David Quig received his BS and MS degrees in Human Nutrition from Virginia Tech and a PhD in Nutritional Biochemistry from the University of Illinois. After a five year stint as a Research Associate studying lipid biochemistry and cardiovascular disease at Cornell University, he was as a Senior Cardiovascular Pharmacologist for seven years with a major pharmaceutical company. For the past 20 years David has served as the Vice President of Scientific Support for Doctor’s Data, Inc. He has focused on toxic metals, methylation and amino acid metabolism, the clinical application of the biochemistry of endogenous detoxification, and the influence of the gastrointestinal metabolome on health and sustained adverse conditions. David regularly speaks at national and international medical conference, and has facilitated and co-authored an array of studies spanning exposure and retention of environmental toxicants, nutritional status and gastrointestinal dysbiosis.
Non-alcoholic Fatty Liver Disease & Methylation: Mechanisms, Assessments and Interventions.
Over the 1.5 days the presenters will address two of the emerging areas of significant health disorders. First to be covered is non-alcoholic fatty liver disease (NAFLD) which now comprises the majority of liver disease burden in the Western world. In particular, the prevalence of NAFLD is rising, in line with increasing prevalence of obesity and insulin resistance, as lifestyles have become increasingly sedentary and dietary patterns have changed.
This “silent” disease comprises a wide spectrum of liver damage, ranging from simple steatosis, to steatohepatitis, to advanced fibrosis, cirrhosis and advanced liver disease. Not all patients presenting with NAFLD are obese. However, the primary initiating factor in the disease process is suggested to be metabolic in origination – insulin resistance/hyperinsulinemia which in turn drives hepatic lipogenesis.
Advanced non-alcoholic fatty liver (termed NASH) is related to increased cardiovascular disease risk independent of traditional cardiovascular risk factors. Patients with NAFLD have higher calcium scores, more arterial inflammation (as measured by carotid intima media thickness) and may present with elevated levels of pro-atherogenic small dense LDL and oxidized LDL (ox-LDL). In turn ox-LDL plays a role in in the progression of NAFLD. Aberrant paracellular permeability of the gastrointestinal endothelial barrier and specific microbiome alterations are also associated with NAFLD.
While NAFLD is the most common cause of persistent abnormalities in liver enzyme test results in North America; elevated liver enzymes (e.g. ALT) are not clinically sensitive or specific enough for diagnostic purposes. Imaging is now used widely in the diagnosis of NAFLD and non-invasive biomarkers can be used to both indicate steatosis and evidence for fibrosis. However, non-traditional biomarkers discussed in these presentations and early diagnosis of metabolic syndrome can lead to more effective remediation and prognosis.
Towards that end a comprehensive cardiometabolomic profile that addresses the most specific risk factors for Metabolic syndrome and CVD can provide the clinician with an abundance of information relevant to NAFLD.
The pathogenesis of NAFLD and its progression is a complex process, a number of diverse parallel processes contribute to the development of steatosis and liver inflammation. The gut microbiome has a key role through the gut-liver axis, together with insulin resistance, hormones secreted from the adipose tissue and obesity.
Changes in the gut microbiota as seen in obesity and insulin resistance have consequences both on energy homeostasis and systemic inflammation secondary to endotoxemia as well as associated influences on the generation and resolution of immune driven inflammation. Part of this process is driven by the inflammasome NLRP3, and dietary metabolites have important roles to play in its resolution.
At the liver level, FFAs overflow may result in endoplasmic reticulum stress and activation of the unfolded protein response or mitochondrial dysfunction and consequent activation of sterile inflammatory responses.
Approaching the intervention of the complex multi triggered pathology requires a broad understanding of the key mechanism, the underlying risks and the utilisation of appropriate nutritional compounds and lifestyle.
The intersecting role of the immune system and how nutritional immunology can provide multiple points of intervention and resolution will be a feature of the second part of day 1. It has become increasingly clear that overlapping and redundant inﬂammatory pathways play pleiotropic and important roles in metabolism and that the metabolic state is a critical determinant of immune function and restoration of tolerance – understanding the metabolic-immunoregulation pathways open up clinical opportunities.
Case histories will be presented throughout the day to ensure translation of the research and mechanistic pathways can result in improved outcomes.
On day 2 the increasingly recognised importance of epigenetics; defined as changes in gene expression that occur without changes in DNA sequence will be explored. Epigenetic processes include DNA methylation, chromatin modifications (histone methylation, acetylation), and miRNA. These processes provide “marks” in the genome by which genes are set to be transcriptionally activated or silenced and are heritable, transmitted from parent to daughter cells during mitosis.
However, epigenomic marks are also responsive to environmental shifts, like changes in nutritional status, and as such, are attractive diet-related targets for the prevention and treatment of conditions in which alteration in methyl expression is involved. These include; Autoimmunity, Cancer, Metabolic disorders, Neurological disorders, Aging and many others.
The presenters will provide an overview of the current state of knowledge regarding dietary factors, lifestyle and laboratory investigations of DNA methylation in the context of health disruptions.
Dietary factors required for methylation reactions are often referred to as “methyl nutrients” and are required for the generation of S-adenosylmethionine, the key methyl donor for DNA, RNA, proteins, and phospholipids.
Methyl nutrients include: vitamins, such as folate, riboflavin, vitamin B12, vitamin B6 (pyridoxal phosphate), and choline; and amino acids, such as methionine, cysteine, glycine, and serine. A summary of contemporary research assessing the relationships between alterations in methyl nutrient status with changes in DNA methylation, highlighting the consequences of methyl nutrient imbalance and health related implications will be presented. This will be followed by a synopsis of the current understanding of how diet-related and lifestyle changes in DNA methylation patterns affect health generation and loss, including the support of associated changes in multiple mechanisms linked to DNA related changes.
The presenters will focus on the mechanisms associated with the array of causative factors, their clinical presentations and interventions and objective laboratory testing that helps refine and address many of the risk factors and outcomes.
Functional Laboratory Assessment: What is Awry in the Metabolism of Essential Methionine and Folate?
The presenters will:
- Stimulate new ideas
- Reinforce current best practice methods
- Challenge entrenched beliefs with evolving comprehension
- Offer new and substantive clinical ideas
- Support the functional medicine approach to patient care
- Diminish the temptation to be protocol driven in treatment plans
- Provoke discussion and review
- Provide networking opportunities
- Make you feel positive about the opportunities for helping more people recover their health safely
Michael Ash DO, ND, BSc, RNT
Michael has for over 25 years explored the relationship between the innate and adaptive immune systems and the gastrointestinal tract. More recently the last 5 years or so have been focused on the historical and environmental relationship between the mitochondria and generation of sterile inflammation. A UK trained DO and ND he built a large functional medicine clinic (25yrs), before retiring from full time practice and focusing on research and clinical translation.
A number of contemporaneous studies have highlighted the importance of the gut microbiota for human health through the regulation of host immune response and energetic metabolism. Microbiota it is becoming clear, interact with host cells in particular by modulating the mitochondrial activities. This mitochondria – microbiota cross-talk is of interest because mitochondria and bacteria share numerous common structural and functional features. Recently a range of studies have exposed a strong association between microbiota quality and diversity and mitochondrial function in the development and potential restitution of NAFLD.
The intestinal microbiome is central to the narrative that NAFLD manifestation is largely a consequence of dysregulated innate immunity in response to persistent pro-inﬂammatory activity. The role of the intestinal microbiome is multi-factorial, functioning as an immunological, metabolic, and protective tool for optimal host health.
In addition, microbiota released metabolites can directly interfere with mitochondrial respiratory chain and ATP production. Some of them, particularly Short Chain Fatty Acids (SCFAs) have beneficial effects on mitochondrial activity, gene transcription and immune homeostasis. All these data suggest that microbiota target mitochondria to regulate its interaction with the host. Imbalance of this cross-talk may results in pathogenic state as observed in many common non communicable illnesses such as NAFLD. Strategies to modulate the quality and diversity of microbiota, improve metabolite induction, and associated microbial capabilities, mediate mitochondrial fitness and competence, improvement in transcription expression and metabolic and metabolite management will be explored as clinical methods for multiple intervention approaches. Food, food concentrates and related molecular pathways will be explored and discussed in context.
David Quig PhD, MS, BS
David’s presentation will address functional laboratory assessment of metabolism of three clinically relevant aspects of methionine metabolism and integrally associated folate derivatives. Genetic (SNPs) and epigenetic factors can affect methylation, transsulfuration and transmethylation pathways. Most important is the patients overall phenotypic expression of the pathways as SNP analysis alone only shows potential metabolic outcomes. Epigenetic factors can act independently or exacerbate potential adverse effects of SNPs.
Epigenetic factors that affect methionine metabolism include environmental toxicants, oxidative stress, proinflammatory cytokines, and nutritional insufficiencies. Among the latter bioactive folate is paramount, and simple assessment of RBC total folate is clinically insufficient. Preliminary research regarding the folate derivatives response to synthetic folic acid by subjects with different MTHFR C677T genotypes will be presented.
Nancy O’Hara, MD MPH FAAP
Dr. Nancy O’Hara is a board certified Pediatrician. Prior to her medical career, Dr. O’Hara taught children with autism. She graduated with highest honors from Bryn Mawr College and as a member of the Alpha Omega Alpha Honor Society from the University of Pennsylvania School of Medicine. She earned a Master’s degree in Public Health from the University of Pittsburgh. After residency, chief residency and general pediatric fellowship at the University of Pittsburgh, Dr. O’ Hara entered general private practice in 1993, and in 1998 began her consultative, integrative practice solely for children with special needs. Since 1999 she has dedicated her practice to the integrative and holistic care of children with neurodevelopmental disorders, ADHD, PANDAS/PANS, OCD, Lyme and Autistic Spectrum Disorder at the Center for Integrative Health, where she is a partner. She is also a leader in the training of clinicians, both in the United States and abroad.
Lyn Patrick, ND
Lyn Patrick ND graduated from Bastyr University in 1984 with a doctorate in naturopathic medicine and has been in private practice as a state licensed naturopathic physician in Arizona and Colorado for the last 30 years.
Dr. Patrick is a published author of numerous articles in peer-reviewed medical journals and has been a Contributing Editor for Alternative Medicine Review, a Medline-indexed journal of complementary/alternative medical research. She speaks internationally on the integrative medical treatment of chronic hepatitis C, environmental medicine, liver disease, endocrine disruption, metal toxicology and other topics.
She is a current member of the Board of Directors of the American College for the Advancement of Medicine (ACAM) and a planner and faculty member for ACAM’s continuing medical education conferences, lecturing in the area of chelation and metal toxicology.
She is a founding partner and educator for Progressive Medical Education, an online continuing education site for primary care providers Progressive Medical Education. She is also a founding partner and presenter at the Environmental Health Symposium, an international environmental medicine conference based in the United States.
In her spare time she enjoys biking, hiking and kayaking the mountains, lakes, and rivers of southwestern Colorado.
Who should attend?
This course is designed for physicians and health care providers who seek to improve their strategies and understanding of the intersecting mechanisms related to NAFLD and Methylation.