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Cynthia joined IMCF as a Board Member in 2010 and then as Executive Director in February 2011. Romayne is a recently retired Nurse Practitioner with a MA in Nursing from the University of Tennessee at Memphis. Sharon Dvora is an art educator and advocate for the creative potential of every individual, at every stage of life.
Kathy is a strong partnership and team builder with the ability to drive successful community-based programs from concept through advancement. Merrill Vargo is CEO emeritus of Pivot Learning Partners, a nonprofit school reform organization that serves a network of approximately 65 school districts and touches the lives of over 2 million children in California. The Integrative Medical Clinic Foundation relies upon the work of a network of faculty, staff, and volunteers from a wide variety of disciplines.
The Integrative Medical Clinic Foundation is a Santa Rosa, CA-based, educational, non-denominational, 501(c)3 nonprofit. ErrorSorry!This page is currently unavailable while we undergo routine maintenance.We apologize for any inconvenience. Integrative medicine refers to the integration of alternative and complementary medicine with traditional allopathic medicine. Because the breadth of alternative medicine cannot be summarized in a single writing, this chapter focuses on one field in integrative medicine, functional medicine.1 Functional medicine is an individualized approach to patient care that focuses on restoring balance to the dysfunctional systems by strengthening the fundamental physiologic processes that underlie them, and by adjusting the environmental inputs that nurture or impair them. Biochemical individuality is the rule rather than the exception and is the result of having thousands of genetic polymorphisms. Proposed mechanisms of aging as well as neurodegenerative and other organ-specific degenerative diseases have focused on the susceptibility of the cell to oxidative stress. Oxidative stress occurs when either endogenously metabolic generated reactive molecules or exogenous reactive substances in the environment interact with biologic structures, resulting in altered cellular physiology. Cells have developed antioxidant defenses to protect cellular proteins, membranes, and nucleic acids.
Oxidative stress can be assessed in the laboratory by measuring oxidized products from cellular damage. The production of ATP from oxidative phosphorylation depends on organic acids generated from the Krebs cycle. Today’s standard American diet is poor in nutrients, rich in calories, high in glycemic load, and deficient in antioxidants. Green tea, rich in catechins, has demonstrated antioxidant properties related to the combination of aromatic and hydroxyl groups that make up the structure of these polyphenols. Curcumin (derived from turmeric, the yellow spice in curries) has been shown to have a broad range of cellular effects in addition to its potent antioxidant activity.
Lycopene, a red carotenoid pigment, is found in a variety of plants including guava, pink grapefruit, watermelon, and tomatoes. In addition to whole foods, dietary supplements used to support these processes include those directed at facilitating energy production at the level of the Krebs cycle and oxidative phosphorylation. CoQ10 (ubiquinone) is a potent antioxidant and also a bioenergetic enzyme that participates in electron transport during oxidative phosphorylation. Many foods and supplements that have primarily been believed to have antioxidant properties also play a role in modulating inflammation, have anticancer properties through cell-signaling pathways, and can influence many physiologic effects through a plethora of other mechanisms and processes. Toxins that are present in our bodies originate from environmental exposures including the air we breathe, water we drink, food we eat, and the complex array of molecules we produce in our bodies that are metabolites of physiologic processes.
Each person has a unique biochemistry to detoxify substrate, which depends on individual genetic makeup, the load of environmental or endogenous toxins, and the substrate available to accomplish this task. Phase I biotransformation can be induced by various substrates or can be competitively inhibited. Although there are many likely processes that ultimately result in altered cellular physiology and the development of malignancies, detoxification and biotransformation play critical roles as a link to make persons either more susceptible or less susceptible to the environmental mediators of cancer development. Diet and nutritional supplements can be used to help balance the biotransformation of estrogen metabolites toward less-carcinogenic precursors.
Indol-3-carbinol (I3C) is a compound found in cruciferous vegetables such as broccoli, cauliflower, cabbage, and Brussels sprouts. Curcumin (the principal curcuminoid of turmeric) is another herb that influences detoxification. Depending on the clinical presentation of the patient and our underlying knowledge of the various detoxification pathways, we have the opportunity to improve the function of these pathways through nutritional supplementation.
Detoxification and biotransformation illustrate the individual approach we need to take with our patients given their unique genetic determinants that are influenced by powerful environmental factors. Immune and inflammatory imbalances can affect every organ system and can manifest as common clinical disorders that include neurodegenerative disorders, coronary heart and peripheral vascular disease, asthma, eczema, inflammatory bowel disease, connective tissue disease, and many other disorders. Advances in genetics and molecular biology have provided us with many new tools to examine the pathogenesis and propagation of immune and inflammatory disorders. Inflammation can be identified on the physical examination by the classic signs and symptoms including redness, increased temperature, swelling, and pain. Coronary artery disease (CAD) has evolved from the concept that atherosclerosis was a localized lipid storage disease that resulted in mechanical obstruction of blood flow to a dynamic process.
Mind-body interventions, such as meditation, result in modulation of the autonomic nervous system, which in turn influences endothelial function. In epidemiologic studies, fish intake has been associated with a reduced risk for the development of CAD and for the risk of sudden death in those patients with existing CAD. Laboratory testing is available to determine the contents and ratios of fatty acids from serum samples. With the recent clinical concerns related to the prostacyclin-mediated adverse effect of COX-2 inhibitors and concern over similar issues with COX-1 inhibition, natural anti-inflammatory agents represent another possible treatment modality for inflammatory conditions such as osteoarthritis and rheumatoid arthritis. Macromolecules must be processed to their basic building blocks to be absorbed via transport mechanisms in the small intestine. One clinical paradigm used extensively in functional medicine is referred to as the 4R model. Infants have been shown to have impaired tight junctions of the enterocytes, and introduction of antigenic foods within the first 6 to 12 months is associated with the development of inflammatory skin conditions. Leaky gut can be related to infections, use of NSAIDs, and the development of dysbiosis related to antibiotic use.
Removal of offending foods by following an oligoantigenic diet and observing clinical improvement is the gold standard for assessing food allergies. Replace, the second approach in the 4R program, refers to the supplementation of digestive factors that may be reduced, therefore preventing optimal function. Probiotics can inhibit pathogenic bacteria through a variety of proposed mechanisms that include competition for bacterial adhesion sites and bactericidal activity against pathogenic bacteria. In addition to reinoculation, the addition of prebiotics can provide nutritional substrate for the beneficial bacteria that in turn results in the production of short-chain fatty acids (SCFAs), which are believed to provide up to 70% of the nutritional energy used by colonic cells. The web of interactions expands as we consider the influence of the GI tract on downstream processes such as inflammation, oxidative stress, and detoxification. The sobering reality is that our youngest generation is predicted to have a shorter lifespan than their parents due to obesity and the development of type 2 diabetes. As health care providers we need to be mindful and vocal to promote positive lifestyle changes through education for our own families, patients, employees, school systems, and other institutions. The clinician must understand the scientific rationale for the use of particular herbs and supplements and must have resources to help guide patients and to prevent drug interactions.
The science supporting the use of supplements is robust, although clinical outcome studies are lacking for various reasons.
Maxwell PR, Rink E, Kumar D, Mendall MA: Antibiotics increase functional abdominal symptoms. Mohanty NK, Saxena S, Singh UP, et al: Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia. Singh S, Chakravarti D, Edney JA, et al: Relative imbalances in the expression of estrogen-metabolizing enzymes in the breast tissue of women with breast carcinoma. Borcea V, Nourooz-Zadeh J, Wolff SP, et al: Alpha-lipoic acid decreases oxidative stress even in diabetic patients with poor glycemic control and albuminuria. Panigrahi M, Sadguna Y, Shivakumar BR, et al: Alpha-lipoic acid protects against reperfusion injury following cerebral ischemia in rats. Markushin Y, Gaikwad N, Zhang H, et al: Potential biomarker for early risk assessment of prostate cancer. Peng CK, Mietus JE, Liu Y, et al: Exaggerated heart rate oscillations during two meditation techniques.
Melamed S, Shirom A, Toker S, et al: Association of fear of terror with low-grade inflammation among apparently healthy employed adults.
Sajadieh A, Nielsen OW, Rasmussen V, et al: Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease.
Lee TH, Hoover RL, Williams JD, et al: Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function.
Adam O, Beringer C, Kless T, et al: Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis.
Card T, Logan RFA, Rodrigues LC, Wheeler JG: Antibiotic use and the development of Crohna€™s disease. Genomic Medicine: Dawning of “Personalized” medicine or an invasion of fear and hype in a broken health care system? She is a designer of hands-on curriculum and community-based projects for schools, synagogues and public audiences. She is a mission driven executive with 20+ years of experience in healthcare operations, development and management. She is a leading contributor to critical areas and innovations in healthcare, including mobile healthcare, health information exchange (HIE), and access to care for underserved groups. I have found that having knowledge and tools in both areas allows me to provide the best care for my patients. Functional medicine looks at the triggers and mediators that lead to a particular clinical state.
One of the exciting frontiers that is emerging in functional medicine is the application of genetic analysis in areas such as inflammation and detoxification. Research in this area has demonstrated the role of oxidative stress-induced mitochondrial dysfunction and the subsequent cascade of mitochondria-initiated cellular apoptosis. Endogenously produced reactive oxygen species (ROS) include molecules such as superoxide, peroxynitrite, peroxyl radicals, hydroxyl, hydroxyl radicals, and singlet oxygen. The unsaturated component of lipid membranes undergoing oxidative damage releases lipid peroxides. To function correctly, the enzymatic processes in the Krebs cycle depend on cofactors that include nicotinamide dinucleotide derived from niacin, FAD derived from riboflavin, and thiamine pyrophosphate derived from thiamine. These processed foods lack the phytonutrients that provide our cells with the information to orchestrate a balanced cellular physiology to prevent cancer and inflammatory conditions. It has potent anti-inflammatory effects that may be related to its ability to inhibit biosynthesis of inflammatory prostaglandins from arachidonic acid and also its inhibitory effect on neutrophil aggregation. Lycopene is a potent antioxidant that might protect vulnerable cellular components from reactive oxygen damage. They can serve as cofactors in the processes for the generation of ATP and as antioxidants to quench aberrant ROS. Primary prevention of cancer and degenerative diseases through the intake of a whole-foods diet seems prudent. The greatest amount of energy that our bodies use outside of our growing years pertains to detoxifying these toxic molecules to prevent oxidative damage to vital intracellular proteins, DNA, and lipid membranes.
High concentrations of CYP 3A4 (a major cytochrome P-450 enzyme involved in metabolism of many drugs) and phase III antiporter activities are found at the tips of intestinal villi.
Because single nucleotide polymorphisms (SNPs) can occur in any combination of the enzymes involved in these processes, some persons present with signs and symptoms of toxicity such as fatigue, neurologic complaints, and cancer whereas others with similar exposures do not present with any problems. Genetic variations through SNPs also occur that can result in either increased or decreased enzyme kinetics. Our diet can have either a positive or negative effect in this cascade of nutragenomic-influenced events.
In general, fruits and vegetables contribute to the upregulation of hepatic detoxification enzymes. I3C can shift the metabolism of estrogen to the protective 2-hydroxy estrogens by upregulating the expression of CYP 1A1 that increases the 2-hydroxylation of estradiol and estrone.

COMT is important in the metabolism of estrogen to products that have lower potential for oxidative DNA damage and reduced inflammatory properties. In vitro and animal studies have shown that curcumin inhibits phase I CYP 1A1 and increases activity of phase II reactions. This web of complex interactions examined in the functional medicine paradigm gives us an opportunity to offer our patients additional options in their quest for health and wellness. Being able to mount an immune response is critical to our survival, but when the response is perpetuated after the insult has been eliminated or as a result of disordered regulation, destruction to the host occurs and results in chronic inflammatory disease processes. Functional medicine provides a paradigm to examine and to modulate these states of dysfunction by applying our understanding of the underlying pathophysiology and the factors that support optimal function.
The molecular mediators of inflammation interact in a complex and synchronous array of events that either serve to destroy invading organisms or that hover in an anticipatory mode in ongoing vigilance that serves to protect the host.
It is now characterized as an inflammatory disorder from its earliest stage in atheroma formation to the clinical hallmark of acute myocardial infarction related to inflammatory-mediated plaque rupture. There is strong evidence of reduced adverse events in patients who have established coronary heart disease and who use stress-reduction techniques.
Serum levels of this protein have been shown to be independently correlated with an increased risk of adverse cardiovascular events. The benefits of supplemental fish oils in the treatment of rheumatoid arthritis are well documented. It is important to make sure that the fish oil supplement has been purified and tested for heavy metals and other contaminants. These herbal preparations might modulate inflammation at various points in the inflammatory pathways, including modulation of cytokine production or production of arachidonic acid proinflammatory products (see Box 3). This food intake is composed of macromolecules, micronutrients that include vitamins and minerals, toxins, and other organisms capable of invasion.
The first approach in the 4R model, remove, refers to the elimination of pathogenic organisms including fungi, pathogenic bacteria, parasites, and other ingested substances that include environmental toxins and foods. Symptoms suggesting IgG-mediated food allergies include irritable bowel syndrome, apthous ulcers in the oral mucosa, serous otitis media, migraine headaches, asthma, chronic sinusitis, nasal congestion (without rhinorrhea), eczema, and memory loss. Elimination diets are typically continued for approximately 1 month, and then food groups are reintroduced every 4 days or so. Hydrochloric acid production in the gastric mucosa is necessary for the optimal digestion of proteins and for the absorption of nutrients such as calcium.
This refers to the supplementation of desirable microorganisms (probiotics) into the GI tract. Probiotics produce metabolites, such as butyric acid, that are beneficial to barrier function and colonocyte health. Examples of prebiotics include fructans, fructo- oligossaccharides, inulin, and arabinogalactans. Nutrients that have been shown to support the repair process of the intestinal epithelium include glutamine, zinc, pantothenic acid, and essential fatty acids.
Stool testing for meat fibers can imply adequacy of HCl and pancreatic enzymes involved in protein digestion. Imagine the scenario where the patient in our office presents with an inflammatory condition such as eczema or rheumatoid arthritis. Since the mid-19th century, the average American lifespan has increased by approximately 2.5 years per decade. There are many different starting points to accomplish this in our patients, including stress reduction, healthy whole-food diets, and exercise.
Pettit treats children and adults of all ages, and common problems such as foreign body in the ear, dizziness, and hearing loss.
She is passionate about teaching, learning, consumer self-efficacy, and the integration of CAM modalities into clinical settings.
She has extensive experience and training in health education, peer engagement, and social outreach.
Vargo’s leadership, Pivot Learning Partners developed a sustainable business model and a series of innovative programs to both develop the education leaders and build the education organizations of the future.
Integrative Medical Clinic Foundation provides scholarship assistance for our programs on a needs basis, whenever possible.
It is clear that allopathic medicine provides many powerful lifesaving treatments to our patients. This takes into account the environmental factors that wash over a patient’s particular genetic uniqueness that then can result in either vitality or dysfunction. It is the role of the clinician to examine this complex web of interactions and develop a treatment plan to help our patients.
Most ROS originate intracellularly in the mitochondria, which converts the energy potential from macronutrients from the diet into cellular energy currency that includes adenosine triphosphate (ATP), reduced nicotinamide adenine dinucleotide (NADH), and reduced flavin adenine dinucleotide (FADH2).
Enzymatic processes that also contribute to antioxidant defense include superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. The production of energy from fatty acids depends on the transport of free fatty acids across the mitochondrial membrane, which requires conjugation to carnitine by the enzyme carnitine palmitoyltransferase I. One of the major polyphenols in green tea, (-)-epigallocatechin-3-gallate (ECGC), has been shown to decrease lipopolysaccharide-induced tumor necrosis factor (TNF) production in a dose-dependent manner.
Many of the substrates used in these processes are conditionally essential, which implies that under certain conditions, optimal function cannot be maintained through endogenous synthesis alone. In its reduced form, dihydrolipoic acid has been demonstrated to have distinct antioxidant actions that include free radical-scavenging activity; it also can regenerate endogenous antioxidants such as glutathione, CoQ10, and vitamins E and C.
We are beginning to have the tools available to identify persons at increased risk for oxidative damage and development of degenerative disease due to their specific genetic polymorphisms. This complex process has to be able to recognize thousands of diverse molecules and perform a highly orchestrated synchronous detoxification process that includes molecular modification by phase I enzymes, conjugation to water soluble molecules by phase II enzymes, and then efflux out of the cells by phase III proteins. Other tissues with significant detoxification systems include the lungs, kidneys, reproductive tissues, and nasal epithelium.
Laboratory testing is currently available for gene panels that are involved in detoxification and biotransformation. Acetaminophen is primarily metabolized through a phase II process that includes sulfation to form acetaminophen sulfate and glucuronidation to form acetaminophen glucuronide. Phase II conjugation may be affected by individual polymorphisms and is also subject to available substrate for conjugation and elimination. Phytonutrients can potentially affect hormone response or metabolism through a variety of mechanisms that include competitive inhibition at receptor sites, induction or inhibition of phase I processes, or upregulation of phase II processes. Research has also shown that I3C induces in vitro tumor cell death by regulating the apoptotic pathway and through selective stimulation of a tumor-suppressor gene. S-adenosylmethionine (SAMe) is a substrate for COMT methylation, and availability of SAMe depends on its own set of factors, which include polymorphisms for methylenetetrahydrofolate reductase (MTHFR), nutritional status, and environmental factors. A 50-year-old patient who is a laboratory technician in an area hospital presents with episodic extreme fatigue that would last for several days following the landing of life flight helicopters at the heliport near his laboratory.
This state of dysfunction was likely present long before the manifestation of the disease process. Factors that support optimal function can be as specific as a nutritional supplement that modulates the inflammatory response or as broad as the mind-body influence on the mediators of inflammation (Box 3).
When this balance is tipped in the direction of activation by any one of a variety of triggers, these processes can then become perpetuated and result in disease processes.
Heart rate variability represents a beat-to-beat variation in the sinoatrial node activation and can be noninvasively measured to determine output of the autonomic nervous system. They are also precursors of eicosanoids, which through their messenger functions influence the inflammatory response of the organism.
Fish oils are mostly composed of the essential fatty acids in the omega-3 family, which includes eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A diet low in arachidonic acid and the addition of fish oil has been shown to produce a superior result to that of diet alone.20 Other inflammatory conditions, including inflammatory bowel disease, immunoglobulin (Ig) A nephropathy, psoriasis, and coronary artery disease, are modified by fish oils.
Clinical trials for specific conditions have been performed with herbal preparations and can help direct the clinician in the use of these agents. The gastrointestinal (GI) tract must function in an optimal fashion to be able to process and absorb these molecules and to keep invading organisms or toxins from entering the host. Hydrochloric acid production in the stomach, pancreatic enzyme production, loss of tight junctions of the small bowel intestinal epithelium (causing leaky gut), and dysbiosis can all result in GI dysfunction and downstream effects. Food allergy is believed to be mediated by the passage of incompletely digested proteins across the intestinal epithelium, where it stimulates an immune response with the production of IgG antibodies. IgG-mediated food allergy might trigger other disorders (through stimulation of the immune system via immune complexes) such as rheumatoid arthritis and inflammatory bowel disorders. Lactulose is not normally absorbed, and an elevated ratio might suggest impaired mucosal integrity. If symptoms recur with re-introduction (it can take a week of continued ingestion to develop clinical symptoms due to the delayed type of response from immune complex formation), then that food is identified as a possible trigger.
This balance, involving hundreds of species of bacteria, can be impaired through the use of antibiotics and through exposure to environmental toxins.
Studies have demonstrated the effectiveness of probiotics in children with viral diarrhea illness. Glutamine represents the major metabolic fuel for the epithelial cells in the small intestine.
We know that approximately 70% of cancers and other disease processes are a result of the environment and 30% are related to genetic predisposition. Healthy lifestyle activities are associated with decreased disability, illness, and a more functional status. As a Feldenkrais Practitioner, she is a founding member of the Practitioner Team at the Integrative Medical Clinic of Santa Rosa.
She is a Certified Balint Leader, working healthcare providers that explore the emotional aspects of provider-patient relations.
However, we need to offer our patients with chronic medical disorders an integrated approach, taking into account their individual situations, the interactions between the environment, and their particular genetic uniqueness.
The environmental effect can be as broad as the mind’s influence on the psychoneuroendocrine system or as narrow as a conditionally essential nutrient in a metabolic pathway that has been affected by an environmental toxin. Through the process of oxidative phosphorylation in the mitochondria, molecular oxygen is consumed and reduced to water.
Oxidation of guanosine molecules in DNA produces 8-hydroxydeoxyguanosine (8OHdG), which has a close relation with neuronal oxidative stress. The richly pigmented phytochemicals in vegetables and fruits serve antioxidant functions, and intake of vegetables and fruits has been associated with a decreased risk of some cancers. Clinical trials have also demonstrated a prevention or reduction of the progression of high-grade prostate intraepithelial neoplasms into prostate cancer.
It has also been shown to reduce doxorubicin-induced myocardial toxicity in patients receiving chemotherapy without compromising the chemotherapeutic effectiveness. Targeted dietary and nutraceutical supplemental therapy is possible for these people based on sound scientific data and inferences (Box 1). Hundreds of proteins participate in these processes, which are highly dependent on having the necessary substrate available to complete these processes. The ability of the nasal epithelium to detoxify xenobiotics is important so that loss of our ability to detect scents due to habituation does not occur. Obtaining gene panels on our patients might help us determine this aspect of their risk for developing diseases related to detoxification.
A study of the expression of estrogen-metabolizing enzymes in human breast tissue has found increased levels of CYP 1B1(increased enzyme activity) and decreased levels of catechol-O-methyl-transferase (COMT) in patients with breast cancer.9 Both of these are common polymorphisms found in the general population. It remains to be seen through clinical trials whether whole food or supplement use can influence clinical outcomes.
Supplementation with SAMe in patients who have COMT polymorphisms, in addition to folic acid, and vitamins B12, and vitamins B2 and B6 for those with MTHFR polymorphisms, can supply the needed substrate to favor the metabolism of estrogen to noncarcinogenic molecules. It also downs regulates molecules in the inflammatory pathway, including COX-2, 5-LOX, NF-κB, and TNF.
His physical examination and routine laboratory tests to evaluate the fatigue were unremarkable. Modification of unhealthy lifestyle habits remains the single most powerful strategy for preventing CAD.

Omega-6 and omega-3 fatty acids are the substrates for the production of series 1 and series 3 eicosanoids, respectively, which serve to inhibit the inflammatory response, whereas arachidonic acid-derived eicosanoids of the series 2 family are proinflammatory (Fig.
It is also important to review the concentrations of the actual omega-3 components (EPA and DHA) because the potency varies from product to product.
The microflora of the colon, which is composed of approximately 100 billion bacteria, is also intimately involved in intestinal health and generates metabolic byproducts that support the health of the host in a symbiotic fashion.
Functional disorders such as irritable bowel syndrome can occur as a result of this disordered physiology.
With continued ingestion of these proteins and translocation across the intestinal epithelium due to leaky gut, immune complexes are formed that result in immune activation.
Peptides produced through the partial hydrolysis of gluten and casein that leak across an impaired GI mucosa have opioid properties and can result in neurobehavioral symptoms.
Food allergy testing for IgG antibodies is also commercially available and can help guide decisions regarding dietary modifications. Osteoporosis has been described in patients taking proton pump inhibitors, which may be related to this mechanism. The environmental influence on the colonization of the intestinal microflora begins at the time of delivery and continues for the first 2 years of life.
Pantothenic acid (vitamin B5) is needed for the production of coenzyme A (CoA) and acyl carrier proteins (ACP).
The environment washes over the genes to result in either an inhibition or potentiation of genetic expression.
The lifestyle factors that have the highest correlation to health are smoking, body mass index, and exercise.
Traditionally they survived in a hostile environment where the next meal was not necessarily around the corner. We have the opportunity to affect the children, grandchildren, and future generations of the patients we serve. She serves as Medical Director of the Integrative Medical Clinic of Santa Rosa. Ellen is leading the Foundation’s efforts in person-centered care and integrative medicine to all residents of Sonoma County. She is passionate about encouraging personal empowerment and agency in health, and strongly believes in the Imagine You model.
Vargo works as an independent consultant working to support both nonprofit and public education leaders. It is estimated that there are more than 2 million polymorphisms that can potentially affect the way a person experiences health or disease.
The ideal of having outcome studies for many of these proposed treatments is a story in progress.
The fragrance produced by a rose must be metabolized by our detoxification system to allow the system to become resensitized so we can to continue to perceive the fragrance. Specific minimally processed whole foods or nutritional supplements can be prescribed to optimize the function of these processes. If these pathways are impaired or compromised by depletion of essential cofactors, acetaminophen undergoes phase I biotransformation to N-acetyl-p-benzoquinone imine (NAPQI).
Reactive intermediates produced through phase I processes are conjugated by phase II processes.
Moreover, the flora of the colon can influence detoxification and estrogen metabolism through the bacterial production of κ-glucuronidase, which deconjugates glucuronyl side chains, resulting in enterohepatic recirculation of the transformed molecule, leading to increased toxic load. Green tea also affects detoxification by affecting phase I and phase II enzyme activity, has anti-inflammatory effects.
Symptoms suggesting a detoxification issue included a perceived heightened olfactory sensitivity to exhaust and diesel fumes (this may be related to enhanced elimination of these substances through phase I detoxification in the nasal epithelium, thus increasing sensitivity due to a reduction of neuronal habituation). The host’s susceptibility to inflammatory processes can be related to genetic uniqueness as manifested by cell membrane proteins involved in antigen presentation and cytokine polymorphisms. Several studies have shown the positive effect of aerobic exercise on various cytokines that are associated with inflammation. Like the thiazolidinedione class of drugs used in diabetes management, fish oils are also peroxisome proliferator-activated receptor (PPAR) γ agonists that can modulate the expression of this family of genes.
Dosing recommendations for specific conditions are varied and range from 1 to 9 g of omega-3 fatty acids. Disruption of this flora (dysbiosis) can result in the production of toxic bacterial metabolites or the reduction in beneficial byproducts.
This is in contrast to the traditional concept of food allergy, which is IgE mediated and can represent a life-threatening, immediate type of immune reaction. The results from these tests seem to be quite variable, so proceeding straight to the elimination diet is a better practice if possible.
Pancreatic enzymes may be functionally deficient in a variety of clinical conditions including eczema and steatorrhea. The maternal microflora inoculates the infant and influences the development of this symbiotic relationship and eventual milieu of the GI tract. The use of probiotics together (synbiotics) has been shown to be beneficial in specific clinical situations. CoA is a cofactor in more than 70 enzymatic pathways, and ACP is an essential cofactor for the fatty acid synthase complex. Stool cultures can assess quantitative measures of Lactobacillus and Bifidobacteria along with pathogenic bacteria and yeast. Our hypothetical patient then received antibiotics or had some other insult that favored the development of a dysbiosis and leaky gut that in turn resulted in immune complex formation and activation of cytokines. The greatest focus of prevention by allopathic and integrative medicine practitioners should be geared toward smoking cessation, consuming a healthy diet, achieving a healthy body weight, and regular exercise. To survive in this environment, they needed to develop thrifty genes so that in times when food was available they could store it efficiently. Becky is a former member of the Sonoma County Violence Profile Committee, and the Community Health Worker Advisory Board at SRJC. These ROS molecules, if left unchecked, damage cellular structures such as mitochondrial membranes, proteins, and DNA.
NAPQI is a highly reactive molecule, and if it is not rapidly conjugated with glutathione, it will cause cellular toxicity. In the case of acetaminophen toxicity, ethanol induction of CYP 2E1 results in increased production of NAPQI. This example illustrates the weblike interaction of molecular processes that is the rule rather than the exception in biologic systems.
Green tea polyphenols have been studied as cardiovascular disease and chemopreventive agents.11-13 Many phytonutrients have been demonstrated to have a broad range of effects on a variety of cellular physiologies including detoxification, inflammation, and oxidative stress (Fig.
Genomic testing on this patient revealed polymorphisms in the phase I enzymes CYP 1B1 and CYP 2E1. Triggers and mediators of inflammatory responses include infections, dietary factors, environmental toxins, and even the bacterial composition of the digestive tract.
Healthy diets, such as a Mediterranean diet, reduce the intake of saturated fats and thus lower the precursor intake of arachidonic acid and affect the cascade of proinflammatory prostaglandins and leukotrienes.14 Whole foods, especially those rich in phytonutrients, have beneficial effects due to their antioxidant and anti-inflammatory properties.
An example of this effect is the lowering of triglyceride levels through fish oil supplementation. It can take several months to notice a clinical response in patients with active inflammatory disorders. Approximately 60% of the immune system is located in the GI tract and is referred to as the gastrointestinal associated lymphoid tissue (GALT).
The symptoms in patients with irritable bowel syndrome can improve with the addition of empirical supplemental pancreatic enzymes.
Essential fatty acids such as omega-3 from fish oils are involved in cell membrane function and also have anti-inflammatory properties.
He also inherited an SNP that results in the enhanced production of an inflammatory cytokine, which in turn is expressed in this inflammatory condition for which he is now being evaluated. As our knowledge in molecular medicine advances, we can now demonstrate that these activities have associated biologic markers that show improvement in cellular function, decreased inflammatory mediators, and a reduction in oxidative stress.
When their environment changed and highly processed, nutrient-poor, calorie-dense food became immediately available in the convenience store or at the fast-food establishment, their genotype continued in its thrifty mode and resulted in the development of obesity and type 2 diabetes with its myriad of complications, human suffering, and health care costs. She was instrumental in co-creating the curriculum for the pioneering Health Navigation Certificate Program co-sponsored by IMCF and the Extended Education Department at Sonoma State University. She is a member of Sonoma Health Action Steering Committee and Committee for Healthcare Improvement.
Mitochondrial DNA is especially vulnerable to oxidative damage because it lacks the protective and repair mechanisms found in nuclear DNA. If the phase I cytochrome P-450 enzyme CYP 2E1 is induced to promote biotransformation to NAPQI, or if essential cofactors for phase II conjugation are lacking, the outcome favors production of this reactive intermediate, which can cause cellular damage and possibly liver failure.
At the same time, a fasting state can deplete the limited supply of sulfur-containing amino acids used as phase II substrates. Polymorphisms for phase II enzymes included a null genetic expression (no gene present) for hepatic glutathione-S-transferase. We again begin to appreciate the weblike interactions that the mediators of inflammation have on virtually all the organ systems of the patient.
Meals with high glycemic loads (which include highly processed or quickly digested macronutrients) can induce an inflammatory response as monitored by levels of C-reactive protein (CRP).
Although omega-3 fatty acids can affect platelet aggregation, no data suggest any increased risk of hemorrhagic events.
Activation of GALT can have far-reaching downstream effects, as can be seen in the peripheral manifestations of inflammatory bowel syndrome or gluten sensitivity.
Within each of these groups of bacteria, there are many species, and each has its unique characteristics and produces different effects in clinical trials. In patients with irritable bowel syndrome, empirical treatments with these supplements in a stepwise fashion can result in significant clinical improvements that might not have been evident based on laboratory results. His diet consists of highly processed inflammatory foods, which is the usual complement of the standard American diet. Thus, we can now look for a molecular basis for what we have shown to be either a beneficial or detrimental lifestyle. This imbalanced state can result in liver toxicity at what we would consider normal doses of acetaminophen.
This combination of environmental and genetic interactions could result in the rapid conversion of hydrocarbons to reactive intermediates by phase I that could not be optimally conjugated by phase II, resulting in toxic metabolites and the manifestation of his symptoms. A whole-food diet has a lower glycemic index, because foods are digested slowly and the fluctuations of blood glucose levels are less pronounced. However, caution is suggested when adding omega-3 fatty acids to the diet of patients who are taking anticoagulants or antiplatelet therapy. The GI system can have large effects on either keeping physiologic processes in balance or initiating and perpetuating imbalances in inflammation, oxidation, and detoxification, which are often manifest in organ systems that seem far removed from the GI system. After enough hits, the mitochondria and the bioenergetics of the cell are altered in ways that can result in cellular apoptosis and loss of organ function.
Treatment was initiated with a combination of supplements and herbs that supported phase II detoxification through the addition of antioxidants and cofactors. Fish oils should be discontinued one week before surgical procedures to decrease the risk of hemorrhage. If it is possible to intervene in this state of dysfunction and supply the needed nutrients or achieve lifestyle changes, then disease could be prevented. Within weeks, his clinical symptoms resolved completely after years of intermittent fatigue due to environmental exposures.
Understanding these interconnections gives us additional tools to evaluate and treat our patients in a more comprehensive manner. As an additional preventive strategy, this patient should also include in his diet cruciferous vegetables and phytonutrients to favor the conversion of estrogen to safer metabolites, which could also result in a lower risk of prostate and other cancers.

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