N-Acetyl Cysteine and Glutathione in Health and Cancer-Pharmacogenomics, Research, and Clinical Practice: Hypothesis and Review.

Context: Glutathione (GSH) is a major intracellular antioxidant capable of scavenging free radicals and detoxifying electrophiles from endogenous and exogenous sources via the free thiol group. GSH plays an important role in a multiple cellular process, including cell differentiation, proliferation, and apoptosis. Pharmacogenomics has demonstrated its important role as a key element in cellular health. Objective: The study intended to examine the benefits of using GSH pharmacogenomics as a therapy to prevent side effects and interactions with antineoplastic agents in the diagnosis and treatment of malignancies. Design: The research team performed a narrative review using the Google scholar and PubMed electronic databases. Conclusions: In summary, the involvement of GSH in the carcinogenesis and drug resistance of tumor cells is clear and well understood, but further studies, aimed at understanding the GSH-driven molecular pathways, might be crucial to designing new therapeutic strategies to fight cancer progression, overcoming chemoresistance, using in combination with immunotherapies, and preventing or minimizing their negative side effects.

Toward the Definition of Personalized Nutrition: A Proposal by The American Nutrition Association.

Personalized nutrition holds tremendous potential to improve human health. Despite exponential growth, the field has yet to be clearly delineated and a consensus definition of the term "personalized nutrition" (PN) has not been developed. Defining and delineating the field will foster standardization and scalability in research, data, training, products, services, and clinical practice; and assist in driving favorable policy. Building on the seminal work of pioneering thought leaders across disciplines, we propose that personalized nutrition be defined as: a field that leverages human individuality to drive nutrition strategies that prevent, manage, and treat disease and optimize health, and be delineated by three synergistic elements: PN science and data, PN professional education and training, and PN guidance and therapeutics. Herein we describe the application of PN in these areas and discuss challenges and solutions that the field faces as it evolves. This and future work will contribute to the continued refinement and growth of the field of PN.Teaching pointsPN approaches can be most effective when there is consensus regarding its definition and applications.PN can be delineated into three main areas of application: PN science and data, PN education and training, PN guidance and therapeutics.PN science and data foster understanding about the impact of genetic, phenotypic, biochemical and nutritional inputs on an individual's health.PN education and training equip a variety of healthcare professionals to apply PN strategies in many healthcare settings.PN professionals have greater ability to tailor interventions via PN guidance and therapeutics.Favorable policy allows PN to be more fully integrated into the healthcare system.

Personalized Nutrition: Translating the Science of NutriGenomics Into Practice: Proceedings From the 2018 American College of Nutrition Meeting.

Adverse reactions to foods and adverse drug reactions are inherent in product defects, medication errors, and differences in individual drug exposure. Pharmacogenetics is the study of genetic causes of individual variations in drug response and pharmacogenomics more broadly involves genome-wide analysis of the genetic determinants of drug efficacy and toxicity. The similarity of nutritional genomics and pharmacogenomics stems from the innate goal to identify genetic variants associated with metabolism and disease. Thus, nutrigenomics can be thought of as encompassing gene-diet interactions involving diverse compounds that are present in even the simplest foods. The advances in the knowledge base of the complex interactions among genotype, diet, lifestyle, and environment is the cornerstone that continues to elicit changes in current medical practice to ultimately yield personalized nutrition recommendations for health and risk assessment. This information could be used to understand how foods and dietary supplements uniquely affect the health of individuals and, hence, wellness. The individual's gut microbiota is not only paramount but pivotal in embracing the multiple-functional relationships with complex metabolic mechanisms involved in maintaining cellular homeostasis. The genetic revolution has ushered in an exciting era, one in which many new opportunities are expected for nutrition professionals with expertise in nutritional genomics. The American College of Nutrition's conference focused on "Personalized Nutrition: Translating the Science of NutriGenomics Into Practice" was designed to help to provide the education needed for the professional engagement of providers in the personalized medicine era.

The Phytoneuroendocrine System: Connecting Plants to Human Systems Biology.

Traditional medicine, exemplified by systems such as Ayurveda, inherently adopts a holistic framework. This framework extends beyond mere consideration of the human body to encompass broader systems of health, integrating elements of nature, particularly plants. Over time, there has been a notable integration between traditional medical philosophies and modern scientific methodologies. This integration is evident in published works that blend these disciplines, resulting in the creation of innovative terminology, such as «Ayurnutrigenomics¼. Concurrently, the lexicon within medical science has evolved to highlight the connection of body systems, as illustrated by terms like «gut-brain axis¼, which emphasize the relationship between physiological and psychological factors. This integration of perspectives is further demonstrated by terms such as «psychoneuroendocrine¼ and «mind-heart-body¼, reflecting a holistic approach to health. Alongside the emergence of these novel terms, there has been a proliferation of literature exploring the diverse functions of plants, particularly focusing on phytonutrients such as those found in the polyphenol category of compounds. In many ways, these emerging findings suggest a fundamental relationship between humans and plants, aligning with the principles of traditional medicine and indicating a profound connection between the two. Thus, in harmony with the increasing recognition of the interconnectedness between human systems biology, the study of phytochemicals, and the ability of plants to influence neuroendocrine responses, this article proposes a new term: the phytoneuroendocrine system.

Not All Maca Is Created Equal: A Review of Colors, Nutrition, Phytochemicals, and Clinical Uses.

Maca (Lepidium meyenii, Lepidium peruvianum) is part of the Brassicaceae family and grows at high altitudes in the Peruvian Andes mountain range (3500-5000 m). Historically, it has been used as a nutrient-dense food and for its medicinal properties, primarily in enhancing energy and fertility. Scientific research has validated these traditional uses and other clinical applications by elucidating maca's mechanisms of action, nutrition, and phytochemical content. However, research over the last twenty years has identified up to seventeen different colors (phenotypes) of maca. The color, hypocotyl size, growing location, cultivation, and post-harvest processing methods can have a significant effect on the nutrition content, phytochemical profile, and clinical application. Yet, research differentiating the colors of maca and clinical applications remains limited. In this review, research on the nutrition, phytochemicals, and various colors of maca, including black, red, yellow (predominant colors), purple, gray (lesser-known colors), and any combination of colors, including proprietary formulations, will be discussed based on available preclinical and clinical trials. The gaps, deficiencies, and conflicts in the studies will be detailed, along with quality, safety, and efficacy criteria, highlighting the need for future research to specify all these factors of the maca used in publications.

Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations.

Public health recommendations for lifestyle modification, including diet and physical activity, have been widely disseminated for the prevention and treatment of disease. These guidelines are intended for the overall population without significant consideration for the individual with respect to one's genes and environment. Personalized lifestyle medicine is a newly developed term that refers to an approach to medicine in which an individual's health metrics from point-of-care diagnostics are used to develop lifestyle medicine-oriented therapeutic strategies for improving individual health outcomes in managing chronic disease. Examples of the application of personalized lifestyle medicine to patient care include the identification of genetic variants through laboratory tests and/or functional biomarkers for the purpose of designing patient-specific prescriptions for diet, exercise, stress, and environment. Personalized lifestyle medicine can provide solutions to chronic health problems by harnessing innovative and evolving technologies based on recent discoveries in genomics, epigenetics, systems biology, life and behavioral sciences, and diagnostics and clinical medicine. A comprehensive, personalized approach to medicine is required to promote the safety of therapeutics and reduce the cost of chronic disease. Personalized lifestyle medicine may provide a novel means of addressing a patient's health by empowering them with information they need to regain control of their health.

Reply to Pluta, R. Comment on "Minich et al. Is Melatonin the "Next Vitamin D"?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements. Nutrients 2022, 14, 3934".

We would like to thank Dr. Pluta for his thoughtful comments [...].

Is Melatonin the "Next Vitamin D"?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements.

Melatonin has become a popular dietary supplement, most known as a chronobiotic, and for establishing healthy sleep. Research over the last decade into cancer, Alzheimer's disease, multiple sclerosis, fertility, PCOS, and many other conditions, combined with the COVID-19 pandemic, has led to greater awareness of melatonin because of its ability to act as a potent antioxidant, immune-active agent, and mitochondrial regulator. There are distinct similarities between melatonin and vitamin D in the depth and breadth of their impact on health. Both act as hormones, affect multiple systems through their immune-modulating, anti-inflammatory functions, are found in the skin, and are responsive to sunlight and darkness. In fact, there may be similarities between the widespread concern about vitamin D deficiency as a "sunlight deficiency" and reduced melatonin secretion as a result of "darkness deficiency" from overexposure to artificial blue light. The trend toward greater use of melatonin supplements has resulted in concern about its safety, especially higher doses, long-term use, and application in certain populations (e.g., children). This review aims to evaluate the recent data on melatonin's mechanisms, its clinical uses beyond sleep, safety concerns, and a thorough summary of therapeutic considerations concerning dietary supplementation, including the different formats available (animal, synthetic, and phytomelatonin), dosing, timing, contraindications, and nutrient combinations.

A program consisting of a phytonutrient-rich medical food and an elimination diet ameliorated fibromyalgia symptoms and promoted toxic-element detoxification in a pilot trial.

BACKGROUND: An effective treatment for fibromyalgia (FM) has yet to become available. OBJECTIVE: To assess the efficacy ofa lifestyle program consisting of a modified elimination diet and a supplemental medical food on clinical symptoms of FM assessed by the Fibromyalgia Impact Questionnaire (FIQ), FibroQuest Symptoms Survey (FibroQuest), Medical Symptoms Questionnaire (MSQ), metallothionein mRNA expression, and urinary toxic element excretion. METHODS: Eight women (aged 48-74 years) were enrolled in an 8-week pilot trial employing a sequential design. During the initial 4-week Program A (control), participants consumed a modified US Department of Agriculture food pyramid diet and a rice protein powder supplement that provided basic macronutrient support. During the second 4-week Program B (intervention), participants consumed a modified elimination diet and a phytonutrient-rich medical food. RESULTS: Compared to baseline, both programs showed trends toward lower mean FIQ total score, MSQ total score, and FibroQuest total score, FIQ stiffness score, and FibroQuest headaches score. Compared to Program A, Program B resulted in a significant decrease (P< .05) in the FIQpain score and stiffness score. Participants also had better pain tolerance at five tender points during Program B than during Program A. Higher metallothionein mRNA expression was observed during Program B. An increase in creatinine-adjusted mercury excretion and suggestive increase in creatinine-adjusted arsenic excretion were noted when Program B was compared to baseline. Urinary mercury/arsenic concentrations were inversely associated with FIQand FibroQuest scores. CONCLUSIONS: Program B was shown to be a safe and efficacious botanically derived medical food treatment program for the amelioration of FM symptoms.

Hop rho iso-alpha acids, berberine, vitamin D3 and vitamin K1 favorably impact biomarkers of bone turnover in postmenopausal women in a 14-week trial.

Osteoporosis is a major health issue facing postmenopausal women. Increased production of pro-inflammatory cytokines resulting from declining estrogen leads to increased bone resorption. Nutrition can have a positive impact on osteoporosis prevention and amelioration. The objective of this study was to investigate the impact of targeted phytochemicals and nutrients essential for bone health on bone turnover markers in healthy postmenopausal women. In this 14-week, single-blinded, 2-arm placebo-controlled pilot study, all women were instructed to consume a modified Mediterranean-style low-glycemic-load diet and to engage in limited aerobic exercise; 17 randomized to the placebo and 16 to the treatment arm (receiving 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D(3) and 500 microg vitamin K(1), twice daily). Thirty-two women completed the study. Baseline nutrient intake did not differ between arms. At 14 weeks, the treatment arm exhibited an estimated 31% mean reduction (P = 0.02) in serum osteocalcin (a marker of bone turnover), whereas the placebo arm exhibited a 19% increase (P = 0.03) compared to baseline. Serum 25-hydroxyvitamin D (25(OH)D) increased by 13% (P = 0.24) in the treatment arm and decreased by 25% (P < 0.01) in the placebo arm. The between-arm differences for OC and 25(OH)D were statistically significant. Serum IGF-I was increased in both arms, but the increase was more significant in the treatment arm at 14 weeks (P < 0.01). Treatment with hop rho iso-alpha acids, berberine sulfate trihydrate, vitamin D(3) and vitamin K(1) produced a more favorable bone biomarker profile that supports a healthy bone metabolism.

Corrigendum to "A Review of the Science of Colorful, Plant-Based Food and Practical Strategies for "Eating the Rainbow"".

[This corrects the article DOI: 10.1155/2019/2125070.].

Is There Such a Thing as "Anti-Nutrients"? A Narrative Review of Perceived Problematic Plant Compounds.

Plant-based diets are associated with reduced risk of lifestyle-induced chronic diseases. The thousands of phytochemicals they contain are implicated in cellular-based mechanisms to promote antioxidant defense and reduce inflammation. While recommendations encourage the intake of fruits and vegetables, most people fall short of their target daily intake. Despite the need to increase plant-food consumption, there have been some concerns raised about whether they are beneficial because of the various 'anti-nutrient' compounds they contain. Some of these anti-nutrients that have been called into question included lectins, oxalates, goitrogens, phytoestrogens, phytates, and tannins. As a result, there may be select individuals with specific health conditions who elect to decrease their plant food intake despite potential benefits. The purpose of this narrative review is to examine the science of these 'anti-nutrients' and weigh the evidence of whether these compounds pose an actual health threat.

A Review of the Science of Colorful, Plant-Based Food and Practical Strategies for "Eating the Rainbow".

Over the past decades, thousands of published studies have amassed supporting recommendations to consume fruits and vegetables for physiological and psychological health. Newer research has emerged to suggest that these plant-based foods contain a plethora of not only vitamins and minerals, but perhaps, most importantly, phytonutrients. These phytonutrients have known pleiotropic effects on cellular structure and function, ultimately resulting in the modulation of protein kinases and subsequent epigenetic modification in a manner that leads to improved outcomes. Even though eating fruits and vegetables is a well-known feature of a healthy dietary pattern, population intakes continue to be below federal recommendations. To encourage consumers to include fruits and vegetables into their diet, an "eat by color" approach is proposed in this review. Although each individual food may have numerous effects based on its constituents, the goal of this simplified approach was to identify general patterns of benefits based on the preponderance of scientific data and known mechanisms of food-based constituents. It is suggested that such a consumer-oriented categorization of these plant-based foods may lead to greater recognition of their importance in the daily diet throughout the lifespan. Other adjunctive strategies to heighten awareness of fruits and vegetables are discussed.

A Review of Dietary (Phyto)Nutrients for Glutathione Support.

Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.

A review of the clinical efficacy and safety of cruciferous vegetable phytochemicals.

Supplementation with the crucifer-derived phytochemicals indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) has been an area of active interest due to their role in estrogen metabolism. This review addresses the debate about which cruciferous compound to use clinically by evaluating their efficacy and safety. Significantly more clinical trials are available for I3C than for DIM. I3C leads to beneficial shifts in hormone markers, and limited evidence suggests that DIM may result in a similar effect. More research in humans is needed to further address whether DIM poses any safety risk. Current data do not suggest that DIM provides enhanced clinical benefits over I3C.

Acid-alkaline balance: role in chronic disease and detoxification.

In conclusion, the increasing dietary acid load in the contemporary diet can lead to a disruption in acid-alkaline homeostasis in various body compartments and eventually result in chronic disease through repeated borrowing of the body's alkaline reserves. Adjustment of tissue alkalinity, particularly within the kidney proximal tubules, can lead to the more effective excretion of toxins from the body. Metabolic detoxification using a high vegetable diet in conjunction with supplementation of an effective alkalizing compound, such as potassium citrate, may shift the body's reserves to become more alkaline.

Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application.

Research into human biotransformation and elimination systems continues to evolve. Various clinical and in vivo studies have been undertaken to evaluate the effects of foods and food-derived components on the activity of detoxification pathways, including phase I cytochrome P450 enzymes, phase II conjugation enzymes, Nrf2 signaling, and metallothionein. This review summarizes the research in this area to date, highlighting the potential for foods and nutrients to support and/or modulate detoxification functions. Clinical applications to alter detoxification pathway activity and improve patient outcomes are considered, drawing on the growing understanding of the relationship between detoxification functions and different disease states, genetic polymorphisms, and drug-nutrient interactions. Some caution is recommended, however, due to the limitations of current research as well as indications that many nutrients exert biphasic, dose-dependent effects and that genetic polymorphisms may alter outcomes. A whole-foods approach may, therefore, be prudent.

Nutritional supplementation of hop rho iso-alpha acids, berberine, vitamin D3, and vitamin K1 produces a favorable bone biomarker profile supporting healthy bone metabolism in postmenopausal women with metabolic syndrome.

Metabolic syndrome poses additional risk for postmenopausal women who are already at risk for osteoporosis. We hypothesized that a nutritional supplement containing anti-inflammatory phytochemicals and essential bone nutrients would produce a favorable bone biomarker profile in postmenopausal women with metabolic syndrome. In this 14-week, randomized trial, 51 women were instructed to consume a modified Mediterranean-style, low-glycemic-load diet and to engage in aerobic exercise. Those in the intervention arm (n = 25) additionally received 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D3, and 500 µg vitamin K1 twice daily. Forty-five women completed the study. Baseline nutrient intake did not differ between arms. Compared with baseline, the intervention arm exhibited an approximate 25% mean decrease (P < .001) in serum osteocalcin (indicative of bone turnover), whereas the placebo arm exhibited a 21% increase (P = .003). Serum 25-hydroxyvitamin D increased 23% (P = .001) in the intervention arm and decreased 12% (P = .03) in the placebo arm. The between-arm differences for osteocalcin and 25-hydroxyvitamin D were statistically significant. Serum insulin-like growth factor I was statistically increased in both arms, but the between-arm differences were not statistically significant. Subanalysis showed that among those in the highest tertile of baseline insulin-like growth factor I, the intervention arm exhibited a significant increase in amino-terminal propeptide of type I collagen, whereas the placebo arm showed a significant decrease at 14 weeks. Treatment with rho iso-alpha acids, berberine, vitamin D3, and vitamin K1 produced a more favorable bone biomarker profile indicative of healthy bone metabolism in postmenopausal women with metabolic syndrome.

Hop and Acacia Phytochemicals Decreased Lipotoxicity in 3T3-L1 Adipocytes, db/db Mice, and Individuals with Metabolic Syndrome.

The plant-based compounds rho-iso-alpha acids (RIAA) from Humulus lupulus (hops) and proanthocyanidins (PAC) from Acacia nilotica have been shown to modulate insulin signaling in vitro. We investigated their effects on triglyceride (TG) deposition in 3T3-L1 adipocytes, glucose and insulin in obese mouse models, and metabolic syndrome markers in adults with metabolic syndrome. The combination of RIAA and PAC synergistically increased TG content and adiponectin secretion in 3T3-L1 adipocytes under hyperinsulinemic conditions and reduced glucose or insulin in obese mice. In a clinical trial, tablets containing 100 mg RIAA and 500 mg PAC or placebo were administered to metabolic syndrome subjects (3 tablets/day, n = 35; 6 tablets/day, n = 34; or placebo, n = 35) for 12 weeks. Compared to placebo, subjects taking 3 tablets daily showed greater reductions in TG, TG : HDL, fasting insulin, and HOMA scores. The combination of RIAA : PAC at 1 : 5 (wt : wt) favorably modulates dysregulated lipids in insulin resistance and metabolic syndrome.