Top 10 Nutritional Therapies · 2020. 8. 29. · Top 10 Nutritional Therapies for a Healthy Pain and Inflammation Response Presented by David Hogsed, D.O.M., A.P. 1 Disclaimer The

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Top 10 Nutritional Therapiesfor a Healthy Pain and Inflammation Response

Presented by David Hogsed, D.O.M., A.P.

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Disclaimer

The following statements have not been evaluated by the Food & Drug Administration. These products are food supplements designed to supplement the diet and support normal physiology & biochemistry, & are not intended to diagnose, treat, cure or prevent any disease.

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• 1. Atorvastatin (Lipitor)

• 2. Levothyroxine (Synthroid)

• 3. Lisinopril (Prinivil, Zestril)

• 4. Gabapentin (Neurontin)

• 5. Amlodipine (Norvasc)

• 6. Hydrocodone/acetaminophen (Vicodin, Norco)

• 7. Amoxicillin (Amoxil)

• 8. Omeprazole (Prilosec)

• 9. Metformin (Glucophage)

• 10. Losartan (Cozaar)

Top 10 Prescribed Drugs 2019 Beckerhospitalreview.com May 2nd

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Epocrates.com

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Lipitor epocrates.com

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New CDC report: More than 100 million Americans have diabetes or prediabetescdc.gov, July 18th, 2017

More than 100 million U.S. adults are now living with diabetes or prediabetes, according to a new report released today by the Centers for Disease Control and Prevention (CDC).

The report finds that as of 2015, 30.3 million Americans – 9.4 percent of the U.S. population –have diabetes. Another 84.1 million have prediabetes, a condition that if not treated often leads to type 2 diabetes within five years.

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Must have 3 or more of the following• Abdominal obesity

(Greater than 40 inches men, greater than 35 inches women)

• Dyslipidemia(high triglycerides, low HDL cholesterol)

• Hyperglycemia(fasting glucose above 100)

• Hypertension (systolic blood pressure above 130, diastolic BP above 85)

Metabolic Syndrome Criteria

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Simple Lab Tests for Blood Sugar Stress and Insulin Resistance

• Glucose

• Hemoglobin A1C

• Lipid panel

• Fasting insulin

• Uric Acid

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Evexiadiagnostics.com

• Deeply discounted lab tests through Lab Corp

• Enter code ‘STANDARD’ when registering to receive $150 off registration fee

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2015 Detox overview

#1 Low Carb Diet

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Dietdoctor.com

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#2 Bioavailable Curcumin

Turmeric

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Most Popular Supplements Survey Consumerlab.com February 24, 2018

1. Vitamin D

2. Fish Oil

3. CoQ10

4. Magnesium

5. Curcumin/Turmeric

6. Multivitamins

7. Probiotics

8. Vitamin C

9. Vitamin B Complex

10. Vitamin B12

11. Calcium

12. Apple Cider Vinegar

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Diseases linked to chronic inflammation:

• Diabetes and pre diabetes

• Cancer

• Cardiovascular disease

• Neurodegenerative diseases

• Skin conditions

• Digestive disorders

• Asthma

• Allergies

• Autoimmune disease

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Curcumin supports a healthy inflammatory response

✓ Inhibits NFkB✓ Reduces serum levels of: • TNFα,IL-1β2 ,IL-6 •MCP-1

✓ Diminishes chondrocyte production of CXCL8 (IL-8)

✓ Modulates PLA2 ✓ Modulates COX-2 ✓ Modulates 5-LOX

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Turmeric Quality Issues Consumerlab.com April 4th, 2017

Summary: • Two out of 11 popular supplements contained only about 50% of the curcumin

compounds that their label claimed.

• There was a wide range in the amount of curcuminoids provided (from 30 mg to 950 mg per daily serving), as well as in cost (from 20 cents to $8.87 for an equivalent amount of curcuminoids)

• Two-thirds of the supplements included a bioavailability enhancer which may significantly increase the amount of curcumin which can be absorbed and used by the body.

• Three turmeric spices exceeded limits applied by ConsumerLab.com for filth due to elevated numbers of insect fragments found in samples.

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Curcuminoid Bioavailability

• Low circulating levels in plasma

• Limited distribution in body tissues

• High levels of phase II conjugated curcuminoids, which have less activity (as opposed to “free” or unchanged curcumin)

• Rapid metabolism

Krishnakumar IM, Abhilash R, Kumar D et al. J Funct Foods 2012; 4(1): 348-357

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Bioavailable Forms of Curcumin

• Curcuminoid Phospholipid Complex

• A pharmacokinetic study in 9 healthy volunteers published in 2011 used a high-level design

• Curcuminoid conjugates were determined: established that CPC delivered around 30 times (27 to 31) bioavailability compared with curcuminoids alone

• However only phase-2 curcuminoid metabolites (less effective) could be detected

Cuomo J, Appendino G, Dern AS et al. J Nat Prod 2011; 74(4): 664-669

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What Makes Curcuma-Galactomannosides CGM Unique?

Curcuma-Galactomannosides(CGM)

FENUGREEKTURMERIC

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CGM resulted in 24.8 times uplift (absorption) and was found to maintain up to 74% free curcuminoids in the plasma (utilization)

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CGM and the Blood-Brain Barrier

• An in vivo study confirmed the increased bioavailability of CGM formulation in comparison to unenhanced curcumin

• Maximum level of free curcuminoids in brain tissues: after administration of CGM was 343 ng/g at 2 hours compared to unenhanced curcumin at just 1.4 ng/g

• CGM delivered 245 times more free curcuminoids!

Krishnakumar IM, Abhilash Maliakel, Gopakumar G et al. J Funct Foods 2015; 14: 215-225

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74 year old with Rheumatoid arthritis

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#3 Fish Oil

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Trends in the use of complementary health approaches among adults: United States, 2002-2012. National health statistics reports; no 79. Hyattsville, MD: National Center for Health Statistics. 2015.

nih.gov/research/statistics/NHIS/2012/natural-products/trends

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CodliveroildeliveryWikimediacommons,AuthorMinistryofInformationPhotoDivisionPhotographer

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Snowden SG, Ebshiana AA, Hye A, An Y, Pletnikova O, O’Brien R, et al. (2017) Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study. PLoS Med14(3): e1002266. https://doi.org/10.1371/journal.pmed.1002266

Omega Fatty Acid Metabolic Pathways lead to a Balance & Control of Immune Modulation that can Reduce an Inflammatory Response in Targeted Cell Function

1. Omega 6 fatty acids shown to be associated with increased inflammation levels2. Omega 3 and high ratio of 3’s to 6’s associated with reduced levels of inflammation

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Omega-6 Overload The estimated per capita consumption of soybean oil, the most common source of n-6FA in the Western diet, increased greater than a 1000-fold from 1909 to 1999 in the United States, now contributing almost 8% of all calories consumed.

©2020 Standard Process Inc. All rights reserved. LN00995 06/2020

Blasbalg T, Hibbeln J, Ramsden C, Majchrzak S, Rawlings R: Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr 93:950– 962, 2011

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Omega 3/6 Ratio Testing Options

• OmegaQuant(available through Standard Process or Amazon.com)

• Omega-3 and -6 Fatty Acids(Evexiadiagnostics.com)

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§ The endocannabinoid system (ECS) was discovered by Dr. Rafael Mechoulam, the father of cannabis based medicines.

§ The endocannabinoid system (ECS) is composed of three main cannabinoid receptors, endocannabinoids, and metabolic enzymes – serves an essential function in the human body: restoring homeostasis via various physiological and regulatory mechanisms.

§ In 1992, at the Hebrew University in Jerusalem, Dr. Lumir Hanus along with American researcher Dr. William Devane discovered the first endocannabinoid anandamide

The Endocannabinoid System - ECS


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Components of the ECS are present and vital in nearly every area of the human body. Thus, disruption of the ECS has a serious, negative impact on human health. The ECS is responsible for multiple homeostatic roles:§ Relaxation

§ Metabolism§ Sleep

§ Memory§ Neuroprotection§ Immunity and inflammation

§ Appetite § Pain and emotional memory

The Endocannabinoid System - ECS


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The Three Key Components of the ECS are:

1. Endocannabinoids (ligands): small molecules that activate cannabinoid receptors.

2. Cannabinoid receptors: found on the surface of cells. CB-1 and CB-2 are the receptor types with different functions.

3. Metabolic enzymes: break down endocannabinoids after they are used.


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PUFA’s are precursors for endocannabinoids

McDougle, Daniel R., Josephine E. Watson, Amr A. Abdeen, RehemanAdili, Megan P. Caputo, John E. Krapf, Rodney W. Johnson, Kristopher A. Kilian, Michael Holinstat, and Aditi Das. 2017. 'Anti-inflammatory ω-3 endocannabinoid epoxides', Proceedings of the National Academy of Sciences, 114: E6034-E43.


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AbstractPolyunsaturated fatty acids (PUFAs) are lipid derivatives of omega-3 (docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA) or of omega-6 (arachidonic acid, ARA) synthesized from membrane phospholipids and used as a precursor for endocannabinoids (ECs). They mediate significant effects in the fine-tune adjustment of body homeostasis. Phyto- and synthetic cannabinoids also rule the daily life of billions worldwide, as they are involved in obesity, depression and drug addiction. Consequently, there is growing interest to reveal novel active compounds in this field. Cloning of cannabinoid receptors in the 90s and the identification of the endogenous mediators arachidonylethanolamide (anandamide, AEA) and 2-arachidonyglycerol (2-AG), led to the characterization of the endocannabinoid system (ECS), together with their metabolizing enzymes and membrane transporters.

Today, the ECS is known to be involved in diverse functions such as appetite control, food intake, energy balance, neuroprotection, neurodegenerative diseases, stroke, mood disorders, emesis, modulation of pain, inflammatory responses, as well as in cancer therapy. Western diet as well as restriction of micronutrients and fatty acids, such as DHA, could be related to altered production of pro-inflammatory mediators (e.g. eicosanoids) and ECs, contributing to the progression of cardiovascular diseases, diabetes, obesity, depression or impairing conditions, such as Alzheimer' s disease….PMID: 28686542

Polyunsaturated fatty acids and endocannabinoids in health and disease.

McDougle, Daniel R., Josephine E. Watson, Amr A. Abdeen, RehemanAdili, Megan P. Caputo, John E. Krapf, Rodney W. Johnson, Kristopher A. Kilian, Michael Holinstat, and Aditi Das. 2017. 'Anti-inflammatory ω-3 endocannabinoid epoxides', Proceedings of the National Academy of Sciences, 114: E6034-E43.


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§ The endogenous arachidonate-based lipids, anandamide (N-arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG); these are known as "endocannabinoids" and are physiological ligands for the cannabinoid receptors. Endocannabinoids are all eicosanoids.

§ The enzymes that synthesize and degrade the endocannabinoids, such as FAAH or MAGL.

Endocannabinoids


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Anandamide - The “Bliss Chemical”• The name of this endocannabinoid is derived from the Sanskrit word ‘Ananda’

which means ‘bliss’.

• Anandamide attaches to the CB1 receptor, and has positive effects on our mood, feelings and perceptions 1. It is degraded primarily by the (FAAH) enzyme, which converts anandamide into ethanolamine and arachidonic acid

• Neurologically speaking it is a neurotransmitter that helps :• Produce new nerve cells 2

• Reduces inflammation in the brain 3

• Regulates functions that produce memory 2

• Reward and motivation processes 3

• Treatment of anxiety and mood disorders 2

1. Scherma, Maria, Julie Medalie, Walter Fratta, Subramanian K. Vadivel, Alexandros Makriyannis, Daniele Piomelli, Eva Mikics, Jozsef Haller, Sevil Yasar, Gianluigi Tanda, and Steven R. Goldberg. 2008. 'The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition', Neuropharmacology, 54: 129-40.2. Prospéro-García, Oscar, Octavio Amancio-Belmont, Alline L. Becerril Meléndez, Alejandra E. Ruiz-Contreras, and Mónica Méndez-Díaz. 2016. 'Endocannabinoids and sleep', Neuroscience & Biobehavioral Reviews, 71: 671-79.3. McDougle, Daniel R., Josephine E. Watson, Amr A. Abdeen, Reheman Adili, Megan P. Caputo, John E. Krapf, Rodney W. Johnson, Kristopher A. Kilian, Michael Holinstat, and Aditi Das. 2017. 'Anti-inflammatory ω-3 endocannabinoid epoxides', Proceedings of the National Academy of Sciences, 114: E6034-E43.


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AnandamideIt’s been found that people that have less anandamide have a greater correlation with certain mental health issues.

Both depression and schizophrenia have been associated with low anandamide levels.


Mol Med Rep. 2016 Oct;14(4):2899-903. Endocannabinoid system: Role in depression, reward and pain control (Review). Huang WJ1, Chen WW1, Zhang X1.

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2-Arachidonoylglycerol (2-AG)• 2-Arachidonoylglycerol (2-AG) is an

endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol.

• It is present at relatively high levels in the central nervous system, with cannabinoid neuromodulatory effects.

• 2-AG is susceptible to degradation primarily by an enzyme in the body called MAGL

Ueda, Natsuo, Kazuhito Tsuboi, Toru Uyama, and Taira Ohnishi. 2011. 'Biosynthesis and degradation of the endocannabinoid 2-arachidonoylglycerol', Biofactors, 37: 1-7.


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2-Arachidonoylglycerol (2-AG)• 2-AG exerts a modulating influence on the following:

• Immunity1.• Reduced Inflammation1.• Insulin sensitivity2.• Pain Signaling1.• Bone Remodeling3.• Reduced COX-2 activity in the brain (protect neurons) and throughout

the body1.

1. Turcotte, Caroline, Francois Chouinard, Julie S. Lefebvre, and Nicolas Flamand. 2015. 'Regulation of inflammation by cannabinoids, the endocannabinoids 2-arachidonoyl-glycerol and arachidonoyl-ethanolamide, and their metabolites', Journal of Leukocyte Biology, 97: 1049-70.2. Motaghedi, Roja, and Timothy E. McGraw. 2008. 'The CB1 Endocannabinoid System Modulates Adipocyte Insulin Sensitivity', Obesity, 16: 1727-34.3. Elefteriou, Florent. 2008. 'Regulation of bone remodeling by the central and peripheral nervous system', Archives of Biochemistry and Biophysics, 473: 231-36.


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• Cannabinoid receptors (CBs) are the primary targets of the ECS, bound by endocannabinoids that are produced on demand in response to elevated intracellular calcium levels in neurons.

• After eCBs bind a receptor to inhibit the release of neurotransmitters and exert a particular effect on the body, they are degraded via metabolic enzymes in a process called hydrolysis.

Endocannabinoid Receptors


Cannabinoid Receptor

Presynaptic(Sending Neuron)

Neurotransmitters

Lipid Precursors(Fat Calls)

Receptors

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Cannabinoid Receptor 1 (CB1) is associated with psychoactive, neuromodulatory, and analgesic effects. CB1 is mostly expressed in the brain, adipocytes (fat cells), hepatocytes (liver cells), and musculoskeletal tissues.

Cannabinoid Receptor 2 (CB2) is associated with anti-inflammatory and immunomodulatory effects. CB2 is expressed in body cells controlling immune function and (potentially) the central nervous system (CNS). Additionally, research suggests that secondary metabolites from phytonutrients in plant-based foods enhance the activity of CB2 receptors and confer healthy inflammatory responses.

Endocannabinoid Receptors - CB1 & CB2


CB2SpleenBonesSkinImmune SystemLiver Bone MarrowPancreas

BrainLungsVascular SystemMusclesGastrointestinal TractReproductive OrgansImmune SystemLiverBone MarrowPancreas

CB1

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PUFA’s role in the endocannabinoid system

• Studies have revealed that omega-3 Deficiency reduces endocannabinoid production and receptor activity in the body.

• Maintaining a healthier O3 to O6 ratio along with phytocannabinoidsupplementation from hemp extracts will help to support proper functioning of ECS tone.

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Why I Give Bioavailable Curcumin and Fish Oil to 99.999% of My Patients

• Multi-purpose

• Amount of supporting research

• Cost effective

• Low dose

• Synergistic with many other supplements

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#4 Boswellia Serrata

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Boswellia Main Actions: • anti-inflammatory • antiarthritic

Key Indications: • rheumatoid arthritis • osteoarthritis • crohn’s disease • ulcerative colitis • asthma

Actions and indications taken from The Ultimate Herbal Compendium by Kerry Bone

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• Herbal actions

• Indications

• Contraindications

• Correct dosage

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Synergistic Benefits

Boswellia Turmeric

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Boswellia and Turmeric Synergy

e-Monitor No. 46, April 2014 “12-week trial involving 30 patients with osteoarthritis (OA) of the knee. Patients were randomly assigned to take either 700 mg/day of turmeric extract (90.5% curcuminoids and 7.5% essential oil) with 300 mg/day Boswellia extract (75% boswellic acids, 10% AKBA) or 200 mg/day of the drug Celebrex.

At the completion of the trial, 64% of the patients in the herbal group were no longer classified as moderate to severe, versus only 39% in the drug group. Otherwise, there was no overall difference in pain severity, walking distance and joint tenderness between the two groups. The authors concluded that the efficacy and tolerability of the herbal combination was superior to Celebrex for the treatment of active OA.”

Clinical evaluation of a formulation containing Curcuma longa and Boswellia serrata extracts in the management of knee osteoarthritis.Molecular Medicine Reports 2013 Nov;8(5):1542-8.

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Boswellia and the ECS

An active component of Boswellia called b-amyrin has shown to inhibit MAGL which can result in increasing 2-AG tone1,2.

1. Chicca, A, J Marazzi, and J Gertsch. 2012. 'The antinociceptive triterpene β-amyrin inhibits 2-arachidonoylglycerol (2-AG) hydrolysis without directly targeting cannabinoid receptors', British journal of pharmacology, 167: 1596-608.

2. Bekana, Deribachew, Tesfahun Kebede, Mulugeta Assefa, and Habtemariam Kassa. 2014. 'Comparative phytochemical analyses of resins of Boswellia species (B. papyrifera (Del.) Hochst., B. neglecta S. Moore, and B. rivae Engl.) from Northwestern, Southern, and Southeastern Ethiopia', ISRN Analytical Chemistry, 2014.


Boswellia Serrata

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Boswellia Quality Concerns

Antioxidant and Ex Vivo Immune System Regulatory Properties of Boswellia serrata Extracts.Oxidative Medicine and Cellular Longevity. 2017 March;7468064.

Survey on the Quality of the Top-Selling European and American Botanical Dietary Supplements Containing BoswellicAcids.Planta Medica. 2016 Apr;82(6):573-9. doi: 10.1055/s-0042-103497

Both studies identified boswellia extracts that contained NO detectable levels of the boswellic acid AKBA

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Inflammation Essentials

What every patient can benefit from: • Bioavailable Curcumin • Fish oil

For extra inflammation support: • Boswellia Serrata• Hemp Oil

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© 2 0 1 9 S ta n d a r d P r o c e s s I n c . A l l r ig h t s r e s e r v e d . L N 1 3 9 8 0 1 /1 9

TurmericFishOilBoswelliaHempOil

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#5 Pulsed Electromagnetic Field Therapy (PEMF)

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Every Living Thing is Dependent on Earth’s Electromagnetic Energy Field

Earth’s energy is measured at 25 to 65 microtesla’s and pulses approximately 7.83 times per second.

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FDA Approved Uses of PEMF

• In 1979, for the healing of nonunion fractures.

• In 1998, for urinary incontinence and muscle stimulation.

• In 2004, for cervical fusion patients at high-risk of non-fusion.

• In 2006, for treatment of depression and anxiety.

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Pubmed.gov ‘PEMF’ search results

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● Cells need to be charged to perform vital metabolic function● PEMF is an outside energy source proven to restore a more optimal charge

Our bodies are electrical; each cell is in essence a battery that can accumulate and store energy vital for cellular metabolism.

“...bioelectric phenomena of the cell membrane are vital functions of the living organism.”

- Bioelectromagnetism by Jaako Malmivuo & Robert Plonsey

PEMF: The Foundational Biohack Technology

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● Efficacy of Pulsed Low-Frequency Magnetic Field Therapy on Patients with Chronic Low Back Pain: A Randomized Double-Blind Placebo-Controlled Trial (Asian Spine Journal 2020 Feb;14(1):33-42).

● The effects of extremely low-frequency pulsed electromagnetic fields on analgesia in the nitric oxide pathway (Nitric Oxide 2019 Nov 1;92:49-54).

PEMF for Analgesic Support

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● Pulsed electromagnetic fields increased the anti-inflammatory effect of A₂A and A₃ adenosine receptors in human T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts PLOS One 2013 May 31;8(5):e65561. doi: 10.1371/journal.pone.0065561.

● Pulsed Electromagnetic Fields Reduce Interleukin-6 Expression in Intervertebral Disc Cells Via Nuclear Factor-κβ and Mitogen-Activated Protein Kinase p38 Pathways Spine 2019 2019 Nov 15;44(22)

PEMF to Support Inflammatory Responses

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● Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration Stem Cell Research Therapy 2020 Feb 3;11(1):46).

● Pulsed electromagnetic field (PEMF) treatment reduces expression of genes associated with disc degeneration in human intervertebral disc cells.Spine Journal 2016 Jun;16(6):770-6.

PEMF for Healing Support

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PEMF for Healing Support Effect of pulsed electromagnetic field on mandibular fracture healing: A randomized control trial, (RCT) (Journal of Stomatology Oral and Maxillofacial Surgery 2019 Nov;120(5):390-396).

Conclusion: PEMF therapy postoperatively leads to increased bone density, faster recovery, increased formation of new bone, a further opening of the mouth, and decreased pain.

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PEMF for Peripheral Nerve Support

● Pulsed magnetic field treatment as antineuropathic pain therapy (Reviews in Neuroscience 2017 Oct 26;28(7):751-758).

● The change of HCN1/HCN2 mRNA expression in peripheral nerve after chronic constriction injury induced neuropathy followed by pulsed electromagnetic field therapy (Oncotarget 2017 Jan 3;8(1):1110-1116).

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Pemfinfo.com

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Personal Clinical Experience with Pain Management Using High Intensity PEMF

● Low back

● Neck

● Shoulder

● Ankle

● Headache ● Neuropathy

Dry eye

Colitis

Orchitis

Ileocecal valve

Sinus Bronchitis

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Oskawellness.com Pulsecenters.com

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#6 Connective Tissue Healing Support

Bone Gotu Kola

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Bone Broth (Glycine, proline, alanine, chondroitin sulfate,

glucosamine, hyaluronic acid, phosphorus)

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Gotu KolaCentella asiatica

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Gotu Kola

Main Actions:

• healing promoter

• vulnerary

• anti inflammatory

• adaptogenic

• nervine Tonic

• antifibrotic

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Gotu Kola Key Indications:• promote healing• prevent adhesions • post surgery • varicose veins • venous insufficiency • varicose ulcer • hemorrhoids • burns

• cellulitis

• diabetic neuropathy • diabetic ulcer • peptic ulcer • disc prolapse • fractures • scleroderma • psoriasis

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Gotu Kola Research (connective tissue)

In vitro and in vivo modulation of cartilage degradation by a standardized Centella asiatica fraction. Experimental Biology and Medicine, 2009 Jun;234(6):617-23.

Gene expression changes in the human fibroblast induced by Centellaasiatica triterpenoids. Planta Medica, 2003 Aug;69(8):725-32.

Triterpenes with healing activity: A systematic review.The Journal of Dermatological Treatment 2015 Oct;26(5):465-70

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Gotu Kola-The Healing Herb Phytotherapists Perspective No. 115 October 2007

“In a study of 227 patients, treatment with Gotu Kola actives for a period of 2 to 18 months had therapeutic value in both preventing and reducing keloids.”Bosse JP, Papillon J, Frenette G et al. Ann Plast Surg 1979; 3(1): 13-21

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Gotu Kola Research(neuroprotection)

Neuroprotective effect of a standardized extract of Centella asiaticaECa233 in rotenone-induced parkinsonism rats.Phytomedicine. 2018 May 15;44:65-73.

Neuroprotective role of Asiatic acid in aluminum chloride induced rat model of Alzheimer’s disease Frontiers in Bioscience (Schol Ed). 2018 Jan 1;10:262-275.

Centella asiatica triterpene extract is effective in treating diabetic neuropathy – A pilot study. Neurology 2012; 78(Meeting Abstracts 1): P03.192

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Phytocannabinoids


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Endocannabinoid System: Quick SummaryEndocannabinoids: Made by the body

1. Anandamide (AEA) 2. 2-Arachidonoylglycerol (2-AG)

Cannabinoid receptors

CB1 à Brain CB2 à Immune system, brain

Endocannabinoid degrading enzymes

Anandamide à Fatty acid amide hydrolase (FAAH)


Zajkowska ZE, Englund A, Zunszain PA. Towards a personalized treatment in depression: endocannabinoids, inflammation and stress response. Pharmacogenomics. 2014 Apr;15(5):687-98

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§ Plant based compounds for which our bodies respond similarly to cannabinoids that we produce.

§ Plants that contain compounds that interact with the ECS system include:§ Hemp§ Carrot§ Echinacea

Phytocannabinoids

Russo, Ethan B. 2016. 'Beyond Cannabis: Plants and the Endocannabinoid System', Trends in Pharmacological Sciences, 37: 594-605.


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Nutritional Support for the ECS: Hemp vs Marijuana• While both are considered Cannabis sativa, there has been a great deal

of confusion about hemp products and many people don’t understand the distinction between hemp and marijuana 1.

• In simplest terms, marijuana contains significant amounts of the psychoactive phytocannabinoid known as THC 2.

• Industrial Hemp is cultivated very differently and has very little if any THC after extraction 2.

• Hemp stalk in particular is also a source of many beneficial phytocannabinoids 2.

1. Malone, Trey, and Kevin Gomez. 2019. 'Hemp in the United States: A Case Study of Regulatory Path Dependence', Applied Economic Perspectives and Policy, 41: 199-214.

2. Fike, John. 2016. 'Industrial Hemp: Renewed Opportunities for an Ancient Crop', Critical Reviews in Plant Sciences, 35: 406-24.


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Fats Found in Hemp Seeds

• Hemp seeds contains essential fatty acids including linoleic acid (omega-6) and alpha-linolenic acid (omega-3), with the ratio of Omega 6 to Omega 3 around 3:1

• They are also a good source of gamma linolenic acid (GLA), a polyunsaturated fatty acid which can have anti-inflammatory effects.


Hempseed as a nutritional resource: An overview. Callaway JC. Euphytica. 140: 65-72, 2004.

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Wisdom in Nature- Full Spectrum Hemp


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Phytocannabinoids Found In Hemp

Hemp phytocannabinoids work to inhibit Fatty Acid Amide Hydrolase (FAAH). This inhibition creates higher levels of endocannabinoids like anandamide.


Deutsch DG. A Personal Retrospective: Elevating Anandamide (AEA) by Targeting Fatty Acid Amide Hydrolase (FAAH) and the FattyAcid Binding Proteins (FABPs). Front Pharmacol. 2016;7:370. Published 2016 Oct 13.

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The ECS in Pain & Inflammation

• CB1 receptors are densely located in the limbic area of the brain which is key in the emotional expression of pain. In the spinal cord, CB1 receptors help regulate the transmission of pain to the brain by inhibiting neurotransmitters associated with pain sensation.

• CB2 receptors are widely located on immune cells and are a perfect target for influencing inflammatory pain processing.


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The ECS & Sleep• CB1 receptors may be localized in sleep-inducing

areas in the brain.

• Pre-clinical data indicates the activation of the CB1 receptor i.e. by Anandamide may lead to an induction of sleep.

• ECB’s have been shown to influence melanin-concentrating hormone(MCH), located in the hypothalamus, which promotes REM sleep and helps restore sleep in animals with insomnia.


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The ECS & Sleep2-AG into the lateral hypothalamus increases REM sleep and cFos expression in melanin concentrating hormone neurons in rats.

AbstractOrexins/hypocretins (OX) and melanin-concentrating hormone (MCH) neurons located in the lateral hypothalamus seem to modulate different stages of the sleep-wake cycle. OX are necessary for wakefulness and MCH appears to regulate rapid eye movement sleep (REMS). Likewise, endocannabinoids, the endogenous ligands for cannabinoid receptors 1 and 2 (CB1R, CB2R), also modulate REMS in rats. Moreover, it has been shown that the activation of the CB1R in the lateral hypothalamus of rats excites MCH neurons while inhibiting OX neurons in in vitro preparations. Hence, we assessed the effects of 2-arachidonoylglicerol (2-AG, an endocannabinoid) in the lateral hypothalamus on the sleep-wake cycle of rats. We also utilized the CB1R inverse agonist AM251 to further support the involvement of this receptor, and we performed double immunofluorescence experiments to detect c-Fos, as a marker of neural activation, in OX and in MCH neurons to determine which neurons were activated. Our results indicate that 2-AG increases REMS through CB1R activation, and increases c-Fos expression in MCH neurons. These results suggest that endocannabinoid activation of the CB1R in the lateral hypothalamus, which activates MCH neurons, is one mechanism by which REMS is triggered.

Perez-Morales, M., A. K. De La Herran-Arita, M. Mendez-Diaz, A. E. Ruiz-Contreras, R. Drucker-Colin, and O. Prospero-Garcia. 2013. '2-AG into the lateral hypothalamus increases REM sleep and cFos expression in melanin concentrating hormone neurons in rats', Pharmacol BiochemBehav, 108: 1-7.


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Endocannabinoid System & HPA Axis Regulation

• Endocannabinoids modulate CRH

• Chronic stress downregulates CB-1

• Cortisol interacts with hypothalamus to release endocannabinoids which suppress CRH

• This switches off hypothalamic stress response to stop cortisol release


Zajkowska ZE, Englund A, Zunszain PA. Towards a personalized treatment in depression: endocannabinoids, inflammation and stress response. Pharmacogenomics. 2014 Apr;15(5):687-98Uchoa ET, Aguilera G, Herman JP, etal, Novel aspects of glucocorticoid actions. J Neuroendocrinol. 2014 Sep;26(9):557-72

Herman JP, McKlveen JM, Solomon MB, etal, Neural regulation of the stress response: glucocorticoid feedback mechanisms. Braz J Med Biol Res. 2012 Apr;45(4):292-8. Epub 2012 Mar 29

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• Central anandamide deficiency predicts stress-induced anxiety in animal studies.

• Preclinical studies show animals with genetic deficiencies of 2-AG induce both anxiety and depression states while increasing 2-AG reduces anxiety and stress behavior.

The ECS & Stress/Anxiety


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Regulation of endocannabinoid signaling by stress: implications for stress-related affective disorders.

Abstract…Disrupted endocannabinoid signaling, on the other hand, is associated with an inability to adapt to chronic stress. Therapeutically, these data suggest that the endocannabinoid system could be dysregulated in affective disorders, such as depression, which are characterized by maladaptive stress coping. In this review, we discuss the evidence demonstrating that the endocannabinoid system is affected by and can oppose the effects of prolonged stress and, as such, represents a potential target for the development of novel antidepressant agents.

Gorzalka, B. B., Hill, M. N., & Hillard, C. J. (2008). Regulation of endocannabinoid signaling by stress: implications for stress-related affective disorders. Neuroscience & Biobehavioral Reviews, 32(6), 1152-1160.

The ECS & Stress/Anxiety


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The ECS & Bone Health• Both 2-AG and anandamide, and their

receptors, CB1 and CB2, are present in osteoblast and osteoclasts.

• The communication between the CNS and our bones is vital to the proper building of healthy bone tissue.

• Anandamide stimulates CB1 receptors in bone, which sends signals to suppress the release of norepinephrine- a hormone that inhibits bone formation.


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The ECS & Bone Health

A collaboration investigating endocannabinoid signaling in brain and bone.AbstractInterest in the central nervous system effects was initially the main focus of the research, but it soon became evident that the endocannabinoid system affects virtually every organ…Thus, activation of CB2 stimulates bone formation and represses bone resorption, whereas the genetic disruption of CB2 results in an osteoporosis-like phenotype. This signaling mechanism is clinically relevant, as shown by the association of polymorphisms in the CB2 receptor gene, CNR2, with bone density and osteoporosis. Finally, the review provides a summary of the recently discovered role of endocannabinoid signaling in one elongation. This review will also discuss the benefits of interdisciplinary and international collaborations.

Zimmer, A. (2016). A collaboration investigating endocannabinoid signaling in brain and bone. Journal of basic and clinical physiology and pharmacology, 27(3), 229-235.


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Echinacea and the ECS • The Alkylamides in Echinacea have been found to act

on the CB2 cannabinoid receptor to regulate cytokine synthesis and to support immune function.

• Alkylamides mimic anandamide and prevent their degradation from FAAH.


1. Raduner S, Majewska A, Chen J, et al. Alkylamides from Echinacea are a new class of cannabinomimetics Cannabinoid type 2 receptor-dependent and-independent immunomodulatory effects. J Biol Chem2006;281(20):14192-14206.

2. Planta Med. 2005 Aug;71(8):701-5. The endocannabinoid system as a target for alkamides from Echinacea angustifolia roots. Woelkart K1, Xu W, Pei Y, Makriyannis A, Picone RP, Bauer R.

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Boswellia and the ECS

An active component of Boswellia called b-amyrin has shown to inhibit MAGL which can result in increasing 2-AG tone1,2.

1. Chicca, A, J Marazzi, and J Gertsch. 2012. 'The antinociceptive triterpene β-amyrin inhibits 2-arachidonoylglycerol (2-AG) hydrolysis without directly targeting cannabinoid receptors', British journal of pharmacology, 167: 1596-608.

2. Bekana, Deribachew, Tesfahun Kebede, Mulugeta Assefa, and Habtemariam Kassa. 2014. 'Comparative phytochemical analyses of resins of Boswellia species (B. papyrifera (Del.) Hochst., B. neglecta S. Moore, and B. rivae Engl.) from Northwestern, Southern, and Southeastern Ethiopia', ISRN Analytical Chemistry, 2014.


Boswellia Serrata

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Other Ways To Increase Endocannabinoid Levels• Exercise (anandamide)

• Cold exposure has been shown to increase endocannabinoid levels.

• Olive Oil: Oleic acid it has been shown to increase CB1 receptors.

• Spinal manipulation

• Probiotics (lactobacillus has been shown to increase CB-2 activity)


1. Onifer SM, Sozio RS, Long CR. Role for Endocannabinoids in Spinal Manipulative Therapy Analgesia?. Evid Based Complement Alternat Med. 2019;2019:2878352. Published 2019 Jul 15.

2. Sharkey KA, Wiley JW. The Role of the Endocannabinoid System in the Brain-Gut Axis. Gastroenterology. 2016;151(2):252–266.

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Simplified Support for the ECS


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#8 California Poppy

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Plant based compounds for which our bodies respond similarly to cannabinoids that we produce.

Plants that contain compounds that interact with the ECS system:§ Hemp§ Carrot§ Echinacea

Cannabinoids- Phytocannabinoids

R u s s o , E t h a n B . 2 0 1 6 . 'B e y o n d C a n n a b is : P la n t s a n d t h e E n d o c a n n a b in o id S y s t e m ' , T r e n d s in P h a r m a c o lo g ic a l S c ie n c e s , 3 7 : 5 9 4 - 6 0 5 .

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California Poppy

Main Actions: • Anxiolytic

• Mild Sedative

• Analgesic

• Hypnotic

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California Poppy Key Indications

• Neuralgia

• Sciatica

• Trigeminal neuralgia

• Toothache

• Tension headache

• Insomnia

• Anxiety

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#9 Corydalis

Main Actions • Mild Sedative

• Hypnotic

• Analgesic

• Antiarrhythmic

• Spasmolytic

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Corydalis

Key Indications: • Pain management, especially for visceral pain • Irritable bowel syndrome • Spasmodic or congestive dysmenorrhea • Tension headache • Insomnia • Anxiety • Emotional Stress • Cardiac arrhythmias • Palpitations

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#10 White Willow Barksalix alba

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Willow Bark

Main Actions:

• Analgesic

• Anti-inflammatory

• Antirheumatic

• Antipyretic

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Willow Bark Key Indications:

• Osteoarthritis

• Rheumatoid arthritis

• Low back pain

• Ankylosing spondylitis

• Fever

• Migraine headache

• Tension headache

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Willow Bark Clinical Study

• Involved 922 physicians and 4271 patients in Germany.

• Over 6-8 weeks, patients with arthritis or back pain took willow bark standardized to contain 60 mg of Salicin per tablet.

• Patients were asked to rate their pain on a scale of 1-10.

• Average pain intensity reduced from 6.4-3.7 points in the first 4 weeks of treatment and had fallen further to 2.7 points after 8 weeks.

• 97% reported a reduction in pain and 18% no pain at all.

Werner G, Scheithe K. Congress Phytopharmaka and PhytotherapyPresented in Berlin, February 26-28, 2004.

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Top 10 Nutritional Therapies for Pain and Inflammation Management

• Low(er) carb diet

• Bioavailable curcumin

• Fish oil

• Boswellia

• PEMF

• Connective tissue healing support

• Hemp oil

• California poppy

• Corydalis

• White willow bark

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Recommended Resources

• Standardprocess.com (whole food supplements)

• Dietdoctor.com (comprehensive low carb and intermittent fasting resource)

• Pulsecenters.com (high intensity PEMF devices for clinical use)

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Top 10 Nutritional Therapies · 2020. 8. 29. · Top 10 Nutritional Therapies for a Healthy Pain and Inflammation Response Presented by David Hogsed, D.O.M., A.P. 1 Disclaimer The