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.

Isolation of bitter acids from hops (Humulus lupulus L.) using countercurrent chromatography.

Commercially available hops (Humulus lupulus L.) bitter acid extracts contain a mixture of three major congeners (co-, n-, and ad-) in addition to cis/trans diastereomers for each congener. Individual isomerized α-acids were obtained by the consecutive application of two separate countercurrent chromatography methods. First, individual isomerized α-acid congeners as a mixture of cis/trans diastereomers were obtained using a solvent system consisting of hexane and aqueous buffer. The second purification, capable of separating cis/trans diastereomers, was accomplished using a quaternary solvent system; an alternative procedure using ß-cyclodextrin followed by countercurrent chromatography was also investigated. The NaBH(4) reduction of the purified isomerized α-acid compounds followed by countercurrent chromatography purification resulted in individual ρ iso α-acids (>95%). Similarly, catalytic hydrogenation of the purified isomerized α-acid compounds followed by countercurrent chromatography purification produced individual tetrahydro isomerized α-acids (>95%). Reported herein is a widely applicable approach that focuses on three critical variables--solvent system composition, pH, and buffer-to-sample ratio--that enable the efficient purification of individual bitter acids (≥95%) from commercially available hops extracts.

Therapeutic Use of Omega-3 Fatty Acids for Immune Disorders In Search of the Ideal Omega-3 Supplement.

There has been continuing growth in the understanding of the role that omega-3 fatty acid supplements play in the support of immune function. The progress in both the basic science and clinical research surrounding the impact of various formulations of omega-3 fatty acid supplements on immune function has resulted in the recognition that the impact of these supplements is beyond that of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docasahexaenoic acid (DHA) alone, and includes other fatty acids containing omega-3 derivatives termed pro-resolving mediators, along with vitamins A and D found naturally in some marine oils. The research on omega-3 oil supplements has also highlighted the importance that the supplement formulation be derived from a certified sustainable source, free of heavy metals and organic pollutants, minimally processed, and composed of the natural triglyceride form of the fatty acids for improved safety and effectiveness in providing immune support.

Glutathione, Orthomolecular Medicine, and Nutraceutical Therapy.

It was more than 70 years ago that Linus Pauling identified sickle cell anemia as a molecular disease associated with alteration in oxygen metabolism in the red blood cell due to the monogenetic substitution of a single amino acid in hemoglobin. It's been 50 years since he first wrote about the concept of Orthomolecular Medicine, which focuses on adjusting the physiological levels of molecules with nutrient-derived precursors (now termed nutraceuticals) to promote optimal health. We now see these concepts being applied in the nutraceutical management of sickle cell anemia using glutamate as a precursor of glutathione and other conditions associated with oxidative stress.

Clinical Understanding of the Sleep-Immune Connection.

The science of sleep is becoming better understood all the time, and here is a fact that has only recently been revealed: sleep and immune system function have a bidirectional relationship. The disturbance of sleep can create an alteration in immune function. The opposite is also true, in that activation of the immune system can create a disturbance in sleep cycling. This dynamic can ultimately create a feed-forward loop of increasing immune dysfunction and sleep disruption. These systems are intimately intertwined. The clinical approach should be to intervene upstream in the regulation of the fundamental systems that control both sleep and immune function. Through the implementation of this approach, the treatment will focus on the cause of the epigenetic modulation of the sleep-immune system imbalance, and not just its effects and symptomatology.

Functional Medicine Past, Present, and Future.

Embedded within the Functional Medicine model is the potential for reversibility of altered function. This perspective is inherently different from the Mendelian concept of genetics, which is grounded in the construct of dominate and recessive genetic characteristics. Mendel's work was obviously groundbreaking, but it has also contributed to a deterministic mindset about disease. Many people-even today-believe that health and disease are locked into the genes of every individual. Modern genomic research continues to reveal that the concept of genetic determinism can be (and should be) challenged. The functional interaction of our lifestyle, diet, environment, behavior, and social structure with our genome and epigenome greatly determines our health outcomes. It has been discovered that our aging epigenome can even be rejuvenated. The epigenomic structure is also a powerful predictor of disease outcome and life expectancy. As our understanding of genetic and epigenetic expression patterns grows, the implications for personalized Functional Medicine intervention programs are truly revolutionary.

Our Healing Journey: Restoring Connection, Finding Hope and Evolving Wellness.

Wellness is more than the simple absence of disease. As such, health can be envisioned as a journey to a state of optimal wellness and not a simple destination. To measure progress on such a journey, defining wellness by measures other than disease risk factors and biomarkers is necessary. Health can be defined by five areas of functionality: metabolic, physical, emotional, cognitive, and behavioral. Indeed, an individual's behaviors are the outward expression of an inward integration of the metabolic, physical, emotional, and cognitive functions in a fully actualized mind, body, and spirit. Personalized Lifestyle Medicine recognizes the importance of facilitating lasting behavioral change but facilitating this change may be difficult and may resist standard practice models. It is our proposal that a major obstacle on the journey to achieving full wellness is the brokenness of an individual's connections to self, to purpose, to community, and to the environment. Programs aimed both at defining an individual's authentic self and providing patient education using Functional Medicine's unique philosophy can facilitate a patient's creation of a lasting vision that is the work of successful behavioral change.

Genetic Biomarkers of Metabolic Detoxification for Personalized Lifestyle Medicine.

Metabolic detoxification (detox)-or biotransformation-is a physiological function that removes toxic substances from our body. Genetic variability and dietary factors may affect the function of detox enzymes, thus impacting the body's sensitivity to toxic substances of endogenous and exogenous origin. From a genetic perspective, most of the current knowledge relies on observational studies in humans or experimental models in vivo and in vitro, with very limited proof of causality and clinical value. This review provides health practitioners with a list of single nucleotide polymorphisms (SNPs) located within genes involved in Phase I and Phase II detoxification reactions, for which evidence of clinical utility does exist. We have selected these SNPs based on their association with interindividual variability of detox metabolism in response to certain nutrients in the context of human clinical trials. In order to facilitate clinical interpretation and usage of these SNPs, we provide, for each of them, a strength of evidence score based on recent guidelines for genotype-based dietary advice. We also present the association of these SNPs with functional biomarkers of detox metabolism in a pragmatic clinical trial, the LIFEHOUSE study.

Personalized Lifestyle Intervention and Functional Evaluation Health Outcomes SurvEy: Presentation of the LIFEHOUSE Study Using N-of-One Tent-Umbrella-Bucket Design.

The working definition of health is often the simple absence of diagnosed disease. This common standard is limiting given that changes in functional health status represent early warning signs of impending health declines. Longitudinal assessment of functional health status may foster prevention of disease occurrence and modify disease progression. The LIFEHOUSE (Lifestyle Intervention and Functional Evaluation-Health Outcomes SurvEy) longitudinal research project explores the impact of personalized lifestyle medicine approaches on functional health determinants. Utilizing an adaptive tent-umbrella-bucket design, the LIFEHOUSE study follows the functional health outcomes of adult participants recruited from a self-insured employee population. Participants were each allocated to the tent of an all-inclusive N-of-one case series. After assessing medical history, nutritional physical exam, baseline functional status (utilizing validated tools to measure metabolic, physical, cognitive, emotional and behavioral functional capacity), serum biomarkers, and genomic and microbiome markers, participants were assigned to applicable umbrellas and buckets. Personalized health programs were developed and implemented using systems biology formalism and functional medicine clinical approaches. The comprehensive database (currently 369 analyzable participants) will yield novel interdisciplinary big-health data and facilitate topological analyses focusing on the interactome among each participant's genomics, microbiome, diet, lifestyle and environment.

META060 inhibits osteoclastogenesis and matrix metalloproteinases in vitro and reduces bone and cartilage degradation in a mouse model of rheumatoid arthritis.

OBJECTIVE: The multikinase inhibitor META060 has been shown to inhibit NF-kappaB activation and expression of markers of inflammation. This study was undertaken to investigate the effect of META060 on biomarkers associated with bone and cartilage degradation in vitro and its antiinflammatory efficacy in vivo in both acute and chronic inflammation models. METHODS: Glycogen synthase kinase 3beta (GSK3beta)-dependent beta-catenin phosphorylation was evaluated in RAW 264.7 macrophages to assess kinase inhibition. The inhibition of osteoclastogenesis and tartrate-resistant acid phosphatase (TRAP) activity was evaluated in RANKL-treated RAW 264.7 cells. The inhibition of interleukin-1beta (IL-1beta)-mediated markers of inflammation was analyzed in human rheumatoid arthritis synovial fibroblasts (RASFs). Mice with carrageenan-induced acute inflammation and collagen-induced arthritis (CIA) were used to assess efficacy. RESULTS: META060 inhibited the activity of kinases (spleen tyrosine kinase [Syk], Bruton's tyrosine kinase [Btk], phosphatidylinositol 3-kinase [PI 3-kinase], and GSK3) associated with RA and inhibited beta-catenin phosphorylation. META060 inhibited osteoclastogenesis, as indicated by decreased transformation of RAW 264.7 cells to osteoclasts and reduced TRAP activity, and inhibited IL-1beta-activated prostaglandin E(2), matrix metalloproteinase 3, IL-6, IL-8, and monocyte chemotactic protein 1 in RASFs. In mice with acute inflammation, oral administration of META060 reduced paw swelling similar to the effect of aspirin. In mice with CIA, META060 significantly reduced the arthritis index and decreased bone, joint, and cartilage degradation. Serum IL-6 concentrations in these mice were inhibited in a dose-dependent manner. CONCLUSION: Our findings indicate that META060 reduces swelling in a model of acute inflammation and inhibits bone and cartilage destruction in a model of chronic inflammation. Its efficacy is associated with the inhibition of multiple protein kinases, including Syk, Btk, PI 3-kinase, and GSK3. These results warrant further clinical testing of META060 for its therapeutic potential in the treatment of inflammatory diseases.

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.

Application of Phytochemicals in Immune Disorders: Their Roles Beyond Antioxidants.

We are witnessing increased global pressure on immune system function as a result of climate change, exposure to xenobiotics, poor quality diets, increased psycho-social stress, and exposure to new infectious agents. Understanding how various phytochemicals and their metabolic byproducts produced by the microbiome modulate immune-related signal transduction pathways has opened a new chapter in medical nutrition that moves far beyond that of generalized antioxidant effects. Not only is precision nutrition now possible, there is an urgent need for it.

Prostate Cancer Risk Connection to Immunity, Hormones, and the Microbiome.

The evidence that diet and lifestyle play an important role in prostate health and disease is now clear. The clinical research indicates that a minimally processed, plant-food-based diet that is high in fiber, vitamins, and minerals, and includes diverse sources of phytonutrients is associated with improved prostate health and reduction in prostate cancer risk, as defined by PSA levels. A Mediterranean diet and the program developed and studied under the direction of Dr. Dean Ornish are two examples of effective approaches. The mechanisms by which specific diet and lifestyle intervention improves prostate health are still under investigation. There is, however, increasing evidence that dietary components that favorably influence the composition of the intestinal microbiome have significant impact on androgen exposure to the prostate, and contribute to the reduction in both prostate cancer risk and progression.

COVID-19 Risk: Clinical Tools for Assessing and Personalizing Immunity.

Researchers and clinicians all over the world are struggling to bring the spread of SARS-CoV-2 under control. Whether we refer to COVID-19 as a pandemic (a widely used word) or a syndemic (a new emerging term), we now know that specific immunotypes have been linked to both risk to infection and presentation of this disease. Application of assessment tools that support a fuller understanding of individual immune system status is next-level care that providers must prepare for and deliver. Commonly used biometric devices already gather data that can be relevant and useful to a phenotypic evaluation of immune function. These variables include pulse rate, blood oxygenation, sleep cycles, respiration rate, heart rate variability, continuous blood glucose monitoring, and ambulatory blood pressure. When coupled with traditional blood analytes and measurements of nutrient status, a more complete picture of immunological function may be revealed. Innovative questionnaires and algorithms can also be helpful additions to a clinician's toolkit. In a therapeutic relationship between provider and patient, this approach may lead to options for personalized immune intervention using diet, medical nutrition, and lifestyle medicine.

Why the Pegan Diet Makes Sense.

In 1985, S. Boyd Eaton and Melvin Konner published a landmark paper in the New England Journal of Medicine. The title was "Paleolithic Nutrition: A Consideration of Its Nature and Current Implications," and this work postulated that an increase in the prevalence of chronic disease among modern humans is the result of a dietary composition that is incompatible with both our genetic ancestry and natural metabolic function. Over the intervening decades, numerous theories about optimal dietary approaches have been put forth and much debate has ensued. Among researchers and the public, we have witnessed vocal advocates emerge in support of the paleolithic philosophy of encouraging mild ketosis, while others passionately argue for plant-based vegetarianism. There is now evidence that neither extreme provides superior health benefits in isolation. According to numerous clinical studies, a hybrid approach may convey a positive and multifactorial influence on the intestinal microbiome, the metabolome, proteomics, and overall health outcomes. A Mediterranean-style diet has been widely studied, and a new concept-Pegan, which is a contraction of the words paleo and vegan-is now gaining worldwide attention.

A Discovery that Reframes the Whole of Global Healthcare in the 21st Century: The Importance of the Imprintome.

Within the genome exists a specific subset of genes whose expression is controlled by epigenetic marks. These tags can be modified by lifestyle factors including diet, behavior, environment and social interactions. Differences in genetic expression, despite identical genes, is explained in part through metastable epialleles-alleles that, while genetically indistinguishable, are variably expressed as a function of epigenetic modification. As a group, these metastable epialleles have been given a unique descriptive name: the imprintome. This breakthrough in understanding genetic expression has led to a wider recognition that our genes are fundamentally controlled at two levels. One is the hardware of the genetic code, which is modified slowly by natural selection through mutational changes in the genome over centuries of time. The other is the software that controls the expression of our genetic code, converting nucleotide sequences into phenotype in response to the imprinting of our epigenome. Acting as a rapid translator for real time changes, the imprintome responds to environmental and lifestyle inputs by genomic methylation and histone modifications that affect promoter accessibility and transcription factor activity. In application, this understanding of the plasticity of the imprintome necessitates a rethinking of both health and disease states. It's a concept that cuts across all forms of healthcare: physical, metabolic, and cognitive-behavioral interventions. But at the same time, it is an aggregating concept-one that brings disciplines together to collaborate on the personalization of health and the delivery of truly individualized care. This article reviews the development of the concept of the imprintome, as well as clinical studies supporting its importance as a potential driver of change in global health care.

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.

Reflections on the COVID-19 Pandemic.

There is an emerging understanding that the severity of viral infections is not only related to the nature of the viral vector, but also to various social and biological factors, a number of which can be modified. The recent COVID-19 pandemic raises the issue as to what approaches might be important in reducing the severity of future viral pandemics beyond that of the pursuit of specific immunization to the vector and the development of drugs to treat its unique mechanism of replication. There is now evidence that lifestyle and environmental factors can serve as immunoadjuvants. Personalized lifestyle and environmental factors may therefore play a significant role in determining both the infectivity and pathogenicity of viruses. Once identified, these factors lend themselves to specific personalized intervention. This intervention focuses on renewal of immune system function through diet, activity, fluid intake, sleep, intestinal microbiome composition, and stress management. As more is learned about the factors that influence the function of specific components of the immune system, it becomes more evident that these modifiable factors have significant impact on the individual response to a viral exposure.

The Long Haul of COVID-19 Recovery: Immune Rejuvenation versus Immune Support.

With the COVID-19 pandemic still affecting communities all over the world and "Long Haul" chronic health issues emerging, it is time for us to look back at past multi-symptom health conditions that required a different approach to their treatment, beyond just managing symptoms. It is important for us to consider how to apply what we have learned about immune rejuvenation and its impact on conditions associated with chronic immune dysfunction. We know more than we ever have before about how to reduce chronic inflammation at its source through the support of selective immune cell autophagy/mitophagy and improved immune cell mitochondrial activity, followed by remodeling of the immune epigenome, and-ultimately-a reset of immune function.

What is the Best Way to Assess Functional Health?: The History of the Development and Application of the Patient Reported Outcome Measurement Information System (PROMIS).

For more than seven decades, the World Health Organization has defined health as a "state of complete physical, mental and social well-being and not merely the absence of disease or infirmity." Among researchers and clinicians, translation of this definition into outcomes measurements has proven challenging. The Patient-Reported Outcomes Measurement Information System (PROMIS) is an initiative connected to the National Institutes of Health Roadmap for Medical Research. Recently, this tool was successfully applied in a comparative evaluation of intervention models (the Functional Medicine model versus the standard-of-care model for primary medicine) in patients with chronic health complaints. This study demonstrated that information derived from validated patient-reported outcomes surveys can be used to design clinical research approaches focused on improving health and well-being.