Fat and carbohydrate are the major fuel sources utilised for oxidative, mitochondrial ATP resynthesis during human skeletal muscle contraction. The relative contribution of these two substrates to ATP resynthesis and total energy expenditure during exercise can vary substantially, and is predominantly determined by fuel availability and exercise intensity and duration. For example, the increased ATP demand that occurs with an increase in exercise intensity is met by increases in both fat and carbohydrate oxidation up to an intensity of approximately 60–70 % of maximal oxygen consumption. When exercise intensity increases beyond this workload, skeletal muscle carbohydrate utilisation is accelerated, which results in a reduction and inhibition of the relative and absolute contribution of fat oxidation to total energy expenditure. However, the precise mechanisms regulating muscle fuel selection and underpinning the decline in fat oxidation remain unclear. This brief review will primarily address the theory that a carbohydrate flux-mediated reduction in the availability of muscle carnitine to the mitochondrial enzyme carnitine palmitoyltransferase 1, a rate-limiting step in mitochondrial fat translocation, is a key mechanism for the decline in fat oxidation during high-intensity exercise. This is discussed in relation to recent work in this area investigating fuel metabolism at various exercise intensities and taking advantage of the discovery that skeletal muscle carnitine content can be nutritionally increased in vivo in human subjects.

Although obesity has now been widely accepted to be an important risk factor for cancer survival, the associations between BMI and cancer mortality have not been consistently linear. Although morbid obesity has clearly been associated with worse survival, some studies have suggested a U-shaped association with no adverse association with overweight or lower levels of obesity. This ‘obesity paradox’ may be due to the fact that BMI likely incompletely captures key measures of body composition, including distribution of skeletal muscle and adipose tissue. Fat and lean body mass can be measured using clinically acquired computed tomography scans. Many of the earlier studies focused on patients with metastatic cancer. However, skeletal muscle loss in the metastatic setting may reflect end-stage disease processes. Therefore, this article focuses on the clinical implication of low skeletal muscle mass in early-stage non-metastatic breast and colorectal cancer where measures of body composition have been shown to be strong predictors of disease-free survival and overall survival and also chemotherapy toxicity and operative risk.

Newly diagnosed cancer patients are frequently found suffering from a metastatic disease, which poses additional challenges to the delivery of effective therapies. Chemotherapy and radiotherapy are associated with side effects which reduce tolerance to treatment and likelihood of tumour response. Identifying preventable factors of reduced response to therapy would translate into better care of cancer patients. Among other factors, malnutrition, as diagnosed by non-volitional weight loss, and cachexia, as revealed by sarcopenia, are universally recognised negative prognostic factors. Less certainty exists on the role of nutrition therapy in improving cancer patients’ body composition and clinical outcome. The reasons for the lack of convincing evidence are manifold, mostly related to the poor design of nutritional trials. Metastatic cancer patients should receive a quantitatively and qualitatively adequate diet, and in case of reduced tolerance of food, artificial nutrition is indicated. Most importantly, nutritional care should target the underlying mechanisms of reduced food intake/impaired anabolic response, and aim at minimising the impact of catabolic crisis, to maximise the recovery phase. The combined and early use of supplemental energies and proteins, as well as modulators of inflammatory response has been shown to improve nutritional status and may also benefit clinical outcome. When part of early palliative care, nutrition therapy improves cancer patients’ quality of life and may prolong survival at a fraction of the costs of developing new drugs.

Life on earth has evolved during the past several billion years under relatively bright days and dark night conditions. The wide-spread adoption of electric lights during the past century exposed animals, both human and non-human, to significant light at night for the first time in their evolutionary history. Endogenous circadian clocks depend on light to entrain to the external daily environment and seasonal rhythms depend on clear nightly melatonin signals to assess time of year. Thus, light at night can derange temporal adaptations. Indeed, disruption of naturally evolved light–dark cycles results in several physiological and behavioural changes with potentially serious implications for physiology, behaviour and mood. In this review, data from night-shift workers on their elevated risk for metabolic disorders, as well as data from animal studies will be discussed. Night-shift workers are predisposed to obesity and dysregulated metabolism that may result from disrupted circadian rhythms. Although studies in human subjects are correlative, animal studies have revealed several mechanisms through which light at night may exert its effects on metabolism by disrupting circadian rhythms that are associated with inflammation, both in the brain and in the periphery. Disruption of the typical timing of food intake is a key effect of light at night and subsequent metabolic dysregulation. Strategies to avoid the effects of light at night on body mass dysregulation should be pursued.

The age-related loss of skeletal muscle mass and function is caused, at least in part, by a reduced muscle protein synthetic response to protein ingestion. The magnitude and duration of the postprandial muscle protein synthetic response to ingested protein is dependent on the quantity and quality of the protein consumed. This review characterises the anabolic properties of animal-derived and plant-based dietary protein sources in older adults. While approximately 60 % of dietary protein consumed worldwide is derived from plant sources, plant-based proteins generally exhibit lower digestibility, lower leucine content and deficiencies in certain essential amino acids such as lysine and methionine, which compromise the availability of a complete amino acid profile required for muscle protein synthesis. Based on currently available scientific evidence, animal-derived proteins may be considered more anabolic than plant-based protein sources. However, the production and consumption of animal-derived protein sources is associated with higher greenhouse gas emissions, while plant-based protein sources may be considered more environmentally sustainable. Theoretically, the lower anabolic capacity of plant-based proteins can be compensated for by ingesting a greater dose of protein or by combining various plant-based proteins to provide a more favourable amino acid profile. In addition, leucine co-ingestion can further augment the postprandial muscle protein synthetic response. Finally, prior exercise or n-3 fatty acid supplementation have been shown to sensitise skeletal muscle to the anabolic properties of dietary protein. Applying one or more of these strategies may support the maintenance of muscle mass with ageing when diets rich in plant-based protein are consumed.

CVD are characterised by a multi-factorial pathogenesis. Key pathogenetic steps in the development of CVD are the occurrence of endothelial dysfunction and formation of atherosclerotic lesions. Reduced nitric oxide (NO) bioavailability is a primary event in the initiation of the atherosclerotic cascade. NO is a free radical with multiple physiological functions including the regulation of vascular resistance, coagulation, immunity and oxidative metabolism. The synthesis of NO proceeds via two distinct pathways identified as enzymatic and non-enzymatic. The former involves the conversion of arginine into NO by the NO synthases, whilst the latter comprises a two-step reducing process converting inorganic nitrate $({\rm NO}_3^ - )$ into nitrite and subsequently NO.

Inorganic ${\rm NO}_3^ - $ is present in water and food, particularly beetroot and green leafy vegetables. Several investigations have therefore used the non-enzymatic NO pathway as a target for nutritional supplementation (${\rm NO}_3^ - $ salts) or dietary interventions (high-${\rm NO}_3^ - $ foods) to increase NO bioavailability and impact on cardiovascular outcomes. Some studies have reported positive effects of dietary ${\rm NO}_3^ - $ on systolic blood pressure and endothelial function in patients with hypertension and chronic heart failure. Nevertheless, results have been inconsistent and the size of the effect appears to be declining in older individuals. Additionally, there is a paucity of studies for disorders such as diabetes, CHD and chronic kidney failure. Thus, whilst dietary ${\rm NO}_3^ - $ supplementation could represent an effective and viable strategy for the primary and secondary prevention of age-related cardiovascular and metabolic diseases, more large-scale, robust studies are awaited to confirm or refute this notion.

Globally, an estimated 46 million people are currently living with dementia and this figure is projected to increase 3-fold by 2050, highlighting this major public health concern and its substantial associated healthcare costs. With pharmacological treatment yet to reach fruition, the emphasis on evidence-based preventative lifestyle strategies is becoming increasingly important and several modifiable lifestyle factors have been identified that may preserve cognitive health. These include good cardiovascular health, physical activity, low alcohol intake, smoking and a healthy diet, with growing interest in vitamin D. The aim of the present paper is to review the evidence supporting the potential roles of vitamin D in ageing and cognitive health in community-dwelling older adults. Furthermore, to describe the utility and challenges of cognitive assessments and outcomes when investigating vitamin D in this context. Evidence indicates that serum 25-hydroxyvitamin D (25(OH)D) may impact brain health. There is a biological plausibility from animal models that vitamin D may influence neurodegenerative disorders, through several mechanisms. Epidemiological evidence supports associations between low serum 25(OH)D concentrations and poorer cognitive performance in community-dwelling older populations, although an optimal 25(OH)D level for cognitive health could not be determined. The effect of raising 25(OH)D concentrations on cognitive function remains unclear, as there is a paucity of interventional evidence. At a minimum, it seems prudent to aim to prevent vitamin D deficiency in older adults, with other known common protective lifestyle factors, as a viable component of brain health strategies.

By virtue of reducing dietary energy density, low-calorie sweeteners (LCS) can be expected to decrease overall energy intake and thereby decrease body weight. Such effects will be limited by the amount of sugar replaced by LCS, and the dynamics of appetite and weight control (e.g., acute compensatory eating, and an increase in appetite and decrease in energy expenditure accompanying weight loss). Consistent with these predictions, short-term intervention studies show incomplete compensation for the consumption of LCS v. sugar, and longer-term intervention studies (from 4 weeks to 40 months duration) show small decreases in energy intake and body weight with LCS v. sugar. Despite this evidence, there are claims that LCS undermine weight management. Three claims are that: (1) LCS disrupt the learned control of energy intake (sweet taste confusion hypothesis); (2) exposure to sweetness increases desire for sweetness (sweet tooth hypothesis); (3) consumers might consciously overcompensate for ‘calories saved’ when they know they are consuming LCS (conscious overcompensation hypothesis). None of these claims stands up to close examination. In any case, the results of the intervention studies comparing LCS v. sugar indicate that the effect of energy dilution outweighs any tendency LCS might conceivably have to increase energy intake.

Cancer-associated malnutrition is driven by reduced dietary intake and by underlying metabolic changes (such as inflammation, anabolic resistance, proteolysis, lipolysis and futile cycling) induced by the tumour and activated immune cells. Cytotoxic and targeted chemotherapies also elicit proteolysis and lipolysis at the tissue level. In this review, we summarise specific mediators and chemotherapy effects that provoke excess proteolysis in muscle and excess lipolysis in adipose tissue. A nutritionally relevant question is whether and to what degree these catabolic changes can be reversed by nutritional therapy. In skeletal muscle, tumour factors and chemotherapy drugs activate intracellular signals that result in the suppression of protein synthesis and activation of a transcriptional programme leading to autophagy and degradation of myofibrillar proteins. Cancer nutrition therapy is intended to ensure adequate provision of energy fuels and a complete repertoire of biosynthetic building blocks. There is some promising evidence that cancer- and chemotherapy-associated metabolic alterations may also be corrected by certain individual nutrients. The amino acids leucine and arginine provided in the diet at least partially reverse anabolic suppression in muscle, while n-3 PUFA inhibit the transcriptional activation of muscle catabolism. Optimal conditions for exploiting these anabolic and anti-catabolic effects are currently under study, with the overall aim of net improvements in muscle mass, functionality, performance status and treatment tolerance.

Due to increased longevity, women can expect to live more than one-third of their lives in a post-menopausal state, which is characterised by low circulating levels of oestrogen and progesterone. The aim of this review is to provide insights into current knowledge of the effect of female hormones (or lack of female hormones) on skeletal muscle protein turnover at rest and in response to exercise. This review is primarily based on data from human trials. Many elderly post-menopausal women experience physical disabilities and loss of independence related to sarcopenia, which reduces life quality and is associated with substantial financial costs. Resistance training and dietary optimisation can counteract or at least decelerate the degenerative ageing process, but lack of oestrogen in post-menopausal women may reduce their sensitivity to these anabolic stimuli and accelerate muscle loss. Tendons and ligaments are also affected by sex hormones, but the effect seems to differ between endogenous and exogenous female hormones. Furthermore, the effect seems to depend on the age, and as a result influence the biomechanical properties of the ligaments and tendons differentially. Based on the present knowledge oestrogen seems to play a significant role with regard to skeletal muscle protein turnover. Therefore, oestrogen/hormonal replacement therapy may counteract the degenerative changes in skeletal muscle. Nevertheless, there is a need for greater insight into the direct and indirect mechanistic effects of female hormones before any evidence-based recommendations regarding type, dose, duration and timing of hormone replacement therapy can be provided.