Phase IBiotransformation

Phase IIConjugation

Phase IIIElimination

Reactive intermediate substances

Free radicals

Antioxidant enzymes

X

X

Leading edge nutrients

• Xanthohumol

• Broccoli sprout and floret powder, broccoli seed extract

• Superoxide dismutase (SOD)

• Isomaltooligosaccharides (IMO)

• N-acetylcysteine (NAC)

Fiber

© 2016 Metagenics, Inc.

Metabolic DetoxificationThe power of Keap1-Nrf2 activation

• Cruciferous vegetables such as broccoli accumulate significant concentrations of glucoraphanin (a glucosinolate)

• Glucoraphanin is converted in vivo to biologically active sulforaphane (an isothiocyanate). This conversion requires myrosinase enzyme

• Sulforaphane (SF) is a potent activator of the body’s own antioxidant and detoxifying enzymes via the Keap1/Nrf2 pathway and is the compound responsible for the many positive health benefits associated with Broccoli consumption

Glucoraphanin Sulforaphane

Myrosinase

+ Glucose

10-Day Detox

2) A capsular formulation to support detoxification: supports detoxification. Provides bifunctional support to enhance the activities of several liver detox enzymes while promoting balanced activity of Phase I and Phase II detox pathways

3) Eating plan: a modified elimination diet rich in vitamins, minerals, and phytonutrients reduces the allergen and toxin load, helping the body to detoxify efficiently:

a) Listing of foods to choose from for Days 1 – 10b) Sample recipes/menu plan for each dayc) 3 meals a day

© 2016 Metagenics, Inc.

Nutrients that balance Phase I & Phase II enzymes

• Ellagic acid from pomegranates• Catechin from decaffeinated green tea• Watercress glucosinolates

Support multiple Phase II detoxification pathways

• Sulfation: N-acetylcysteine, Sodium Sulfate• Acetylation: Vitamin B5, Magnesium• Methylation: Vitamin B12, Choline, 5-MTHF

Antioxidant and overall liver function support

• N-Acetylcysteine• Silymarin• Vitamin C & Vitamin A

Additional Daily SupportAddition of a daily phytonutrient supplement recommended to support balanced clearance of toxins

Take a Probiotic to Detoxify the Body

• Two new studies: taking a probiotic can help body detoxify

• Nutrition journal: 1) Probiotics help detoxify body of heavy metals, free radicals, and

dangerous bacteria by enhancing natural antioxidant status in body

2) Probiotic also significantly increased glutathione status (the number one internal antioxidant in the body) and decreased malondialdehyde

Asemi, A., Jazayeri, S. et al. Effect of Daily Consumption of Probiotic Yogurt on Oxidative Stress in Pregnant Women. Annals of Nutritional Medicine, 2012. 60(1), 62-28Ejtahed, H. Mohtadi-Nia, J. et al. Probiotic Yogurt Improves Antioxidant Status in Type-2 Diabetic Patients. Nutrition, 2012. 28, 539-543

10-Day Detox Protocol

• Nutritional Detox Powder: 2 scp. BID

• A capsular formulation to support detoxification: 2 caps BID

• Modified elimination diet

• Probiotic – lactobacillus acidophilus, NCFM, b. lactis Bi-07: 1 cap daily

• 15 or 60 billion live organisms

Liver Detoxification of Estrogens

• Metabolism of estrogen takes place primarily in the liver

• Promoting favorable phase I and phase II estrogen clearance is key for female performance and long-term health

Birth control pills + Hormone Replace Therapy = exogenous estrogen

Estrogens, whether you make them or take them,Or whether you have been unknowingly intoxicated by them,You need to get rid of them every day . . .IN A HEALTHY WAY!

E2 Intermediate ExcretableForm

Estrogen Elimination Basics

Problems with detoxification occur when:

1) Nutritional (micro or macro) deficiencies lead to poorly performing enzymes

2) Genetic alterations lead to poorly performing enzymes

3) Estrogen elimination is impaired through constipation or increase beta-glucuronidase

4) Underlying liver or gall bladder disease

E2 Intermediate ExcretableForm

Action of Beta-Glucuronidase

Glucuronidationof estrogen in

liver

Conjugated estrogen

excreted in bile

Excreted in stool

Cleaves glucuronide

Release of free estrogen

Re-absorption:Systemic

estrogen toxicity

+++ Beta-Glucuronidase

Probiotics

30-Day Female Estrogen Detox

Part 2

• Women’s estrogen detox formula: 2 scps BID

• Detox support capsules: Provides bifunctional support to enhance the activities of several liver detox enzymes while promoting balanced activity of Phase I and Phase II detox pathways (3 caps BID)

• Methylation support formula: Involves conjugating methyl groups to toxins and SAMe (2 tablets on empty stomach)

• Eating Plan: a modified elimination diet rich in vitamins, minerals, and phytonutrients reducing the allergen and toxin load, helping the body to detoxify efficiency.

Detox

Daily bifunctional support for detoxification:

• Supports the balance between Phase I and Phase II

• Provides nutrients used to support multiple Phase II detoxification pathways

• Silymarin and other traditional herbs provide antioxidant activity and supports overall liver function

Formula for Balanced Clearance of Toxins Through Phase I and Phase II

Ellagic acid induces transcription of the rat

glutathione S-transferase-Ya geneGarfinkel L, Garfinkel D.

Induction of glutathione S-transferase (GST) enzymes

can increase detoxification of carcinogens and reduce

carcinogen-induced mutagenesis and tumorigenesis. To

determine if the anticarcinogen ellagic acid induces

cellular enzymes which detoxify carcinogens, we

examined the effect of ellagic acid on the expression of

glutathione S-transferase-Ya. Rats fed ellagic acid

demonstrated significant increases in total hepatic GST

activity, hepatic GST-Ya activity and hepatic GST-Ya

mRNA. To determine if the observed increase in GST-Ya

mRNA was due to ellagic acid inducing transcription of

the GST-Ya gene, transfection studies were performed

with plasmid constructs containing various portions of

the 5' regulatory region of the rat GST-Ya gene. The

transfection studies demonstrated that ellagic acid

increased GST-Ya mRNA by inducing transcription of

the GST-Ya gene and demonstrated that this induction is

mediated through the antioxidant responsive element of

the GST-Ya gene.

Comparative chemopreventive mechanisms of green tea, black tea and selected polyphenol extracts measured by in vitro bioassaysSteele VE, Kelloff GJ, Balentine D, Boone CW, Mehta R, Bagheri D, Sigman CC, Zhu S, Sharma S.

Black tea extracts (hot aqueous, polyphenols and theaflavins) and green tea extracts (hot aqueous, polyphenols, epicatechin, epicatechin gallate, epigallocatechin and epigallocatechin gallate) were tested in nine standardized cell culture assays for comparative cancer chemopreventive properties. Most black and green tea extracts strongly inhibited neoplastic transformation in mouse mammary organ cultures, rat tracheal epithelial cells and human lung tumor epithelial cells. Nearly all tea fractions strongly inhibited benzo[a]pyrene adduct formation with human DNA. Induction of phase II enzymes, glutathione-S-transferase and quinone reductase, were enhanced by nearly all tea fractions, while glutathione was induced by only a few fractions. Ornithine decarboxylase activity was inhibited by nearly all the green tea fractions, but none of the black tea fractions..

Bifunctional Modulators support balance between Phase I and Phase II

Decrease of plasma and urinary oxidative

metabolites of acetaminophen after

consumption of watercress by human

volunteers.Chen L, Mohr SN, Yang CS.

To investigate the effect of the consumption of watercress

(Nasturtium officinale R. Br.), a cruciferous vegetable, on

acetaminophen metabolism, the pharmacokinetics of

acetaminophen and its metabolites were studied in a

crossover trial of human volunteers. A single oral dose of

acetaminophen (1 gm) was given 10 hours after ingestion

of watercress homogenates (50 gm). In comparison with

acetaminophen only, the ingestion of watercress resulted in

a significant reduction in the area under the plasma

cysteine acetaminophen (Cys-acetaminophen)

concentration-time curve and in the peak plasma Cys-

acetaminophen concentration by 28% +/- 3% and by 21%

+/- 4% (mean +/- SE; n = 7; p < 0.005), respectively.

Carcinogenesis. 2000 Jan;21(1):63-7● Carcinogenesis. 2000 Jan;21(1):63-7 ● Clin Pharmacol Ther. 1996 Dec;60(6):651-60

Inhibit overproduction of Phase I enzymes and up-regulate production of Phase II enzymes with:

• Decaffeinated green tea catechins

• Ellagic acid

• Watercress glucosinolates

AntioxidantsThe missing piece to support glutathione

Help reduce free radical formation

Function in the regeneration of glutathione

Aid in phase II detoxification

Antioxidant functionDetoxifying function

GSH

GSHGSSG

G R

Neutralized counterparts

G P x

Free radicals, H2O2

organic peroxides

NADP+ NADPH

GSH

X

G S T

Further breakdownand excretion

GSH = glutathione; = glutathione disulfide; = xenobiotics

GST = glutathione S-transferase; GPx = glutathione peroxidase; GR = glutathione reductase

GSSG

x

X

Glutathione: Antioxidant and detoxifying function

Niacinamide

Selenium

N-acetyl-L-cysteine

Broccoli extract

Vitamin C

Kidney Detoxification/Health

Formulated with NAC, targeted vitamins, and traditional Chinese herbs to help protect kidneys from oxidative stress

Promote healthy kidney detoxification

Support cardiovascular health for individuals with renal stress concerns

Designed to help protect kidneys from oxidative stress

Provide your patients with a powerful formula for balanced daily detoxification

• Bifunctional detoxification support:

• Methylated vit. B12, folic acid with nutrients to balance phase I and phase II

• Antioxidant protection and detoxification support:

• Vit. C, selenium, niacin (niacinamide), n-acetyl-L-cysteine (NAC), broccoli extract

• Kidney detoxification and kidney health:• Vit. B6, B12, Folate, cordyceps, Chinese salvia, NAC

Heavy Metals: A Global Problem

Cadmium inhaled from polluted air and eaten in food raised in contaminated soil

Lead exposure comes from numerous sources, including drinking water, contaminated soil, household dust, and lead-based paint in older homes

Body’s natural mechanism for eliminating heavy metals

Metallothionein

Binds to heavy metals

in the cell

Transports heavy metal

out of the cell to the liver

Liver

Conjugated with glutathione (phase

II detoxification) transformed to mercapturate

Mercapturate

Excreted via urine or stool

Metallothionein

Support metabolism of heavy metals but do not facilitate excretion of certain healthful minerals (calcium, magnesium, selenium, zinc)

Metabolic Detoxification The importance of metallothionein for support of heavy metal metabolism

PhytonutrientsMetal-

activated transcription

factor-1

Metallothionein-1

Spent hops (Humuluslupulus), pomegranate rind extract (Punica granatum), prune skin extract (Prunus

domestica), watercress plant extract (Nasturitum

officinalis)

Heavy-Metal Detox – On-Going Care

1) Formulation to provide on-going liver and kidney detoxification

2) Supports the genetic expression of enzymes involved in the metabolism of heavy metals (3 tabs BID)

3) Minimum 30 days

Promoting Weight loss without Supporting Detox is Malpractice!

Persistent Organic Pollutants

DETOXFat Loss Patients!Weight Loss May Push

Toxins Into Bloodstream

“Serum concentrations of most POPs were higher in those with long-term weight loss”Int J Obes (Lond). 2010 Sep 7

Juicing and other fasting programs can actually deprive your body of essential nutrients needed to support detoxification.

Problems when fasting without detoxification support

• Calorie restricted and protein deficient diets lead to rapid breakdown of adipose tissue (lipolysis) resulting in surge of toxins into the circulation, thus precipitating an iatrogenic “health crisis”

• Lack of fiber impedes fecal excretion and increases enterohepaticrecirculation

• Insufficient calories impairs biotransformation (detoxification is highly energy dependent, especially phase II), compounding toxic overload

Detoxification – 21st Century Model

• Body’s innate process of removing or altering metabolic wastes and acquired toxins

• Enables the body to perform its life processes unencumbered by detrimental elements and disruptive molecules

• Body’s natural innate processes to “recycle” or “take out the trash”

Healthy, Lean, Strong

91 year-old Betty Calman shows off the peacock pose

Are You Kidding Me?

• Tampons and pads are regulated by the FDA as medical devices

• Medical devices are not required to disclose ingredients

• Tampons – made from cotton, rayon, pulp fiber

• 94% of cotton in U.S. = GMO!

Are You Kidding Me? (cont’d)

• These materials may contain toxic disinfection by-products:a) From chlorine bleaching

b) Dioxins, furans, DBP

c) Pesticides from non-organic cotton

• FDA recommends that tampons be free of dioxine, etc…

• It is not a requirement

• Studies have shown the toxins are present in brands studied

FYI

• Feminine-care products are classified as “cosmetics” by FDA

• Means no specific tests are required to demonstrate their safety

• Avoid fragranced tampons

• Use “unscented” products

• Chlorine-free or unbleached tampons/pads

• Use organic – chemical-free (non-GMO particles)

Try This…

• Burn an organic tampon/pad – it burns slow and clean

• Burn a commercial brand (undisclosed ingredients)

Creates black smoke and thick residue

Indicates the pad has dioxins

Post Detox…

Acid / Alkaline Balance

pH Balance

APO –ENZYMES(Inactive)

ACTIVE ENZYME

COMPLEX

ENZYMECO-FACTORS

(vitamins, minerals, etc)

pH Balance

APO –ENZYMES(Inactive)

MUCH LESSACTIVE

ENZYME COMPLEX

ENZYMECO-FACTORS

(vitamins, minerals, Etc)

Acidic pH < 7.0(Salivary)

pH Balance

APO –ENZYMES(Inactive)

MUCH MOREACTIVE

ENZYME COMPLEX

ENZYMECO-FACTORS

(vitamins, minerals, Etc)

Alkaline pH > 7.0 (Salivary)

Key Concept

Even if the nutrient

cofactors are available

to catalyze the

enzymatic reactions,

the enzyme activity

will be greatly

diminished if the

body pH is not

optimal

With all the vitamins that I take,

why do I still feel lousy?

pH balance and acid buffering are critical to human health and slowing the aging process

Whole Body Alkalization

5.8 & belowDangerous Range. Seek assistance of a licensed professional

6.0 – 6.2Unhealthy Range. Consider proper dietary changes

6.4 – 6.8Moderate Range. Consider slight dietary adjustments

7.0 – 7.4Optimal Rangefor a 24-hour period

8.0 – 9.0Too Alkaline. While not common, this is unhealthy

pH Balance & PMA

Salivary pH as a marker of plasma adiponectin concentrations in women

Conclusion:

• Results suggest that salivary pH is significant correlate of plasma adiponectin levels in women

• Salivary pH – a simple, inexpensive and noninvasive measure, could be promising avenue

Tremblay M, et al. Diabetol Metab Syndr. 2012

Most People Over 40 Are Acidic

• Most people’s diet and lifestyle are acidic

• Foods – dairy, meats, trans-fats, cooked oils, refined sugars, coffee, and carbonated drinks

• Stress, drugs, alcohol, stimulants are acidic

Most People Over 40 Are Acidic (cont’d)

• Research conducted at University of San Francisco Department of Medicine revealed:a) As we get older, our bodies accumulate acid wastes

b) Significant decreasing alkaline reserves from age 20 to 90

c) Alkaline reserves remain fairly constant until 40, at which point they decrease significantly

d) Most adult degenerative diseases (obesity, diabetes, CVD, osteoporosis) appear at age 40

e) Believed that examination of alkaline reserves warranted consideration for these diseases

J. Gerontology A Biol Sci Med Sci. Jan 1996, 51(1):B91-9

Smart Evaluations: Total ORACFN

Free Radical “Most Wanted” List: Nutrients to counteract

Hydroxyl• Most reactive of the ROS• Incapable of elimination by

body’s endogenous enzymes

Linked to DNA damage & cancerTurmeric, garlic, basil, oregano, cinnamon

Peroxyl Associated with CVD/atherosclerosisBroccoli sprout, onion, tomato, carrot, spinach, kale, Brussel sprouts

PeroxynitriteChronic inflammation & breakdownof vital proteins (collagen)

Acerola, quercetin, acai, mangosteen

Singlet oxygen Linked to cholesterol problems & CVDBlackcurrant, blueberry, cherry, acai, blackberry, raspberry

Super oxide anionToxic-free radicals leading to DNA damage & mitochondrial diseases

Apple, elderberry, blue corn

Whole Body Alkalization (cont’d)

• Acid/alkaline balance – helps entire internal biochemical environment

Formulation with combination of select phytonutrients, vitamins and minerals demonstrated to increase total functional ORAC

Daily organic superfruit and greens

Potassium citrate

Glutamine

STAMP out inflammation

S Stress, Sleep, Sugars

T Toxins

A Allergies, Acidity, Anemia

M Microbes, Mitochondria, Methylation

P Poor diet, Poor posture

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Q & A

Integration of Functional Nutrition

Day 2

Where we are…

• Tremendous discussion and various studies on how to lose weight and keep it off

• The end result of obesity is chronic disease – CVD and diabetes• Medical costs - high in the Canada from obesity• Exercise in teenage years may prevent weight gain• Those who exercise were metabolically healthier, better insulin sensitivity

and lower levels of bad cholesterol • Key – exercises developed different gut microbes than dieters, even though

they ate same food• Metabolisms change once body contains large amounts of fat• Better avoid weight gain in the first place!

30% of Canadians obese60% are obese and overweight

35% of Americans from 40-59 y/o are obese

• 13 out of 14 contestants gained all their weight back

• Showed that body will fight back for years

• A basic biological reality

• Slimmer but hungrier

• Losing a key hormone

• The brain sets the calories