Circadian rhythms, metabolic processes and dietary intake are inextricably linked. Timing of food intake is a modifiable temporal cue for the circadian system and may be influenced by numerous factors, including individual chronotype – an indicator of an individual’s circadian rhythm in relation to the light–dark cycle. This scoping review examines temporal patterns of eating across chronotypes and assesses tools that have been used to collect data on temporal patterns of eating and chronotype. A systematic search identified thirty-six studies in which aspects of temporal patterns of eating, including meal timings; meal skipping; energy distribution across the day; meal frequency; time interval between meals, or meals and wake/sleep times; midpoint of food/energy intake; meal regularity; and duration of eating window, were presented in relation to chronotype. Findings indicate that, compared with morning chronotypes, evening chronotypes tend to skip meals more frequently, have later mealtimes, and distribute greater energy intake towards later times of the day. More studies should explore the difference in meal regularity and duration of eating window amongst chronotypes. Currently, tools used in collecting data on chronotype and temporal patterns of eating are varied, limiting the direct comparison of findings between studies. Development of a standardised assessment tool will allow future studies to confidently compare findings to inform the development and assessment of guidelines that provide recommendations on temporal patterns of eating for optimal health.

The cardiometabolic syndrome (MetS) is a clustering of related metabolic abnormalities including abdominal adiposity, insulin resistance, hypertension, dyslipidaemia and increased inflammatory and thrombotic markers, which is linked to increased risk of type 2 diabetes, CVD and overall mortality. Several cross-sectional and prospective studies have shown an association between low vitamin D status, as indicated by concentrations of serum 25-hydroxyvitamin D (s25(OH)D), and increased prevalence of the MetS and individual CVD risk factors. These epidemiological observations are supported by mechanistic studies but experimental data are limited. The available data from intervention studies are largely confounded as most vitamin D supplementation trials were mainly carried out to explore the role of Ca in CVD and include Ca in the treatment arms. Inadequate consideration of seasonal effects on s25(OH)D concentrations is also a common design flaw in most studies. Further complications arise from shared risk factors such as adiposity and ageing, which predispose individuals to exhibit both a more pronounced risk profile and relatively lower s25(OH)D concentrations. In conclusion, while epidemiological associations are promising and a rationale for low vitamin D status as a potentially modifiable risk factor for CVD is supported by mechanistic data, suitable experimental data from appropriately designed trials are just beginning to emerge. As yet, this body of literature is too immature to draw firm conclusions on the role of vitamin D in CVD prevention. Carefully controlled vitamin D trials in well-described population groups using intervention doses that are titrated against target s25(OH)D concentrations could yield potentially valuable outcomes that may have a positive impact on CVD risk modification.

Evolutionary medicine acknowledges that many chronic degenerative diseases result from conflicts between our rapidly changing environment, our dietary habits included, and our genome, which has remained virtually unchanged since the Palaeolithic era. Reconstruction of the diet before the Agricultural and Industrial Revolutions is therefore indicated, but hampered by the ongoing debate on our ancestors' ecological niche. Arguments and their counterarguments regarding evolutionary medicine are updated and the evidence for the long-reigning hypothesis of human evolution on the arid savanna is weighed against the hypothesis that man evolved in the proximity of water. Evidence from various disciplines is discussed, including the study of palaeo-environments, comparative anatomy, biogeochemistry, archaeology, anthropology, (patho)physiology and epidemiology. Although our ancestors had much lower life expectancies, the current evidence does neither support the misconception that during the Palaeolithic there were no elderly nor that they had poor health. Rather than rejecting the possibility of ‘healthy ageing’, the default assumption should be that healthy ageing posed an evolutionary advantage for human survival. There is ample evidence that our ancestors lived in a land–water ecosystem and extracted a substantial part of their diets from both terrestrial and aquatic resources. Rather than rejecting this possibility by lack of evidence, the default assumption should be that hominins, living in coastal ecosystems with catchable aquatic resources, consumed these resources. Finally, the composition and merits of so-called ‘Palaeolithic diets’, based on different hominin niche-reconstructions, are evaluated. The benefits of these diets illustrate that it is time to incorporate this knowledge into dietary recommendations.

Heart failure (HF) is a complex clinical syndrome that represents a major cause of morbidity and mortality in Western countries. Several nutraceuticals have shown interesting clinical results in HF prevention as well as in the treatment of the early stages of the disease, alone or in combination with pharmacological therapy. The aim of the present expert opinion position paper is to summarise the available clinical evidence on the role of phytochemicals in HF prevention and/or treatment that might be considered in those patients not treated optimally as well as in those with low therapy adherence. The level of evidence and the strength of recommendation of particular HF treatment options were weighed up and graded according to predefined scales. A systematic search strategy was developed to identify trials in PubMed (January 1970 to June 2019). The terms ‘nutraceuticals’, ‘dietary supplements’, ‘herbal drug’ and ‘heart failure’ or ‘left verntricular dysfunction’ were used in the literature search. The experts discussed and agreed on the recommendation levels. Available clinical trials reported that the intake of some nutraceuticals (hawthorn, coenzyme Q10, l-carnitine, d-ribose, carnosine, vitamin D, probiotics, n-3 PUFA and beet nitrates) might be associated with improvements in self-perceived quality of life and/or functional parameters such as left ventricular ejection fraction, stroke volume and cardiac output in HF patients, with minimal or no side effects. Those benefits tended to be greater in earlier HF stages. Available clinical evidence supports the usefulness of supplementation with some nutraceuticals to improve HF management in addition to evidence-based pharmacological therapy.

Interaction between a healthy microbiome and the immune system leads to body homeostasis, as dysbiosis in microbiome content and loss of diversity may result in disease development. Due to the ability of probiotics to help and modify microbiome constitution, probiotics are now widely used for the prevention and treatment of different gastrointestinal, inflammatory, and, more recently, respiratory diseases. In this regard, chronic respiratory diseases including chronic obstructive pulmonary disease (COPD), asthma and allergic rhinitis are among the most common and complicated respiratory diseases with no specific treatment until now. Accordingly, many studies have evaluated the therapeutic efficacy of probiotic administration (mostly via the oral route and much lesser nasal route) on chronic respiratory diseases. We tried to summarise and evaluate these studies to give a perspective of probiotic therapy via both the oral and nasal routes for respiratory infections (in general) and chronic respiratory diseases (specifically). We finally concluded that probiotics might be useful for allergic diseases. For asthmatic patients, probiotics can modulate serum cytokines and IgE and decrease eosinophilia, but with no significant reduction in clinical symptoms. For COPD, only limited studies were found with uncertain clinical efficacy. For intranasal administration, although some studies propose more efficiency than the oral route, more clinical evaluations are warranted.

Although stearic acid is a saturated fatty acid, its influence on plasma cholesterol acid other health variables is neutral; possibly owing in part to poor absorption. Reduced absorption of stearic acid from particular triacylglycerols, cocoa butter and novel fats formulated with short- and long-chain acid triacylglycerol molecules (Salatrims) has been attributed to high intakes. However, the circumstances and causes of poor stearic acid digestion from triacylglycerols are unclear; published data were therefore collected and analysed, with emphasis on human studies. Of twenty-eight studies conducted in adults, most are in men (>90%). The assertion that reduced absorption is due to a high intake of stearoyl groups is not supported: dietary intakes of stearoyl of 0·05–0·65 g stearic acid equivalent/kg body weight (cf typical intake of 0·2 g stearic acid equivalent/kg body weight in the Western diet) indicate that the ‘true’ digestibility of stearoyl is 0·98 (SE 0·01) g/g, with apparent digestibility less than this value at low intakes owing to endogenous stearic acid excretion and to inter-publication variation of unidentified cause. The neutral health impact of stearic acid must be due to factors other than availability. Exceptions include cocoa butter, Salatrims and tristearin, for which digestibility is an additional factor. The efficiency with which human subjects digest stearoyl from cocoa butter still remains uncertain, while the digestion of total long-chain fat from this source is 0·89–0·95 g/g, high in comparison with 0·33 g/g for Salatrim 23CA and 0·15 g/g for tristearin in their prepared states. Salatrims contain the highest proportion of long-chain fatty acids that are stearic acid-rich other than tristearin, which is the main component of fully-hydrogenated soyabean and rapeseed oil. Analysis shows that apparent digestibility of stearic acid is associated with stearoyl density within the triacylglycerol molecule and that, in Salatrims, the occurrence of short-chain fatty acids in place of long-chain fatty acids increases this density. Soap formation appears not to be a major factor in the reduced digestion of stearic acid from tristearin under regular dietary circumstances, but both microcrystallinity and reduced digestibility of tri-, di- and monostearoylglycerols appears to be important. Solubilisation of high-melting-point tristearin in low-melting-point oils improves the digestibility of its stearic acid, particularly when emulsified or liquidized at above melting point. However, without such artificial aids, the digestive tracts of the rat, dog and man have a low capacity for emulsifying and digesting stearic acid from tristearin. Reduced digestibility of stearic acid from Salatrim 23CA also appears to be attributable to reduced digestibility of di- and monostearoylglycerols and is particularly due to remnants with the 1- or 3-stearoylglycerol intact after initial hydrolytic cleavage. Short-chain organic acid in Salatrim 23CA, which is readily hydrolysed, leaves such remnants. Unlike tristearin, Salatrim 23CA melts at body temperature and mixing it with low-melting-point oils is not expected to cause further disruption of microcrystalline structures to aid digestibility of its stearoyl groups. The low digestibility of stearoyl in Salatrim 23CA, together with the occurrence of short-chain organic acids in this product, account for its relatively low nutritional energy value (about 20 kJ (5 kcal)/g) compared with traditional fats (37 kJ (9 kcal)/g) and low fat value (<20:37 kJ/kJ; <5:9 kcal/kcal) relative to traditional fats. In part these differences are because of minor effects of Salatrim 23CA on the excretion of other fat and protein, due to the bulking properties of this poorly-digestible fat.

Epidemiological evidence consistently shows that diets high in fresh fruit and vegetables significantly lower cancer risk. Given the postulated role of oxidative DNA damage in carcinogenesis, the assumption has been made that it is the antioxidant properties of food constituents, such as vitamin C, E and carotenoids, which confer protection. However, epidemiological studies with specific antioxidants, either singly or in combination, have not, on the whole, supported this hypothesis. In contrast, studies examining the in vitro effect of antioxidants upon oxidative DNA damage have generally been supportive, in terms of preventing damage induction. The same, however, cannot be said for the in vivo intervention studies where overall the results have been equivocal. Nevertheless, recent work has suggested that some dietary antioxidants may confer protective properties through a novel mechanism, unrelated to their conventional free-radical scavenging abilities. Upregulation of antioxidant defence, xenobiotic metabolism, or DNA-repair genes may all limit cellular damage and hence promote maintenance of cell integrity. However, until further work has clarified whether dietary supplementation with antioxidants confers a reduced risk of cancer and the mechanism by which this effect is exerted, the recommendation for a diet rich in fruit and vegetables remains valid empirically.

Increasing clinical and experimental evidence accumulated during the past few decades supports an important role for dietary advanced glycation endproducts (AGE) in the pathogenesis of many chronic non-infectious diseases, such as type 2 diabetes, CVD and others, that are reaching epidemic proportions in the Western world. Although AGE are compounds widely recognised as generated in excess in the body in diabetic patients, the potential importance of exogenous AGE, mostly of dietary origin, has been largely ignored in the general nutrition audience. In the present review we aim to describe dietary AGE, their mechanisms of formation and absorption into the body as well as their main mechanisms of action. We will present in detail current evidence of their potential role in the development of several chronic non-infectious clinical conditions, some general suggestions on how to restrict them in the diet and evidence regarding the potential benefits of lowering their consumption.

The last few decades have witnessed a global rise in the number of older individuals. Despite this demographic shift, morbidity within this population group is high. Many factors influence healthspan; however, an obesity pandemic is emerging as a significant determinant of older people’s health. It is well established that obesity adversely affects several metabolic systems. However, due to its close association with overall cardiometabolic health, the impact that obesity has on cholesterol metabolism needs to be recognised. The aim of the present review is to critically discuss the effects that obesity has on cholesterol metabolism and to reveal its significance for healthy ageing.

Hormesis defines an effect where exposure to a low dose of a toxic agent results in a beneficial response. It has been described in organisms exposed to low-dose radiation, heat stress, and chemicals. The effect is characterised by a J-shaped dose–response as opposed to a linear dose–response. Confirmation of the general phenomena of hormesis has proved difficult due to the lack of appropriate methodology and the absence of well-defined mechanisms to support the experimental observations. In the nutritional field there are few reports of its existence. The clearest illustration of the effect is seen in animals that are energy restricted when there is a clear benefit in the reduction of age-related disease, and an extension of maximum lifespan. DNA microarray experiments have shown that there is a down regulation of the stress-response genes that are up regulated through the ageing process. Electrophilic phytochemicals, that have been shown to have beneficial health effects at low doses, up regulate the antioxidant–electrophile response element. This probably occurs through an alteration in the redox state of the target cells which causes activation of protein kinases, the activation of the Nrf2 transcription factor and the up regulation of the phase II enzymes, similar to responses that occur under mild chemical stress. This situation might enable organisms to adapt to stress such that the effects of a subsequent exposure to a harmful challenge are reduced. There may be a permanent alteration in cellular homeostasis, or redox state, if the low level exposure is maintained. It remains to be proven if such a situation occurs in response to chronic low-dose exposure to dietary phytochemicals such that the target cells are better able to respond to a subsequent stress challenge.

Iodine deficiency affects an estimated 241 million school-aged children in the world. Little is known about iodine deficiency in relation to auditory function, except for the fact that deaf–mutism is one of the features of cretinism. In the present review, we documented the scientific knowledge on the role of iodine and hypothyroidism in the auditory system. We found that ear development and hearing function depend on thyroid hormones. Multiple pathways are involved in this, including both inner ear morphology as well as neurological processes. Conductive as well as sensorineural hearing loss is found in studies with animals that were rendered hypothyroidic. In humans, auditory impairment is reported frequently in relation to hypothyroidism, ranging from mild disturbances to severe handicap. Auditory impairment has been related more explicitly to congenital hypothyroidism than to acquired hypothyroidism. The critical period for thyroid function-related hearing maturation is the first and second trimesters of pregnancy. Although only a limited number of studies have directly investigated the relationship between iodine deficiency and auditory function, most studies point toward an association. However, evidence from good randomised controlled trials is lacking. Inclusion of auditory outcomes in iodine supplementation studies is therefore to be recommended, especially for trials in pregnancy. Hearing deficit is an invisible abnormality, but has major consequences for educational and social skills if not detected. In view of this, auditory impairment should be mapped in iodine-deficient areas in order to realistically estimate the magnitude of the problem.

The theory, in brief outline here, implicating deficiency of Cu in the aetiology and pathophysiology of IHD explains more attributes of the disease than any other theory. This theory satisfies several of Hill’s criteria of a half-century ago for deducing association between an environmental feature and presence of an illness. Most important is the temporal association between the rise of IHD and the decrease in dietary Cu since the 1930s along with a parallel increase in the supplementation of pregnant women with Fe, a Cu antagonist. There are more than eighty anatomical, chemical and physiological similarities between animals deficient in Cu and individuals with IHD. Few of these similarities have been produced by other dietary manipulations because feeding cholesterol induces Cu deficiency in animals. The most recent of these to be identified is decreased serum dehydroepiandrosterone. Some concomitant aspects of Cu metabolism and utilisation have been identified in other theories about heart disease: fetal programming, homocysteine, and Fe overload.

Vitamin E (α-, β-, γ- and δ-tocopherol and -tocotrienol) is an essential factor in the human diet and regularly taken as a dietary supplement by many people, who act under the assumption that it may be good for their health and can do no harm. With the publication of meta-analyses reporting increased mortality in persons taking vitamin E supplements, the safety of the micronutrient was questioned and interactions with prescription drugs were suggested as one potentially underlying mechanism. Here, we review the evidence in the scientific literature for adverse vitamin E–drug interactions and discuss the potential of each of the eight vitamin E congeners to alter the activity of drugs. In summary, there is no evidence from animal models or randomised controlled human trials to suggest that the intake of tocopherols and tocotrienols at nutritionally relevant doses may cause adverse nutrient–drug interactions. Consumption of high-dose vitamin E supplements ( ≥  300 mg/d), however, may lead to interactions with the drugs aspirin, warfarin, tamoxifen and cyclosporine A that may alter their activities. For the majority of drugs, however, interactions with vitamin E, even at high doses, have not been observed and are thus unlikely.

N and S metabolisms are closely interwoven throughout both the plant and animal kingdoms. The essentiality of S relates to its participation in the structure of S-containing amino acids (SAA), to its inclusion in many sulfonated molecules, and to a myriad of metabolic and catalytic reactions of vital importance. Methionine (Met) is the indispensable SAA supplied by food proteins and its plasma homeostasis is achieved via a number of highly efficient regulatory mechanisms. In all conditions characterised by a negative body protein balance such as in dietary restriction or cytokine-induced hypercatabolic losses, N and S endogenous pools manifest parallel tissue depletion rates. Adaptive conservation of N and S body stores is reached by a functional restraint of the trans-sulfuration cascade, through the depression of cystathionine β-synthase activity. As a result, upstream accumulation of homocysteine favours its re-methylation conversion to Met which helps maintain metabolic pathways of survival value. In addition to the measurement of vitamin indices, that of plasma transthyretin, a sensitive marker of protein nutritional status, is proposed to identify the fluctuations of the total body N component accountable for the alterations of homocysteine concentrations in body fluids.