body chemistry balancing and the relationship between inflammation, pain, sleep disorders and...

Body Chemistry Balancing and the Relationship

between Inflammation, Pain, Sleep Disorders and

Blood/Urine Chemistry

Body Chemistry Balancing and the Relationship

between Inflammation, Pain, Sleep Disorders and

Blood/Urine Chemistry

What are TMJ Disorders?What are TMJ Disorders?• Temporomandibular Disorders are a

collection of poorly understood conditions characterized by pain in the jaw and surrounding tissues and limitations in jaw movements

• It is a highly complex disease involving genetic and hormonal influences as well as a myriad of complex biological factors

• People diagnosed with TMJD may experience other symptoms and medical conditions that go unrecognized

• Temporomandibular Disorders are a collection of poorly understood conditions characterized by pain in the jaw and surrounding tissues and limitations in jaw movements

• It is a highly complex disease involving genetic and hormonal influences as well as a myriad of complex biological factors

• People diagnosed with TMJD may experience other symptoms and medical conditions that go unrecognized

Who is Affected by TMJD?Who is Affected by TMJD?• Incidence is between 5% and 12%• Higher incidence among younger persons• At least twice as prevalent in women than

men and as high as 9x in some studies• Women using supplemental estrogen or

oral contraceptives are more likely to seek treatment for these conditions

• National Institute of Dental and Craniofacial Health http://www.nidcr.nih.gov/datastatistics

• Incidence is between 5% and 12%• Higher incidence among younger persons• At least twice as prevalent in women than

men and as high as 9x in some studies• Women using supplemental estrogen or

oral contraceptives are more likely to seek treatment for these conditions


http://www.nidcr.nih.gov/datastatistics


Overlapping conditions with TMJD

Overlapping conditions with TMJD

• Allergies• Chronic fatigue

syndrome• Chronic headaches-

migraine & tension• Dizziness• Ear pain and tinnitus• Vestibular disorder• Fibromyalgia• Interstitial cystitis

• Allergies• Chronic fatigue

syndrome• Chronic headaches-

migraine & tension• Dizziness• Ear pain and tinnitus• Vestibular disorder• Fibromyalgia• Interstitial cystitis

• Irritable bowel syndrome

• Meniere’s disease• Movement disorders• Multiple chemical

sensitivity• Rheumatoid arthritis• Sleep disorders• Vulvodynia• Depression

• Irritable bowel syndrome

• Meniere’s disease• Movement disorders• Multiple chemical

sensitivity• Rheumatoid arthritis• Sleep disorders• Vulvodynia• Depression

OPPERA ProjectNational Institute of Dental and Craniofacial Research www.nidcr.nih.gov

OPPERA ProjectNational Institute of Dental and Craniofacial Research www.nidcr.nih.gov

• 3400 patients to determine biological, psychological and genetic factors in TMJD

• TMJD - second leading cause of facial/head pain

• Rationale and authors conclusion:– “These findings are in agreement with various case-

control studies which suggest it is inappropriate to consider TMD in isolation”

– “Rather, regional and widespread chronic pain conditions represent ‘overlapping’ conditions and should be considered as part of a ‘continuum’ than distinct entities with distinct etiologies”

• 3400 patients to determine biological, psychological and genetic factors in TMJD

• TMJD - second leading cause of facial/head pain

• Rationale and authors conclusion:– “These findings are in agreement with various case-

control studies which suggest it is inappropriate to consider TMD in isolation”

– “Rather, regional and widespread chronic pain conditions represent ‘overlapping’ conditions and should be considered as part of a ‘continuum’ than distinct entities with distinct etiologies”

Dysregulation Spectrum SyndromeCluster of Modern “Diseases” Muhammad Yunis MD University of Illinois


Dysregulation Spectrum SyndromeInterventions Improving DSS


Estrogen Dominance in TMJD Estrogen Dominance in TMJD

• More women than men (9:1)• Women using supplemental estrogen

or oral contraceptives are more likely to seek treatment for these conditions


• TMJD has receptors for both estrogen and progesterone J Oral Maxillofac Surg. 1993

Oct;51(10):1096-100.• Higher estrogen levels in TMJD women

Minerva Stomatol. 2004 Nov-Dec;53(11-12):651-60.

• More women than men (9:1)• Women using supplemental estrogen

or oral contraceptives are more likely to seek treatment for these conditions


• TMJD has receptors for both estrogen and progesterone J Oral Maxillofac Surg. 1993

Oct;51(10):1096-100.• Higher estrogen levels in TMJD women

Minerva Stomatol. 2004 Nov-Dec;53(11-12):651-60.





Excess EstrogenExcess Estrogen• Upregulates nerve and muscle

sensitivity• Symptoms can include

– Insomnia/ Anxiety– Water retention/ Breast tenderness– Fibromyalgic syndrome

• Upregulates nerve and muscle sensitivity

• Symptoms can include– Insomnia/ Anxiety– Water retention/ Breast tenderness– Fibromyalgic syndrome

ProgesteroneProgesterone• Downregulates nerve sensitivity• Downregulates glutamate

excitotoxicity in neurons (Nilsen et al. (2002) Endocrinology 143:205-212.)

• Downregulates cardiac ischemia in women Rosano G, et al. (2000) J Am Coll Cardiol 36:2154-2159

• NOTE: human progesterone NOT synthetic progestin

• Downregulates nerve sensitivity• Downregulates glutamate

excitotoxicity in neurons (Nilsen et al. (2002) Endocrinology 143:205-212.)

• Downregulates cardiac ischemia in women Rosano G, et al. (2000) J Am Coll Cardiol 36:2154-2159

• NOTE: human progesterone NOT synthetic progestin

Causes of Estrogen Dominance

Causes of Estrogen Dominance

• Ovaries which naturally produce progesterone are affected by– Drugs (oral contraceptives)– Environment xenoestrogens– Age (menopause)– Nutrition– Antibiotics

• Ovaries which naturally produce progesterone are affected by– Drugs (oral contraceptives)– Environment xenoestrogens– Age (menopause)– Nutrition– Antibiotics

Female Patient – 22 Yrs OldFemale Patient – 22 Yrs Old

Female Patient – 45 Yrs OldFemale Patient – 45 Yrs Old

Nutritional and Dietary Effects on Estrogen


• High insulin increases aromatase increasing estrogen

• Vitamin D expresses progesterone and estrogen receptors

• Cruciferous vegetables increase estrogen metabolism

• Anti-oxidants prevent oxidation of estrogen metabolites to potent estrogen compounds

• Methylation 2 and 4 methoxyestrones B12, folate and B6 dependant

• High insulin increases aromatase increasing estrogen

• Vitamin D expresses progesterone and estrogen receptors

• Cruciferous vegetables increase estrogen metabolism

• Anti-oxidants prevent oxidation of estrogen metabolites to potent estrogen compounds

• Methylation 2 and 4 methoxyestrones B12, folate and B6 dependant


(cont’d)


(cont’d)• Ovaries sensitive to iron• B-glucuronidase in bowel destroyed by

antibiotics, preservatives and poor diet• Phytoestrogens in vegetables modulate

estrogen receptors• Magnesium essential for COMT

enzymes and glucuronyl transferase• Low vitamin E associated with elevated

estrogen levels

• Ovaries sensitive to iron• B-glucuronidase in bowel destroyed by

antibiotics, preservatives and poor diet• Phytoestrogens in vegetables modulate

estrogen receptors• Magnesium essential for COMT

enzymes and glucuronyl transferase• Low vitamin E associated with elevated

estrogen levels

Obesity and High Insulin and Pain

Obesity and High Insulin and Pain

• Elevated glucose and fluxes in blood glucose decrease threshold of pain and maximum pain tolerated

• Obesity correlates to fibromyalgic pain

– Okifuji, A. et al. (2010) Relationship Between Fibromyalgia and Obesity in Pain, Function, Mood, and Sleep. The Journal of Pain, 11 (12): 1329

– Gerald K. Morley et al. (1984) Mechanism of pain in diabetic peripheral neuropathy: Effect of glucose on pain perception in humans. The American Journal of Medicine Volume 77, Issue 1, Pages 79-82

• Elevated glucose and fluxes in blood glucose decrease threshold of pain and maximum pain tolerated

• Obesity correlates to fibromyalgic pain

– Okifuji, A. et al. (2010) Relationship Between Fibromyalgia and Obesity in Pain, Function, Mood, and Sleep. The Journal of Pain, 11 (12): 1329

– Gerald K. Morley et al. (1984) Mechanism of pain in diabetic peripheral neuropathy: Effect of glucose on pain perception in humans. The American Journal of Medicine Volume 77, Issue 1, Pages 79-82

• Lowell Science 2005• First step in type 2 diabetes is

mitochondrial dysfunction of skeletal muscle.

• Then mitochondrial dysfunction of b-cells pancreas

• Warburg effect-increase lactate.

• Lowell Science 2005• First step in type 2 diabetes is

mitochondrial dysfunction of skeletal muscle.

• Then mitochondrial dysfunction of b-cells pancreas

• Warburg effect-increase lactate.

Type 2 Diabetes and Mitochondrial Dysfunction

Type 2 Diabetes and Mitochondrial Dysfunction

• #1 killer• If it can kill, it has proven to lead to

higher rates of pain and inflammation• Leads to higher rates of cancer, heart

disease, depression, low energy, lack of mental focus, etc.

• Hip to waist ratio men <0.95: women<0.8

• University of Guelph study– What people ate for breakfast “was the

cause of high insulin” Am. J. Clin. Nutr. (2008) 87: 1254-61.

• #1 killer• If it can kill, it has proven to lead to

higher rates of pain and inflammation• Leads to higher rates of cancer, heart

disease, depression, low energy, lack of mental focus, etc.

• Hip to waist ratio men <0.95: women<0.8

• University of Guelph study– What people ate for breakfast “was the

cause of high insulin” Am. J. Clin. Nutr. (2008) 87: 1254-61.

High Insulin/Diabetes, ObesityHigh Insulin/Diabetes, Obesity

• Fasting blood sugar above 5.0• Post prandiol challenge-insulin, blood

sugar• Serum potassium effect 3rd quartile• BMI• Magnesium glycinate 200-300mg• Chromium 500-1000mcg• Vitamin D (lab values)

• Fasting blood sugar above 5.0• Post prandiol challenge-insulin, blood

sugar• Serum potassium effect 3rd quartile• BMI• Magnesium glycinate 200-300mg• Chromium 500-1000mcg• Vitamin D (lab values)

High Insulin/Diabetes, ObesityHigh Insulin/Diabetes, Obesity

• Skipping breakfast or lacking protein makes blood sugar worse and contributes to weight gain

• Salad everywhere• Overweight women eating significant

protein at breakfast ate 300 calories less per day (30 pounds weight loss)

Van der Wal (2005) J Am Coll Nutr 24:510-515

• Skipping breakfast or lacking protein makes blood sugar worse and contributes to weight gain

• Salad everywhere• Overweight women eating significant

protein at breakfast ate 300 calories less per day (30 pounds weight loss)

Van der Wal (2005) J Am Coll Nutr 24:510-515

“No Protein at Breakfast” Syndrome

“No Protein at Breakfast” Syndrome

Anatomy of a Sugar Craving Anatomy of a Sugar Craving

• #1 High insulin• #2 Low serotonin and dopamine

• “any drug or substance that mobilizes neurotransmitters depletes them”

• This explains how anti-depressant medications increase weight as well as drug “tolerance”

• #1 High insulin• #2 Low serotonin and dopamine

• “any drug or substance that mobilizes neurotransmitters depletes them”

• This explains how anti-depressant medications increase weight as well as drug “tolerance”

Gluten and TMJDGluten and TMJD• IGA gluten intolerance increases risk of DSS• Oral cavity can give a clinical clue for early

diagnosis of gluten intolerance• Recurrent aphthous ulcers/stomatitis, dental

enamel defects• Atrophic glossitis• Dermatitis herpatiformis• Sjogren’s syndrome• Oral lichen planus • Bucci P, et al. (2006) Oral aphthous ulcers and dental enamel defects in children with coeliac disease. Acta Paediatr. 95:203–

207. • Lahteenoja H, et al. (1998) Oral mucosal changes in coeliac patients on a gluten-free diet. Eur J Oral Sci. 106:899–906. • Scully C, Porter SR, Eveson JW. (1993) Oral lichen planus and coeliac disease. Lancet. 341:1660

• IGA gluten intolerance increases risk of DSS• Oral cavity can give a clinical clue for early

diagnosis of gluten intolerance• Recurrent aphthous ulcers/stomatitis, dental

enamel defects• Atrophic glossitis• Dermatitis herpatiformis• Sjogren’s syndrome• Oral lichen planus • Bucci P, et al. (2006) Oral aphthous ulcers and dental enamel defects in children with coeliac disease. Acta Paediatr. 95:203–

207. • Lahteenoja H, et al. (1998) Oral mucosal changes in coeliac patients on a gluten-free diet. Eur J Oral Sci. 106:899–906. • Scully C, Porter SR, Eveson JW. (1993) Oral lichen planus and coeliac disease. Lancet. 341:1660

• In Canada, 12 years before diagnosis• Clinical chameleon• 30 fold increase in auto-immune

disorders• Thyroid dysfunction, type 1 diabetes• Unexplained micronutrient

deficiencies • Irritable Bowel Syndrome • Family history: 5-15% increased risk• Testing www.enterolab.com TTG

• In Canada, 12 years before diagnosis• Clinical chameleon• 30 fold increase in auto-immune

disorders• Thyroid dysfunction, type 1 diabetes• Unexplained micronutrient

deficiencies • Irritable Bowel Syndrome • Family history: 5-15% increased risk• Testing www.enterolab.com TTG

Gluten Intolerance CluesGluten Intolerance Clues

http://www.enterolab.com/

http://www.enterolab.com/

Enamel Defects in Gluten IntoleranceEnamel Defects in Gluten Intolerance

Nutritional, Biochemical and Hormonal Influences on

Neurotransmitter Balance

Nutritional, Biochemical and Hormonal Influences on

Neurotransmitter Balance• Virtually every single hormone

including sex hormones• Thyroid and insulin have proven to

impact neurotransmitter balance• Every single micro- and

macronutrient appear to affect neurotransmitter balance

• Virtually every single hormone including sex hormones

• Thyroid and insulin have proven to impact neurotransmitter balance

• Every single micro- and macronutrient appear to affect neurotransmitter balance

Nutritional & Biochemical Influences on Neurotransmitter Balance

Nutritional & Biochemical Influences on Neurotransmitter Balance

• Magnesium COMT dependent• Copper metabolism of excess

norepinephrine• Zinc - SOD dismutase• B12, folate, B6 - methylation• Vitamin D - expression of serotonin and

dopamine receptors• Amino acid/Protein - direct precursors• Mitochondrial Function • Vitamin C and E, anti-oxidants -

catecholamine metabolism• Iron

• Magnesium COMT dependent• Copper metabolism of excess

norepinephrine• Zinc - SOD dismutase• B12, folate, B6 - methylation• Vitamin D - expression of serotonin and

dopamine receptors• Amino acid/Protein - direct precursors• Mitochondrial Function • Vitamin C and E, anti-oxidants -

catecholamine metabolism• Iron

Pharmaceutical Approaches to TMJD

Pharmaceutical Approaches to TMJD

• Three medications in the USA are labeled for treatment of fibromyalgia- related symptoms

• Serotonin and norepinephrine reuptake inhibitors duloxetin (Cymbalta) and milnacipran (Savella)

• A2-gamma inhibitor Pregabalin (Lyrica) essentially blocking calcium influx and blocking downstream excitatory substance P, glutamate and norepinephrine

• Three medications in the USA are labeled for treatment of fibromyalgia- related symptoms

• Serotonin and norepinephrine reuptake inhibitors duloxetin (Cymbalta) and milnacipran (Savella)

• A2-gamma inhibitor Pregabalin (Lyrica) essentially blocking calcium influx and blocking downstream excitatory substance P, glutamate and norepinephrine

2008 Eular European Guidelines

2008 Eular European Guidelines

• Guidelines for management of “fibromyalgic syndrome”

• 59 studies reviewed• “Pain in patients with fibromyalgia is

likely a result of an imbalance of excitatory and inhibitory neurotransmitters”

• “An individual’s response to a particular medication is dependent on his or her unique pathophysiology”

• Guidelines for management of “fibromyalgic syndrome”

• 59 studies reviewed• “Pain in patients with fibromyalgia is

likely a result of an imbalance of excitatory and inhibitory neurotransmitters”

• “An individual’s response to a particular medication is dependent on his or her unique pathophysiology”

Eular European Guidelines“Fibromyalgic Conditions”Eular European Guidelines“Fibromyalgic Conditions”

Recommended

AmitriptylineFluoxetineDuloxetineMilnacipranPramipexole (mirapex)PregabalinTramadol

Opiods and steroids not recommended

Recommended

AmitriptylineFluoxetineDuloxetineMilnacipranPramipexole (mirapex)PregabalinTramadol

Opiods and steroids not recommended

Reviewed with evidence

• Gabapentin• Naltrexone

• NSAIDS• Muscle relaxants

Reviewed with evidence

• Gabapentin• Naltrexone

• NSAIDS• Muscle relaxants

Medication ConsiderationsMedication Considerations• If localized, use anti-inflammatories and Tylenol• Tramadol has shown benefit & is a SNRI as well• Newer agents Cymbalta and Lyrica have more

evidence for benefit in “fibromyalgia-like conditions”

• Cymbalta superior in fatigue, depression• Lyrica superior with insomnia • Gabapentin as good as Lyrica• Older agents have more info but less specific study• Amino acids most gentle and biologically superior

for balancing of neurotransmitters• If localized, transdermal pain gels can be

considered

• If localized, use anti-inflammatories and Tylenol• Tramadol has shown benefit & is a SNRI as well• Newer agents Cymbalta and Lyrica have more

evidence for benefit in “fibromyalgia-like conditions”

• Cymbalta superior in fatigue, depression• Lyrica superior with insomnia • Gabapentin as good as Lyrica• Older agents have more info but less specific study• Amino acids most gentle and biologically superior

for balancing of neurotransmitters• If localized, transdermal pain gels can be

considered

“Lipoderm” Novel Delivery System to TM Joint

“Lipoderm” Novel Delivery System to TM Joint

• Gabapentin 4%• Cyclobenzaprine 2%• Ketoprofen 6%• Magnesium glycinate 2%• Clonidine 0.2%• In Lipoderm transdermal delivery

system - applied to TMJ joint 3 times daily

• Gabapentin 4%• Cyclobenzaprine 2%• Ketoprofen 6%• Magnesium glycinate 2%• Clonidine 0.2%• In Lipoderm transdermal delivery

system - applied to TMJ joint 3 times daily

“Less Is Often Best”Slogan of the TMJ Association“Less Is Often Best”

Slogan of the TMJ Association

• Generally discomfort is temporary and will go away with little or no treatment

• Treat the co-morbid conditions as a complex and with prioritization i.e. depression, irritable bowel, PMS, insomnia, high insulin

• Hip-to-waist ratio is one the best indicators of high insulin – it is a disaster and can be regulated easily

• Generally discomfort is temporary and will go away with little or no treatment

• Treat the co-morbid conditions as a complex and with prioritization i.e. depression, irritable bowel, PMS, insomnia, high insulin

• Hip-to-waist ratio is one the best indicators of high insulin – it is a disaster and can be regulated easily

“Less Is Often Best”Slogan of the TMJ Association“Less Is Often Best”

Slogan of the TMJ Association• Magnesium is the most common

deficient nutrient and is effective in balancing estrogen, neurotransmitters and muscle relaxation as a calcium channel regulator, particularly glycinate

• If hormones are implicated, use diet and nutrients first– if hormones are indicated then add progesterone first

• If bowel/oral cavity is affected with many of DSS issues, pay attention to possibility of gluten intolerance

• Magnesium is the most common deficient nutrient and is effective in balancing estrogen, neurotransmitters and muscle relaxation as a calcium channel regulator, particularly glycinate

• If hormones are implicated, use diet and nutrients first– if hormones are indicated then add progesterone first

• If bowel/oral cavity is affected with many of DSS issues, pay attention to possibility of gluten intolerance

It’s the Environment: We have not changed our

“genes”

It’s the Environment: We have not changed our

“genes”• TMJD is a modern disease - we

must look at the biochemical environment, diet, nutrition and assessments to reflect this.

• TMJD is a modern disease - we must look at the biochemical environment, diet, nutrition and assessments to reflect this.

Population Aging and The Determinants of Healthcare Expenditures: The Case of Hospital, Medical and Pharmaceutical Care in British Columbia 1996-2006

Population Aging and The Determinants of Healthcare Expenditures: The Case of Hospital, Medical and Pharmaceutical Care in British Columbia 1996-2006• Morgan, S. and Cunningham, C. (2011)

Healthcare Policy 7(1): 68-79

• 80 billion US$ in USA for chronic health “fibromyalgic” conditions in up to 50 million women

• Morgan, S. and Cunningham, C. (2011) Healthcare Policy 7(1): 68-79

• 80 billion US$ in USA for chronic health “fibromyalgic” conditions in up to 50 million women

TMJD/Fibromyalgia/DSS “costs” as Part of a Constellation of Symptoms

TMJD/Fibromyalgia/DSS “costs” as Part of a Constellation of Symptoms• Journal of Health Advisory Study in BC • Ballooning of healthcare costs not related

to aging• Related to more and more specialists, and

increase in neuropsychiatric medications• These conditions are the modern health

care dilemma• #1 cause of physicians’ visits--energy

• Journal of Health Advisory Study in BC • Ballooning of healthcare costs not related

to aging• Related to more and more specialists, and

increase in neuropsychiatric medications• These conditions are the modern health

care dilemma• #1 cause of physicians’ visits--energy

What is Happening NOWWhat is Happening NOW

• Referral to specialists who only focus on their area of expertise

• Signs in offices “please discuss only one complaint per visit”

• Reliance on anti-depressant meds with poor outcomes

• Explosion of costs without results

• Referral to specialists who only focus on their area of expertise

• Signs in offices “please discuss only one complaint per visit”

• Reliance on anti-depressant meds with poor outcomes

• Explosion of costs without results

Meta-Analysis of all Studies of Anti-depressant

Medications

Meta-Analysis of all Studies of Anti-depressant

Medications• In mild to moderate depression,

anti-depressant medication does not help better than placebo

• Any medication that mobilizes neurotransmitters deplete, disrupt and disturb

JAMA (2010) 303(1): 47-53

• In mild to moderate depression, anti-depressant medication does not help better than placebo

• Any medication that mobilizes neurotransmitters deplete, disrupt and disturb

JAMA (2010) 303(1): 47-53

• Provides evidenced-based approaches for nutritional, dietary and hormonal intervention

• Over 60 panels tested thru blood and urine• Assessment of Hormones (adrenals, thyroid,

sex hormones)• Assessment of Nutritional Biochemistry

(vitamins, minerals, amino acids, fats, proteins, toxicology)

• Assessment of Neurotransmitters (mood, sleep, appetite…)

• Bowel function assessed -NO gluten testing• Available NutriChem clinic www.nutrichem.com

• Provides evidenced-based approaches for nutritional, dietary and hormonal intervention

• Over 60 panels tested thru blood and urine• Assessment of Hormones (adrenals, thyroid,

sex hormones)• Assessment of Nutritional Biochemistry

(vitamins, minerals, amino acids, fats, proteins, toxicology)

• Assessment of Neurotransmitters (mood, sleep, appetite…)

• Bowel function assessed -NO gluten testing• Available NutriChem clinic www.nutrichem.com

Body Chemistry Balancing Testing and DSS (TMJD)

Body Chemistry Balancing Testing and DSS (TMJD)

• Macronutrition-protein-food sensitivities-insulin/sugar

• Micronutrient status• Hormone status and balance• Neurotransmitter status and balance• Environment -drugs

-stress-toxins, xenoestrogens

• You are what you eat

• Macronutrition-protein-food sensitivities-insulin/sugar

• Micronutrient status• Hormone status and balance• Neurotransmitter status and balance• Environment -drugs

-stress-toxins, xenoestrogens

• You are what you eat

Pyramid of Modern DSSIntervention

Pyramid of Modern DSSIntervention

What We Need To Do What We Need To Do • Health Practitioners increasing scope

of practice and outlook• Dentists, pharmacists, GP’s

specialists, naturopaths, nutritionists• More sophisticated and in-depth

assessment tools able to look at multiple dimensions

• Our clients know that everything in body is related

• Health Practitioners increasing scope of practice and outlook

• Dentists, pharmacists, GP’s specialists, naturopaths, nutritionists

• More sophisticated and in-depth assessment tools able to look at multiple dimensions

• Our clients know that everything in body is related

body chemistry balancing and the relationship between inflammation, pain, sleep disorders and...

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