Stephen Holt MD-A4M_ Pivotal Components of Innovative Therapeutics

8/8/2019 Stephen Holt MD-A4M_ Pivotal Components of Innovative Therapeutics

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Obesity Management: Pivotal

Components of InnovativeTherapeutics

Stephen Holt MD, LLD (Hon.) DSc, ChB., PhD, DNM,FRCP (C), MRCP (UK), FACP, FACG, FACN,

FACAM, OSJ

Distinguished Professor of Medicine (Emeritus)Scientific Advisor, Natural Clinician LLC


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MULTIPRONGED OBESITY TREATMENT

Calorie restriction (high/low diet),exercise, behaviour modification,

adjuncts (supplements or drugs)

In many individuals, overweight status

goes hand in hand with Metabolic

Syndrome X, an inflammatory status

(OBESITIS), body toxicity and genetics

Managing obesity and related diseasein a unitary manner has no role in

Medical Practice. Connect the Dots!


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PIVOTAL PATHOGENESIS TO CONSIDER IN

A THERAPEUTIC APPROACH TO OBESITY

Metabolic Syndrome X

Inflammation

Oxidative Stress

Toxic Lipogenesis

Energy regulation

Thermogenesis


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REDEFINING SYNDROME X

Classic Definition: Obesity,Hypercholesterolemia, High

Blood Pressure, Linked by

Insulin Resistance.

Syndrome X, Y and Z.., an

expanded definitionincorporating a novel unifying

concept of common diseases


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THE PUBLIC HEALTH RISK

Syndrome X increases risk for :

Type II Diabetes Mellitus

Cardiovascular Disease

Cardiovascular Deaths

Deaths from ALL CAUSESAm.J.Epidemiol, 148, 958, 1998.


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INTEGRATIVE MEDICINE FOR

SYNDROME X

While proper management of the

individual abnormalities of this

syndrome can reduce morbidity andmortality, it seems unlikely that

management of the individual

abnormalities of this syndrome

provides better outcomes than a

more integrated strategy

CDC, Atlanta, Ga., JAMA 2002


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SYNDROME X NUTRITIONAL FACTORS

OBESITY: Thermogenic agents (Advantra Z,

Fucoxanthin), Hoodia, fiber, green tea and green coffeebean extract, starch blocker, chromium, fat blockers

HYPERTENSION: fiber, botanicals unpredictable

OXIDATIVE STRESS: alpha lipoic acid, AGES, redoxbalanced, hydrophilic and lipophilic

HOMOCYSTEINE: B6, B12, folate, TMG

INSULIN RESISTANCE: fish oil (EPA), alpha lipoic acid,

vitamin and mineral support, other agents

BLOOD LIPID: soy, fish oil, guggul, garlic etc.

INFLAMMATION: EPA, curcumin, Vit C etc.


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OBESITIS

Epidemiological links between obesityand inflammation have been proposed for>40y, obesity is an inflammatory status

Glucose and fat intake induceinflammation by oxidative stress or the

activation of transcription factors. Reductions in macronutrient intake in

obese subjects reduces oxidative stressand the production of inflammatory

mediators (1000kcal/day, 4 weeks or 48hr fast).

Managing weight control withoutmanaging inflammation may be nihilistic


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OBESITIS

30% of the total amount of cytokine IL-6is derived from adipose tissue.

Decrease in CRP and IL-18 are noted

with weight loss (reduction in

inflammatory biomarkers with weight loss

EPA valuable in correct dosage with

compliance (delivery with enteric coating)

Adipocytokines [leptin, adiponectin andvisfatin], adiponectin lowers TNF-alpha

Final common pathway oxidative stress


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: Fat tissue, normal weight mouse

:Fat tissue, from fat mouse (ob/ob)


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POTENTIAL MECHANISMS OF OBESITIS


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OBESITIS


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INSULIN RESISTANCE

New concepts of inflammation-inducedinsulin resistance.

Two transcription factor signaling pathways: 1. NF-kB pathway and 2. c-Jun NH2-

terminal kinase (JNK) pathway. Thesepathways are linked to the pro-inflammatoryeffects of obesity and related insulinresistance.

Pathways are activated by pro-inflammatorystimuli e.g. cytokines (TNF-alpha).

Potential mediators of insulin resistanceinclude IL-6, IL-10, TNF-alpha, CRP, IL-8


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New discoveries of circulating factors thatsignal energy reserves which also signal thebrain, adipose tissue, liver, muscle and theimmune system.

Research surrounding the discovery ofleptin led to the identification of otherchemical signals eg. adiponectin, resistin,retinoid binding protein 4, visfatin, visceraladipose-tissue derived serine proteaseinhibitor, plasminogen activator inhibitor 1,adipsin, cytokines and chemokines, adiposeproduction of corticosteroids and othercomplex chemical messengers.

ENERGY BALANCE AND METABOLISM:

REGULATED BY ADIPOCYTES


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LEPTIN PRODUCTION IN ADIPOCYTES


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Toxic Lipogenesis (Holt, 2003)

A concept that toxins stored in fattissue alter energy metabolism and

favor weight gain (detoxification).

The notion that the Pot Belly is a new,

useless and dangerous endocrineorgan that signals visceral adiposity

with its poisonous stores.

Some organochemicals are growthpromoters and induce lipogenesis

Detoxifying fat stores is difficult


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DRUGS AND NUTRACEUTICALS


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Weight Loss Nutraceuticals or

Drugs are Adjuncts Only

A large number of weight loss

products provide false promises

of a quick fix Evidence-based supplements with

variable evidence of safety and

effectiveness include: Advantra Z,Authentic Hoodia Gordonii,

Specific Soluble Fibers.


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THE GLYCEMIC INDEX

Calculations of the glycemic index offood is probably a waste of time.

Understanding factors that controlgastric emptying rate can result ininference about the glycemic index.

Slowing gastric emptying slows glucoseabsorption relevance in acute dosing

C


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GLUCOSE TOLERANCE WITH

SOLUBLE FIBER

Holt S, et al

Effect of

Gel Fiber

Lancet,

March 24th,

1979.


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Thermogenesis

The process of generating heat in theanimal body (Citrus, Seaweed, etc)

Classic thermogenics include amines thatincrease metabolic rate, a function of

beta-3 receptor activity which alsoinduces lipolysis and amino acid uptakein muscle eg ephedrine and synephrine

These classic amines tend to have non-specific adrenergic receptor function withcardiovascular stimulatory effects.

Ma Haung, Citrus peel and Advantra Z


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Citrus Aurantium ExtractWith Standardized

p-Synephrine Content, Patented and

Researched inWeight Control as Advantra Z


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Advantra Z

This extract of Citrus aurantium (bitterorange peel) is thermogenic, lipolytic,ergogenic, mood enhancing, appetite

suppressing and it promotes musclebuilding (Peel off the Weight, HIOM 2009)

A body of evidence indicates that AdvantraZ does not cause the same degree of

cardiovascular or CNS hyper stimulationthat led to the withdrawal of Ephedra


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Advantra Z

Gougeon et al. (Obesity Research,13, 2005, 1187) described anincrease in the thermic effect of food(TEF) by amines isolated from Citrus

aurantium TEF increased by 29% in women

without effects on blood pressure or

pulse rate, but with measurableincrease in epinephrine excretion


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UNREALISTIC

WEIGHT LOSS

EXPECTATOIN


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A LITANY OF NEW PERSPECTIVES:

2010

Clarification of the epidemiology ofobesity.

Fat cell regulation of energy balance

Neuro-hormonal control of appetite. Fuel sensing by the CNS.

Obesitis

Insulin Resistance: Syndrome X Cancer propagation

Drug and nutraceutical approaches


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CONCLUSIONS There is no successful, sustainable stand

alone intervention for weight control

Failing to manage Metabolic Syndrome X

and its associated disorders (Syndrome X,

Y, Z) in the overweight person istantamount to negligence.

Sleep, oxidative stress, inflammation,

nutrition, exercise, behaviour modificationand detoxification are therapeutic targets.

The Multipronged Approach to weight

control must be favored.

Stephen Holt MD-A4M_ Pivotal Components of Innovative Therapeutics

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