Posts

METABOLIC ENDOTOXEMIA

Metabolic endotoxemia is a condition that affects many people in America. In fact, recent studies estimate that over one-third of adults in the United States have this health issue. It’s been estimated that it may soon be indirectly a leading cause of death. Follow us on this week’s blog to learn what it is and how to prevent metabolic endotoxemia.

Metabolic Endotoxemia

Metabolic endotoxemia is the presence of too much LPS (lipopolysaccharides) in the blood. LPS are toxins that reside on the outer membrane of bacteria that would otherwise not be allowed into our bloodstream. The American Diabetes Association identified bacterial lipopolysaccharide (LPS) as the inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes.  LPS triggers a cascade of immune responses. For example, after binding to its receptor TLR4 (TLR4 is a receptor found on the surface of cells that can detect LPS) or CD 14, there is an elevated level of tumor necrosis factor-alpha (TNFα). TNFα is a protein signaling molecule that is an inflammatory mediator that triggers the innate immune response. The innate immune system, as its name implies, is a primitive type of immunity that all living organisms have. In contrast to the adaptive immune system (which is found in humans and other higher-order species), there are no actual distinguishing features between cells belonging to the innate system or adaptive immune system – they simply look different. TNFα activates more TLR4 which results in more TNFα. As you can see, it becomes a vicious cycle leading to chronic inflammation.

LPS also induces cytokine production by activating inflammatory transcription factors known as nuclear factor kappa B (NF-κB). NF-κB is a protein complex that controls the expression of genes involved in immunity and inflammation. Inducing cytokine production helps our bodies fight off infections. However, it also activates the immune response to clear away cells that are injured or damaged by short-term inflammation. If this clearing of dead cells occurs chronically, it can lead to tissue damage and autoimmune diseases where the body starts attacking its own healthy tissues.

DIET & METABOLIC ENDOTOXEMIA

Paracelsus, a Renaissance physician said: “All things are poison; everything is poisonous; there is nothing without poisonous qualities. Only the dose permits something not to be poisonous.” 

The severity of this disorder depends on how much LPS enters circulation and how sensitive an individual’s body is to these inflammatory agents. As expected, diet and lifestyle are critical when it comes to metabolic endotoxemia and other diseases. 

Inflammatory transcription factors are also activated in response to a high-fat diet rich in saturated fats and low in fruits and vegetables. Inflammatory transcription factors are transcription factors that contribute to the initiation, regulation, and mediation of inflammation.

Saturated fatty acids trigger macrophages to create a cascade of inflammatory signals. Saturated fats refer to a type of dietary fat with no double bonds between the carbon atoms. They are typically solid at room temperature and found in foods such as beef, pork, poultry, butterfat (in dairy products), palm kernel oil, lard (in meat products), and cocoa butter. Inflammatory foods have been linked to causing an inflammatory immune response that results in endotoxemia, which is the presence of bacterial endotoxin (LPS) in the bloodstream.

METABOLIC ENDOTOXEMIA AND DISEASE

The relationship between metabolic endotoxemia and the onset of diabetes, obesity, and heart disease is well established. Metabolic endotoxemia causes the body to have increased cortisol levels. This causes increased insulin resistance, which can contribute to type 2 diabetes. Metabolic endotoxemia causes the body to have increased cortisol levels. This causes increased insulin resistance, which can contribute to type 2 diabetes. In a healthy body, insulin resistance may be caused by high cortisol levels in response to stress. This insulin resistance is typically temporary as a protective mechanism for the body, but in most people who are insulin resistant, a high carbohydrate diet makes them even more insulin resistant. So, these individuals will typically crave carbohydrates when their blood sugar is low from the stress cortisol is causing on their bodies with elevated insulin resistance.

Metabolic endotoxemia causes an increase in persistent free radicals, which contributes to chronic inflammation and aging of the cells. An increase in persistent free radicals is not optimal as this can result in the accelerated development of chronic disease. Chronic inflammation is cause for concern because it is associated with elevated risks of cardiovascular disease, Alzheimer’s disease, cancer, and many other chronic diseases. Metabolic endotoxemia also causes oxidative stress. Oxidative stress refers to the process whereby free radicals in cells cause damage to molecules leading to tissue and organ dysfunction. The human body has both antioxidant and anti-inflammatory mechanisms in place that operate in a feedback loop, such as red blood cells, white blood cells, vitamins C and E, uric acid, nitric oxide synthase (NOS), and more. This feedback loop works by protecting the cells from oxidative damage and removing damaged cells. However, there are many variables that can break the loop using mechanisms called hormesis. Hormesis refers to acute stress that leads to a beneficial effect. For example, exercise causes the body to emit oxidizing free radicals because it requires large amounts of ATP (energy) for muscle contraction. Metabolic endotoxemia however is not a beneficial mechanism. It is the result of an overload of free fatty acids (FFAs), cytokines, and NOS-derived NO which cause circulating endotoxins to disrupt the host’s metabolism. 

Additionally, oxidative stress decreases cellular DNA repair. Cellular DNA repair is critical to our overall health and well-being. As we have discussed in recent blogs, DNA repair is critical for maintaining metabolic homeostasis. Failure to maintain metabolic homeostasis due to DNA damage from oxidative stress can lead to obesity, insulin resistance, and even type 2 diabetes.

In addition to causing insulin resistance and oxidative stress, metabolic endotoxemia has been linked to dysfunction of the hypothalamic-pituitary-adrenal axis. Our HPA Axis is critical for maintaining metabolic homeostasis. Our HPA Axis is responsible for the release of cortisol, our main stress hormone. We often think of the HPA Axis as being involved in stress but it involves every organ system in the body and is critical for maintaining normal body functions, including inflammation. Recent studies have established that in vivo administration of bacterial lipopolysaccharide (LPS) enhances hypothalamic-pituitary-adrenal (HPA) axis function by a mechanism involving endotoxin-stimulated cytokine release.  

IMPORTANCE OF DECREASING INFLAMMATORY ALLOSTATIC LOAD

Deceasing our allostatic load is a component of reaching our optimal health.  Allostatic load refers to the wear and tear on the body through stress. Metabolic endotoxemia contributes to the reduction in our allostatic load. Meeting one’s optimal health includes having a healthy weight, healthy blood sugar levels, and low inflammation among many things. The decreasing allostatic load can be done by increasing physical activity and mindfulness, improving nutrition, reducing stress, maintaining social connections, and getting enough sleep. Decreasing the number of factors involved in the allostatic load will help decrease the overall inflammatory response. 

Don’t know where to start? At the Institute for Human Optimization, we will work with you directly to optimize your well-being. No two patients are the same, so we work with you and create a personalized and individual approach to your health concerns. Contact us today to get started.

____________________________________________________

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695328/

https://diabetes.diabetesjournals.org/content/56/7/1761

https://pubmed.ncbi.nlm.nih.gov/14965237/

https://pubmed.ncbi.nlm.nih.gov/8892362/

/0 Comments/by

METABOLOMICS: Bridging the gap from genotype to phenotype

Today, we continue our series on the Omics of Medicine. If you have followed along, you will find that each Omic plays a key role in precision medicine. 

This week we are taking on an important Omics system: Metabolomics. While appreciated for its role in biomarker discovery, metabolomics has emerging applications towards personalized medicine, precision nutrition research, and even agriculture. 

.  .  .

What is metabolomics, the metabolome, and more?

Metabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues, or organisms. Metabolites are small molecules that are the end product of a metabolic process. Metabolites have several functions including but not limited to epigenetic influencing, fuel, structure, signaling, defense, and more!

Metabolites are either primary or secondary.

Primary: directly involved in normal growth, development, and reproduction of an organism. Examples include: Ethanol, Glutamic Acid, Acetic Acid, Glycerol.. 

Secondary: Is not involved in normal growth, development, and reproduction but serves   

an ecological function and its absences is detrimental to the organism.  Examples include: Peptides, Growth Hormones, Antibiotics, Alkaloids, and more. 

In humans, there are thought to be approximately 3000 common metabolites although researchers suspect that there are much more. The metabolome is the complete set of metabolites within a cell. Within a cell many reactions take place such as:

-Binding 

-Dissociation

-Degradation

-Modification

-Classic biochemical reaction

-Transport

These reactions are considered to be anabolic, where you are growing and/or building, or catabolic which is when you break down food and molecules for energy. 

Importance of Metabolomics

The metabolome is considered the closest link to the phenotype and thus, a critical omics discipline in the pursuit of personalized medicine. How? Recall that a phenotype is an individual’s observable traits (e.g, height, eye color, blood type). These traits are mostly determined by your genotype (your set of genes) or by the environment. A phenotypic variation is due to a variation in the genotype, the environment, and how the genotype and environment interact. Omics research is currently exploring how genetic effects on phenotype are being filtered through the metabolome, making it a critical omic to possibly bridge the gap between genotype and phenotype. This will be a powerful tool in informed decision-making, developing drugs, and preventative healthcare.

Uses Today & Future Applications

Precision Nutrition: Metabolomics has emerging applications with precision nutrition which has the goal of customized nutritional recommendations. Utilizing metabolomics data, researchers can make better nutritional recommendations.  For example,  utilizing metabolomic data, when we look at infant formula, it has been optimally formulated to mimic the molecular composition of human milk taking into account the distribution of fatty acids. 

Dietary Analysis: Researchers are using metabolites found in blood and urine to accurately measure dietary intake. This is a gateway to assess eating habits as currently the tools being used rely on our recordation and subject to human error.

Biomarker Discovery: Human metabolites being profiled has accelerated biomarker discovery.

Future of Medicine

Utilizing Omics data will provide us the lens for the molecular microscope to objectively examine individual variability. With metabolomics being used to identify metabolites that alter a phenotype, it is no surprise that many researchers consider metabolomics as the omics discipline closest to the phenotype.

The future of medicine is a precision base medicine approach that takes into account your bio-individuality, environment, lifestyle, and molecular phenotype to find the best clinical care option for you. The Institute for Human Optimization is committed to helping you create a personalized plan for living your longest, healthiest life possible. My team and I leverage the most cutting-edge advances in genetic testing, nutritional analysis, and functional medicine to get to the root biological imbalances that cause aging.

We know that each person is truly unique. From DNA to iris, we all possess a blueprint that is genetically inherited and environmentally influenced. By gaining a deeper appreciation for the person on a molecular level and addressing the root causes driving disease, we can help promote optimized health through our unique scientific, N of 1, approach to individualized care.

The Institute for Human Optimization provides the most comprehensive, data-driven, personalized approach to wellness. It is:

·   Predictive – We use genomics and advanced biomarker testing to risk stratification and empowerment.

·   Personalized – We use data-driven health information to curate actionable change for disease mitigation and prevention.

·   Preventive – We utilize highly individualized programs tailored to your unique genomic blueprint.

·   Participatory – We empower engagement in personal choices, which allows for improved outcomes and enhanced results.

I am so excited about the possibility to support you on this cutting-edge journey to extend your lifespan AND your healthspan. Click here to schedule Your Longevity Equation Epigenetic Consult! Can’t wait to meet you!

/2 Comments/by

PROTEOMICS: THE TRANSLATION OF OUR BLUEPRINT

The technology surrounding proteomics has evolved in recent years providing promising new directions to study for future clinical application and in the pursuit of precision medicine. Moreover, advanced proteomic technology has allowed researchers the platform to improve our understanding of biology.

.  .  .

What is proteomics?

Proteomics refers to the study of proteomes. Proteomes are the entire set of proteins that are expressed by an organism. Proteins are responsible for the function of the cells. Since protein is the main element in food, and with proteins being fundamental to cellular function, proteomic technology can successfully identify the protein content of food, assessing their protein biomarker, and how they change during their production. 

Application of Proteomics in Medicine

Currently, proteomics is being used extensively for biomarker discovery. Biomarkers is defined by the National Institute of Health Biomarkers Definitions Working Group as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” It is a means to a facet of health.

With proteomic technology, we look at proteomic expression to identify protein biomarkers of disease. Biomarkers can be categorized as diagnostic, prognostic, predictive or predisposition biomarkers.

  • Diagnostic: Diagnostic biomarkers are used to confirm that an individual has the presence of a specific disease or health disorder.
  • Prognostic: A prognostic biomarker can showcase how disease will progress when an individual has been diagnosed with a specific disease or health disorder.
  • Predictive: A predictive biomarker is used by clinicians to help determine how well a treatment will work for the individual.
  • Predisposition: A genetic predisposition biomarker is a biomarker that indicates a susceptibility for that individual to develop a specific disease or heath disorder.

Techniques used in Proteomics

Most approaches in proteomic analysis use a bottom-up or top-down approach.

Bottom-up proteomics: is also considered a peptide-level approach as samples are characterized by their amino acid sequences prior to analyzing.

Top-Down proteomics: Unlike bottom-up that digests proteins into peptide sequences, Top-down proteomics analyzes proteins intact. By bypassing the protein digestion step this method is considered less time consuming and simpler.

What are some of the techniques used for proteomic analysis?

  • Ionization: There are two main methods used for the ionization of protein. One is Electrospray Ionization (ESI) is a technique where a high voltage is applied to a liquid to create an aerosol. The other is the matrix-assisted laser desorption ionization (MALDI) that uses a laser energy absorbing matrix to create ions from large molecules with minimal fragmentation. While different techniques are both used in the proteomic analysis by looking at how proteins and peptides react.
  • Analyte Quantitation Methods: Analyte quantitative methods are techniques used to determine the number of proteins in a sample as well as differences between biological samples. This is used to compare samples between healthy and disease patients as well as to identify and quantify changes in individual proteins.

Clinical Applications

Proteomics is used in a host of clinical scenarios from common disease diagnosis and management to the diagnosis of cancer. These biomarkers are used to help assess clinical responses to medical interventions and gauge the severity of illness. For example, hs-CRP is used to assess cardiovascular inflammation. When these protein is elevated in circulation its associated with an increased risk for heart disease and stroke in people who don’t already have it.

Future of Healthcare

This Omics in medicine is important as it improves our understanding of biology by allowing us insight into the vitality of cells. As the vitality of a cell changes, these changes are visible at the proteomic level. Techniques in the proteomic analysis are seeing changes in protein profiles being a future predictive diagnostic tool to assess disease. While technology is advancing, the use of proteomics in healthcare is still very much considered in the discovery phase as full integration is still under works. While we have not reached full clinical utility, the benefits and potential uses are promising with technology rapidly evolving. As medicine continues to advance, the use of proteomics will be a part of precision, personalized approach to medicine.

The Institute for Human Optimization is committed to helping you create a personalized plan for living your longest, healthiest life possible. My team and I leverage the most cutting-edge advances in genetic testing, nutritional analysis, and functional medicine to get to the root biological imbalances that cause aging.

We know that each person is truly unique. From DNA to iris, we all possess a blueprint that is genetically inherited and environmentally influenced. By gaining a deeper appreciation for the person on a molecular level and addressing the root causes driving disease, we can help promote optimized health through our unique scientific, N of 1, approach to individualized care.

The Institute for Human Optimization provides the most comprehensive, data-driven, personalized approach to wellness. It is:

·   Predictive – We use genomics and advanced biomarker testing to risk stratification and empowerment.

·   Personalized – We use data-driven health information to curate actionable change for disease mitigation and prevention.

·   Preventive – We utilize highly individualized programs tailored to your unique genomic blueprint.

·   Participatory – We empower engagement in personal choices, which allows for improved outcomes and enhanced results.

I am so excited about the possibility to support you on this cutting-edge journey to extend your lifespan AND your healthspan. Click here to schedule Your Longevity Equation Epigenetic Consult! Can’t wait to meet you!

/0 Comments/by
, , ,

OMICS OF MEDICINE: GENOMICS

A blueprint of a genetic “you”.

…

Our DNA determines an overwhelming amount of information about who we are, but other factors can also influence our health expression. Over the past few decades, the science and technology, and their applications in genomic have made breakthrough progress. Genomic data and genomic medicine services have become relevant in clinical applications as more and more clinicians use genomic data with the diagnosis and treatment of patients. How is genomics being used in medicine?

Let’s first start with answering: What is a Genomics?

In last week’s blog, we briefly discussed the Human Genome Project – a research project that successfully sequenced for the first time the entire human genome. This landmark effort was a breakthrough biomedical discovery in Genomics. Genomics is the study of your Genome, which is all your genes, including how your genes interact with each other and with your environment.

This is an exciting field in medicine as clinicians and researchers can analyze a genomics approach to understand the mechanisms of disease and work towards a preventative approach.

Clinical Application Difference between Genomics vs Genetics

Genomics refers to the study of your global genomic blueprint and how it orchestrates dynamic biochemical processes which influence your current state of health.

Genetics refers to a specific division of genomic medicine that focuses on rare disease findings associated with specific inherited gene mutations, inborn errors of metabolism.

The Institute for Human Optimization not focusing on the rare and obscure but translating your global genomic blueprint to self-decode and translate this information into actionable outcomes to harness your health potential.

Genomics in Medicine Today

Genomics allows providers to practice in a proactive care delivery mode. Modern genomics is being used in the following:

  • Prenatal Genetic Screening Tests
  • Cancer Research
  • Polygenic Risk Scores
  • Preimplantation diagnosis
  • Companion diagnostics for prescribed drugs
  • Epigenetics and gene regulation
  • Next-generation sequencing
  • Looking at the patient’s exome

Prenatal Genetic Screening Tests: Widely used currently, clinicians use genomic data during first and second trimester Prenatal Genetic Screening Tests which looks at a very small amount of fetal DNA (done by a simple blood draw) which looks at whether the fetus has certain genetic disorders such as Sickle Cell Disease, Cystic Fibrosis, and more.

Cancer Research: Genome sequencing in Cancer is a clinical area where genomics is being heavily researched. By using genomic data, researched have a better understanding of the biology of cancer and are leveraging this to find new ways to treat the disease.  Additionally, utilizing genomic data is a promising step to predict cancer risk, prognosis, and precise response to treatment.  

Polygenic Risk Scores: Additionally, a potential clinical service tool is looking at Polygenic Risk Scores. Polygenic risk scores look at your polygenic genetic architecture to identify genetic variants associated with diseases. With an increasing amount of research correlating Polygenic risk scores with disease status, this information can be useful in clinical decisions with individuals at high genetic risk of disease for risk stratification

Preimplantation Genetic Diagnosis: In Preimplantation Genetic Diagnosis, whole-genome sequencing of embryos prior to implantation is performed for pathogenic variation screening. This is used to prevent the transmission of known genetic diseases.

Companion Diagnostics for Prescribed Drugs: Companion diagnostics are medical devices that are used by clinicians to aid them in deciding which treatments and dosage to give specifically to that individual patient utilizing genomic insights. This medical device can be an in vitro diagnostic or an imagining tool that provides information needed to find a personalized treatment option by identifying what FDA-approved treatment options would be best suited for their individual case.

Epigenetics and Gene Regulation: the National Institute of Environmental Health Sciences defines Epigenetics as ‘a rapidly growing area of science that focuses on the processes that help direct when individual genes are turned on or off.’ Epigenetic regulation of gene expression is at the forefront of modern Genomics currently being used to assess your Biological age.

Next Generation Sequencing (NGS): refers to a method used to sequence DNA. This method is currently used by Pediatricians for Genomic diagnosis of Pediatric disorders. It is also being used by Oncologists for Precision Oncology migrating cancer treatments to a precision medicine approach.

Exome Sequencing: also known as whole-exome sequencing looks at expressed genes to try to find a genetic cause for disease expression. This is a genomic technique that is clinically relevant as most genetic variants in genetic diseases are expressed in the exome.

The Future is a Precision Medicine Approach

Already, more and more individuals have taken the first steps to obtaining information about their genome by using Direct-to-Consumer DNA testing services. More and more, people want to know more about their genome, whether that means information about ancestry, or a more medically information trait of disease, this has sparked consumer interest in personalized information about our health, genealogy, and more.

We have the blueprints to a genetic “you” and scientists have figured out what each specific gene does itself when changed or removed but now understanding how all genes work together in synchrony, and most importantly how to best use genomic information to improve clinical care is still being established.

Despite these challenges, at the Institute for Human Optimization, we are currently utilizing advanced molecular testing to predict how genes are theoretically behaving by assessing their structural makeup and biochemical expressions.

More about The Institute for Human Optimization

The Institute for Human Optimization is committed to helping you create a personalized plan for living your longest, healthiest life possible. My team and I leverage the most cutting-edge advances in genetic testing, nutritional analysis, and functional medicine to get to the root biological imbalances that cause aging.

The Institute for Human Optimization was created with the intention of pursuing a highly personalized approach to longevity medicine to help enhance healthspan. Where lifespan is the actual number of years we’re alive, healthspan is how many of those years are spent in health and wellness.

We believe that a long healthspan – not just a long lifespan – is the most important thing you can cultivate. A long healthspan means you don’t miss out on life as you get older. It means remaining independent and having the vitality to travel and see the world.  A long healthspan means that you can be there – in full body and mind – for the people who need you the most and that every day will feel like a gift.

We know that each person is truly unique. From DNA to iris, we all possess a blueprint that is genetically inherited and environmentally influenced. By gaining a deeper appreciation for the person on a molecular level and addressing the root causes driving disease, we can help promote optimized health through our unique scientific, N of 1, approach to individualized care.

The Institute for Human Optimization provides the most comprehensive, data-driven, personalized approach to wellness. It is:

·   Predictive – We use genomics and advanced biomarker testing to risk stratification and empowerment.

·   Personalized – We use data-driven health information to curate actionable change for disease mitigation and prevention.

·   Preventive – We utilize highly individualized programs tailored to your unique genomic blueprint.

·   Participatory – We empower engagement in personal choices, which allows for improved outcomes and enhanced results.

I am so excited about the possibility to support you on this cutting-edge journey to extend your lifespan AND your healthspan. Click here to schedule Your Longevity Equation Epigenetic Consult! Can’t wait to meet you!

/0 Comments/by