Polycystic Ovary Syndrome (PCOS) is a common hormonal condition affecting women of reproductive age(1). Women with PCOS experience a broad range of clinical symptoms, collectively grouped into reproductive, metabolic, psychological and anthropometric features(2). Complementary therapies, such as nutrient supplementation, have been identified as potential adjunct therapeutic approaches to support currently recommended lifestyle and pharmacological interventions(3). However, evidence for their overall efficacy and safety is inconsistent and unclear. This review aimed to systematically map the available literature on the use of nutrient supplementation for the management of PCOS features, including metabolic, reproductive, psychological and anthropometric. This review followed a systematic approach with literature searches using CINHAL, Cochrane reviews, Medline, PsycINFO, Scopus and LILACS conducted up to April 2022. All types of study designs were included if they reported on the efficacy or association between micronutrient supplementation and/or nutraceuticals on features of PCOS in women (≥ 18 years) with a confirmed diagnosis of PCOS. A total of 317 articles were included involving n = 23,926 women. Forty-three different supplements examined various clinical features of PCOS grouped into metabolic, reproductive, psychological and anthropometric. The most studied supplements included Inositols (n = 83), Vitamin D (n = 51), N-acetylcysteine (n = 25), Omega-3 fatty acids (n = 18) and Biotics (n = 14). Most studies (n = 262; 83%) reported on reproductive features followed by metabolic (n = 212; 66%), anthropometric (n = 181; 57%) and psychological (n = 5; 2%). Less than half (n = 148; 47%) of the included studies reported on the potential for adverse events. Our results highlight that the potential therapeutic benefit of micronutrient and nutraceutical supplementation on psychological features of PCOS warrants future exploration. Additional primary studies that are adequately powered are needed to investigate therapeutic doses needed for clinical benefits. Lastly, a more rigorous approach to monitoring and recording adverse event data is recommended.

The in vitro effects of four nutraceuticals, catechin hydrate, gallic acid, α-tocopherol and ascorbic acid, on the ability of human osteoarthritic chondrocytes of two female obese groups to form articular cartilage (AC) tissues and to reduce inflammation were investigated. Group 1 represented thirteen females in the 50–69 years old range, an average weight of 100 kg and an average body mass index (BMI) of 34⋅06 kg/m2. Group 2 was constituted of three females in the 70–80 years old range, an average weight of 75 kg and an average BMI of 31⋅43 kg/m2. The efficacy of nutraceuticals was assessed in monolayer cultures using histological, colorimetric and mRNA gene expression analyses. AC engineered tissues of group 1 produced less total collagen and COL2A1 (38-fold), and higher COL10A1 (2⋅7-fold), MMP13 (50-fold) and NOS2 (15-fold) mRNA levels than those of group 2. In comparison, engineered tissues of group 1 had a significant decrease in NO levels from day 1 to day 21 (2⋅6-fold), as well as higher mRNA levels of FOXO1 (2-fold) and TNFAIP6 (16-fold) compared to group 2. Catechin hydrate decreased NO levels significantly in group 1 (1⋅5-fold) while increasing NO levels significantly in group 2 (3⋅8-fold). No differences from the negative control were observed in the presence of other nutraceuticals for either group. In conclusion, engineered tissues of the younger but heavier patients responded better to nutraceuticals than those from the older but leaner study participants. Finally, cells of group 2 formed better AC tissues with less inflammation and better extracellular matrix than cells of group 1.

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.

Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.

A mixture of natural ingredients, namely, DHA, phosphatidylcholine, silymarin, choline, curcumin and d-α-tocopherol, was studied in subjects with non-alcoholic fatty liver disease (NAFLD). Primary endpoints were serum levels of hepatic enzymes, and other parameters of liver function, the metabolic syndrome and inflammation were the secondary endpoints. The coagulation–fibrinolysis balance was also thoroughly investigated, as NAFLD is associated with haemostatic alterations, which might contribute to increased cardiovascular risk of this condition. The present study involved a double-blind, randomised, multicentre controlled trial of two parallel groups. Subjects with NAFLD (18–80 years, either sex) received the active or control treatment for 3 months. All assays were performed on a total of 113 subjects before and at the end of supplementation. The hepatic enzymes aspartate aminotransferase (AST), alanine aminotransferase and γ-glutamyl transpeptidase decreased from 23·2 to 3·7 % after treatment, only the AST levels reaching statistical significance. However, no differences were found between control and active groups. Metabolic and inflammatory variables were unchanged, except for a slight (less than 10 %) increase in cholesterol and glucose levels after the active treatment. Coagulation–fibrinolytic parameters were unaffected by either treatment. In conclusion, chronic supplementation with the mixture of dietary compounds was well tolerated and apparently safe in NAFLD subjects. The trial failed to demonstrate any efficacy on relevant physiopathological markers, but its protocol and results may be useful to design future studies with natural compounds.

Nutraceuticals have generated interest as a way to mitigate the cognitive decline in older adults. The aim of this systematic review was to determine the evidence for these claims from the scientific literature in randomised, double-blinded, controlled trials (duration: ≥1 year; participants: n≥100; age(mean): ≥65 years). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched four electronic databases (PubMed, Scopus, CINAHL and Web of Science) and identified twenty-five studies published between the 15·June·2006 and 14·June·2016. Interventions included B-vitamins, n-3 fatty acids, antioxidant vitamins and herbs. Of the B-vitamin studies, four found benefits to cognition with supplementation. The first of these B-vitamin studies, in individuals with mild cognitive impairment (n 266; duration=2 years), included benefit to executive function (P=0·015) and improvements in the Mini-Mental State Examination (MMSE) among participants with baseline homocysteine above 11·3 µmol/l (P<0·001). In the same sample, the second study found cognitive benefits of B-vitamins dependent on the higher baseline plasma n-3 fatty acid status. The third B-vitamin study (n 900; duration=2 years) reported improved performance in immediate (P=0·046) and delayed recall (P=0·013), whereas the fourth study (n 856; duration=2 years) reported slower rate of cognitive decline in the MMSE (P=0·05). One study investigating DHA treatment (n 402; duration=1·5 years) revealed the slower rate of cognitive change in apoE e4 non-carriers (P=0·03). As only five included studies revealed notable benefits, presently based on the specific compounds explored here, there is not compelling evidence to support the use nutraceuticals to improve cognition in the elderly. Future long-term trials of nutraceuticals should investigate interactions with lifestyle, blood biomarkers and genetic risk factors.

Flavonoids are polyphenolic compounds that are widespread in nature, and consumed as part of the human diet in significant amounts. The aim of the present study was to test the intestinal anti-inflammatory activity of apigenin K, a soluble form of apigenin, in two models of rat colitis, namely the trinitrobenzenesulfonic acid (TNBS) model and the dextran sulphate sodium (DSS) model. Apigenin K (1, 3 and 10 mg/kg; by the oral route; n 4–6 per group) was administered as a pre-treatment to rats with TNBS and DSS colitis, and colonic status was checked by macroscopic and biochemical examination. Apigenin K pre-treatment resulted in the amelioration of morphological signs and biochemical markers in the TNBS model. The results demonstrated a reduction in the inflamed area, as well as lower values of score and colonic weight:length ratio compared with the TNBS group. Myeloperoxidase (MPO) activity was reduced by 30 % (P< 0·05). Moreover, apigenin K pre-treatment ameliorated morphological signs and biochemical markers in the DSS model. Thus, macroscopic damage was significantly reduced and the colonic weight:length ratio was lowered by approximately 10 %, while colonic MPO and alkaline phosphatase activities were decreased by 35 and 21 %, respectively (P< 0·05). Apigenin K pre-treatment also tended to normalise the expression of a number of colonic inflammatory markers (e.g. TNF-α, transforming growth factor-β, IL-6, intercellular adhesion molecule 1 or chemokine (C–C motif) ligand 2). In conclusion, apigenin K is found to have anti-inflammatory effects in two preclinical models of inflammatory bowel disease.

Over the last decade the concept of functional foods and nutraceuticals (FFN) has gained support from various stakeholders including the food industry, scientific and academic community, government institutions or regulators, producers and consumers. However, as one begins to evaluate the global FFN industry, several issues emerge including (i) a lack of consensus across jurisdictions for acknowledging safe and efficacious FFN, (ii) challenges regarding the classification of novel food-derived bioactives as FFN or drugs, and (iii) a disconnect between nutrient requirements and dosages of FFN required to facilitate health benefits. The objectives of the present review are to discuss the role of existing stakeholders within the FFN marketplace and identify performance indicators for growth within the FFN sector. In addition, the following report provides feasible resolutions to present and future challenges facing the global FFN industry to ensure sustained long-term growth.

The Berlin Twin Registry has its focus on health research. It is operated as a private company, making twin studies available to academic institutions as well as commercial partners in the area of biotechnology and nutrition. Recruitment is based on invitation in the context of mass media coverage of scientific results. Phenotyping in the unselected twin subjects is directed toward intermediate phenotypes that can bear on common diseases. These phenotypes include proteomic approaches and gene expression. Some results are briefly described to give an impression of the range of research topics and related opportunities for retrospective and prospective collaborative research.

Over a decade of intense research in the field of obesity has led to the knowledge that chronic, excessive adipose tissue expansion leads to an increase in the risk for CVD, type 2 diabetes mellitus and cancer. This is primarily thought to stem from the low-grade, systemic inflammatory response syndrome that characterises adipose tissue in obesity, and this itself is thought to arise from the complex interplay of factors including metabolic endotoxaemia, increased plasma NEFA, hypertrophic adipocytes and localised hypoxia. Plasma concentrations of vitamins and antioxidants are lower in obese individuals than in the non-obese, which is hypothesised to negatively affect the development of inflammation and disease in obesity. This paper provides a review of the current literature investigating the potential of nutraceuticals to ameliorate the development of oxidative stress and inflammation in obesity, thereby limiting the onset of obesity complications. Research has found nutraceuticals able to positively modulate the activity of adipocyte cell lines and further positive effects have been found in other aspects of pathogenic obesity. While their ability to affect weight loss is still controversial, it is clear that they have a great potential to reverse the development of overweight and obesity-related comorbidities; this, however, still requires much research especially that utilising well-structured randomised controlled trials.

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status, and a regulator of energy balance at both the cellular and whole body levels. Although ubiquitously expressed, its function is best understood in skeletal muscle. AMPK contains sites that reversibly bind AMP or ATP, with an increase in cellular AMP:ATP ratio (signalling a fall in cellular energy status) switching on the kinase. In muscle, AMPK activation is therefore triggered by sustained contraction, and appears to be particularly important in the metabolic changes that occur in the transition from resistance to endurance exercise. Once activated, AMPK switches on catabolic processes that generate ATP, while switching off energy-requiring processes not essential in the short term. Thus, it acutely activates glucose uptake (by promoting translocation of the transporter GLUT4 to the membrane) and fatty acid oxidation, while switching off glycogen synthesis and protein synthesis (the later via inactivation of the mammalian target-of-rapamycin pathway). Prolonged AMPK activation also causes some of the chronic adaptations to endurance exercise, such as increased GLUT4 expression and mitochondrial biogenesis. AMPK contains a glycogen-binding domain that causes a sub-fraction to bind to the surface of the glycogen particle, and it can inhibit glycogen synthesis by phosphorylating glycogen synthase. We have shown that AMPK is inhibited by exposed non-reducing ends in glycogen. We are working on the hypothesis that this ensures that glycogen synthesis is rapidly activated when glycogen becomes depleted after exercise, but is switched off again as soon as glycogen stores are replenished.

A food can be regarded as ‘functional’ if it can demonstrate a beneficial efficacy on one or more target functions in the body in a convincing way. Beyond adequate nutritional qualities, functional foods should either improve the state of health and wellbeing and/or reduce the risk of disease. Functional foods that are marketed with claims of heart disease reduction focus primarily on the major risk factors, i.e. cholesterol, diabetes and hypertension. Some of the most innovative products are designed to be enriched with ‘protective’ ingredients, believed to reduce risk. They may contain, for example, soluble fibre (from oat and psyllium), useful both for lowering cholesterol and blood pressure, or fructans, effective in diabetes. Phytosterols and stanols lower LDL-cholesterol in a dose-dependent manner. Soya protein is more hypocholesterolaemic in subjects with very high initial cholesterol and recent data indicate also favourable activities in the metabolic syndrome. n-3 Fatty acids appear to exert significant hypotriacylglycerolaemic effects, possibly partly responsible for their preventive activity. Dark chocolate is gaining much attention for its multifunctional activities, useful both for the prevention of dyslipidaemia as well as hypertension. Finally, consensus opinions about tea and coffee have not emerged yet, and the benefits of vitamin E, garlic, fenugreek and policosanols in the management of dyslipidaemia and prevention of arterial disease are still controversial.

Mushrooms are the fungi that have been used as food since time immemorial. Nutritionally they are a valuable source of health food, which is low in calories, and rich in carbohydrates, essential amino acids, fibre, important vitamins and minerals. Mushrooms have also been used in medicine for centuries in the Orient but their potential as health potentiators and elicitors of immune system is recent. In the last two decades there has been an upsurge on the use of mushrooms as nutraceuticals and many edible species have been thoroughly investigated and authenticated for medicinal use. The species that have been properly analysed for medicinal value are: Ganoderma lucidum (Reishi), Lentinus edodes (Shiitake), Grifola frondosa (Maitake), Agaricus blazei (Hime-matsutake), Cordyceps militaris (Caterpillar fungus), Pleurotus ostreatus (Oyster mushroom) and Hericium erinaceous (Lions mane). There are many more species of cultivated and wild edible and non-edible mushrooms that have been analysed for both their nutritional and nutraceutical components but to a lesser extent than those listed above. The active constituents found in mushrooms are polysaccharides, dietary fibres, oligosaccharides, triterpenoids, peptides and proteins, alcohols and phenols, and mineral elements such as zinc, copper, iodine, selenium and iron, vitamins, amino acids etc. These have been found to boost the immune system, have anti-cancerous properties, act as anti-hypercholesterolaemic and hepato-protective agents, show anti-HIV activity and anti-viral activity, and ameliorate the toxic effect of chemo- and radiotherapy. Many of the species are known to be aphrodisiacs. Many commercial products from these mushrooms are available in the market. Prominent among these are: Lentinan from Lentinus edodes, Concord Sunchih and Reishi Plus from Ganoderma lucidum, Grifon from Grifola frondosa and Didanosine from Cordyceps militaris. The nutraceuticals have been found to relieve the stress and pressure of modern society by stimulating both basic and secondary immune responses of the immune system. There are more than 5000 species of mushrooms recorded from all over the world out of which around 2000 are identified as edible. A large number of the species are yet to be analysed for their nutraceutical/medicinal potential.

Bioactive peptides are specific protein fragments that positively impact the body's function or condition and ultimately may influence health. These peptides are inactive within the sequence of the parent protein and can be released during proteolysis or fermentation. They may exert a number of different activities in vivo, affecting cardiovascular, endocrine, immune and nervous system in addition to nutrient utilization. Hen eggs have traditionally been recognized as an excellent source of protein, vitamins and minerals. Research in the past decade, however, has produced a substantial amount of evidence indicating that hen egg proteins and peptides may exert several diverse biological effects, above and beyond fulfilling basic nutritional requirements. Several biological activities have now been associated with hen egg proteins, including novel antimicrobial activities, immunomodulatory, anti-cancer, and anti-hypertensive activities, highlighting the importance of hen egg proteins in human health, and disease prevention and treatment. Continued research to identify new and existing biological functions of hen egg proteins and their derivatives will help to define new methods to further improve the value of eggs, as a source of numerous biologically active compounds with specific benefits for human and animal health, and secure their role in the therapy and prevention of chronic and infectious disease.

The effect of milks fermented by Lactobacillus helveticus and its non-proteolytic variant on mucosal and tumoral immunity was studied. Milks fermented by Lb. helveticus wild type or its non-proteolytic variant were administered orally to mice for different periods (3, 5 and 7 d). The immune response was assessed by analysing the activity of the peritoneal macrophages, the number of cells secreting IgA associated with the gut-associated lymphoid tissue and with the bronchial-associated lymphoid tissue. The number of cells was determined by direct immunofluorescence. The antitumour activity was monitored by studying the regression of the subcutaneously implanted fibrosarcomas. After 3 d feeding of milk fermented by Lb. helveticus wild type, the number of sIgA increased significantly at both the intestinal and bronchial levels, indicating that a cellular migration had occurred. This effect was not noticeable when milk fermented by Lb. helveticus Protease (−) was orally administered. Both fermented milks (wild type or its variant) exhibited an effect on the activity of the peritoneal macrophages, which might be indirectly correlated to the regression of the fibrosarcoma. Although the mechanism by which the lactic acid bacteria enhance the immune system is not clear, this study clearly suggests that the bioactive compounds released during milk fermentation might contribute to the immunoenhancing properties of these products. By releasing biopeptide, lactic acid bacteria have important implications in modulation of the host's immune response, more specifically its cellular immune response.