AVOA/FLP*

AVOA/FLP*
* Forever Living Products (FLP) is the exclusive distributor of AVOA products
1
Objective
 The objective of this outline is to communicate the status of
the combined efforts of ST&T, its Staff & Consultants and
Researchers as it relates to articulating the safety of AVOA/FLP’s
patented “Stabilized Aloe Vera Gel” and its use in the FLP Aloe
drinks.
The research presented in ST&T binders and reports for
AVOA/FLP are representative of the research conducted on the
AVOA/FLP’s SAVG products only.
The research reports should not be generalized to the whole
Aloe drink market. However, since AVOA/FLP is the largest
producer and distributor of Aloe drinks in North America, the
safety of its products can be representative of consumer safety of
Aloe drinks produced with the highest GMP, QC/QA standards.
2
AVOA/FLP Strategic Plan Outline
 In order to better understand the AVOA/FLP SAVG safety, ST&T and
AVOA/FLP agreed on a strategic plan which consisted of 6 major
points:
1.
2.
3.
4.
5.
6.
Preparation of the GRAS (Generally Recognized as Safe) Petition Report
Additional Research to better understand the safety & use
Animal Studies on company’s core Aloe vera gel product (SAVG)
The Consumer Use & Safety Research Studies
The AVOA/FLP SAVG (gel) is a juice like any other juice in the industry,
which, from its original state, has a toxic component that is removed
during the manufacturing processes.
Cooperate with FDA/NTP regarding the company’s domestic and
international safety/efficacy research relating to its core product (SAVG)
Aloe Vera Basics:
 Aloe barbadensis Miller or Aloe Vera, a semi tropical plant is one of the 250 species
known of Aloe.
 Aloe Vera leaves contain clear juice, which includes 95% water and the remaining
5% contains 75 essential nutrients including Vitamin A, D, C, E, Calcium, Amino Acid
and Enzymes.
 78% of the total solids is comprised of the complex carbohydrate, Acemannan

(this compound has been identified as having immune stimulating properties, and may be responsible for
the putative health benefits derived from Aloe. It is proven to be safe by animal studies referred in the
petition document*)
 In addition to widespread use in topical preparations, Aloe Vera, ingested in the
liquid form, is known to act as an excellent regulator for digestive system and at the
same time provides many essential nutrients.
For detailed compound information and summaries of the clinical studies on Aloe Vera and its gel please
refer to the GRAS Petition file in this binder Section 4
4
Historical use vs.
Modern day Aloe Vera Drinks
 The whole leaf aloe vera plant is rich in
anthraquinones/aloins (a compound known to have
laxative effects in high amounts). Therefore it is
historically used as a laxative.
 However, today’s processors use the inner fillet of the
Aloe vera leaf which does not contain aloins.
 Therefore, inner fillet drink products have
insignificant amounts of aloins that do not produce a
laxative effect.
 Published data indicate that anthraquinones are not
toxic in amounts up to 50mg/1Kg or 1Liter.
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AVOA/FLP Stabilized Aloe Vera Gel
Content information:
 AVOA/FLP’s “Stabilized Aloe Vera Gel” is a safe (low aloin level and produced with
high QC standards) gel derived from the inner fillet of the Aloe vera plants.
 It has been the major component of many Forever Living Drink products that are
sold in US market since 1982.
 AVOA/FLP estimates that over this time period over 400 million 33.8 ounce bottles (1
liter) have been produced and sold world-wide and over 50 million sold for safe
consumption by United States consumers.
SAVG Drink Product List :
Aloe Vera Gel
Aloe Berry Nectar
Forever Aloe Bits N' Peaches
Aloe Juice(lemon-lime flavor)
Forever Freedom
Forever Aloe2Go
Forever Freedom2Go
AVOA/FLP Stabilized Aloe Vera Gel Content
information (per 100gr or 3.52 ounce of SAVG):
GRAS Considerations Based on
Acemannan Content
Because of the high percentage of
acemannan in aloe vera gels, the
safety of acemannan must be
evaluated in light of the GRAS
recommendations for “Stabilized
Aloe vera Gel.”
All animal tests indicated a high
level of safety with all species.*
GRAS Considerations Based on
Anthraquinone Content
For detailed
compound
information please
refer to the GRAS
Petition file in this
binder Section 4
Published data indicate that
anthraquinones are not toxic in
amounts up to 5000 µg/100g. Since
AVOA/FLP’s “Standardized Aloe
Vera Gel” contains approximately
720 µg/100 grams of gel, and their
products are reported to contain 9.8
µg/100 mL, and less than 14% of
any anthraquinone was observed to
be absorbed in an in vitro intestinal
model (Park et al 2009) GRAS
value determinations will not be
limited by anthraquinone
content.*
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The AVOA/FLP SAVG GRAS Report
 ST&T and AVOA/FLP cooperated in order to prepare the Dossier which affirms the GRAS
status of AVOA/FLP’s Aloe Vera Gel. The experts gathered and collated many documents
regarding the safety of AVOA/FLP’s SAVG:
o The world literature for historical uses and scientific articles on aloe vera
o Certification Documents for AVOA/FLP products
o Product related facts: shelf life, physical properties (viscosity, effect on freezing, taste, color,
clarity), consumer complaints, litigation and regulatory facts, self limiting facts, ingredient &
ingredient preparation facts are gathered and included in the GRAS petition file in order to affirm
safety)
o Company’s Manufacturing SOPs are included in order to demonstrate the safety procedures
o An extensive research is done in Poison Control Center databases and literature;
no adverse event report is found regarding the company’s drink products
 GRAS Panel affirmed that the safe level for human consumption of SAVG is
2liters per day per 70kg person when consumed as commercial aloe vera drink.
For detailed information on all of the items listed above please refer to the GRAS Petition file in this binder Section 4
NOTE: Since many publications, do a poor job of describing the aloe material subject (Many papers, especially older ones, use the term “aloe” in a generic manner
regardless of whether the product was aloe gel, aloe leaf, aloe extract, etc.) of the document AVOA/FLP and ST&T initiated their own original research projects.
ST&T has recruited a strategic group of diverse
scientists-experts who affirm the ST&T-AVOA/FLP
SAVG GRAS position:
For the Expert Panel GRAS Affirmation Sheet and
Expert Panel Bios please refer to Binder Section 4
Wallace D. Winters, M.D. Ph.D.
Former Medical Officer, Pacific Region, U. S. Food & Drug Administration (FDA)
Emeritus Professor of Medical Pharmacology, Toxicology & Anesthesiology at
University of California-Davis
Theodore Farber, Ph.D. , DABT
Former Supervisory Pharmacologist & Chief, Toxicology Branch, Hazard
Evaluation Division, Office of Pesticide Programs, EPA
Joseph R. Landolph, Ph.D. , DABT
Associate professor of Molecular Pharmacology and Pharmaceutical
Sciences, USC School of Pharmacy
California State –Carcinogen Identification Committee Prop.65
Ronald J. Amen, Ph.D.
Nutritional Physiologist & FDA Consultant
Regulatory Affairs, Clinical Research,
and General Business strategy Consultant
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Regulatory Actions Taken Regarding Aloe Vera is
Outlined in the GRAS Petition file:
Except for the removal of Aloe vera products which were used as laxatives(containing anthraquinones),
from the list of approved OTC drugs on May 9, 2002, there have not been any actions taken by the FDA.
There have not been any FDA actions against Aloe vera main stream products, based on safety that were
listed.
Aloe vera gel is not listed in EPA's Toxic Substances Control Act (TSCA) Inventory (NLM 1998),
suggesting that Aloe vera gel usage is considered safe by the EPA.
The following email was received on October 26, 2004 by the Company from the FDA following their
request for clarification of whether Aloe vera could be added to foods.
“Dear Mr. Sahlan,
Your inquiry of October 18 to the Food and Drug Administration's Ms. Joan Lytle has been referred by
Ms. Lytle to this FDA office for answer.
Aloe vera is not prohibited as an ingredient in food products in the United States. Nor is FDA aware of
any safety issues concerning such use.
Arthur Whitmore
Industry Outreach Office
Center for Food Safety and Applied Nutrition
Food and Drug Administration”
For more information about the Regulatory actions please refer to the GRAS Petition file in this binder Section 4
10
FDA adverse event reports on Company products, and/or
industry related products are presented in the GRAS dossier
For the company AVOA/FLP ,1 (non serious) report listed in 29 years the product was in
the market.
Despite the wide-spread use of Aloe vera in drinks, dietary supplements, personal care products,
and cosmetics, there have been but few adverse event or side effects reports regarding consumption
or topical application of Aloe vera. Two recent reports (see the GRAS petition document) describe an
aloe extract-induced toxic hepatitis in a total of four women, and a 1998 FDA Special Nutritionals
Adverse Event Monitoring System listed at least 7 cases of adverse events that were suspected to be
caused by the consumption of Aloe vera.
In a 2010 Freedom of Information request for aloe-related adverse events, FDA provided reports on
products from 20 different companies. None of the adverse events were of a serious nature, and only
one of the adverse event reports related to an AVOA/FLP product: In March 2003 a woman
complained that after drinking Forever Living Products’ Aloe Vera Gel she experienced diarrhea. No
other adverse events were found from the FOI search that was related to any other AVOA/FLP
product.”
For a brief summary of the adverse event reports and Aloe Vera
related toxicology test reports please refer to the GRAS Petition file in this binder Section 4
11
Additional information from
USA NATIONAL POISON CONTROL CENTER
DATABASE * regarding the safety of Aloe vera products
Plant exposures, especially via the ingestion route, are very common calls
to poison information centers.
The majority of exposures are associated with little morbidity or mortality.
The American Association of Poison Control Centers has been collecting
poison exposure data since 1983 and out a total of 2,330,162 only 45
fatalities due to plant exposures have been recorded.
None of the documented fatalities involved exposure to Aloe species.
*Provided by Dr. Edward P Krenzelok, PharmD, FAACT, DABAT
Past-President of the American Academy of Clinical Toxicology
Consulting Clinical Toxicologist, Director of Pittsburgh Poison and Drug Information Center
of University of Pittsburgh Medical Center Pittsburgh, PA
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Dr. Krenzelok’s* additional comments on a possible
Aloe Vera-containing beverage exposure
2391 is the number of reported ingestions of Aloe (all Aloe products) over the
last 10 years  a very small percentage compared to all plant exposures.
Regarding that the sales of AVOA/FLP SAVG alone is more than 143 million
bottles (1 liter=33.8 ounce) in the past 10 years, this number is relatively
insignificant.
“Since this is generally such an innocuous exposure, I doubt that any poison center
would have a specific management guideline to address Aloe exposures.”
“ However, if I was presented with an Aloe-containing beverage exposure, I would ask
the following questions:
Symptomatic vs asymptomatic--depending upon the symptoms, referral to a health care facility may be
considered.
Intentional vs unintentional--if intentional, they would be referred to a health care facility (we do this
irrespective of the substance).
Was this an acute or a chronic exposure? The decision process would involve the product. For
example, if the product contained Aloe vera gel and not Aloe vera sap I anticipate that the risk of
adverse effects (especially gastrointestinal) would be lower since the gel does not contain
appreciable amounts of the anthraquinones that are associated with the cathartic effects.”
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Additional Research on AVOA/FLP
SAVG Drinks’ safety :
 ST&T engaged in additional research activities which would help
communicate the safety claim findings before regulatory agencies
and the public:
o A presentation articulating the naturally occurring toxins in other fruits
and vegetables and other juice industries’ manufacturing processes to
eliminate the natural toxins is prepared and presented to AVOA/FLP
o A presentation articulating the Farm to Consumer QA/QC processes for
AVOA/FLP SAVG gel is prepared
o Poison Control Center's protocol/ position on calls for Aloe Vera
suspected ingestions and/or overdoes is presented by Dr Krenzelok.
o ST&T participated in toxicology meetings regarding Aloe Vera safety
issue.
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THE RISK IS RELATIVE….
A presentation articulating the naturally occurring toxins in other fruits and vegetables
and other juice industries’ manufacturing processes to eliminate the natural toxins is
prepared and presented to AVOA/FLP
For the full version of
the “Relative Risks of
Aloe Drink to Other
food/drinks-Updated”
presentation please
refer to Binder Section 1
BRIEFLY…
 ST&T focused its efforts to show that Aloe Vera Juice
industry is not different from any other fruit juice
manufacturing industries.
 Naturally occurring toxins are present in many plant
juices that people consume daily and the juice
manufacturers have developed processes to eliminate
the toxic particles in the final product.
 Aloe Vera Industry, knowing the toxicity of the sap, have
been producing aloe vera juice for over 50 years by using
methods to eliminate sap particles in the final drink
product.
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Farm-to-Consumer QA process
 Quality Assurance steps are audited & determined
 An outline is prepared by ST&T, demonstrating all quality
assurance steps from Farm to the Forever Living Aloe vera
Drink end product
For the full version of “Aloe Vera Gel-From Farm to Consumer Quality Assurance
Steps” presentation please refer to Binder Section 1
16
The Animal Studies
 ST&T has enrolled Animal Toxicology Studies on AVOA/FLP SAVG Gel:
Objective: To prove safety and efficacy of AVOA/FLP Stabilized Aloe Vera Gel products via clinical
animal tests:
• Subchronic Toxicity Studies of AVOA/FLP SAVG on B6C3F1 Mice
• Potential Genotoxicity Studies of AVOA/FLP SAVG
• Acute Toxicity Studies of AVOA/FLP SAVG on B6C3F1 Mice
• *Chronic Toxicity Studies of AVOA/FLP SAVG on B6C3F1 Mice
The Reports on concluded studies show no genetic mutations or adverse effects on
the test subjects related to AVOA/FLP SAVG.
*As of May 2012 this 2 year study has completed its 1st year and it is still in progress.
The Final Reports of the first 3 studies and the 11-Month interim report on the Chronic
Study can be found under Section 5 of this binder.
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The Consumer Use & Safety Research Studies
 ST&T has conducted a 2 leg Post-Market consumer use
study between January 2011 and February 2012 with
approximately 4,000 participants, in order to assess both
the acute and chronic benefits/effects of FLP Aloe drinks
worldwide.
 ST&T collected human use safety and efficacy data from
both:
 Long-term users (worldwide-FLP database)
 First-time users (SF bay Area)
 No serious or continuous side effects are observed when
the data is analyzed. (no Side effects in ~95% of the sample
population; initial, mostly digestive side effects in 5%)
The Final Draft Reports outlining the Outcomes and the Methodology of the 2
Consumer Use Research Studies can be found in the Section 3 of this Binder
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Meetings, exhibitions and presentations to
better understand the safety and efficacy
 ST&T participated in industry and toxicology meetings regarding
Aloe Vera safety issue:
1. SOT Meeting in Washington DC (March 2011)
2. National Toxicology Program Meeting in Durham (May 2011)
3. ST&T Aloe Vera Drink Project informative presentation to AVOA/FLP
distributors in FLP Super Rally in Washington DC (August 2011)
4. North American Congress of Clinical Toxicology Washington DC
meeting – AVOA/FLP Exhibition and FDA officers meetings
(September 2011)
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Society of Toxicology Meeting
(Washington DC , March 2011)
 SOT website, media and literary research are done to prepare a brief AVOA/FLP
SAVG safety dossier to be shared with SOT members and the media
 A presentation articulating the naturally occurring toxins in other fruits and
vegetables and other juice industries’ manufacturing processes to eliminate the
natural toxins is prepared and presented to AVOA/FLP
 Aloin content animal to human dose conversions and analogies are prepared in
order to make the safety claim more understandable.
 A PowerPoint presentation articulating that AVOA/FLP SAVG presents no risk as
the manufacturing process eliminates the toxic components, is prepared with
references to scientists and other fruit juice manufacturing processes.
For the NTP Poster/Presentation in DC during SOT (Society of Toxicology) Meeting Pictures
please see Binder Section 6
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National Toxicology Program
Meeting (Durham, May 2011)
 In this meeting NTP got together with scientists and industry representatives to discuss
the Technical Report on recent 2-year Aloe Vera study.
 Binders & USB Memory Sticks containing up-to-date ST&T Research files and expert
reviews on NTP’s previous and new reports on Aloe Vera are produced. The contents for
the binders are:
o
o
o
o
o
o
o
o
o
o
o
First and Initial Review and Comments on the Technical Report NTP 577 on Aloe Vera 3/20/2011, by Dr. Winters
Questions to address NTP Technical Report – Regarding the recent Aloe Vera Study TR577, by Dr. Winters
A review of NTP Past Studies on Aloe Vera Related Products, by Dr. Winters
Photos Taken in DC at the SOT Meeting of the NTP poster
Relative Risks of Aloe Drink to other food/drinks presentation
Aloe Vera Gel-From Farm to Consumer Quality Assurance Steps presentation
Toxicity Studies of AVOA/FLP Aloe Juice Extract in B6C3F1 Mice – 3 Week Time-point Report
Assessment of Potential Genotoxicity of AVOA/FLP Aloe Juice Extract Report
Status updates & first findings of the Post Market Human Use Study
Dossier in affirmation of the GRAS Status of Aloe Vera of America’s SAVG
NTP TR 577 Technical Report on Aloe Vera
The contents of the
documents listed above are
presented this Binder
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Forever Living Products
Washington DC Super Rally
(August 2011)
 Per AVOA/FLP’s request, ST&T prepared and presented a simple yet highly
informative presentation explaining the scientific research partnership between
ST&T and the company at the annual International Forever Living Super Rally
event.
 Over 4,000 distributors world-wide are educated regarding the safety of
AVOA/FLP/FLP Aloe Vera Drinks and ST&T Research Intl.’s objective and
research studies.
 ST&T Science panel is introduced and brief outcomes of the research
completed to date are shown to the audience
 Distributors’ questions regarding safety are answered in person by ST&T
director and staff.
 ST&T and AVOA/FLP executives got together and discussed the current status
and future of the strategic plan.
For more information, please see the presentation “ST&T Research Update Presentation at FLP Washington DC Super
Rally” Binder Section 6
22
North American Congress of Clinical
Toxicology Washington DC meeting –
AVOA/FLP Exhibition and FDA officers
meetings (September 2011)
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
North American Congress of Clinical Toxicology (NACCT) is an annual
conference that allows an opportunity of physicians, nurses, pharmacists, and
scientists from around the world to participate in the sharing of knowledge on
toxicology issues.
We established an AVOA/FLP booth at the toxicology meeting for all the
scientists to sample and discuss AVOA/FLP Aloe vera drinks.
With Mr. Hardy and Mr. Poore’s help we assembled a professional exhibit and
provided sample aloe vera drinks to scientists.
In order to better articulate our objective, we distributed a informative white
paper: “THE MODERN DAY COMMERCIAL ALOE VERA DRINK: A refreshing
and natural beverage vs. the historical laxative use” which explains the Aloe
vera safety issue from a simple yet sustainable perspective.
It allowed us to educate nearly 1000 senior medical toxicologists who are the
first line contact regarding toxicology questions from the public, media,
academia or governments (on the safety of AVOA/FLP/FLP Aloe vera drink
products).
Being in Washington DC in this time was important to make contact the FDA
Food Division Officers who are responsible for decisions regarding the Aloe
vera drinks.
For more information, please see the presentation “North American Congress of Clinical Toxicology ST&T Event Report”
and the “North American Congress of Clinical Toxicology Aloe Abstract “ in Binder Section 6
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As your research partner ST&T and its expert consultants
are here to help you with your safety/efficacy research and
international regulatory needs…
Ron J. Amen, Ph.D.
Wallace D. Winters, M.D. Ph.D.
Gus Kousoulas, Ph. D
Joseph R. Landolph,
Ph.D. , DABT
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