship which carried supplies to the fur-forts in Hudson Bay. He entered the service of the company, and for ten years lived at Moose Factory, gaining familiarity with Arctic life during the severe winters. In 1845 his true career as an Arctic explorer began in his undertaking the leadership of a small expedition to explore a considerable extent of the coast-line of the Arctic Sea. In June, 1846, he set out on this expedition from York Factory, coasted along the west side of Hudson Bay, and wintered on the shore of Repulse Bay. Early in 1847 he made an extensive land journey to the north and west, with the result that 700 miles of new coast were surveyed, almost filling the gap between Ross's work in Boothia and Parry's at Fury and Hecla strait. In 1850 Dr. Rae published an account of this expedition in the form of a book of 250 pages. This was, curiously enough, his only permanent contribution to geographical literature, his subsequent journeys being recorded merely in formal reports published in the Journal of the Royal Geographical Society. After this journey Rae came to London,but was almost immediately induced to join the first land expedition sent to seek for Sir John Franklin, under the leadership of Sir John Richardson. The expedition was unsuccessful as to its primary purpose of finding traces of Franklin, but it effected a satisfactory survey of the whole coast between the Mackenzie and Coppermine rivers. In 1851 Rae received the command of another boat expedition for the Hudson Bay Company, in the course of which he thoroughly explored and mapped the south coast of Wollaston Land and Victoria Land, still searching vainly for traces of Franklin's party. On his return from this arduous undertaking, which he conducted throughout with conspicuous daring and sagacity, he had to travel on snow-shoes, and himself dragging a sledge, across the whole length of Canada from the Arctic Sea, through Fort Garry (now Winnipeg) until he reached United States territory. His total walking on this expedition was over 5000 miles, of which 700 miles were traversed for the first time. On returning to England in 1852 the gold medal of the Royal Geographical Society was presented to him by Sir Roderick Murchison in a speech, the cordial terms of which showed how fully Dr. Rae's genius for Arctic travel with the minimum of equipment and at infinitesimal expense was appreciated by the highest authorities. In no wise deterred by the hardships of his earlier campaigns, Rae left England early in 1853 to continue his work in the far north; the Hudson Bay Company equipping an expedition on condition that he would lead it personally. He completed the survey of King William's Land on this occasion, proving it to be an island; 1100 miles of sledging were accomplished in the process, of which 400 miles were new discovery. But the really important result of this expedition was Dr. Rae's meeting with the first evidence of Sir John Franklin's fate, from the story of a party of wandering Eskimo. The tribe encountered were in possession of many personal relics of members of that ill-fated expedition, which Rae secured and brought home. When he returned to England with the news so long searched for and so anxiously awaited, the Admiralty, which had spent large sums in fitting out successive expeditions,concluded that the fate of Franklin was decided beyond a doubt, and accordingly awarded to Dr. Rae the sum of £10,000 offered by Government to the first who brought back decisive information. The justice of this award was at the time strongly objected to by Lady Franklin, and although no further action was taken by Government she continued to organise private expeditions, which, while proving in effect the correctness of Dr. Rae's information from the Eskimo, served in no small degree to advance the geographical survey of the polar area.

The aim of this study was to examine the effect of three different fatty acid (FA)-rich meals enriched in either saturated (SFA), monounsaturated (MUFA), or polyunsaturated (PUFA) on postprandial metabolic responses in premenopausal, normal weight women. For this randomized, single-blind, crossover study three high-fat (HF) meals rich in either SFA, MUFA, or PUFA (65% energy from fat; 35% of participants’ total daily energy needs) were tested. For each visit, anthropometrics and resting metabolic rate were measured following a 12-15h fast. Then, participants consumed one of the HF meals and respiratory gases were collected using indirect calorimetry for 3h postprandially. Energy expenditure (EE) following a SFA-rich meal was a significantly higher than a MUFA-rich meal (p=0.04; η2 = .19) but SFA was not significantly different from PUFA. There was a trend towards significance in EE between PUFA and MUFA (p=0.06). After adjusting for fat-free mass (FFM), there were no longer condition or time effects for EE, although FFM remained a significant predictor (p=0.005; η2=.45). There were no significant differences between conditions for dietary induced thermogenesis (DIT) or substrate oxidation. A relationship between fat-mass (FM) and both total fat oxidation (r=.62; p=0.025) and total change in respiratory exchange ratio following a MUFA-rich meal, was observed (r=-.55; p=0.05). In conclusion, weight loss through increases in EE may be best achieved by increasing FFM rather than selection of FA type. Further, a relationship exists between FM and fat oxidation following a MUFA-rich meal, most likely due to an unidentified mechanism.

Previous investigations have mostly studied an individual methyl donor nutrient in relation to psychological disorders and the findings were inconsistent. We investigated the association of methyl donor micronutrients (folate, B6, B12, choline, betaine, and methionine) with psychological disorders (depression, anxiety, psychological distress) in Iranian adults. In this cross-sectional study, dietary intakes of 3299 adults were collected using a validated food frequency questionnaire. Methyl donor micronutrient score (MDMS) was calculated based on energy-adjusted deciles of each nutrient. Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire (GHQ), validated for Iranians, have been applied to assess depression, anxiety, and psychological distress. Participants had a mean age of 36.3±7.9 years, of whom 58.5% were women. After considering potential confounders, adults in the top quartile of MDMS, compared to the bottom one, had decreased odds of anxiety (OR: 0.53, 95%CI: 0.37–0.75), depression (OR: 0.75, 95%CI: 0.58–0.97) and psychological distress (OR: 0.61, 95%CI: 0.46–0.80). Stratified analysis revealed that the highest category of MDMS among men was related to a 68% lower odds of anxiety (95%CI: 0.15–0.68). Among women, the top quartile of MDMS was protectively associated with anxiety (OR: 0.60, 95%CI: 0.40–0.90), depression (OR: 0.68, 95%CI: 0.50–0.93) and psychological distress (OR: 0.53, 95%CI: 0.38–0.74). Overweight and obese subjects in the highest quartile of MDMS had a 67%, 35%, and 53% lower odds of anxiety (95%CI: 0.20–0.56), depression (95%CI: 0.44–0.94), and psychological distress (95%CI: 0.31–0.70), respectively. We found that high consumption of methyl donor micronutrients was related to a reduced odds of psychological disorders, especially in women and overweight or obese individuals. Further prospective studies are needed to affirm these findings.

Objective:Limiting SFA intake may minimise the risk of CHD. However, such reduction often leads to increased intake of carbohydrates. We aimed to evaluate associations and the interplay of carbohydrate and SFA intake on CHD risk.Design:Prospective cohort study.Setting:We followed participants in the Hordaland Health Study, Norway from 1997–1999 through 2009. Information on carbohydrate and SFA intake was obtained from a FFQ and analysed as continuous and categorical (quartiles) variables. Multivariable Cox regression estimated hazard ratios (HR) and 95 % CI. Theoretical substitution analyses modelled the substitution of carbohydrates with other nutrients. CHD was defined as fatal or non-fatal CHD (ICD9 codes 410–414 and ICD10 codes I20–I25).Participants:2995 men and women, aged 46–49 years.Results:Adjusting for age, sex, energy intake, physical activity and smoking, SFA was associated with lower risk (HRQ4 v. Q1 0·44, 95 % CI 0·26, 0·76, Ptrend = 0·002). For carbohydrates, the opposite pattern was observed (HRQ4 v. Q1 2·10, 95 % CI 1·22, 3·63, Ptrend = 0·003). SFA from cheese was associated with lower CHD risk (HRQ4 v. Q1 0·44, 95 % CI 0·24, 0·83, Ptrend = 0·006), while there were no associations between SFA from other food items and CHD. A 5 E% substitution of carbohydrates with total fat, but not SFA, was associated with lower CHD risk (HR 0·75, 95 % CI 0·62, 0·90).Conclusions:Higher intake of predominantly high glycaemic carbohydrates and lower intake of SFA, specifically lower intake from cheese, were associated with higher CHD risk. Substituting carbohydrates with total fat, but not SFA, was associated with significantly lower risk of CHD.

Alzheimer’s disease (AD) is the most common major neurocognitive disorder of aging. Although largely ignored until about a decade ago, accumulating evidence suggests that deteriorating brain energy metabolism plays a key role in the development and/or progression of AD-associated cognitive decline. Brain glucose hypometabolism is a well-established biomarker in AD but was mostly assumed to be a consequence of neuronal dysfunction and death. However, its presence in cognitively asymptomatic populations at higher risk of AD strongly suggests that it is actually a pre-symptomatic component in the development of AD. The question then arises as to whether progressive AD-related cognitive decline could be prevented or slowed down by correcting or bypassing this progressive ‘brain energy gap’. In this review, we provide an overview of research on brain glucose and ketone metabolism in AD and its prodromal condition – mild cognitive impairment (MCI) - to provide a clearer basis for proposing keto-therapeutics as a strategy for brain energy rescue in AD. We also discuss studies using ketogenic interventions and their impact on plasma ketone levels, brain energetics and cognitive performance in MCI and AD. Given that exercise has several overlapping metabolic effects with ketones, we propose that in combination these two approaches might be synergistic for brain health during aging. As cause-and-effect relationships between the different hallmarks of AD are emerging, further research efforts should focus on optimizing the efficacy, acceptability and accessibility of keto-therapeutics in AD and populations at risk of AD.

This study investigated metabolic, endocrine, appetite, and mood responses to a maximal eating occasion in fourteen men (mean ±SD: age 28 ±5 y, body mass 77.2 ±6.6 kg, body mass index 24.2 ±2.2 kg·m-2) who completed two trials in a randomised crossover design. On each occasion participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until ‘comfortably full’ (ad libitum) and on the other until they ‘could not eat another bite’ (maximal). Mean [95% CI] energy intake was double in the maximal (13,024 [10964, 15084] kJ; 3113 [2620,3605] kcal) compared with the ad libitum trial (6627 [5708,7547] kJ; 1584 [1364,1804] kcal). Serum insulin iAUC increased ~1.5-fold in the maximal compared with ad libitum trial (mean [95% CI] ad libitum 51.1 [33.3,69.0] nmol·L-1·4 h, maximal 78.8 [55.0,102.6] nmol·L-1·4 h, p < 0.01), but glucose iAUC did not differ between trials (ad libitum 94.3 [30.3,158.2] mmol·L-1·4 h, maximal 126.5 [76.9,176.0] mmol·L-1·4 h, p = 0.19). TAG iAUC was ~1.5-fold greater in the maximal versus ad libitum trial (ad libitum 98.6 [69.9,127.2] mmol·L-1·4 h, maximal 146.4 [88.6,204.1] mmol·L-1·4 h, p < 0.01). Total GLP-1, GIP, and PYY iAUC were greater in the maximal compared with ad libitum trial (p

On 7 September 1191, a fierce battle took place in Arsuf (Palestine) between the Crusaders (marching south towards Jerusalem) led by King Richard the Lionheart and the Ayyubid army commanded by the sultan Saladin. The confrontation lasted for most of the day and terminated with a victory of the Crusaders, proving Richard’s courage as a soldier and his skill as a commander while denting Saladin’s reputation as an invincible warrior. The site (today known as Apollonia) holds the ruins of a Crusader castle perched on a cliff over the sea. We recovered plenty of pottery shards among which we could distinguish those of the Crusaders from those of the Ayyubid army. Extraction of food remnants confirmed that the Crusaders’ diet consisted mostly of pig and sheep meat (together with cheese), with a minimum of carbohydrates (what today would be termed a “ketogenic” diet), whereas the Muslim army consumed mostly carbohydrates (wheat, Triticum durum, Hordeum vulgare), together with fruits and vegetables, with minimal levels of sheep meat and cheese. As a result, the Crusaders’ diet had a positive effect on their slenderness and “cardio”. This might have been why the Ayyubid army lost ca. 10 times more soldiers in Arsuf. Shrewdness of leaders and soldiers’ equipment and willingness to fight are, of course, the main ingredients of victory, but diet too might not have a secondary role and help to tip the balance.

Pancreatic cancer (PC) is one of the most lethal diseases, with a 5‑year survival rate of

Ketogenic diet (KD) and pulsatile dexamethasone therapy (PDT) are commonly used in the treatment of children with drug resistant epilepsy. Potential side effects of the KD are hypoglycemia, whereas PDT might lead to hyperglycemia. One practical option to measure glucose concentrations regularly is the flash glucose monitoring system (FGM). In this single-center study in Germany, two pediatric patients with epilepsy (age: 6.0 and 6.8 years) received FGM from the beginning of the KD over six months, in the year 2020, and one patient (9.8 years) was observed for one month on PDT and switched to the KD thereafter. Glucose concentrations were measured by using an FGM system and capillary blood measurement. Seizure frequency, changes in cognition, motor performance, social behavior, and sleep quality were evaluated. The mean hypoglycemia rate per day (65 mg/dL and lower) declined significantly in patient 1 and 2 after three months. Patient 3 showed in total seven hyperglycemic events during PDT. Patient 1 became seizure free. Improvement of attention and memory performance were reported. FGM during the KD as a treatment for drug resistant epilepsies in childhood is a practical option to explore and to avoid hypoglycemia during the KD and hyperglycemia during PDT.