Stephen Holt MD-Therapeutic Principles for Dietary Supplement Research

8/8/2019 Stephen Holt MD-Therapeutic Principles for Dietary Supplement Research

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THERAPEUTIC PRINCIPLES FOR

DIETARY SUPPLEMENT RESEARCHAND DEVELOPMENT

DIETARY SUPPLEMENT DISPENSATION IN

CLINICAL PRACTICE

Stephen Holt, MD, PhD, LLD, ND et al

Distinguished Professor of Medicine, NYCPM, NY,President WONMP

Distinguished Professor of Medicine, NYCPM, ScientificAdvisor, Natural Clinician LLC


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HISTORIC PERSPECTIVES

Pharmacognosy: the study of

natural products used in medicine

Ancient discipline of medicalscience

Pharmakon = drug, Gnosis =

knowledge


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CONCEPTS

Natural medicine cannot integrate intogeneral medical practice without ascientific base.

Botanicals or herbs are drugs and

many drugs are botanicals or herbs, orsynthetic copies.

Dietary supplement manufacturersexhibit widespread ignorance about

pharmaceutical science. Hiding behind mythical and magical

thinking is no longer acceptable inintegrative medicine.


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CONCEPTS

Some natural clinicians baulk at attemptsto explain the bioactivity of naturaltherapies within the framework of currentscientific knowledge.

While sympathy exists for this position,our understanding of pharmacodynamiceffects of herbs, botanicals or nutrientsmust be based on scientific principle.

Conversations about clinicalpharmacology among dietary supplementmanufacturers are rare and practicallynon-existent with their customer base.


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DRUG OR NUTRACEUTICAL

DISPOSITION If dietary supplements are to be used astherapeutic agents, there must be somerespect for basic pharmacologic concepts.

The concepts are A, D, M and E. One may look critically at some dietary

supplements by simply consideringfactors that influence absorption,

distribution, metabolism and excretion ofchemical compounds [drugs ornutraceuticals].


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ABSORPTION

Absorption is a complex function of routeof delivery, chemical characteristics,processes of movement across

absorption barriers and physiologicalevents such as gastric emptying, ormodified by presence of disease, age etc.

Some nutraceuticals claim that they have

absorption and bioavailability that cannotbe present, based on simple scientificprinciples.


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ABSORPTION [examples]

FISH OIL: Unstable in regularformulations, denatured by gastric acid,power is with EPA. Dosage requirements

high, compliance issues, triplebioavailability with enteric coat.Standard fish oil products passe.

SHARK CARTILAGE: solid or extract,

enzymatic degradation of antiangiogenicproteins, buccal absorption a fairy tale,interesting facilitated absorption by aleaky gut.


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DISTRIBUTION

Drug distribution is often uneven:different tissue binding, different PH orpermeability of tissues.

Example: Antioxidant Therapy: Idealantioxidant has lipophilic and hydrophilicprofiles and acts in a wide REDOX range.

Single high dosage antioxidants have

dangerous pro-oxidant effects. Most antioxidant supplements do not use

the correct principles of formulation.


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METABOLISM

The process of chemical alteration ofdrugs in the body.

A primary but not exclusive function of

the liver. Inactive and active metabolites are

produced, by synthetic or non-syntheticreactions.

Example: Isoflavones: genistein/genistin,conjugation eg daidzein sulfate. Acomplicated story.


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EXCRETION

Elimination from the body, primarily bythe kidneys.

A real concern exists with age related

reduction in renal function andnutraceutical dosage adjustment.

Some complex mechanisms exist egreabsorption transport mechanisms,

tubular secretion and biliary excretionwith enterohepatic cycling.


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GENERAL ISSUES

Dietary Supplements are the main stay ofalternative and complementary medicine.

Growth overall in OTC sales.

Contemporary switch to naturalremedies.

The natural remedy first line option aswell as the last line option.


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DSHEA 1994

Grassroots consumer lobby

Defining a dietary supplement

Section 3 : vitamins, minerals, herbs etc

Safety : risk of illness or injury

Section 5 : publications, balanced, not

labels

Labeling protocols : honest label ( section3)

The enigma: not to be used


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THE DIETARY SUPPLEMENT

INDUSTRY IN THE USADSHEA 1994 IS PIVOTAL

PRE-DSHEA

Russian Roulette Claims?

Skepticism?

Frequent Failures?

Roller Coaster Industry?

POST-DSHEA


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DSHEA- BASED MODEL

WEAK SUPPORTINGDATA

DIETARY SUPPLEMENT

?

CREATE PLATFORM

SELL WITH CLAIM

PEER ACCEPTANCE

SUCCESS FAILURE

STRONG R & D

PRODUCT AS A DIETARYSUPPLEMENT

BODY STRUCTURE FUNCTIONCLAIM

PEER ACCEPTANCE

SELL (PHASE IV AND

V)

SUSTAINED


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A PEEK INTO THE INDUSTRY

The product of the month

The evidence based formula

Condition specific formulations CEO survey reveals scientific-

based, new formulations are of

major importance Who formulated the supplements

you use in your practice?


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KEY PUBLIC HEALTH

INITIATIVES Lifestyle medicine combined withnutritional interventions have

overshadowed allopathic approaches

for many public health problems

First line options for disease

prevention are not rooted generally in

drugs or surgery. Many factors have moved consumers

of health care to the new paradigm of

simple, gentle and more natural

interventions


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KEY PUBLIC HEALTH

INITIATIVES Adult obesity

Childhood obesity (A Dead-Loss

Disorder) Cardiovascular health

Cancer

Arthritis Osteoporosis

Etc


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THE KEY PUBLIC HEALTH

INITIATIVE The metabolic syndrome

(SYNDROME X)

A complex disorder rooted ingenetics, adverse lifestyle withprimary nutritional precipitation

Defining Syndrome X


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THE UNKNOWN EPIDEMIC


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REDEFINING SYNDROME X

Classic Definition: Obesity,Hypercholesterolemia, High Bloo

Pressure, Linked by Insulin

Resistance.

Syndrome X, Y and Z.., an

expanded definition incorporatinga novel unifying concept of

common diseases


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SUPER-SIZING AMERICA

Americans exude

complacency about

their overweight

status

Obesity is part of a

metabolic syndrome

Syndrome X is

under diagnosedand often mistreated

by conventional

medicine


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CAUSES OF SYNDROME X:

The Double Whopper Brain

Sedentary Lifestyle

Genetic Tendency

Substance Abuse


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THE PUBLIC HEALTH RISK

Syndrome X increases risk for :

Maturity Onset Diabetes Mellitus

Cardiovascular DiseaseCardiovascular Deaths

Deaths from ALL CAUSES

Am.J.Epidemiol, 148, 958, 1998.


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INTEGRATED MEDICINE FOR

SYNDROME X

While proper management of the

individual abnormalities of this syndrome

can reduce morbidity and mortality, it

seems unlikely that management of theindividual abnormalities of this syndrome

provides better outcomes than a more

integrated strategy CDC, Atlanta, Ga.


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SYNDROME X : THERAPEUTICS

Soluble fiber eg oat beta glucan hydrocolloid

Soy Protein 25 g/day

Omega 3 fatty acids (EPA)

Chromium

Alpha lipoic acid Vanadium

Antioxidants eg ellagic acid, bioflavonoids

Starch blockers

Cinnamon Maitake

Green coffee bean extract

Hoodia gordonii


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HOODIA GORDONII


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WHICH ARE QUICK FIXWHICH ARE QUICK FIX

PROMISES?PROMISES? Drugs Phentermine, FenDrugs Phentermine, Fen--phen,phen,

Sibutramine, OrlisatSibutramine, Orlisat

OTC: Phenylpropanolamine,OTC: Phenylpropanolamine,Pyruvate, Chromium Picolinate,Pyruvate, Chromium Picolinate,

Conjugated Linoleic Acid,Conjugated Linoleic Acid,

Hydroxycritic Acid, Omega 3 FattyHydroxycritic Acid, Omega 3 Fatty

Acids?Acids?

The power of green tea liquidThe power of green tea liquid

concentrateconcentrate


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UnrealisticUnrealistic

weight lossweight lossexpectationexpectation


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WHAT IS HOODIAWHAT IS HOODIA

GORDONII?GORDONII?


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THE SAN BUSHMENTHE SAN BUSHMEN


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THE MODERN SANTHE MODERN SAN

BUSHMENBUSHMEN


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THE SUCCULENTTHE SUCCULENT

PLANTPLANT


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HOODIA NURSERYHOODIA NURSERY


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HOODIA CULTIVATIONHOODIA CULTIVATION


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HOODIAHOODIA

PROCESSINGPROCESSING


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REPORTED EFFECTS OFREPORTED EFFECTS OF

HOODIAHOODIA Hunger and thirst suppressionHunger and thirst suppression

Energizing effectsEnergizing effects

Aphrodisiac effectsAphrodisiac effects

Suppression of gastric acidSuppression of gastric acid

Contention effective as extractContention effective as extractcontaining steroidal glycosidescontaining steroidal glycosidesor effective as a dietaryor effective as a dietary

supplement?supplement?


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CONTRARIAN MODERN USECONTRARIAN MODERN USE

OF HOODIAOF HOODIA


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HOODIAHOODIA

COMMERCIALIZATIONCOMMERCIALIZATION

Multiple patent filingMultiple patent filing

Drug development pathwayDrug development pathway

Extracted sterol glycosidesExtracted sterol glycosides

Food additiveFood additive

Contention about patentsContention about patentsDietary supplementDietary supplement


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PROPERTIES OF HOODIAPROPERTIES OF HOODIA

Folklore useFolklore use

Ethnobotanical factsEthnobotanical facts Whole plant/ plantWhole plant/ plant

extractsextracts

Steroidal glycosidesSteroidal glycosides

Animal studiesAnimal studies


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THE GLYCEMIC INDEX

Calculations of the glycemic index of

food is probably a waste of time.

Understanding factors that controlgastric emptying rate can result in

inference about the glycemic index.

Slowing gastric emptying slows

glucose absorption relevance in

acute dosing


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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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LOWERING CHOLESTEROL

When the treatment is worse than

the disease

Diet Exercise

Aggregate benefits of Soluble

Fiber, Soy Protein, Omega 3 fattyacids, Garlic, and others [synergy]


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GLUCOSE TOLERANCE WITH SOLUBLE

FIBER

Holt S, et al

Effect of GelFiber

Lancet,

March 24th,

1979.


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FIBER

Holt S, et al

Effect ofGel Fiber

Lancet,

March

24th, 1979.


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FIBER

Holt S, et al

Effect of Gel FiberLancet,

March 24th, 1979.


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ACTION SYNDROME X

NUTRITIONAL FACTORS

HYPERLIPIDEMIA

Beta glucan effect

Chromium

AntioxidantSUGAR BLOCKER

GLYCEMIC INDEX

Slows glucose

absorption Reduces insulin surges

ANTIOXIDANT

INSULIN RESISTANCE

alpha lipoic acid

Chromium

WEIGHT CONTROL Satiety promotion

Appetite suppression

HOMOCYSTEINE

B6, B12, FolateBLOOD PRESSURE


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DIETARY SUPPLEMENTS AS A

PROFIT CENTER

Declining revenue for cognitive activity inclinical practice

Dietary supplement dispensaries are a

major profit center Supplement sales promote return visits

and precipitate spontaneous demandsfrom patients for disease prevention

Margins on sales are high Supporting literature saves consultation

time


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ETHICS

Physicians must not engage in selfreferral

Private labels with physician identity

are problematic

State licensing authorities have mixed

beliefs about supplement sales

At law, dietary supplements are not to

be used to prevent or treat any disease Medical practice should not be

legislated


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CONCLUSION The interface between alternative medicine

and allopathic medicine is increasinglyindistinct

At least three quarters of all patients in an

out-patient, hospital, clinic are taking

supplements, some of which are worthless

A doctor who sells a dietary supplement

that is available in retail will ruin their

practice [A HUGE ISSUE] Supplement dispensation by healthcare

professionals will lead to the responsible

use of dietary supplements

Documents

Stephen Holt MD-Therapeutic Principles for Dietary Supplement Research