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Oxalate Metabolites

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Copyright© 2019. Health Training Associates, LLC. All rights reserved.

(Advanced OAT Mastery Course Lecture for Module #4)

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DisclaimerThe material contained within this document/presentation and subsequent support

documents for the Advanced OAT Mastery Course (AOAT) is not intended to replace the services and/or medical advice of a licensed health care practitioner, nor is it meant to encourage diagnosis and treatment of disease. It is for health education purposes only based on the clinical experiences of its authors. Health Training Associates, LLC., Kurt N.

Woeller, D.O., Tracy Tranchitella, N.D. or any of its associates and members do not accept legal responsibility for any problems arising from your personal experimentation with the health education information described herein. Any application of suggestions

set forth in the following portions of this document/presentation and other support documents of the AOAT (or other courses from Integrative Medicine Academy) is at the

reader/listener’s discretion and sole risk. As a health practitioner you are solely responsible for implementing treatment strategies for your patients or clients.

Implementation or experimentation with any supplements, herbs, dietary changes, medications, and/or lifestyle changes, etc., discussed in this course, including support

documents and member forum, is done so at your sole risk. As an individual you accept full responsibility for using/implementing any health education information discussed in this course and understand that experimentation with supplements, medications,

herbs, dietary changes, etc. needs to be discussed with your (or your child’s) personal physician first.

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Support Documents for Module #4

• Oxalate Control (PDF article)

• Low Oxalate Program (handout)

• High Oxalate Food List (handout)

• Module #4 Action Plan (PDF)

• Lecture slides (PDF)

• Lecture slides: note-taking (PDF)

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• Oxalate – what is it?

• Organ and cell damage examples

• Links to Aspergillus mold

• The chemistry of oxalates

• Hyperoxaluria types

• Treating high oxalate, including supplements

• Ethylene glycol toxicity

• Bonus lectures

Lecture Overview

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Oxalate – What Is It?

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What is Oxalate?

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• Oxalate is a naturally occurring molecule, containing two double bonded oxygens and two carbon atoms, found abundantly in plants. It can also be produced in humans and from various fungi.

• It is not a nutrient in humans and can lead to kidney stones in susceptible individuals.

• In plants, oxalate helps to reduce extra calcium.

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What is Oxalate?

• Oxalate, and its acid form, is an organic compound obtained from three primary sources:

• Diet

• Fungus, such as mold and yeast

• Metabolism

• Oxalic acid is the most acidic organic acid in body fluids.

• Ethylene glycol (antifreeze) – toxicity effects are from oxalate crystal formation and acidosis.

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• Sandy and grainy stools

• Bladder irritability, urethral pain, vulvar pain

• Pain on urination (but, no confirmation of infection)

• Eye pain (eye poking in some children)

• Body aches, burning feeling in muscles

• Fibromyalgia-like discomfort

• Moodiness, irritability, and aggressive behavior – often seen in autism.

• Tendon pain, trigger point tenderness, increased tension in muscles with movement.

Common Patient Complaints/Observations

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Vulvodynia

• It is a syndrome of unexplained vulvar pain, frequently accompanied by physical disabilities, limitation of daily activities, sexual dysfunction and psychological distress.

• The patient's vulvar pain usually has an acute onset and, in most cases, becomes a chronic problem lasting months to years.

• The pain is often described as burning or stinging, or a feeling of rawness and irritation.

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• Cyclic vulvovaginitis is believed to be a reaction to yeast, which may be detected at times, and not detected at other times with KOH preparation or fungal cultures.

• Because of the link with Candida, treatment for cyclic vulvovaginitis may include anti-candida medication even if cultures are not positive.

• Other treatments for vulvodynia are a low-oxalate diet and the addition of oral calcium citrate (Citracal), two tablets (200 mg/950 mg each), two to three times a day.

Vulvodynia. Julius F. Metts, M.D. Ref:Vulvodynia and Vulvar Vestibulitis: Challenges in Diagnosis and Management.

March 15, 1999 - American Academy of Family Physicians

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Measured on OAT

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Oxalic Acid

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Oxalic Acid & Calcium Oxalate

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Calcium Oxalate

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Organ Damage Examples

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Normal Kidney

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Staghorn Oxalate Crystal in Kidney

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Oxalate Crystals in Bone

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Oxalate Crystals in Brain

Oxalate crystal in meninges

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Oxalate Crystal in Nerve Tissue

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Thyroid Oxalate Accumulation

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October 1953

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Links to Aspergillus Mold

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Oxalate Metal Complexes from Aspergillus

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Aspergillosis

• Aspergillosis is an infection caused by Aspergillus

• Most people breathe in Aspergillus spores every day without becoming ill. Individuals with weakened immunity or existing lung disease are at higher risk for Aspergillosis.

• The types of health problems caused by Aspergillus include allergic reactions, lung infections and infections in other organs.

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Aspergillus Toxicity

• Most prevalent mold group in the environment and has caused billions of dollars in damage to crops and livestock.

• Most common Aspergillus mycotoxins are aflatoxin, ochratoxin, patuli and fumagillin.

• Aspergillus toxins have been found in all major cereal crops, e.g. peanuts, corn, rice.

• They can also be found in eggs, milk and meat from animals fed contaminated grains.

• There are approximately 180 species of Aspergillus, but fewer than 40 of them are known to cause infections in humans.

• Aspergillus fumigatus is the most common cause of human Aspergillusinfections. Other common species include A. flavus, A. terreus, and A. niger

• The liver is the main target of these toxins.

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Respiratory Diseases

• Allergic bronchopulmonary aspergillosis (ABPA) –wheezing, shortness of breath, cough and fever (in rare cases).

• Allergic Aspergillus sinusitis – stuffiness, runny nose, headache, reduced ability to smell.

• Chronic pulmonary aspergillosis - weight loss, cough, coughing up blood, fatigue, shortness of breath.

• Aspergilloma (“fungus ball”) – cough, coughing up blood, shortness of breath.

• Invasive Aspergillosis – infection spreads to other parts of the body.

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Thoracic CT 9 months (A, B, C) and 3 weeks (D, E, F) before arrival at our hospital and upon admission (G, H, I). Old inflammatory and cystic changes in right upper lobe (A and B); Fungal, ball-like lesion 2.5 cm in diameter with air space consolidation in right upper lobe (D and E) and mild consolidation in right lower

lobe (F); Right lung (G) and left middle lobe (H) are replaced by massive consolidation with air and bilateral pleural effusion is evident (I).

Source: J Thorac Dis. 2013 Aug; 5(4): E174–E178

Calcium oxalate crystal deposition in a patient with Aspergilloma due to Aspergillus niger

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Organic Acids Test – Page #1

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Markers #2, #4, #5 and #6 linked to Aspergillus exposure

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Aspergillus niger

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Aspergillus niger Secretes Citrate to Increase Iron Bioavailability - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Organic-acid-

production-in-A-niger-N402-and-its-derivatives-Metabolic-routes-for_fig1_318858213 [accessed 14 Dec, 2019]

Oxaloacetate hydrolase

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Fungal Biology ReviewsVolume 28, Issues 2–3, October 2014, Pages 36-55 -

https://doi.org/10.1016/j.fbr.2014.05.001

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Cellular Damage Examples

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“This study may provide insights into the damage to renal epithelial cells induced by urinary crystals…”

“…(oxalate) exposure lead to subcellular

organelle injury…”

“…reactive oxygen species, mitochondrial membrane potential, cell cycle, and cell apoptosis…”

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Endosomes aide in cell membrane

transport

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Mitochondria

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Oxidative Stress Kills

Mitochondria

Nutritional Deficiencies

Myco

toxin

s

ATP

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Redox Biol. 2018 May; 15: 207–215. 10.1016/j.redox.2017.12.003

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Main effect of oxalate at the mitochondrial level is generation of reactive oxygen species, free radical damage and mitochondrial swelling.

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Net 2 ATP

Krebs Cycle

Nicotinamide adenine dinucleotide

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Last step in glycolysis inhibited by oxalate

Inhibited by oxalate

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Importance of Pyruvic Acid in Metabolism

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The Chemistry of Oxalate

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Solubility Factors

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Solubility Problem With Oxalate

[Oxalate]-- + [Ca]++ CaOxalateInsolublesoluble soluble

Ksp is indicator ofStrength of reaction

The higher the solubility product constant is, the more soluble the compound

Its value indicates the degree to which a compound dissociates in water

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Oxalate Interconversions

COOH

COOH

COOH

COO-

OxalicAcid

COO-

COO-Oxalate,dibasic

Ca++Zn++Hg++

Oxalate, monobasic

pK 1.27

pK 4.28

Conjugate bases

pH where there are equal amountsof oxalic acid and its monobasic form

pH where oxalate becomes dibasic

50At the pH of blood (7.4) most oxalates in the dibasic form

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Oxalate Chelates Mercury

COOH

COOH

OxalicAcid

COO-

COO-Oxalate,dibasic

Hg++

COOH

COO-

Oxalate, monobasic

HOOC

-OOC+Hg+

Depositsin bone,other tissues

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Solubility is the Factor That Determines Oxalate and Heavy Metal Toxicity

Salt Ksp (solubility product constant)

Mercury I 1.75 X 10-13

Lead 8.6 X 10-10

Copper II 4.4 X 10-10

Zinc 1.4 X 10-9

Cadmium 1.42 X 10-8

Calcium 1.5 X 10-8

Magnesium 8.5 X 10-5

The smaller the value of the Ksp, the greater insolubility of

the salt. For example, the lower the Ksp value for Mercury versus Calcium

means it is more insoluble -less likely to dissociate.

The larger the number in the negative exponent, the smaller the numerical value

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The Mercury-Oxalate Salt is approximately 100,000K less soluble than Calcium-Oxalate.

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Some Facts About Oxalate Chemistry

• At the pH of blood most oxalate is in the dibasic form.

• Oxalates can form salts with a wide variety of metals.

• Calcium levels in blood are relatively constant, but oxalates levels can vary widely.

• It is the oxalate level in the blood which tends to drive calcium (or other mineral/metal) oxalate crystal formation in tissues.

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Magnesium & Vitamin B6 Deficiency

1. Invest Urol. 1966 Sep;4(2):133-42. Calcium oxalate lithiasis produced by pyridoxine deficiency and inhibition with high magnesium diets. Lyon ES, et. al.

2. J Urol. 1982 Mar;127(3):598-604. Effects of magnesium deficiency on intratubular calcium oxalate formation and crystalluria in hyperoxaluricrats. Rushton HG, Spector M.

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Nutrients that can be taken to aide in oxalate reduction.

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GlyoxylateGlycerate

Glycolatehydroxypyruvate

GRHPRGlyoxylate reductaseHydroxypyruvic reductaseType II Hyperoxaluria

GlycolateOxidase (GO)

B-6Glycine

LDHLactatedehydrogenase

Oxalate AscorbateArabinose

YeastFungi

AGTAlanineGlyoxylateAminoTransferaseType IHyperoxaluria

Ethylene glycol

Oxalate Metabolism

hydroxyproline

Protein,Gelatin

Protein

Collagen

Candidacollagenase

Isocitric acid lyase – candida and fungi

Glycolate

Fruits, Vegetables

55Oxalates diet

diet

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Hyperoxaluria Types

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Hyperoxaluria Types

• Type I (PH1) - Primary Hyperoxaluria Type 1 is caused by the deficiency of the oxalate breakdown liver specific enzyme called alanine:glyoxylate aminotransferase (AGT):

• AGT is a Vitamin B6 dependent enzyme

• Leads to high glyoxylic acid which is then converted to glycolate by the enzyme GRHPR or to oxalate by LDH (lactate dehydrogenase).

• Elevated Oxalate and Glycolate (glycolic on the OAT).

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Sugar cane, sugar beets, fruits are sources of

Glycolic Acid

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Hyperoxaluria: A gut-kidney axis - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Overview-of-endogenous-oxalate-synthesis-

pathways-PH-I-III-primary-hyperoxaluria-types_fig1_51594456 [accessed 14 Dec, 2019]

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• Type 2 (PH2) – Primary Hyperoxaluria Type 2 is caused by the deficiency of Glyoxylate reductase/hydroxypyruvate reductase (GRHFR):

• It is often less severe that Type 1 usually causing kidney stone damage versus end-stage kidney failure.

• Tend to see elevated Oxalate and Glycerate (glyceric on OAT).

Hyperoxaluria Types

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Hyperoxaluria: A gut-kidney axis - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Overview-of-endogenous-oxalate-synthesis-

pathways-PH-I-III-primary-hyperoxaluria-types_fig1_51594456 [accessed 14 Dec, 2019]

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Secondary Hyperoxaluria

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Secondary Hyperoxaluria

• Fungal production

• Increased digestive absorption

• Dietary consumption

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0

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xa

late

mm

ol/

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ati

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AutisticSpectrumN=100

NormalChildrenN=16

p <10-16

t-test

Comparison of Urine Oxalate in Autistic-Spectrum and Neurotypical Children

Oxalate above 90 is consistent with

genetic hyperoxaluria36%

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Correlation between urine arabinose and oxalate

Oxalate mmol/mol creatinine

R=0.597

Arabinose mmol/mol creatinine

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Hyperoxaluria: A gut-kidney axis - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Proposed-mechanism-of-oxalate-handling-across-liver-

stomach-and-intestinal-tract-Cl_fig2_51594456 [accessed 14 Dec, 2019]

SLC26A6 - It is an anion-exchanger expressed in the apical membrane

of the kidney proximal tubule,

the apical membranes of

the duct cells in the pancreas, and the villi of the duodenum

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A model for the molecular mechanism of slc26a6 and NaDC-1 reciprocal regulation in epithelia. The apical slc26a6 and NaDC-1 are present in a complex to allow their interaction. The

interaction is mediated by the slc26a6 STAS domain and the NaDC-1 ICL1. When interacting, slc26a6 inhibits NaDC-1, while NaDC-1 activates slc26a6. The result is retention of citrate in the

filtrate and perhaps other luminal fluids to chelate part of the Ca2+ to allow safe oxalate excretion. When minimal oxalate excretion is required, the interaction between slc26a6 and

NaDC-1 relaxes to increase the activity of NaDC-1 and citrate absorption and salvage. Disruption of this regulation in disease states leads to Ca2+/oxalate stone formation.

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Treating High Oxalate

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Resource Article

73Document Section of Module #4

Foods High in Oxalate

Good Place To Start

• Spinach• Soy Products• Nuts (including nut

milk and butters).• Berries (including berry

juice and jams).

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Soy protein is probably not a good food for human-Linda Massey, Ph.D., at Washington St U.

• During their testing, the researchers found the highest oxalate levels in textured soy protein, which contains up to 638 milligrams of oxalate per 85-gram serving.

• Soy cheese had the lowest oxalate content, at 16 milligrams per serving.

• Spinach, measured during previous research, has approximately 543 milligrams per one-cup (2 oz. fresh) serving.

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Green Smoothie

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Townsend Letter Jan 2015 issue 378, pgs. 52-55

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MSDS Safety Sheet For Oxalate

• Symptoms of oral ingestion: headache, muscle cramps and tetany (sharp flexion of the wrist and ankle joints, muscle twitching, cramps and convulsions), weak and irregular heartbeat, drop in blood pressure, signs of heart failure.

• Large doses rapidly cause shock, convulsions, coma and possible death.

• Mean lethal dose by ingestion of oxalates is 10-15 grams, but the lowest reported fatal dose of a related salt, potassium oxalate, was 5 grams.

• Amount of oxalates in spinach (two cups = 150 grams). A green smoothie is 15 grams, a potentially lethal dose

• Google: 609,000+ articles recommending green smoothies

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0

2000

4000

6000

8000

10000

12000

14000

16000

100 mg

15,000 mg

Mean USA Diet per day One green smoothie

Oxalate intake mg

Oxalate Consumption in USA

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Other Support

Vitamin B6

Probiotics

Calcium + Magnesium

Treat Yeast

Diet

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Oxalate Dumping

• Sandy or grainy stools

• Pain with urination

• Urinary urgency

• Irritability, moodiness, etc.

• ‘Potty’ accidents

• Painful bowel movements

• Possible rash – red bumps on skin, hives, may be itchy

• Yeast flare

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Remove Oxalate VERY SLOWLY From The Diet

• 5-10% per week

• For high oxalate patients, this could take a couple months or more.

• Removing them quickly can cause “dumping” symptoms, pain and can overwhelm the system.

© Julie Matthews • Nourishing Hope82

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Cooking to Reduce High Oxalate

• Reduction from boiling and soaking – reduces soluble oxalate by approx. 50%. Discard the water eating.

• Roasting at high heat for 30 minutes can reduce oxalates in tubers.

• Not enough to make extremely high oxalate foods low enough to consume for a low oxalate diet:

• Extremely high oxalates foods: Beets, sweet potato, spinach, Swiss Chard and amaranth reduced by 50% will still be very high.

• Although, cooking can help get medium/high vegetables (12-20 mg) into an acceptable range.

83© Julie Matthews • Nourishing Hope

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Supplement Support for High Oxalate

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Y Y Y Y

- Oxalate -- Oxalate -

- Oxalate -- Oxalate -

Ca++Ca++

Ca++

Ca++

Ca++

Ca++ CalciumOxalateCrystalsinsoluble

Eliminated in stool

Oxalate Crystal Formation in GI tract

Candida

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Y Y Y Y

- Oxalate -- Oxalate -

- Oxalate -- Oxalate -

Ca++Ca++

Ca++

Ca++

Ca++

Ca++

Oxalate crystal formation in GI tractwhen fatty acids are high and/or

poorly absorbed

- Fatty acid

- Fatty acid

• Fatty acid calcium complexes form insoluble soaps• Calcium not available to combine with oxalate• More oxalate absorbed from GI tract

Calcium/Magnesium Citrate (capsule)

• 1 to 2 capsules before high oxalate meals to help prevent oxalate absorption.

• Capsules can be swallowed or opened up and mixed into food or drink.

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2 capsules = 147 mg of calcium & 96 mg of magnesium

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Calcium Chewable w/Magnesium

• 1 tablet with meals containing low to medium oxalates.

• 2 tablets with meals containing high oxalates.

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1 tablet = 247 mg of calcium & 50 mg of magnesium

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High Dose Probiotics

1 to 2 capsules daily (two capsules =

225 billion organisms)

½ to 1 packet (one packet = 225 billion organism)

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Visbiome replaces VSL#3

2 capsules = 225 billion organisms 90

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Vitamin B6

• Pyridoxine HCL

• Helps in oxalate metabolism enzyme function.

• 25mg to 100mg daily

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Hydrate

• Consume ½ body weight in ounces of liquid daily.

• For example, a 150 lbs. (68kg) person should drink approximately 75 ounces (2.2 liters) of fluids daily.

• 1 fluid ounce = 0.0295 liters

• Adjust consumption with increased activity.

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Document section of Module #4

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Document section of Module #4

Biotin at 5 grams+ daily

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Ethylene Glycol Toxicity

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Revisited

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https://www.ebmconsult.com/articles/ethylene-glycol-toxicology

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Lynn Turner (July 13, 1968 – August 30, 2010), born Julia Lynn Womack, was an

American convicted murderer. In 1995, her husband, Glenn Turner, died after allegedly being sick with the flu. In 2001, the death of

what had been described as her common law husband, Randy Thompson, under

remarkably similar circumstances, aroused the suspicion of law enforcement. After

investigation, it was determined by authorities that Lynn Turner had murdered both her husbands by poisoning them with ethylene glycol-based antifreeze. She was

tried for Glenn Turner's murder in 2004. She was found guilty and went to trial again for

murdering Randy Thompson in 2007, ultimately being convicted. Turner died in prison on August 30, 2010. The cause of death was an apparent suicide by toxic overdose of blood pressure medication.

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Metabolic acidosis

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Ascorbic Acid and Oxalate

Bonus Lecture for Module #4

(Lecture slides PDF available)

Bonus Lecture

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Case Studies in High Oxalate

Bonus Lecture for Module #4

(Lecture slides PDF available)

Bonus Lecture

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Module #4 Action Plan

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Document section of Module #4

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Topic

• Glycolytic Metabolites:• Comprehensive overview of the Glycolytic Metabolites

section of the OAT.

• Each glycolytic metabolite marker discussed in detail

• Clinical correlation of glycolytic metabolites to various health problems, e.g. chronic fatigue, mitochondrial dysfunction, mold toxicity.

• Various treatment options for elevated Glycolytic Cycle Metabolite markers.

• Other laboratory tests to consider based on positive findings in the Glycolytic Metabolites section of the OAT.

Module #5

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Thank You

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AdvancedOATMasteryCourse.comAdvancedOATMasteryCourse@gmail.com

Kurt N. Woeller, D.O.

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