INSIDER S GUIDE Organic Acids: Dysbiosis By Ron Grisanti, D.C. & Dicken Weatherby, N.D.

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1 Functional Medicine University s Functional Diagnostic Medicine Training Program INSIDER S GUIDE Organic Acids: Dysbiosis By Ron Grisanti, D.C. & Dicken Weatherby, N.D. Limits of Liability & Disclaimer of Warranty We have designed this book to provide information in regard to the subject matter covered. It is made available with the understanding that the authors are not liable for the misconception or misuse of information provided. The purpose of this book is to educate. It is not meant to be a comprehensive source for the topic covered, and is not intended as a substitute for medical diagnosis or treatment, or intended as a substitute for medical counseling. Information contained in this book should not be construed as a claim or representation that any treatment, process or interpretation mentioned constitutes a cure, palliative, or ameliorative. The information covered is intended to supplement the practitioner s knowledge of their patient. It should be considered as adjunctive support to other diagnostic medical procedures. This material contains elements protected under International and Federal Copyright laws and treaties. Any unauthorized reprint or use of this material is prohibited Functional Medicine Training Program Page 1 of 15

2 Contents CONTENTS... 2 ORGANIC ACIDS (DYSBIOSIS)... 3 AN OVERVIEW... 3 THE ORGANIC ACIDS FOR DYSBIOSIS... 4 THE VALUE OF ORGANIC ACIDS COMPARED TO STOOL ANALYSIS IN DETECTING DYSBIOSIS... 4 CLINICAL INTEREPRETATION... 6 BENZOATE Ingestion of benzoic acid (a common food component) HIPPURATE CAUSES OF HIGH LEVELS P-HYDROXYPHENYLACETATE (HPA) D-LACTATE CITRAMALIC ACID DIHYDROXYPHENYLPROPIONIC ACID (DHPPA) PHENYLACETIC ACID (PAA) SUCCINIC ACID INDOLEACETIC ACID (IAA) TARTARIC ACID & ARABINOSE P-HYDROXYBENZOATE AND P-HYDROXYPHENYLACETATE INDICAN TRICARBALLYLATE Functional Medicine Training Program Page 2 of 15

3 An Overview Organic Acids (Dysbiosis) The Organic Acid Comprehensive Profile is like an emission test performed on your car the exhaust is examined to see how efficiently the engine is burning fuel. Similarly, certain compounds in your urine called organic acids reveal the efficiency of your body s machinery. Many organic acids result from the metabolic pathways, or chemical reactions, your body uses to transform food into energy, growth, maintenance, and repair of body tissue. Like spark plugs that ignite fuel in a car engine, vitamins and other essential nutrients are necessary for these chemical reactions that power your metabolic machinery. Thousands of these reactions occur in your body every second and are the basis of your level of health and vitality. The figure below illustrates a well-functioning metabolic pathway. Molecule A is converted to Molecule B by the enzyme AB. Molecule B is converted to Molecule C by the enzyme BC and so on, all the way down the metabolic pathway. Many enzymes require nutrients such as specific vitamins and minerals in order to perform their functions in converting one molecule to another. If specific nutrients are not available in adequate amounts, important reactions cannot occur as well as they should. The illustration below shows what happens when the nutrient is not present in adequate amounts so that enzyme AB functions inefficiently. A small amount of Molecule A is converted to Molecule B and the remainder builds up and spills into the urine. Notice that Molecules C through D downstream are also affected. Visualize this process as a dam blocking a stream very little water flowing downstream and an overflow occurring upstream. The Organic Acid Comprehensive Profile measures the Functional Medicine Training Program Page 3 of 15

4 overflow of certain organic acids in your urine to determine what blockages may be occurring in your metabolic pathways due to nutrient insufficiencies or other issues. High levels of many organic acids can indicate which nutrient insufficiencies may be affecting your health. Other organic acids come from toxins you have been exposed to, and still others show how your body is responding to toxins. When these are high and sometimes low, you are able to outline an effective treatment for The Organic Acids for Dysbiosis Organic Acid Profiling specific for dysbiosis measures the by-products of microbial metabolism that are excreted in urine, making it particularly useful in detecting the existence of pathogenic microbial overgrowth. Organic acids commonly cover a broad range of microbial by-products and are valuable in providing key information for cellular and mitochondrial energy metabolism, neurotransmitter metabolism, nutritional assessment of vitamins and minerals and gastrointestinal function and dysbiosis. The focus in this lesson will be exclusively devoted to GI function and dysbiosis. This tests allows the examiner to assess microbial overgrowth and guide and monitor therapy. The Value of Organic Acids Compared to Stool Analysis In Detecting Dysbiosis While stool testing has been the long-established method for identifying dysbiosis, "there is increasing support that the fecal microbiota does not accurately reflect the colonic condition. When pathogens are distributed throughout the small and large intestines due to chronic infestation, their identification in stool is possible. Stool testing does not reveal the situation in the small intestine, however, and there is increasing evidence that the fecal microbiota does not mirror the colonic situation. Consequently, the major limitations of stool testing are its high degree of false negatives and the greater potential of missing a significant dysbiotic clinical situation. A client with negative stool specimen can have dysbiosis markers in urine, revealing metabolic by-products of pathogenic microbiota growing in the small intestine. Functional Medicine Training Program Page 4 of 15

5 Functional Medicine Training Program Page 5 of 15

6 Clinical Interepretation Benzoate Benzoate is metabolized in Phase II glycine conjugation to hippurate. Enzymes from gut bacteria may reverse this process, producing high benzoic acid Bacterial deamination of the amino acid phenylalanine also produces benzoate. Benzoate is produced by intestinal bacteria. It can also occur in the urine because of exposure to foods that contain benzoate as a preservative, such as pickles and lunchmeats. The amino acid glycine and vitamin B5 are required to eliminate benzoate from your body. When benzoate is high, regardless of the source, these nutrients will help to lower the level. Inadequate conversion to hippurate in the liver. Glycine and pantothenic acid are the rate-limiting factors Malabsorption of phenylalanine due to low HCL in stomach Ingestion of benzoic acid (a common food component) Preservative in packaged foods, Functional Medicine Training Program Page 6 of 15

7 Pickles Lunch meats Natural ingredient of cranberries. **Suspect when other bacterial markers are not elevated. Rule out high-benzoate foods (e.g., plums, prunes, rhubarb, cranberries, preservative in foods) Glycine Pantothenic acid Pre-Probiotics Antibiotics Decrease sugars Hippurate Hepatic Phase II glycine conjugation of benzoate One of the most abundant compounds in normal urine Hippurate is made as your liver metabolizes benzoate in preparation for elimination. Bacteria also convert certain food components (polyphenols) into hippurate. Generally, high hippurate is a marker for bacterial overgrowth in the intestines. When no other bacterial markers are high, heavy dietary intake of benzoate is indicated Internal bacteria convert polyphenols, such as catechin from dietary sources (tea, apple cider) into benzoic acid and excreted as hippuric acid Excessive intake of pickles, lunch meats and cranberries Malabsorption of phyenylalanine due to low HCL in stomach Rule out high-benzoate foods (e.g., plums, prunes, rhubarb, cranberries, preservative in foods) Glycine Pantothenic acid Pre-Probiotics Antibiotics Functional Medicine Training Program Page 7 of 15

8 Decrease sugars p-hydroxyphenylacetate (HPA) Derived from Tyrosine Not a product of normal human metabolism Malabsorption of tyrosine due to low HCL in stomach Dysbiosis: Rule out the presence of Proteus vulgaris, Clostridium Difficile, Giardia, Anaerobic bacteria Lactose intolerance Malabsorption of phyenylalanine due to low HCL in stomach Pre-Probiotics Antibiotics: Metronidazole for Clostridia or Giardia Natural anti-microbial complex Decrease sugars D-Lactate A Neurotoxic at elevated concentrations When carbohydrate malabsorption is present, the otherwise favorable genus Lactobacillus,or other D-lactate producing strains, can overgrow and produce toxic amounts of D-lactate. D-Lactate goes up when species that are normally beneficial, such as Lactobacillus acidophilus, are too high. An elevation of L acidophilus in the small intestine can be a result of an inability to absorb carbohydrates. Probiotics containing beneficial bacteria other than lactobacillus should be given to restore the balance of beneficial flora. Functional Medicine Training Program Page 8 of 15

9 Citramalic Acid Metabolite of yeast or anaerobic bacteria, including Clostridia Overgrowth of bacterial pathogens Antifungals Antimicrobials Anti-yeast diet Probiotics Dihydroxyphenylpropionic Acid (DHPPA) Intestinal bacterial overgrowth Produced when Clostridia acts upon unabsorbed tryptophan, tyrosine, or phenylalanine) Presence of elevated levels of DHPPA in the urine may thus suggest overgrowth of Clostridia and/or Pseudomonas, as well as a degree of malabsorption of aromatic amino acids Clostridium overgrowth Pre and Probiotics (Saccharomyces Boulardii) Antibiotics: Metronidazole (Flagyl) Natural Anti-Microbial Complex Decrease sugar Investigate possible causes of malabsorption (Gluten sensitivity? Food allergy? Functional Medicine Training Program Page 9 of 15

10 Phenylacetic Acid (PAA) Produced from bacterial degradation of unabsorbed phenylalanine Intestinal bacterial overgrowth Malabsorption of phenylalanine due to low HCL in stomach Possible gastric hypochlorhydria Suspect Clostridia overgrowth Pre and Probiotics (Saccharomyces Boulardii) Antibiotics: Metronidazole (Flagyl) Natural Anti-Microbial Complex Decrease sugar Investigate possible causes of malabsorption (Gluten sensitivity? Food allergy? Consider mucosal support agents, betaine HCl Succinic Acid Produced from bacterial degradation of unabsorbed glutamine; also Citric Acid Cycle intermediate) Bacterial degradation of glutamine (e.g., dysbiosis or UTI); OR insufficiencies of Iron (Fe) or B2 (as FAD) (metabolism in Citric Acid Cycle) Correct malabsorption, dysbiosis, or UTI (Gluten sensitivity? Food allergy?) Mucosal support agents Iron and/or Riboflavin Functional Medicine Training Program Page 10 of 15

11 Functional Medicine Training Program Page 11 of 15

12 Indoleacetic Acid (IAA) Produced from bacterial degradation of unabsorbed tryptophan Malabsorption of tryptophan Possible gastric hypochlorhydria Investigate possible causes of malabsorption (Gluten sensitivity? Food allergy?) Mucosal support agents, betaine HCl Functional Medicine Training Program Page 12 of 15

13 Tartaric Acid & Arabinose Breakdown product of hyaluronic acid, also contained in some foods Ingestion of tartaric acid-containing foods (fruits, especially grapes, raisins, or wine; also as cream of tartar in some soft drinks and baked goods; OR possible joint inflammation leading to release of hyaluronic acid. Ingestion of arabinose rich containing foods (apples, plums, cherries, grapes) Elevated urine tartrate can be the result of (intestinal) yeast overgrowth. Rule out tartaric acid-containing foods Address any joint inflammation Natural Anti-Microbial Complex Decrease sugar p-hydroxybenzoate and p-hydroxyphenylacetate These are made by different kinds of bacteria from food components. Certain antibiotics will cause an increase in this type of bacteria. Functional Medicine Training Program Page 13 of 15

14 Indican The Indican tests for the presence of indol, a metabolic byproduct of the action of intestinal bacteria on the amino acid tryptophan. The level of indican is an index of the efficiency of protein digestion. High levels indicate bacterial overgrowth in the small intestine. High levels strong indicator of poor protein digestion Protein Digestion Insufficient gastric hydrochloric acid, insufficient digestive enzymes, adverse food reactions, parasitic infection, fungal infection, overgrowth of bacteria that metabolize specific proteins, hypermotility of the small intestine, or other gastrointestinal dysfunction can compromise protein digestion. Indican excretion is reduced when the intestines are populated with strains of lactobacillus. Improved protein digestion Tricarballylate Produced by strains of bacteria that are likely to grow after use of antibiotics and acid-blocking drugs. It binds tightly to minerals such as magnesium, calcium and zinc, blocking their absorption, making mineral levels low when this compound is high. Functional Medicine Training Program Page 14 of 15

15 Functional Medicine Training Program Page 15 of 15

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