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Mushrooms and derivates are well known to the scientific community for having different health benefits and exhibit a wide range of pharmacological activities, including lipid-lowering, antihypertensive, antidiabetic, antimicrobic, antiallergic, anti-inflammatory, anticancer, immunomodulating, neuroprotective and osteoprotective actions. In Europe, medical mushrooms are mainly marketed in the form of food supplements as single components or combined with other nutraceuticals. In this context, the first peculiarity that distinguishes it is the safety established through the "history of consumption" that characterizes that mushroom. However, the cultivation of medicinal mushrooms on a large scale is performed mainly in China, where most of the production facilities do not have internationally recognized good manufacturing practices, despite that many European companies that sell myotherapies are supplied by Chinese manufacturers. This is particularly evident in Italy, where an arsenal of mushroom products is marketed in the form of powders and extracts not always of ascertained origin and sometimes of doubtful taxonomic identification, and thus not meeting the quality criteria required. The growing interest in mycotherapy involves a strong commitment from the scientific community to propose supplements of safe origin and genetic purity as well as to promote clinical trials to evaluate its real effects on humans. The purpose of this research is to analyze different mushroom-based dietary supplements used in medicine as monotherapy on the Italian market and to evaluate their composition and quality. The molecular identification of the sequences with those deposited in GenBank allowed for identifying 6 out of 19 samples, matching with those deposited belonging to the species indicated in the label, i.e., Lentinula edodes (samples 1, 4, 12 and 18) and Ganoderma lucidum (samples 5 and 10). Samples containing Ganoderma, labeled in the commercial product as G. lucidum, showed sequences that showed homology of 100% and 99% with G. resinaceum and G. sichuanense. An additional investigation was carried out in order to determine the active fungal ingredients, such as ergosterol, aflatoxins, heavy metals, nicotine and total glucan. The results obtained and shown in the manuscript highlight how the data were not only in line with what is expected with respect to what is indicated in the labels. [ABSTRACT FROM AUTHOR]

Sarcopenia is a syndrome characterized by a decline in muscular mass, strength, and function with advancing age. The risk of falls, fragility, hospitalization, and death is considerably increased in the senior population due to sarcopenia. Although there is no conclusive evidence for drug treatment, resistance training has been unanimously recognized as a first-line treatment for managing sarcopenia, and numerous studies have also pointed to the combination of nutritional supplementation and resistance training as a more effective intervention to improve quality of life for people with sarcopenia. People with both malnutrition and sarcopenia have a higher mortality rate, so identifying people at risk of malnutrition and intervening early is extremely important to avoid sarcopenia and its associated problems. This article provides important information for dietary interventions in sarcopenia by summarizing the discoveries and developments of nutritional supplements such as protein, leucine, β-hydroxy-β-methylbutyric acid, vitamin D, vitamin C, vitamin E, omega-3 fatty acids, creatine, inorganic nitrate, probiotics, minerals, collagen peptides, and polyphenols in the management of sarcopenia.

Purpose: The word ‘diet’ usually encompasses the consumption of food that includes all the necessary nutrients required for the optimal functioning of the body. Nutritional supplements hold a supreme position due to the demanding lifestyles or medical conditions in this current era. Although medical literature has sufficient evidence exploring the effect of nutrients on general health, this systematic review aimed at specifically evaluating the role of nutritional supplements on oral health in adults. Methods: PRISMA guidelines were followed in conducting this systematic review where four electronic databases including Scopus, PubMed, EMBASE, and Web of Science were reviewed. Based on the inclusion criteria, four studies exploring the effect of oral nutritional supplements on oral health among the adult population were included in this systematic review. Results: This review generated evidence suggesting a positive effect of nutritional supplements on oral health. These findings were depicted in the form of a reduction in plaque scores, probing depths, gingival inflammation, and greater improvement in periodontal healing among individuals with higher intakes of nutritional supplements within recommended doses. Conclusions: The systematic review outlines the positive impact of consuming nutritional supplements in the recommended dosage on oral health. Additionally, this review stresses the necessity for interventional studies to further investigate the effects of nutritional supplements on oral health, particularly in regard to periodontal healing. PROSPERO registration: CRD42021287797 (27/11/2021).

Dietary supplements are widely utilized by cancer patients as part of a complementary and integrative approach to their healthcare. However, a significant portion of patients refrain from discussing their supplement use with their physicians, often due to the perceived indifference or negativity of their healthcare providers. This communication gap exposes patients to unreliable information sources and potential risks associated with uninformed supplementation. As the healthcare landscape evolves, there is an increasing recognition of the pivotal role that physicians play in guiding patients’ healthcare decisions. A patient-centered perspective prioritizes the provision of evidence-based information tailored to the individual’s needs. It advocates for open discussions about potential risks and fosters shared decision making, respecting patient autonomy. Additionally, this approach involves offering alternative options, documenting patient preferences, and ensuring ongoing support while coordinating with the healthcare team. To address these evolving needs, healthcare providers must adopt a transformative perspective, becoming expert guides who engage with their patients as informed and empowered participants. This revised approach emphasizes an open dialogue that balances presenting facts and acknowledging uncertainties surrounding dietary supplement use. Our narrative review of the literature underscores the importance of a practical approach, centered on transparent discussions and respect for patient autonomy. By following this approach, healthcare providers can empower patients to navigate the complexities of dietary supplement use within the context of cancer care, thereby safeguarding patient safety and overall well-being. Notably, our proposed tool highlights the utilization of reliable sources, the risk stratification of supplements, specific recommendations, and subsequent monitoring, providing a structured framework for informed decision making.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that is associated with significant morbidity, mortality, and healthcare costs. The burden of respiratory symptoms and airflow limitation can translate to reduced physical activity, in turn contributing to poor exercise capacity, muscle dysfunction, and body composition abnormalities. These extrapulmonary features of the disease are targeted during pulmonary rehabilitation, which provides patients with tailored therapies to improve the physical and emotional status. Patients with COPD can be divided into metabolic phenotypes, including cachectic, sarcopenic, normal weight, obese, and sarcopenic with hidden obesity. To date, there have been many studies performed investigating the individual effects of exercise training programs as well as nutritional and pharmacological treatments to improve exercise capacity and body composition in patients with COPD. However, little research is available investigating the combined effect of exercise training with nutritional or pharmacological treatments on these outcomes. Therefore, this review focuses on exploring the potential additional beneficial effects of combinations of exercise training and nutritional or pharmacological treatments to target exercise capacity and body composition in patients with COPD with different metabolic phenotypes.

Regular physical activity and the use of nutritional supplements, including antioxidants, are recognized as efficacious approaches for the prevention and mitigation of obesity-related complications. This study investigated the effects of 12 weeks of CrossFit training combined with astaxanthin (ASX) supplementation on some plasma adipokines in males with obesity. Sixty-eight males with obesity (BMI: 33.6 ± 1.4 kg·m−2) were randomly assigned into four groups: the control group (CG; n = 11), ASX supplementation group (SG; n = 11), CrossFit group (TG; n = 11), and training plus supplement group (TSG; n = 11). Participants underwent 12 weeks of supplementation with ASX or placebo (20 mg/day capsule daily), CrossFit training, or a combination of both interventions. Plasma levels of semaphorin 3C (SEMA3C), apelin, chemerin, omentin1, visfatin, resistin, adiponectin, leptin, vaspin, and RBP4 were measured 72 h before the first training session and after the last training session. The plasma levels of all measured adipokines were significantly altered in SG, TG, and TSG groups (p < 0.05). The reduction of resistin was significantly higher in TSG than in SG (p < 0.05). The plasma levels of omentin1 were significantly higher in both training groups of TG and TSG than SG (p < 0.05), although such a meaningful difference was not observed between both training groups (p > 0.05). Significant differences were found in the reductions of plasma levels of vaspin, visfatin, apelin, RBP4, chemerin, and SEMA3C between the SG and TSG groups (p < 0.05). The study found that a 12-week intervention using ASX supplementation and CrossFit exercises resulted in significant improvements in several adipokines among male individuals with obesity. Notably, the combined approach of supplementation and training had the most pronounced results. The findings presented in this study indicate that the supplementation of ASX and participation in CrossFit exercise have the potential to be effective therapies in mitigating complications associated with obesity and enhancing metabolic health.

This study compared the energy, macronutrient, and micronutrient intake in elite and sub-elite Australian football players and compared nutritional intake to current recommendations. Sports nutrition knowledge was also quantified and compared between elite and sub-elite players. Nutritional intake was quantified in elite (n = 35) and sub-elite (n = 31) players using the Automated Self-Administered 24-Hour Dietary Assessment Tool. The 88-item Sports Nutrition Knowledge Questionnaire was used to quantify knowledge related to general nutrition concepts, fluid, recovery, weight control, and supplements. Elite players had a higher nutritional intake (mean ± SD) for energy (14,140 ± 5,887 kJ [elite players] vs 10,412 ± 3,316 kJ [sub-elite players]; P =.002) and fat (40% ± 6% [elite players] vs 34% ± 6% [sub-elite players]; P <.001). Protein intake exceeded the recommended intake in 77% of elite players and 68% of sub-elite players, and carbohydrate intake was below the recommended intake for 91% of elite players and 97% of sub-elite players. Sodium intake recommendations were exceeded by 100% of elite and sub-elite players. Both elite and sub-elite players answered 51% of the Sports Nutrition Knowledge Questionnaire questions correctly. The percentage of correctly answered questions specific to supplements was 27% for elite players and 18% for sub-elite players. The results of the current investigation suggest that Australian football players' nutritional intake is inconsistent with current recommendations for macronutrients and some micronutrients. Furthermore, players may benefit from additional knowledge of the risks and benefits of supplement use. [ABSTRACT FROM AUTHOR]

Summary: Background and aims: Proper nutrition to optimise immune function is mandatory as at present there is no specific medicine to cure COVID-19. Our study aimed to investigate the use of nutritional supplements and their key immunity enhancing components among Sri Lankans. Methods: This current study was an online survey conducted during the period from 27th May to 2nd June 2021 disseminated via various social media platforms. Details were collected on highlighting the frequency and composition of nutritional supplements consumed. Results: In a total of 3707 responders, a proportion of 25.5% (944) of the participants took supplements regularly, and 32.6% (1210), 14.5% (538), 27.4% (1015) intake were occasionally, rarely and never respectively. Older participants (>40 years of age) had a significantly higher intake of supplements than the younger counterpart of 31–35 years age group (OR: 0.604; 95% CI, 0.451–0.809; p < 0.001). Almost half (46.0%) took vitamin C supplements and females tend to take more (OR: 1.325; 95% CI, 1.120–1.567; p < 0.001) of vitamin C when compared to males. Comparatively to the other groups regarding monthly income, the participants with the highest income category are more likely to take vitamin D (OR:1.899; 95% CI, 1.034–3.490; p = 0.039) and multivitamin (OR: 3.222; 95% CI, 1.737–5.977; p < 0.001). The most commonly used main ingredient in home-made remedy was coriander in Sri Lanka. Conclusion: The use of nutritional supplements and natural products to improve immunity during the pandemic were frequent among Sri Lankan adults. In general, older, female gender and high income was significantly associated with increased intake of the nutrient supplements.

IntroductionSeveral studies in developing countries found that more need-based training is required for health care providers (HCPs) in child malnutrition management.MethodsAn exploratory cross-sectional study was conducted to explore barriers to providing adequate nutrition care as perceived by the healthcare providers (HCPs) in the child malnutrition clinic at a Children's University Hospital in Egypt. Participants were selected using the purposive sampling technique. Five out of seven HCPs in the clinic were included (two male physicians, one female physician, and two female nurses). Qualitative data were collected through in-depth interviews. The interview guide consisted of semi-structured open-ended questions. Quantitative data were the resulting scores from the scoring system used to assess the understandability and actionability of the patient education materials (PEMs) that are available in the clinic. The Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P) for the scoring. Statistical analysis: The thematic content analysis technique was employed for qualitative data. The percent score was generated for the PEM actionability and understandability for quantitative data.ResultsMost common child malnutrition conditions encountered by HCPs were nutritional deficiencies. Barriers to the delivery of adequate nutrition care to children were physician-centered: limited nutrition education in the medical school, health system-centered: an insufficient number of HCPs, lack of nutritional supplements, lack of patient education materials (PEMs) that suit the characteristics of the served community, lack of updated standard of practice (SOP) and guidelines, inadequate nutrition training of HCPs, and insufficient time for each patient, and caregivers-centered: the low socioeconomic status and false cultural, nutritional beliefs.ConclusionThere are different barriers to adequate nutrition care for child malnutrition in low-resource healthcare settings. Mainly nutritional deficiencies. Most of the barriers were health system-related in the form of insufficient resources (shortage of workforce; concerning the high caseload, nutritional supplements, and PEMs) and inadequate management of resources (lack of skill-based training, lack of updated SOP and guidelines, and lack of properly designed PEMs that facilitate communication with the target caregivers).

Background: COVID-19 causes moderate to severe illness and is spreading globally. During a pandemic, vitamins and minerals are vital to health. Therefore, the prevalence and epidemiology of supplement use in Saudi Arabia during the COVID-19 pandemic must be known. Methods: This cross-sectional study was conducted in Saudi Arabia using an online survey. The study was conducted from June to March 2022 on both adults and children. The link to the survey was shared on social media platforms. The survey included questions on participants' demographics, vaccination status, supplements they used, and side effects of supplements. Participation in this study was optional, and there was no obligation to participate. There was a declaration about the aim of the study and different objectives before starting the survey. Results: The present study reported that most of the participants reported that they used vitamin C (64.6 %), zinc (51.9 %), multivitamins (46.1 %), black seeds (26.7 %), garlic (Allium sativum) (15.4 %), omega-3 (22.1 %), vitamin D (22.2 %), echinacea (10.1 %), manuka honey (26.0 %), curcumin (13.6 %), ginger (22.5 %), royal jelly (12.9 %), and propolis (7.5 %) before and during the COVID-19 pandemic period. These supplements were used more frequently by subjects during the pandemic than before. Discussion and conclusion: The respondents' risk of these supplements’ use may partially reflect the public's behavioral response during a pandemic. Future studies can document the health beliefs and motivations of nutritional supplement users.

Introduction: The management of refractory immune thrombocytopenia (ITP) is challenging and difficult. The treatment was mainly comprised of cytotoxic and immunosuppressed drugs that rarely lead to long-term remission but potentially cause severe and dangerous side effects. Our current study is a retrospective clinical analysis of refractory ITP patients who underwent phytotherapy as nutritional supplements. Methods: A retrospective clinical analysis of 15 refractory immune thrombocytopenia (ITP) patients aged 12–64 with ITP history for more than 24 months before the enrollments. All patients presented with low platelet count (< 30 × 109/L) and moderate to severe bleeding symptoms such as extensive petechiae, bruising, epistaxis, prolonged menses, rectal bleeding, and hematuria. The patients underwent supportive phytotherapy as nutritional supplements using herbal extracts with hemostatic, immunomodulating, and platelet function augmenting functions Results: The 6-month retrospective clinical evaluation indicated that phytotherapy might offer an effective and safe solution for controlling bleeding symptoms and improving platelet counts for refractory ITP patients. Moreover, phytotherapy also significantly improved patients' red cell count, hemoglobulin, and liver enzyme levels compared to baseline data. Conclusions: In individual cases and economically disadvantaged regions, investigating and applying an appropriate combination of phytotherapy based on scientific knowledge and traditional folk medical experiences might offer an effective, inexpensive, and safe solution for refractory ITP and other bleeding disorders.

Background: The haphazard use of supplements without proper consultation from a health expert can lead to side effects, especially in youngsters. These supplements have very few regulations nationwide, and practically, no effort has been taken to make the public aware of its ill effects, besides warnings issued by the manufacturing companies on the products. Methodology: A cross-sectional study among 2nd -3rd MBBS students studying in a medical college was carried out to study the prevalence of use of supplementary nutrition, its type, source of information, and preferred type of supplements. Results: The overall proportion of dietary supplement use among medical college students participated in this study was 29.4%. Multivitamins, protein powders, and energy drinks were the most preferred type and the reasons mentioned for intake were for general well-being to avoid future illness and muscle-building purpose. Conclusion: More awareness among frequent and haphazard users who are on supplementary nutrition without any medical opinion should be incorporated to avoid side effects created by unregulated nutritional supplements available in market. [ABSTRACT FROM AUTHOR]

To promote the rational use of cabozantinib (CBZ), this paper studied the influence of several nutritional supplements on the interaction between CBZ and bovine serum albumin (BSA), an appropriate alternative model for human serum albumin (HSA) that is one of the important transporter proteins in plasma, by fluorescence spectroscopy and UV–vis spectroscopy. The results showed that CBZ could quench the fluorescence of BSA via a dynamic–static quenching process, and the six nutritional supplements did not change the quenching mode of BSA by CBZ. However, all of them could reduce the binding constant of the CBZ–BSA system at 293 K and increase the polarity around tryptophan residues. Among them, nicotinamide and vitamin B12 (VB12) had a greater effect on the binding constants of the CBZ–BSA system. In the meantime, the thermodynamic parameters of the CBZ–BSA system were examined, indicating that the interaction of CBZ with BSA was spontaneous and dominated by hydrophobic forces. Further research discovered that the combining of CBZ with BSA was primarily located within Site I of BSA, and the binding distance r was 2.48 nm. Consequently, while taking CBZ, patients should use VB12 and nicotinamide carefully, which may interfere with the transport of drugs. [ABSTRACT FROM AUTHOR]

Background: No study has evaluated the effect of macronutrient feedings on golf performance. Aim: Determine the effect of feedings during simulated golf game using a randomized cross-over study design. Methods: Male participants (n = 6, USGA handicap index 8.5 ± 6.72) played three standardized nine-hole rounds, consuming 30 g of carbohydrate, 15 g + 15 g protein and carbohydrate, or a zero-calorie control. Measurements of driving, chipping, and putting distance and accuracy were taken, as well as perceived levels of fatigue and alertness. Results: No relevant differences (P > 0.05) were seen in golf performance or alertness, but self-reported fatigue differed between conditions (P = 0.02), with scores of 2.5 (0.8 to 3.6) for the combination of carbohydrate and protein, 3.0 (1.5 to 4.3) for carbohydrate, and 4.0 (2.9 to 6.5) for the control, with higher levels indicating more fatigue. Conclusion: Macronutrient feedings led to a significantly lower level of self-reported fatigue without affecting golf performance and alertness compared to a control. [ABSTRACT FROM AUTHOR]

With an increase in life expectancy and decrease of quality-of-life couple with the high prevalence of diseases, diet is expected to play a key function in sustaining human health. Nutritionists, food technologists and medical experts are working in synergy to cater for the increasing demand of food with associated therapeutic benefits, commonly known as functional food, that may improve well-being and reduce the risk of diseases. Interestingly, the marine ecosystem, due to its abundant and phenomenal biodiversity of marine organisms, constitutes a vital source of a panoply of healthy foods supply for the thriving functional food industry. Marine organisms such as seaweeds, sea cucumbers, sponges, and mollusks amongst others are sources of thousands of biologically active metabolites with antioxidant, anti-parasitic, antiviral, anti-inflammatory and anticancer properties. Given the growing number of research and interest to probe into the therapeutic roles of marine products, this review was designed to provide a comprehensive summary of the therapeutic properties of marine organisms (macroalgae, sea cucumbers and fish among others) which are consumed worldwide, in addition to their potentials and as sources of functional ingredients for developing novel food and fostering wellness. The gap between research development and actual commercialization, and future prospects of marine-based products also summarized to some extent. [ABSTRACT FROM AUTHOR]

Currently, the nutraceutical approach to treat dyslipidaemia is increasing in use, and in many cases is used by physicians as the first choice in the treatment of patients with borderline values. Nutraceuticals represent an excellent opportunity to treat the preliminary conditions not yet showing the pathological signs of dyslipidaemia. Their general safety, the patient's confidence, the convincing proof of efficacy and the reasonable costs prompted the market of new preparations. Despite this premise, many nutraceutical products are poorly formulated and do not meet the minimum requirements to ensure efficacy in normalizing blood lipid profiles, promoting cardiovascular protection, and normalizing disorders of glycemic metabolism. In this context, bioaccessibility and bioavailability of the active compounds is a crucial issue. Little attention is paid to the proper formulations needed to improve the overall bioavailability of the active molecules. According to these data, many products prove to be insufficient to ensure full enteric absorption. The present review analysed the literature in the field of nutraceuticals for the treatment of dyslipidemia, focusing on resveratrol, red yeast rice, berberine, and plant sterols, which are among the nutraceuticals with the greatest formulation problems, highlighting bioavailability and the most suitable formulations. [ABSTRACT FROM AUTHOR]

The detection of a putative 18‐methyl‐19‐nortestosterone metabolite in a forensic bodybuilder's urine sample collected as part of a criminal proceeding has triggered a follow‐up investigation. Four different dietary supplements in the possession of the suspect were examined with regard to possible precursor steroids. This led to the detection of the declared ingredient methoxydienone, which was confirmed by both, GC–MSMS and LC‐HRMSMS. As neither 18‐methyl‐testosterone, nor 18‐methyl‐19‐nortestosterone were detectable in the supplements, the possibility that the metabolite originates from methoxydienone was investigated. For this purpose, the metabolic fate of methoxydienone was studied in vitro using human HepG2 cells and in vivo by a single oral administration. While the 18‐methyl‐19‐nortestosterone metabolite was not generated by HepG2 cells incubated with methoxydienone, it was observed in the urine samples collected at 2, 6, 10 and 24 h after methoxydienone administration. Moreover, the potential binding of methoxydienone as ligand to the human androgen receptor was modelled in silico in comparison with 18‐methylnandrolone, for which androgen receptor activation had been shown in an in vitro approach before. In conclusion, we could ascribe the presence of the 18‐methyl‐19‐nortestosterone metabolite in a forensic urine sample to originate from methoxydienone present in dietary supplements. Methoxydienone was observed to slowly degrade by demethylation of the methoxy substituent in liquid solutions. While no compound‐specific intermediates were identified that allowed differentiation from other 18‐methyl steroids, the 18‐methyl‐19‐nortestosterone metabolite proved to be a suitable marker for reliable detection in doping analysis. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aims to assess how nutrition can be addressed in the integrative oncology setting, taking into account cancer patients' unmet needs as they relate to nutrition in cancer care and the evidence-based information that is available on this topic. Recent Findings: During and after cancer treatment, nutrition is an important component of supportive care, for patients and their family members. Current scientific data consistently show that poor nutrition can reduce survival and decrease adherence to cancer treatments. Unfortunately, the limited availability of dietitians makes access to individualized nutrition counseling challenging, and many cancer patients still do not receive adequate nutritional support. As a result, one of the main unmet needs of patients and their families through the whole cancer trajectory is accessible and up-to-date evidence-based nutritional counseling that emphasizes basic healthy nutrition. The popularity of complementary and integrative medicine among patients with cancer makes the integrative oncology setting an excellent avenue for providing such support. A suggested simple approach that utilizes World Cancer Research Fund/American Institute for Cancer Research and American Cancer Society basic information is described. This approach can be easily incorporated into integrative oncology settings, while reserving the role for the registered dietician to address underweight patients, patients with malnutrition, and patients with more complicated dietary situations. Summary: The integrative oncology setting is in a unique place in oncology that can be utilized for enhancing dissemination of healthy nutrition information and addressing the unmet needs expressed by patients and families. [ABSTRACT FROM AUTHOR]

Aims: With this study; it was aimed to determine the use of various medications or nutritional supplements to support immune system and opinions, usage status and attitudes towards the drugs currently used / recommended for the treatment of COVID-19, and the factors affecting drug use during the COVID-19 pandemic according to the condition of having COVID-19. Methods: The descriptive research was conducted in Family Medicine outpatient clinics. Data were collected with a questionnaire prepared by the researchers through the internet (sites on social media) due to the pandemic. The e-questionnaire form was shared on the internet a total of 10 times at 6-day intervals. Results: 1484 people participated, 60.8% were female, 51.5% was a healthcare professional. While 23.3% had a known disease; 19.3% of them had COVID-19 infection, 79% of them received outpatient medication. Although not recommended, it was observed that the most used drugs were Vitamin C and antipyretic drugs, followed by vitamin D and antibiotics. 87.5% who have had COVID-19 infection stated that they used the drugs as suggested/written on to them. The reasons of those who did not use drugs: fear of its side effects, not seeing it necessary, using herbal products and observing and using it if necessary. People who had live a person under the age of 18 living in the same household (p=0.042), who had a chronical disease (p=0.014) and who were regularly drug users (p=0.003) were reported that they used drugs as suggested / written on them. Conclusion: Infodemic causes the spread of false information about the disease and its treat-ment both among the public and in scientific circles. The results of our study also support this situation. The healthcare system should be structured in accordance with the pandemic condi-tions in order to explain the importance of the use of medicines.

[Display omitted] • Metabolomics allow for the output of nutritional supplements to be measured after they are utilized by the gut microbiome. • After digestion, portions of nutritional supplements make it to the gut microbiota and are subsequently metabolized. • AG1 supplementation led to a change in 57 polar metabolites during colonic fermentation by ex vivo human gut microbiota. • Clinical investigation must be done to confirm the presence of these metabolites and measure the beneficial health outcomes. Metabolomics is a critical approach to fully understand the metabolic repercussions of a nutritional supplement on the gut microbiota. Here, a proof of principle study was conducted via a metabolomic survey of polar metabolites to explore the effect of AG1 on the metabolic output of the human gut microbiota, in vitro , using the Simulator of the Human Intestinal Microbial Ecosystem® (SHIME). Aliquots were isolated from the fecal slurry at baseline (0 h), 1 h, 24 h, and 48 h of colonic fermentation simulation. Chemical analysis at these timepoints detected a total of 165 metabolites with 57, 21, and 14 specific metabolites being significantly altered by AG1 relative to the blank controls at 1 h, 24 h, and 48 h, respectively. Many of these metabolites likely resulted from AG1 directly as a supplement, but several of these metabolites also likely arose specifically from microbial metabolism. [ABSTRACT FROM AUTHOR]

Heat stress will cause a series of response in the living system and the most significant impact is on brain functions. The aim of this article is to develop nutritional supplements that can alleviate cognitive decline caused by heat stress. In this article, we screen functional food factors which can prevent or relieve effects on heat stress injury based on bioinformatics. 129 function factors related to the crossover targets were obtained, and a food database related to the prevention of high-temperature impairment was constructed. After a series of scoring standards combined with food classification, two formulas—nutrition fortifier formula (tyrosine and multivitamin B) and plant compound formula (quercetin, proanthocyanidin, and naringin) were investigated using animal experiments to determine their ability to prevent cognitive impairment of heat-stressed animals. Our results demonstrated that certain functional food factors and our two designed formulations significantly prevent cognitive impairment of heat-stressed animals.Further mechanism was carried out by cell viability assay, reactive oxygen species assay, real-time quantitative PCR and Western blot. The results showed that the plant compound formula diluted 4000 times had the best relieving effect on HT22 after heat stress, and this concentration formula can significantly alleviate the elevated levels of reactive oxygen species caused by heat stress. This formula also can significantly down-regulate IL-1β, IL-6, TNF-α, IL-10, iNOS and COX-2 expression. Likewise, Western blot results showed that the formula could activate the cAMP pathway and increase the expression of phosphorylated PKA and BDNF in hippocampal cells.

AimsTo assess the associations of vitamin and/or nutritional supplements (VNS) with falls among patients with diabetes.Methods9,141 and 21,489 middle-aged participants with diabetes from Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and UK Biobank were included. Use of VNS was collected at baseline, and fall events were recorded using annual questionnaires in ACCORD and electric records in UK Biobank during follow-up. The associations of VNS use with fall risk were analyzed using logistic regression models in ACCORD and Fine-Gray sub-distribution hazard models in UK Biobank. The role of specific supplements was also estimated in UK Biobank, adjusting for confounding factors and multiple comparisons.Results45.9% (4,193/9,141, 5.5 median follow-up years) patients in ACCORD and 10.5% (2,251/21,489, 11.9 median follow-up years) in UK Biobank experienced fall and in-patient events during follow-up, respectively. In ACCORD, VNS using was associated with an increased risk of fall (full-adjusted odds ratio [OR]: 1.26, P < 0.05). In UK Biobank, despite no significant association between VNS overall and in-patient fall, vitamin B, calcium, and iron using increased the risk of falls significantly (full-adjusted hazard ratio range: 1.31–1.37, P < 0.05).ConclusionsUse of specific VNS increased the risk of fall among patients with diabetes. The non-indicative use of nutritional supplements for patients with diabetes might be inadvisable.

Osteoarthritis (OA) is a joint disease characterized by inflammation of the synovium, angiogenesis, cartilage degradation, and osteophyte formation. Harpagophytum Procumbens DC. ex Meisn., Boswellia Serrata Roxb., Curcuma longa L., Bromelain and Escin (Aesculus hippocastanum) are plants which extracts, together to Bromelain and Escin (Aesculus hippocastanum) are traditionally used in OA. However, their mechanistic role remains unclear. We aimed to investigate whether these bioactives alone or in combination (as in Flonat Fast®) can suppress TNF-α-induced inflammation, angiogenesis, and osteophyte formation using two cell models involved in OA: endothelial cells and monocytes. Each plant extract was evaluated for its polyphenol content, antioxidant activity, and toxicity. In endothelial cells and monocytes, expression of genes involved in OA was assessed, functional assays for inflammation and angiogenesis were performed, and impairment of reactive oxygen species production (ROS) was evaluated. Exposure of cells to the bioactives alone and in combination before cytokine stimulation resulted in differential counterregulation of several gene and protein expressions, including those for cyclooxygenases-2, metalloproteinase-9, transforming growth factor β1, and bone morphogenic protein-2. We demonstrated that these bioactives modulated monocyte adhesion to endothelial cells as well as cell migration and endothelial angiogenesis. Consistent with radical scavenging activity in the cell-free system, the bioactives curbed TNF-α-stimulated intracellular ROS production. We confirmed the potential anti-inflammatory and antiangiogenic effects of the combination of Harpagophytum procumbens, Boswellia, Curcuma, Bromelain, and Escin and provided new mechanistic evidence for their use in OA. However, further clinical studies are needed to evaluate the true clinical utility of these bioactives as supportive, preventive, and therapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Setting up and conducting a randomised controlled trial (RCT) has many challenges—particularly trials that include vulnerable individuals with behavioural problems or who reside in facilities that focus on care as opposed to research. These populations are underrepresented in RCTs. Approach: In our paper, we describe the challenges and practical lessons learned from two RCTs in two care settings involving long‐stay psychiatric inpatients and people with intellectual disabilities. We describe five main difficulties and how these were overcome: (1) multisite setting, (2) inclusion of vulnerable participants, (3) nutritional supplements and placebos, (4) assessment of behavioural outcomes, and (5) collecting bio samples. Conclusions: By sharing these practical experiences, we hope to inform other researchers how to optimally design their trials, while avoiding and minimising the difficulties that we encountered, and to facilitate the implementation of a trial. Both trials were registered in the Clinical Trials Register (RCT A: NCT02498106; RCT B: NCT03212092). [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD). Curcumin has been shown to exert glucose-lowering and anti-atherosclerotic effects in type 2 diabetes. Hence, we investigated curcumin's effects on atherogenesis markers, fatty liver, insulin resistance, and adipose tissue-related indicators in patients with NAFLD. In this secondary analysis of a 12-week randomized controlled trial, fifty-two patients with NAFLD received lifestyle modification. In addition, they were randomly allocated to either the curcumin group (1.5 g/day) or the matching placebo. Outcome variables (assessed before and after the study) were: the fatty liver index (FLI), hepatic steatosis index (HSI), fatty liver score (FLS), BMI, age, ALT, TG score (BAAT), triglyceride glucose (TyG) index, Castelli risk index-I (CRI-I), Castelli risk index-II (CRI-II), TG/HDL–C ratio, atherogenic coefficient (AC), atherogenic index of plasma (AIP), lipoprotein combine index (LCI), cholesterol index (CHOLINDEX), lipid accumulation product (LAP), body adiposity index (BAI), visceral adiposity index (VAI), metabolic score for visceral fat (METS-VF), visceral adipose tissue (VAT), and waist-to-height ratio (WHtR) values. The TyG index decreased in the curcumin group and increased in the placebo group, with a significant difference between the groups (p = 0.029). However, a between-group change was not significant after adjustment for multiple testing. Other indices were not significantly different between the groups either before or after multiple test correction. After the intervention, there was a lower number of patients with severe fatty liver (FLI ≥ 60) and metabolic syndrome in the curcumin group compared to the placebo (p = 0.021 and p = 0.012, respectively). In conclusion, curcumin offers no additional cardiometabolic benefits to lifestyle intervention in patients with NAFLD. [ABSTRACT FROM AUTHOR]

Aim: To implement a childhood cancer-specific nutritional algorithm adapted for the South African context for interventions at time-set intervals to evaluate differences in the nutritional status of newly diagnosed children with cancer., Method: Children with newly diagnosed cancer were assessed for stunting, underweight, wasting, and moderate to severe malnutrition (MUAC < -2SD and < - 3 SD) between October 2018 and December 2020 in a longitudinal nutritional assessment study with monthly assessments. Two pediatric oncology units (POUs) served as the intervention group that implemented the nutritional algorithm-directed intervention and three other POUs formed the control group that implemented standard supportive nutritional care., Results: A total of 320 patients were enrolled with a median age of 6.1 years (range three months to 15.3 years) and a male-to-female ratio of 1.1:1. The malnourished patients in the intervention group showed significant improvement at six months after diagnosis for stunting (P = 0.028), underweight (P < 0.001), and wasting until month five (P = 0.014). The improvements in the control group were not significant. Moderate acute malnutrition (MAM) significantly improved over the first six months of cancer treatment in the intervention group (P < 0.001), while MAM improvement was only significant in the control group for the children under five years of age (P = 0.004). The difference in mean z-scores over time for the nutritional parameters between the intervention and control groups was insignificant., Conclusion: We established that the nutritional algorithm adapted for South Africa as an intervention tool for childhood cancer assisted in optimizing nutritional interventions and improved nutritional outcomes over the first six months of cancer treatment., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Dietary supplements including vitamins, minerals, and natural health products are commonly consumed by those aiming to optimize fertility and pregnancy outcomes. The aim of this survey was to describe supplementation practices among individuals who were pregnant or trying to conceive in Vancouver, Canada. An online survey was conducted among 500 individuals who were pregnant ( n  = 250) or trying to conceive ( n  = 250). Participants met a substantial proportion of vitamin and mineral recommendations through supplements alone. Exceptions included calcium, magnesium, and choline, with median (interquartile range (IQR)) supplementation doses reported by those who were pregnant and trying to conceive, respectively, of: 250 (200 and 250 mg) and 250 (200 and 250 mg), 50 (50 and 75 mg) and 50 (50 and 90 mg), and 53 (10 and 150 mg) and 55 (10 and 100 mg), as compared to perinatal recommendations of 1000 mg/day (calcium), 350 mg/day (magnesium), and 450 mg/day (choline). Conversely, median (IQR) doses of folate reported by those who were pregnant and trying to conceive, respectively, were: 1000 (780 and 1000 µg) and 1000 (800 and 1000 µg), with ∼70% overall (337/471) reporting doses ≥1000 µg (the tolerable upper intake level). Most participants (451/500; 90%) reported supplementation with a prenatal multivitamin; of these, 83% reported that supplementation occurred daily. Overall, as diet was not considered, we cannot ascertain whether recommendations for calcium, magnesium, and choline were met through the combination of supplements and foods; however, we believe that additional supplementation with choline may be required to meet recommendations in pregnancy. Excessive folate supplementation has been previously identified as a concern throughout North America; here, we provide further evidence for excessively high doses consumed via supplements., Competing Interests: The authors declare there are no competing interests.

Background: We assessed the relationship of changes in upper and lower body lean mass with muscle strength, endurance and power responses following two high protein diets (1.6 or 3.2 g . kg -1. d -1 ) during 16 weeks of either concurrent training (CT) or resistance training (RT) in resistance-trained young males., Methods: Forty-eight resistance-trained young males (age: 26 ± 6 yr., body mass index: 25.6 ± 2.9 kg.m -2 ) performed 16 weeks (four sessions·wk. -1 ) of CT or RT with either 1.6 g . kg -1. d -1 protein (CT + 1.6; n  = 12; RT + 1.6; n  = 12) or 3.2 g . kg -1. d -1 protein (CT + 3.2; n  = 12; RT + 3.2; n  = 12). Relationships between upper (left arm + right arm + trunk lean mass) and lower body (left leg + right leg lean mass) lean mass changes with changes in muscle performance were assessed using Pearson's correlation coefficients., Results: For upper body, non-significant weak positive relationships were observed between change in upper body lean mass and change in pull-up ( r  = 0.183, p  = 0.234), absolute chest press strength ( r  = 0.159, p  = 0.302), chest press endurance ( r  = 0.041, p  = 0.792), and relative chest press strength ( r  = 0.097, p  = 0.529) while non-significant weak negative relationships were observed for changes in absolute upper body power ( r  = -0.236, p  = 0.123) and relative upper body power ( r  = -0.203, p  = 0.185). For lower body, non-significant weak positive relationships were observed between the change in lower body lean mass with change in vertical jump ( r  = 0.145, p  = 0.346), absolute lower body power ( r  = 0.109, p  = 0.480), absolute leg press strength ( r  = 0.073, p  = 0.638), leg press endurance ( r < 0.001, p  = 0.998), relative leg press strength ( r  = 0.089, p  = 0.564), and relative lower body power ( r = 0.150, p  = 0.332)., Conclusion: Changes in muscle strength, endurance and power adaptation responses following 16 weeks of either CT or RT with different high protein intakes were not associated with changes in lean mass in resistance-trained young males. These findings indicate that muscle hypertrophy has a small, or negligible, contributory role in promoting functional adaptations with RT or CT, at least over a 16-week period., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bagheri, Karimi, Camera, Scott, Bashirzad, Sadeghi, Kargarfard and Dutheil.)

Background: Pathogenesis of seborrheic dermatitis involves lipid secretion by sebaceous glands, Malassezia colonization, and an inflammatory response with skin barrier disruption. Each of these pathways could be modulated by diet, obesity, and nutritional supplements. Current treatment options provide only temporary control of the condition; thus, it is essential to recognize modifiable lifestyle factors that may play a role in determining disease severity., Objective: This study aimed to summarize published evidence on diet, nutritional supplements, alcohol, obesity, and micronutrients in patients with seborrheic dermatitis and to provide useful insights into areas of further research., Methods: A literature search of Scopus, PubMed, and MEDLINE (Ovid interface) for English language papers published between 1993 and 2023 was conducted on April 16, 2023. Case-control studies, cohort studies, and randomized controlled trials with 5 or more subjects conducted on adult participants (>14 years) were included, case reports, case series, and review papers were excluded due to insufficient level of evidence., Results: A total of 13 studies, 8 case-control, 3 cross-sectional, and 2 randomized controlled trials, involving 13,906 patients were included. Seborrheic dermatitis was correlated with significantly increased copper, manganese, iron, calcium, and magnesium concentrations and significantly lower serum zinc and vitamin D and E concentrations. Adherence to the Western diet was associated with a higher risk for seborrheic dermatitis in female patients and an increased consumption of fruit was associated with a lower risk of seborrheic dermatitis in all patients. The prebiotic Triphala improved patient satisfaction and decreased scalp sebum levels over 8 weeks. Most studies find associations between regular alcohol use and seborrheic dermatitis, but the association between BMI and obesity on seborrheic dermatitis severity and prevalence is mixed., Conclusions: This review sheds light on specific promising areas of research that require further study, including the need for interventional studies evaluating serum zinc, vitamin D, and vitamin E supplementation for seborrheic dermatitis. The negative consequences of a Western diet, alcohol use, obesity, and the benefits of fruit consumption are well known; however, to fully understand their specific relationships to seborrheic dermatitis, further cohort or interventional studies are needed., Trial Registration: PROSPERO CRD42023417768; https://tinyurl.com/bdcta893., (©Emily Woolhiser, Noah Keime, Arya Patel, Isaac Weber, Madeline Adelman, Robert P Dellavalle. Originally published in JMIR Dermatology (http://derma.jmir.org), 05.08.2024.)

Summary: Objective: This study aimed to assess the Saudi population's beliefs regarding the consumption of nutritional supplements and herbal products for the prevention and treatment of COVID-19 in Riyadh. Methods: A cross-sectional study that included 1460 participants aged between 12 and 86 years was conducted in Riyadh, Saudi Arabia, between October 01, 2020, and October 30, 2020, via an online survey using a questionnaire. The questionnaire was uploaded as a Google Doc file on Google Drive, and a link to the survey was distributed to respondents via social media platforms (Twitter, WhatsApp, and Instagram). The survey instrument included 30 questions, including sociodemographic characteristics and the use of nutritional supplements and herbal products. Results: The findings of our study revealed a significant increase in intake and the frequency of consumption of nutritional supplements and herbal products during the COVID-19 pandemic period than before the COVID-19 pandemic. Social media and the Internet (29.7%) and relatives or friends (14.7%) were the main motivators for the participants to try herbal products. The majority of the participants reported using zinc (72.9%), vitamin C (56.0%), garlic (Allium sativum) (53.8%), and cinnamon (52.0%) during the COVID-19 pandemic period. Conclusion: In conclusion, the findings of our study demonstrated that the intake of nutritional supplements and herbal products increased among the general population in Saudi Arabia during the COVID-19 pandemic period to protect them from the disease. In addition, the intake of nutritional supplements and herbal products should be evidence-based to ensure patient safety.

OBJECTIVES Delayed onset muscle soreness (DOMS) is discomfort that occurs within 8-24hrs following an unaccustomed bout of physical activity that peaks within 24-27hrs and slowly resolves on its own. White willow bark (WWB) is a nutritional supplement that is believed to have anti-inflammatory and analgesic properties like aspirin but without the risk of GI adverse effects. The purpose of this investigation is to determine the effectiveness of WWB on alleviating the symptoms of DOMS following exercise. METHODS Twenty-five individuals volunteered to participate and were randomly assigned to take WWB (798mg salicin) or placebo for 5 days following a lower body resistance training session which consisted of 5X10 lunges at 40% body weight (BW) and 3X fatigue leg press at 75%BW. Test procedures included visual analog scale (VAS), mid-thigh circumference and pressure pain threshold. VAS was measured pre, all five days of the supplementation period and day 6 (post-supplementation). All other variables were measured at pre, immediate, day 3(72hrs), and day 6 (post-supplementation). RESULTS No condition X time interaction was observed (p > 0.05) for any variable. However, VAS scores were lower in the WWB compared to the placebo for all time frames. There was a significant main effect of time for VAS scores indicating muscle soreness for hamstrings (p < 0.001), gluteal (p < 0.001), gastrocnemius (p < 0.001) and quadriceps (p < 0.001). In addition, there was a significant main effect of time for right midthigh pressure pain threshold (p = 0.02), mid-right (p < 0.001) and mid-left (p < 0.001) thigh circumference. CONCLUSIONS WWB may reduce subjective feelings of muscle soreness and appears to have analgesic properties.

Cancer cachexia is a multi-organ syndrome with unintentional weight loss, sarcopenia, and systemic inflammation. Gastrointestinal (GI) cancer patients are more susceptible to cachexia development due to impaired nutrient absorption and digestion. Given the widespread availability and relatively low cost of dietary supplements, we examined the evidence and effects of fish oil (omega-3 fatty acids), melatonin, probiotics, and green tea for managing symptoms of GI cancer cachexia. A literature review of four specific supplements was conducted using PubMed, Google Scholar, and CINAHL without a date restriction. Of 4621 available literature references, 26 articles were eligible for review. Fish oil decreased C-reactive protein and maintained CD4+ cell count, while melatonin indicated inconsistent findings on managing cachexia, but was well-tolerated. Probiotics decreased serum pro-inflammatory biomarkers and increased the tolerability of chemotherapy by reducing side effects. Green tea preparations and extracts showed a decreased risk of developing various cancers and did not impact tumor growth, survival, or adverse effects. Among these four supplements, probiotics are most promising for further research in preventing systemic inflammation and maintaining adequate absorption of nutrients to prevent the progression of cancer cachexia. Supplements may benefit treatment outcomes in cancer cachexia without side effects while supporting nutritional and therapeutic needs.

Lipoic acid (LA) is a mitochondrial coenzyme that, depending on the concentration and exposure time, can behave as an antioxidant or pro-oxidant agent and has a proven ability to modulate metabolism by promoting lipid and glucose oxidation for energy production. To assess the effects of LA on energy metabolism and redox balance over time, Artemia sp. nauplii was used as an animal model. The administered concentrations of the antioxidant were 0.05, 0.1, 0.5, 1.0, 5.0, and 10.0 µM. Therefore, possible differences in protein, triglyceride, glucose, and lactate concentrations in the artemia samples and total ammoniacal nitrogen (TAN) in the culture water were evaluated. We also measured the effects of LA on in vivo activity of the electron transport system (ETS), antioxidant capacity, and production of reactive oxygen species (ROS) at 6, 12, 18, and 24 h post-hatching. There was a decrease in glucose concentration in the LA-treated animals, and a decrease in ammonia production was observed in the 0.5 µM LA treatment. ETS activity was positively regulated by the addition of LA, with the most significant effects at concentrations of 5.0 and 10.0 µM at 12 and 24 h. For ETS activity, treatments with LA presented the highest values at 24 h, a period when ROS production decreased significantly, for the treatment with 10.0 µM. LA showed positive regulation of energy metabolism together with a decrease in ROS and TAN excretion.

Nutritional supplements have been widely used in colorectal cancer (CRC) patients. The aim of this network meta-analysis (NMA) was to compare the effects of different nutritional supplements on inflammation, nutritional status, and clinical outcomes in CRC patients. Four electronic databases were searched until December 2022. Randomized controlled trials (RCTs) comparing nutritional supplements of omega-3 fatty acids (omega-3), arginine, vitamin D, glutamine, probiotics, or their combinations with placebo or standard treatment were selected. The outcomes were inflammatory indicators, nutritional indicators, and clinical outcomes. A random-effects Bayesian NMA was performed to rank the effect of each supplement. In total, 34 studies involving 2841 participants were included. Glutamine was superior in decreasing tumor necrosis factor-α (MD −25.2; 95% CrI [−32.62, −17.95]), whereas combined omega-3 and arginine supplementation was more effective in decreasing interleukin-6 (MD −61.41; 95% CrI [−97.85, −24.85]). No nutritional supplements significantly maintained nutritional indicators in CRC patients. Regarding clinical outcomes, glutamine ranked highest in reducing the length of hospital stay (MD −3.71; 95% CrI [−5.89, −1.72]) and the incidence of wound infections (RR 0.12; 95% CrI [0, 0.85]), and probiotics were rated as best in reducing the incidence of pneumonia (RR 0.38; 95% CrI [0.15, 0.81]). Future well-designed RCTs are needed to further confirm these findings.

As aging women take relatively high counts of medications and nutritional supplements, each addition to their supplements roster increases the likelihood of experiencing adverse health outcomes. Given these public health implications, we isolate the effects of chronological age and old age stereotypes in driving up the number of nutritional supplements taken by middle age and older women in the United States. We use multiple models that converge on the finding that middle age women, but not older women, who highly endorse negative old age stereotypes take more supplements than their age peers who fail to highly endorse negative old age stereotypes. [ABSTRACT FROM AUTHOR]

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Objective: To determine the efficacy, safety, and durability of the use of AHCC supplementation for 6 months to support the host immune system to clear high-risk human papillomavirus (HPV) infections. The AHCC supplement is a proprietary, standardized extract of cultured lentinula edodes mycelia (AHCC®, Amino Up, Ltd., Sapporo, Japan) that has been shown to have unique immune modulatory benefits. Study Design: This was a randomized, double-blind, placebo-controlled study (CTN: NCT02405533) in 50 women over 30 years of age with confirmed persistent high-risk HPV infections for greater than 2 years. Patients were randomized to placebo once daily for 12 months (N = 25) or AHCC 3-g supplementation by mouth once daily on empty stomach for 6 months followed by 6 months of placebo (N = 25). Every 3 months, patients were evaluated with HPV DNA and HPV RNA testing as well as a blood sample collected to evaluate a panel of immune markers including interferon-alpha, interferon-beta (IFN-β), interferon-gamma (IFN-γ), IgG1, T lymphocytes, and natural killer (NK) cell levels. At the completion of the 12-month study period, patients on the placebo arm were given the option to continue on the study to receive AHCC supplementation unblinded for 6 months with the same follow-up appointments and testing as the intervention arm. Results: Fifty women with high-risk HPV were enrolled, and 41 completed the study. Fourteen (63.6%) of the 22 patients in the AHCC supplementation arm were HPV RNA/HPV DNA negative after 6 months, with 64.3% (9/14) achieving a durable response defined as being HPV RNA/HPV DNA negative 6 months off supplementation. On the placebo arm, two (10.5%) of 19 patients were HPV negative at 12 months. In the twelve placebo arm patients who elected to continue on the unblinded study, 50% (n = 6) were HPV RNA/HPV DNA negative after 6 months of AHCC supplementation. At the time of completion of the study, there were a total of 34 patients (22 blinded and 12 unblinded) who had received AHCC supplementation with an overall response rate of 58.8% that cleared HPV persistent infections. At the time of enrollment, the mean IFN-β level was 60.5 ± 37.6 pg/ml in women with confirmed persistent HPV infections. Suppression of IFN-β to less than 20 pg/ml correlated with an increase in T lymphocytes and IFN-γ and durable clearance of HPV infections in women who received AHCC supplementation. Conclusion: Results from this phase II study demonstrated that AHCC 3 g once daily was effective to support the host immune system to eliminate persistent HPV infections and was well tolerated with no significant adverse side effects reported. The duration of AHCC supplementation required beyond the first negative result needs more evaluation to optimize success for durable outcomes. The suppression of the IFN-β level to less than 20 pg/ml correlated with clearance of HPV infections and merits further evaluation as a clinical tool for monitoring patients with HPV infections. Clinical Trial Registration: clinicaltrials.gov/ct2/, identifier NCT02405533 [ABSTRACT FROM AUTHOR]