 |
|
Current group: bionet.neuroscience
Neotame: The Next-Generation Sweetener, Indra Prakash et al, Food Technology 2002 July 56(7): 36-40, 41. free full plain text, 6 pages, without figures: methanol, formaldehyde, formic acid toxicity, Murray 2005.01.24 rmforall
|
|
| | From: | Rich Murray | | Subject: | Neotame: The Next-Generation Sweetener, Indra Prakash et al, Food Technology 2002 July 56(7): 36-40, 41. free full plain text, 6 pages, without figures: methanol, formaldehyde, formic acid toxicity, Murray 2005.01.24 rmforall | | Date: | Mon, 24 Jan 2005 01:12:26 -0700 |
|
|
 |
*******************************************************************
http://groups.yahoo.com/group/aspartameNM/message/1149
Neotame: The Next-Generation Sweetener, Indra Prakash et al, Food
Technology 2002 July 56(7): 36-40, 41. free full plain text, 6 pages,
without figures: methanol, formaldehyde, formic acid toxicity,
Murray 2005.01.24 rmforall
[ Comments by Rich Murray are in square bracketts.
Neotame quickly releases its 8% by weight methanol component into the human
body upon ingestion.
At a typical concentration of 20 ppm ( milligrams per liter = milligrams per
kilogram ), a liter of diet soda would release 1.6 mg methanol, enough to
trigger migraine and other symptoms in some people sensitized to aspartame
and other methanol, formaldehyde, and folic acid sources.
If a third of the methanol remains in the body as the inevitable cumulative
toxic products, formaldehyde and formic acid, that would be 0.5 mg daily.
http://groups.yahoo.com/group/aspartameNM/message/1145
EPA Preliminary Remedial Goals (PRG) 2003 Oct, air and tap water --
methanol, formaldehyde, formic acid -- sources omitted are methanol from
aspartame, dark wines and liquors, fruit pectins: Murray 2005.01.18 rmforall
[ Introductory summary by Rich Murray: They gave the same data on
2004.10.27. I have put the data for methanol, formaldehyde, and formic acid
together in this plain text version, since oral ingestion of methanol,
whether from the 11% methanol component of aspartame, or the similar level
of methanol impurity in dark wines and liquors, about one part in ten
thousand, inevitably leads to full absorption in the human GI tract. Some
is excreted, but most is largely converted into formaldehyde, and thence
largely converted into formic acid -- both potent, culmulative toxins that
affect all cells and tissues.
Very large amounts of methanol are released by bacterial degradation of
pectins from fruits and vegetables in the human colon:
http://groups.yahoo.com/group/aspartameNM/message/1143
antiseptic? antifungal? antiviral? methanol (formaldehyde, formic acid)
disposition: Bouchard M et al, full plain text, 2001: substantial sources
are degradation of fruit pectins, liquors, aspartame, smoke: Murray
2005.01.05 rmforall
So, the key fact here is the RfDo, a lifetime safe level for daily ingested
oral exposure, which for these three chemicals are:
0.5 mg, 0.15 mg, and 2 mg per kg per day, which for a smallish adult of 60
kg, is 30 mg, 9 mg, and 120 mg daily for methanol, formaldehyde, formic
acid.
However, much more stringent official government standards for formaldhyde
in drinking water exist, both federal and state:
Fully 11% of aspartame is methanol -- 1,120 mg aspartame in 2 L diet soda,
almost six 12-oz cans, gives 123 mg methanol (wood alcohol). However,
about 30% of the methanol remains in the body as cumulative durable toxic
metabolites of formaldehyde and formic acid, 37 mg daily, a gram every
month, accumulating in and affecting every tissue.
If only 10% of the methanol accumulates daily as formaldehyde, that would
give 12 mg daily formaldehyde accumulation-- about 60 times more than the
0.2 mg from 10% retention of the 2 mg EPA daily limit for formaldehyde in
drinking water.
Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.
http://groups.yahoo.com/group/aspartameNM/message/835
ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999:
Murray 2002.05.30 rmforall
This is the same limit published May 2, 2002 for California
http://www.atsdr.cdc.gov/tfacts111.html [excerpts]
Agency for Toxic Substances and Disease Registry
Division of Toxicology
1600 Clifton Road NE, Mailstop E-29
Atlanta, GA 30333 888-422-8737 FAX: (404)498-0057
ATSDRIC@cdc.gov
http://www.atsdr.cdc.gov/contacts.html
Dr. Christopher T. De Rosa, Director, Division of Toxicology
(404) 498-0160 Fax: (404) 498-0094 cyd0@cdc.gov
Spengler, Robert, Sc.D., Associate Administrator for Science
(404) 498-0003 FAX: (404) 498-0081 : RSpengler@cdc.gov
http://www.atsdr.cdc.gov/science/bscroster01.html
Board of Scientific Counselors Roster June 2001
http://www.atsdr.cdc.gov/COM/omweb.html
Mr. Ronnie D. Wilson, the ATSDR Ombudsman
(404) 498 0004 (888) 422 8737] Fax (404) 498 0083 RWilson2@cdc.gov
When all routine avenues have been
exhausted, the ATSDR ombudsman can be
called to impartially investigate, mediate,
and assist in areas where the "system" has
failed. In doing so, this office is not an
advocate for the interests of ATSDR, nor is
it an advocate for business, nor industry,
nor private citizens, nor any other
government entity. It is an advocate for
problem resolution.
ToxFAQsTM for Formaldehyde CAS# 50-00-0 July 1999
Has the federal government made recommendations to protect human health?
The EPA recommends that an adult should not drink water containing more
than 1 milligram of formaldehyde per liter of water (1 mg/L) for a
lifetime exposure, and a child should not drink water
containing more than 10 mg/L for 1 day or 5 mg/L for 10 days.
The Occupational Safety and Health Administration (OSHA) has set a
permissable exposure limit for formaldehyde of 0.75 parts per million
(ppm) for an 8-hour workday, 40-hour workweek. [in air]
The National Institute for Occupational Safety and Health (NIOSH)
recommends an exposure limit of 0.016 ppm. [in air]
Source of Information:
Agency for Toxic Substances and Disease Registry (ATSDR). 1999.
Toxicological profile for formaldehyde. Atlanta, GA: U.S. Department of
Health and Human Services, Public Health Service.
http://www.atsdr.cdc.gov/toxprofiles/tp111.html July 1999
http://groups.yahoo.com/group/aspartameNM/message/1111
Toxicological Profile for Formaldehyde 3/4 plain text, 229 to 342 of 468
pages USA DHHS PHS ATSDR 1999 July: Murray 2004.09.03 rmforall
This is really buried in the 1999 468-page ATSDR report:
" b. Water:
EPA 1-d Health Advisory (child)-draft 10 mg/L EPA 1995;
IRIS 1999 10-d Health Advisory (child)-draft 5 mg/L
Lifetime Health Advisory (adult)-draft 1 mg/L "
Four state water limits are 10 to 100 times more stringent:
" b. Water
Water Quality Criteria: Human Health
CA Drinking water (guideline) 30 µg/L FSTRAC 1995
MD Drinking water (guideline) 10 µg/L
ME Drinking water (guideline) 30 µg/L
NJ Drinking water (guideline) 100 µg/L " ]
http://www.ift.org/publications/docshop/ft_shop/07-02/07_02_pdfs/07-02-df-prakash.pdf
Neotame: The Next-Generation Sweetener, Indra Prakash et al, Food Technology
2002 July 56(7): 36-45, free full plain text, 6 pages, without graphs.
"In addition, since the product is not metabolized to phenylalanine, no
special labeling for individuals with phenylketonuria (PKU) is required."
"Under conditions of use, neotame, unlike aspartame, does not degrade to
phenylalanine. Also unlike aspartame, neotame does not form a
diketopiperazine (DKP) derivative."
"It is a derivative of aspartame and is 30-60 times sweeter than aspartame.
Its actual sweetness potency is dependent on the concentration required in
various food or beverage products."
"In aqueous systems (pH 2-8), the major decomposition pathway of neotame is
through the hydrolysis of the methyl ester to form de-esterified or
de-methylated neotame -
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine (Fig. 3) - which is
also the major metabolite of neotame in humans. Deesterified neotame is not
sweet."
"In a similar study with neotame in a cola drink, increasing the sweetener
concentration from 9 to 46 ppm improved the desirable flavor attributes
(cola flavor, sweet taste, and mouth feel)
but did not increase the undesirable notes (Fig.6)."
"For example, studies have shown that 20% of the carbohydrate sweetener
can be replaced with 2.1 ppm of neotame in a carbonated cola soft drink, and
the taste is indistinguishable from the 100% carbohydrate-sweetened cola
beverage (Fig. 8)."
"Flavor Modification and Enhancement. Neotame can also be used to modify
or enhance a product's flavor - the combined perception of taste, smell, and
aroma.
Products containing vitamins, nutraceuticals, pharmaceuticals, salt
substitutes, and soy in various applications are often either bitter or
harsh in flavor.
The addition of neotame at a subsweetening level modifies or masks
undesirable notes/qualities such as bitterness, astringency, and burning or
cooling sensations. Undesirable attributes, such as the potential bitterness
of caffeine, cocoa, and potassium chloride and the harsh notes of medicinals
and plant extracts, can be modified or masked.
Neotame also reduces the bitter taste of potassium chloride in salt
substitutes, thereby providing a cleaner salty taste. It reduces or
eliminates "beany" flavor notes in soy products. And it modifies or enhances
the attributes of many flavoring chemicals, including essential oils,
oleoresins, plant extracts, reaction flavors, and mixtures thereof (Gerlat
et al., 2000)."
"Cola-Flavored Carbonated Soft Drink. Neotame remained functional for at
least 16 weeks, consistent with currently marketed low-calorie carbonated
soft drinks (Gerlat et al., 1999)."
"The major route of metabolism of neotame is de-esterification. Both neotame
and de-esterified neotame have short plasma half lives, with rapid and
complete elimination (FAP, 1998, 1999)."
"[ Selections from Table 1: typical concentrations of neotame in ppm
(milligrams per liter = milligrams per kilogram) ]
Carbonated soft drinks 2-50
Cola 17
Lemon-lime 14
Root beer 20
Chocolate cake 125
Dairy products 5-50
Yogurt 15
Ice cream 15
Other frozen desserts 30
Chewing gum 10-1,600
Confections 1-200
Hard candy 5-75
Cereals 10-500
Liquid sweetener 10-10,000
Sweetener tablets 50-12,000"
36 FOOD TECHNOLOGY JULY 2002 . VOL. 56, NO. 7
DEVELOPING FOODS
Indra Prakash,
Glenn Corliss,
Rao Ponakala,
and Glen Ishikawa
The authors are, respectively,
Director of Organic Chemistry,
Senior Food Scientist,
Senior Food Scientist,
and Director of R&D, The NutraSweet Co.,
699 Wheeling Rd., Mt. Prospect, IL 60056. Authors Corliss, Ponakala, and
Ishikawa are Professional Members of IFT.
Send reprint requests to author Prakash.
Neotame: The Next-Generation Sweetener
A new sweetener derived from aspartame is thousands of times sweeter
than sugar and does not have the undesirable taste characteristics common
to some high-intensity sweeteners.
Neotame, a new high-intensity sweetener and flavor enhancer, is expected to
receive Food and Drug Administration approval for use in foods and beverages
in the United States soon. Since it will then be the newest approved
sweetener in the U.S., it is appropriate to review its development,
characteristics, and potential uses.
Overview
Neotame is a derivative of the dipeptide composed of the amino acids
aspartic acid and phenylalanine. It is 7,000-13,000 times as sweet as sugar
and 30-60 times as sweet as aspartame. It is manufactured by The NutraSweet
Co., Mt. Prospect, Ill., the company that developed the noncaloric sweetener
aspartame.
It provides zero calories and has a clean, sweet, sugar-like taste with no
undesirable taste characteristics. It is functional in a wide array of
beverages and foods and can be used alone or blended with other
high-intensity or carbohydrate sweeteners.
It is stable under dry conditions, and has comparable stability to aspartame
in aqueous food systems and more stable in neutral pH conditions (e.g.,
baking and yogurt).
The results of numerous safety studies confirm that it is safe for use by
the general population, including children, pregnant women, and people with
diabetes.
In addition, since the product is not metabolized to phenylalanine, no
special labeling for individuals with phenylketonuria (PKU) is required.
Neotame has been approved for general use as a sweetener and flavor enhancer
in Australia and New Zealand and is being reviewed in the U.S. and other
countries.
Discovery and Manufacture
Neotame was the result of a long-term research program by The NutraSweet Co.
to discover new high-intensity sweeteners with desirable taste
characteristics.
Working with The NutraSweet Co., French scientists Claude Nofre and
Jean-Marie Tinti prepared a series of compounds by substituting the terminal
nitrogen of aspartame with a number of hydrophobic groups and determined
their sweetness compared to a 2% solution of sucrose.
Aspartame substituted with a 3,3-dimethylbutyl group was the sweetest of the
compounds tested and was selected as development product and called neotame
(Nofre and Tinti, 1996b, 2000). This compound has the chemical structure as
shown in Fig. 1.
As shown in Fig. 2, neotame can be made in one step by the reaction of
aspartame with 3,3-dimethylbutyraldehyde in methanol, using hydrogen and a
catalyst (palladium or platinum) under mild conditions (Nofre and Tinti,
1996a; Prakash, 1998).
Other possible methods of preparation are from aspartame precursors via the
reductive alkylation with 3,3-dimethylbutyraldehyde; peptide coupling of the
L-aspartic acid derivatives and L-phenylalanine methyl ester; aminolysis of
substituted oxazolidinone derivatives (Prakash, 2001; Prakash and Chapeau,
2000; Prakash et al., 2001b).
FOOD TECHNOLOGY 37 VOL. 56, NO. 7 . JULY 2002 DEVELOPING FOODS
Characteristics
Neotame's physical, chemical, and sensory characteristics make it attractive
for use as a sweetener in foods and beverages.
Chemical Characteristics. Neotame is
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester (CAS
registry No. 165450-17-9, proposed INS No. 961). It is a derivative of a
dipeptide composed of the amino acids aspartic acid and phenylalanine. It
contains both a carboxylic acid and a secondary amino group, with pKa values
of 3.03 and 8.08, respectively. It is capable of forming both acidic and
basic salts, as well as complexes with various metals, thus affording unique
delivery forms having improved solubility and other characteristics.
The two amino acids in neotame, aspartic acid and phenylalanine, are in the
natural L-configuration. The other three possible isomers, L,D-, D,D-, and
D,L-, lack the sweet taste of neotame (Prakash et al., 1999).
.. Physical Characteristics. Neotame is a fairly low-melting hydrate
(80.9-83.4 degrees C). It is a white to off-white crystalline powder with
4.5% water of hydration, the empirical formula C20H30N2O5 . H2O, and a
molecular weight of 396.48.
Its solubility in water is similar to that of aspartame (12.6 g/L vs 10 g/L
at 25 degrees C), but it is more readily soluble than aspartame in some
solvents, such as ethanol, typically used in food systems and
pharmaceuticals. Its
solubility in water and ethyl acetate increases with increasing temperature.
Using neotame in a salt form (e.g., as a phosphate salt) significantly
increases the rate of dissolution.
Stability. The stability of neotame is dependent on pH, moisture, and
temperature. As a dry powder, it is stable for at least five years under
proper storage conditions. In aqueous systems, pH stability follows a
bell-shaped curve at a given temperature. The optimum pH for maximum
stability is about 4.5. As expected, stability decreases with increasing
temperature. Stability can be enhanced by the addition of divalent
or trivalent cations in edible compounds (Schroeder and Wang, 2001b).
In aqueous systems (pH 2-8), the major decomposition pathway of neotame is
through the hydrolysis of the methyl ester to form de-esterified or
de-methylated neotame -
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine (Fig. 3) -
which is also the major metabolite of neotame in humans. Deesterified
neotame is not sweet.
Under conditions of use, neotame, unlike aspartame, does not degrade to
phenylalanine. Also unlike aspartame, neotame does not form a
diketopiperazine (DKP) derivative. Neotame is compatible with reducing
sugars and aldehyde or ketone based flavoring agents.
.. Sweetness. Sucrose is the sweetness standard against which other compounds
are compared. A compound with a "sucrose equivalence" of x% SE is equivalent
in sweetness to an x% solution of sucrose in water. Neotame is approximately
8,000 times as sweet as sucrose and more potent than the high intensity
sweeteners currently marketed in the U.S. - aspartame and acesulfame K (200
times as sweet as sucrose), saccharin (300 times), and sucralose (600
times). It is a derivative of aspartame and is 30-60 times sweeter than
aspartame. Its actual sweetness potency is dependent on the concentration
required in various food or beverage products.
Because of its remarkable sweetness potency, neotame can be used in food and
beverage products at considerably lower concentrations than other
high-intensity sweeteners. In fact, consumer exposure to neotame will be
much lower than exposure to flavoring ingredients such as vanillin,
cinnamon, and menthol commonly
used in foods and beverages.
Fig. 1 - 3-dimensional structure of the neotame molecule
Fig. 2 - Manufacture of neotame by reaction of aspartame with
3,3-dimethylbutyraldehyde
Fig. 3 - Major pathway of degradation of neotame under hydrolytic
conditions
Fig. 4 - Sweetness intensity vs concentration of neotame in water
38 FOOD TECHNOLOGY JULY 2002 . VOL. 56, NO. 7 DEVELOPING FOODS
The concentration-response curve for neotame (Fig. 4) was established using
a trained sensory panel to evaluate the sweetness intensity
of five solutions of neotame at increasing concentrations.
Based on these data, neotame can reach an extrapolated maximum sweetness
intensity (plateau) of 15.1% SE in water.
Sweeteners such as aspartame, acesulfame K, sodium cyclamate, and sodium
saccharin attain their maximum sweetness intensity in water at approximately
16.0, 11.6, 11.3, and 9.0% SE, respectively. In a cola formulation, neotame
reaches a maximum sweetness intensity of 13.4% SE (DuBois et al., 1991).
Taste Profile. A trained descriptive panel evaluated neotame and sucrose
at comparable sweetness levels in water. Neotame's taste profile is very
similar to that of sucrose, with the predominant sensory characteristic
being a very clean, sweet taste.
The sweetness increases as the concentration in water increases, but
other taste attributes such as bitterness, sourness, and metallic taste are
insignificant (Fig. 5). In a similar study with neotame in a cola drink,
increasing the sweetener concentration from 9 to 46 ppm improved the
desirable flavor attributes (cola flavor, sweet taste, and mouth feel) but
did not increase the undesirable notes (Fig.6).
.. Sweetness Temporal Profile. The temporal profile of sweeteners
demonstrates the changes in the perception of sweetness over time. This
property is a key to the functionality of a sweetener and is complementary
to its taste profile. Every sweetener exhibits a characteristic onset or
response time and an extinction time. Most high-intensity sweeteners, in
contrast to sugar, display a prolonged extinction time referred to as
"linger."
As shown in Fig. 7, the sweetness temporal profile of neotame in water is
close to that of aspartame, with a slightly slower onset and slightly longer
linger. A longer sweetness linger can be beneficial in some products, such
as chewing gum, where prolonged sweetness is a desirable quality.
The sweetness temporal profile of neotame may also be modified by the
addition of hydrophobic organic acids, such as cinnamic acid, and certain
amino acids, such as serine and tyrosine (Bishay et al., 2000b; Gerlat et
al., 2000; Prakash et al, 2001a). Taste modifiers may be used in
concentrations necessary to achieve the desired taste profile of a product
for a desired application.
Synergy. Blending of sweeteners is well known to improve taste
characteristics and stability and provide sweetness synergy (Lavia and Hill,
1972; Schiffman et al., 1995; Scott, 1971; Verdi and Hood, 1993; Walters,
1993). A blend of neotame and saccharin provides 14-24% greater sweetness
than would be predicted by adding together the sweetness intensities of the
individual sweeteners (Pajor and Gibes, 2000).
Such synergistic blends offer cost savings by decreasing the total amount of
sweetener needed. Neotame can be blended with nutritive sweeteners as well
as other high-intensity sweeteners such as aspartame, acesulfame salts,
cyclamate, sucralose, saccharin, and others (Nofre and Tinti, 1996b).
Furthermore, the clean sweetness of neotame permits its substitution for
substantial amounts of carbohydrate sweeteners without altering the flavor
of the product.
Because time-intensity profiles of the sweeteners acting synergistically are
different from those of the individual sweeteners and may also be different
from that of sucrose, blends can be selected that combine or emphasize
properties of the different sweeteners. The sweetness of acesulfame K is
generally perceived fairly quickly. It may, therefore, provide some impact
sweetness, but it often fades fairly quickly. Therefore, acesulfame
combines particularly well with sweeteners having a more lasting sweetness,
such as aspartame or neotame.
.. Sugar Substitution. Neotame's clean sweet taste allows the food
technologist to substitute a portion of a carbohydrate sweetener with
neotame while maintaining a taste that is indistinguishable from the 100%
carbohydrate product. For example, studies have shown that 20% of the
carbohydrate sweetener can be replaced with 2.1 ppm of neotame in a
carbonated cola soft drink, and the taste is indistinguishable from the
100% carbohydrate-sweetened cola beverage (Fig. 8). Neotame's potency may
offer an economic benefit and, because it has no calories, a positive
caloric benefit.
Fig. 5-Descriptive taste profile of neotame at various concentrations in
water
Fig. 6-Taste profile of neotame at various concentrations in a colaflavored
carbonated beverage
Fig. 7-Sweetness temporal profile of neotame compared to sucrose and
aspartame at isosweet concentrations in water
FOOD TECHNOLOGY 39 VOL. 56, NO. 7 . JULY 2002 DEVELOPING FOODS
.. Flavor Modification and Enhancement. Neotame can also be used to modify or
enhance a product's flavor - the combined perception of taste, smell, and
aroma.
Products containing vitamins, nutraceuticals, pharmaceuticals, salt
substitutes, and soy in
various applications are often either bitter or harsh in flavor.
The addition of neotame at a subsweetening level modifies or masks
undesirable notes/qualities such as bitterness, astringency, and burning or
cooling sensations.
Undesirable attributes, such as the potential bitterness of caffeine, cocoa,
and potassium chloride and the harsh notes of medicinals and plant extracts,
can be modified or masked.
Neotame also reduces the bitter taste of potassium chloride in salt
substitutes, thereby providing a cleaner salty taste. It reduces or
eliminates "beany" flavor notes in soy products. And it modifies or enhances
the attributes of many flavoring chemicals,
including essential oils, oleoresins, plant extracts, reaction flavors, and
mixtures thereof (Gerlat et al., 2000).
Fig. 8-Descriptive test results of carbonated cola beverages sweetened with
100% high-fructose corn syrup and a 20%/80% blend of HFCS and neotame
Food Applications
Historically, the stability and functionality of a new sweetener or an
ingredient was determined for each food product before the sweetener was
approved. This process generated redundant data. This redundancy could be
avoided if products with similar ingredients and processing conditions could
be reduced to representative test products for evaluation.
The functionality of neotame was demonstrated with a three-dimensional food
matrix model representing the intended conditions of use in foods (Pariza et
al., 1998). Based on experience with aspartame and the structural
similarities of neotame and aspartame, product moisture, process
temperature, and product pH were considered to be the key factors
responsible for neotame stability and were selected to represent the three
dimensions of the matrix.
Test products were prepared according to standard formulas, then packaged
appropriately, stored at temperature conditions of up to 250C and 60%
relative humidity, and evaluated for stability at appropriate intervals.
Neotame concentrations were determined using validated high-performance
liquid chromatography methods.
Functionality (sweetness) of the test products was determined using panels
consisting of 35-50 persons. Samples were appropriately prepared, served,
and evaluated on a scale ranging from 5 ("much too sweet") to 1 ("not at all
sweet"). The samples were considered functional if no more than 75% of the
panelists rated the sweetness as 2 ("not quite sweet enough") and 1.
.. Cola-Flavored Carbonated Soft Drink. Neotame remained functional for at
least 16 weeks, consistent with currently marketed low-calorie carbonated
soft drinks (Gerlat et al., 1999).
Hot-Pack Lemon Tea. Neotame remained functional for approximately 25
weeks.
Powdered Soft Drink. At each evaluation, the sweetness of the
reconstituted drink received a rating of "just about right," indicating that
the product was stable and functional as a sweetener during 52 weeks of
storage.
Tabletop Products. Neotame was considered stable and functional in tabletop
products for at least 156 weeks of storage (FAP, 1998; Towb et al., 2002).
Chewing Gum. Encapsulation improved neotame stability. Double coating with
modified starch and hydroxypropyl methylcellulose protected it from
degradation during storage for 52 weeks (Roefer, 2002).
Dairy Products/Strawberry Yogurt. At the end of a 6-week period, the
typical shelf life of these products, about 98% of the initial neotame
remained. Sensory results showed that neotame had excellent functionality in
yogurt (FAP, 1998; Gaughan et al., 1999).
.. Yellow Cake. Neotame was functional, with 82% of the amount added to the
batter remaining after baking at 3500F. After storage at 250C and 60%
relative humidity for 5 days - which is longer than cakes baked from
commercial mixes are held for optimum freshness - there was only a 4% loss
of neotame. The combined losses of about 20% did not affect sweetener
functionality (Chinn et al., 1999; FAP, 1998).
.. Other Products. Functionality has also been demonstrated in cereals and
cereal-based foods (Ponakala and Corliss, 2000), nutraceuticals (Ponakala et
al., 2000a), pharmaceuticals (Ponakala, 2001), edible gels (Ponakala et al.,
2000b), and confectionery products (Jarrett, 2001).
Table 1 presents some typical use levels of neotame in various foods and
beverages. Since neotame is extremely sweet, the use levels are expressed as
parts per million rather than percentages.
The ranges provided are for neotame used either as a single sweetener or as
a component in a sweetener blend.
Delivery Forms and Benefits
Neotame can be prepared in a wide variety of forms,
including agglomerated (Fotos and Bishay, 2001),
granulated (Dron, 2001),
extruded and spheronized (Dron et al, 2000),
encapsulated (Ponakala et al., 1999),
co-crystallized with sugar (Fotos et al., 2001),
acid salts (Prakash and Wachholder, 2001a),
basic salts (Prakash and Wachholder, 2001b),
sweetener salts (Prakash and Guo, 2000b),
amorphous (Schroeder and Wang, 2001a),
metal complexes (Prakash and Guo, 2000a),
cyclodextrin complexes (Bishay et al., 2000a),
and liquid (Schroeder et al, 2000).
In certain uses, these delivery forms offer various advantages over neotame
powder, such as ease of handling, non-dustiness, and improved solubility
characteristics, bringing greater flexibility to product developers.
Neotame provides several benefits as a sweetener and/or flavor enhancer in
food and beverage systems. It is noncaloric; it requires no PKU labeling; it
is not likely to react with aldehydes and consequently may be compatible
with flavors containing aldehydes.
Because of its high potency, the quantity required to sweeten a
product is about 1/30 to 1/60 of the amount of aspartame required.
It enhances the flavor of some ingredients, such as mint and suppresses the
beany notes of soy, in various food and beverage systems. It masks
bitterness. It can complement the flavor of root beer beverages. In fruit
based juices, because of the increased mouth feel it contributes, juice
solids can be reduced. It has a sparing effect on the flavoring agent
vanillin in puddings; on cocoa, dairy component, and vanillin in chocolate
and cocoa-based products; on dairy and fruit components, such as citric
acid, in yogurt; and on tomato flavor in barbeque sauces.
40 FOOD TECHNOLOGY JULY 2002 . VOL. 56, NO. 7 DEVELOPING FOODS
Safety and Regulatory Status
The results of extensive research done in animals and humans using amounts
of neotame that far exceed expected consumption levels clearly confirm its
safety for the general popu lation, including children, pregnant women, and
people with diabetes.
Neotame is not mutagenic, teratogenic, or carcinogenic and has no effect on
reproduction.
In addition, no special labeling for phenylketonuric individuals is
required.
The major route of metabolism of neotame is de-esterification.
Both neotame and de-esterified neotame have short plasma half lives, with
rapid and complete elimination (FAP, 1998, 1999).
The Food and Drug Administration is currently reviewing a food additive
petition for approval of neotame for general use in food as a sweetener and
flavor enhancer, and petitions for regulatory approval have been filed in a
number of foreign countries. Australia and New Zealand have already approved
use of neotame as a sweetener and flavor enhancer.
Neotame's unique properties will provide the food technologist with another
tool to produce innovative new foods and beverages to meet consumers'
demands for great-tasting foods without all the calories of sugar.
Table 1-Typical neotame concentrations in various products when used as a
sweetener
Product Typical concentration (ppm)
Carbonated soft drinks 2-50
Cola 17
Lemon-lime 14
Root beer 20
Flavored water 15
Still beverages 2-20
Red punch 15
Lemonade 16
Ready-to-drink tea 8
Powdered soft drink, as is 200-2,000
Lemon-flavored 16
Tabletop sweetener, as is 800-4,000
Lemon tea 12
Bakery products 6-130
Cookie 25
Yellow cake 35
Chocolate cake 125
Fillings 25
Frosting 25
Dairy products 5-50
Yogurt 15
Ice cream 15
Other frozen desserts 30
Chewing gum 10-1,600
Confections 1-200
Hard candy 5-75
Cereals 10-500
Extruded 23
Frosting 20
Edible gels 10-1,000
Nutraceuticals 15-250
Pharmaceuticals 1-1,000
Liquid sweetener 10-10,000
Sweetener tablets 50-12,000
REFERENCES
Bishay, I., Fotos, J., Desai, N., Cleary, M., and Schroeder, S. 2000a. The
use of cyclodextrin to stabilize
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester.
PCT intl. applic. WO 00/15049.
Bishay, I., Prakash, I., Desai, N., and Gelman, Y. 2000b. Modification of
the taste and physicochemical properties of neotame using hydrophobic
additives. PCT intl. applic. WO 00/69282.
Chinn, B., Solter, S., Ponakala, S., Ziegler, J., Bakhoum, M., Jarrett, T.,
Paeschke, T., and Corliss, G. 1999. Use of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester in
baked goods, frostings and bakery fillings. PCT intl. applic. WO 99/30566.
Dron, A. 2001. Process for making granulated
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-Lphenylalanine 1-methyl ester. PCT
intl. applic. WO 01/60842.
Dron, A., Bishay, I., Fotos, J., and Trione, M. 2000. Spheronization of
neotame with and without binders. PCT intl. applic. WO 00/57725.
DuBois, G., Walters, D, Schiffman, S., Warwick, Z., Booth, B., Pecore, S.,
Gibes, K., Carr, B., and Brands, L. 1991. Concentration-response
relationships of sweeteners.
Chpt. 20 in "Sweeteners Discovery, Molecular Design, and Chemoreception,"
ed. D.E. Walters, F.T. Orthoefer, and G.E. DuBois, pp. 261-276. Am. Chem.
Soc., Washington, D.C.
FDA. 1998. Monsanto Co.: Filing a food additive petition. FAP 8A4580. Food
and Drug Admin., Fed. Reg. 63: 6762.
FDA. 1999. Monsanto Co.: Filing a food additive petition. FAP 9A4643. Food
and Drug Admin., Fed. Reg. 64: 6100.
Fotos, J. and Bishay, I. 2001. Process for preparing an
N-[N-(3,3-dimethylbutyl)-L-aaspartyl]-L-phenylalanine 1-methyl ester
agglomerate. U.S. patent 6,180,157.
Fotos, J., Bishay, I., Prakash, I., Wachholder, K., and Desai, N. 2001.
Co-crystallization of sugar and
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester.
U.S. patent 6,214,402.
Gaughan, W., Gerlat, P., Ziegler, J., Walters, G., Logli, L., Corliss, G.,
and Finley, J. 1999. Neotame sweetener for dairy products and dairy product
substitutes. PCT intl. applic. WO 99/30578.
Gerlat, P., Hatchwell, L., Walters, G., Miragilo, A., and Sawer, H. 2000.
Use of N-neohexyl-a-aspartyl-L-phenylalanine methyl ester as flavor
modifier. U.S.
patent applic. 09/465,837.
Gerlat, P., Milovanovic, S., Ponakala, S., Ziegler, J., Sawyer, H., and
Walters, G. 1999. Neotame-based sweeteners for beverages. PCT intl. applic.
WO 99/30576.
Gerlat, P., Walters, G., Bishay, I., Prakash, I., Jarrett, T., Desai, N.,
Sawer, H., and Bechert, C.-L. 2000.
Use of additives to modify the taste characteristics of
N-neohexyl-a-aspartyl-L-phenylalanine methyl ester. PCT intl. applic. WO
00/69283.
Jarrett, T. 2001. Confectionery food products sweetened with
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester. PCT
intl. applic. WO 01/010236.
Lavia, A. and Hill, J. 1972. Sweeteners with masked saccharin aftertaste.
French patent 2,087,843.
Nofre, C. and Tinti, J.-M. 1996a. Method of preparing a compound derived
from aspartame, useful as a sweetening agent. U.S. patent 5,510,508.
Nofre, C. and Tinti, J.-M. 1996b. N-substituted derivatives of aspartame
useful as sweetening agents. U.S. patent 5,480,668.
Nofre, C. and Tinti, J.-M. 2000. Neotame: Discovery, properties, utility.
Food Chem. 69: 245-297.
FOOD TECHNOLOGY 45 VOL. 56, NO. 7 . JULY 2002 DEVELOPING FOODS
Pajor, L. and Gibes, K. 2000.
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester
synergistic sweetener blends. U.S. patent 6,048,999.
Pariza, M., Ponakala, S., Gerlat, P., and Andress, S. 1998. Predicting the
functionality of direct food additives. Food Technol. 52(11): 56-60.
Ponakala, S. 2001. Pharmaceutical compositions containing neotame. PCT intl.
applic. WO 01/028590.
Ponakala, S. and Corliss, G. 2000. Cereals and cereal-based food sweetened
with neotame. PCT intl. applic. WO 00/056175.
Ponakala, S., Ziegler, J., Patterson, K., Brahmbhatt, D., Lui, P., Corliss,
G., Chaudhary, V., Towb, A., Bishay, I., and Ansay, A., R. 1999.
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester as a
sweetener in chewing gum. U.S. patent applic. No. 09/465,402.
Ponakala, S., Walters, G., Gerlat, P., and Hatchwell, L. 2000a.
Nutraceuticals having
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester. PCT
intl. applic. WO 00/057726.
Ponakala, S., Walters, G., and Schroeder, S. 2000b. Manufacture of edible
gels sweetened with neotame. PCT intl. applic. WO 00/056176.
Prakash, I. 1998. Method for preparing and purifying an N-alkylated
aspartame derivative. U.S. patent 5,728,862.
Prakash, I. 2001. Synthesis of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester using
oxazolidinone derivatives. PCT intl. applic. WO 01/90138.
Prakash, I. and Chapeau, M.-C. 2000. N-3,3-Dimethylbutyl-L-aspartic acid and
esters thereof, the process of preparing the same, and the process for
preparing
N-(N-(3,3-dimethylbutyl)- L-a-aspartyl)-L-phenylalanine 1-methyl ester
therefrom. U.S. patent 6,077,962.
Prakash, I., and Guo, Z., 2000a. Metal complexes of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester. U.S.
patent 6,146,680.
Prakash, I., and Guo, Z., 2000b. Sweetener salts of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester. U.S.
patent 6,129,942.
Prakash, I., and Wachholder, K. 2001a. Acid salts of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester. U.S.
patent 6,180,156.
Prakash, I. and Wachholder, K. 2001b. Basic salts of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester. U.S.
patent 6,291,004.
Prakash, I., Bishay, I., and Schroeder, S. 1999. Neotame: synthesis,
stereochemistry and sweetness. Synthetic Commun. 29: 4461-4467.
Prakash, I., Bishay, I., Desai, N., and Walters, D. 2001a. Modifying the
temporal profile of the high-potency sweetener neotame. J. Agric. Food Chem.
49: 786-78.
Prakash, I., Scaros, M., Orlovskii, V., and Moore, C. 2001b. A method for
the preparation of N-neohexyl-L-a-aspartyl-L-phenylalanine methyl ester from
imidazolidin-4-one intermediates. PCT intl. applic. WO 01/87927.
Roefer, W. 2002. Unpublished data. Dept. of Analytical Chemistry, The
NutraSweet Co., Mt. Prospect, Ill.
Schiffman, S., Booth, B., Carr, B., Losee, M., Sattely-Miller, E., and
Graham, B. 1995. Investigation of synergism in binary mixtures of
sweeteners. Brain Research Bull. 38(2): 105-120.
Schroeder, S. and Wang, R. 2001a. Amorphous
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]- L-phenylalanine 1-methyl ester. U.S.
patent 6,331,646.
Schroeder, S. and Wang, R. 2001b. Stability enhancement of sweeteners using
salts containing divalent or trivalent cations. PCT intl. applic. WO
01/70049.
Schroeder, S., Wang, R., Ponakala, S., and Choudhary, V. 2000. Method of
preparing liquid compositions for delivery of
N-[N-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester in
food and beverage systems. PCT intl. applic. WO 02/05661.
Scott, D. 1971. Saccharin-dipeptide sweetening compositions. British patent
1,256,995.
Towb, A., Dron, A., and Walters, G. 2002. Drying of neotame with co-agents.
PCT intl. applic. WO 02/05660.
Verdi, R.J. and Hood, L.L. 1993. Advantages of alternative sweetener blends.
Food Technol. 47(6): 94-101.
Walters, E. 1993. High intensity sweetener blends. Food Prod. Design 3(6):
83-92. l
*******************************************************************
http://groups.yahoo.com/group/aspartameNM/message/1141
Nurses Health Study can quickly reveal the extent of aspartame (methanol,
formaldehyde, formic acid) toxicity: Murray 2004.11.21 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1108
faults in 1999 July EPA 468-page formaldehyde profile:
Elzbieta Skrzydlewska PhD, Assc. Prof., Medical U. of Bialystok, Poland,
abstracts -- ethanol, methanol, formaldehyde, formic acid, acetaldehyde,
lipid peroxidation, green tea, aging, Lyme disease:
Murray 2004.08.08 rmforall
Rich Murray, MA Room For All rmforall@comcast.net
1943 Otowi Road, Santa Fe, New Mexico 87505 USA 505-501-2298
http://groups.yahoo.com/group/aspartameNM/messages
139 members, 1,149 posts in a public searchable archive
The moderated newsgroup, bionet.toxicology , has accepted 27 of my long
reviews since March 24:
Dr. Charles "Chuck" A. Miller III rellim@tulane.edu
Associate Professor of Environmental Health Sciences
374 Johnston Building, SL29
Tulane Univ. School of Public Health and Tropical Medicine
1430 Tulane Avenue New Orleans, LA 70112 (504)585-6942
Bionet.toxicology news group http://www.bio.net/hypermail/toxicol/current
[ NutraSweet, Equal, Canderel, Benevia, E951 ]
http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 2002.12.23 rmforall
A very detailed, highly credible account of the dubious approval process for
aspartame in July, 1981 is part of the just released two-hour documentary
"Sweet Misery, A Poisoned World: An Industry Case Study of a Food Supply
In Crisis" by Cori Brackett: cori@soundandfuryproductions.com
http://www.soundandfuryproductions.com/ 520-624-9710
2301 East Broadway, Suite 111 Tucson, AZ 85719
http://groups.yahoo.com/group/aspartame/messages
Aspartame Victims Support Group Edward Bryant Holman, Chief Moderator
840 members, 17,961 posts in a public, searchable archive
http://www.presidiotex.com/aspartame/ bryanth@presidiotex.net
http://www.HolisticMed.com/aspartame mgold@holisticmed.com
Aspartame Toxicity Information Center Mark D. Gold also Co-Moderator
12 East Side Drive #2-18 Concord, NH 03301 603-225-2110
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"
http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 2003.01.12 rmforall EU Scientific Committee on Food, a whitewash
http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references
http://groups.yahoo.com/group/aspartameNM/message/1131
genotoxicity of aspartame in human lymphocytes 2004.07.29 full plain text,
Rencuzogullari E et al, Cukurova University, Adana, Turkey 2004 Aug: Murray
2004.11.06 rmforall
*************************************************************
http://groups.yahoo.com/group/aspartameNM/message/1144
any evidence for neotame toxicity? Dewey: Murray 2005.01.07 rmforall
2005.01.07 Hello Colleagues, I'm interested in any evidence or personal
testimony about neotame toxicity. My reviews of it so far show that there
are no independently (non vested interest financed) public published
scientific studies at all on its safety This is definitely a red flag,
especially given the deplorable record of the aspartame industry for over 3
decades.
Although it has been approved in Australia since summer 2001 and in the USA
since summer 2002, I know of only one product on the market with neotame,
with just one customer complaint, on 2004.10.27, as given below.
On 2002.08.04 I posted to the FDA:
"To cut to the chase, for me, the key fact revealed in the FDA approval
report is: "In contrast, the methanol content of neotame-sweetened
carbonated beverages is estimated to be 1.37 mg/L." This is the same
as 1.37 ppm, about 18% of the EPA limit of 7.8 ppm for drinking water
That sounds pretty safe, at first sight.
A liter of diet soda contains about 560 mg aspartame, of which 10% is
methanol, 56 mg, which is 41 times the amount of 1.37 mg methanol
from the neotame that gives the same sweetness.
However, we give in this complaint many reports of aspartame reactors
reacting severely and quickly to aspartame doses of
1.5 mg for a breath mint, 4 mg for a medicine pill, and 6-8 mg for a
stick of chewing gum.
Since methanol is 10% of the aspartame, we find methanol doses of
..15 mg for a breath mint, .4 mg for a medicine pill, and .6-.8 mg for
a stick of chewing gum..
So, if the methanol from neotame is fairly fully released into the inner
surfaces of the mouth, or into the GI tract, and an aspartame reactor
consumes 1, 2, or 4 liters of neotame diet drink, he would have a dose
of 1.37, 2.74, or 5.48 mg of methanol. A single can of neotame diet
soda gives 0.25 mg methanol. So, these levels very probably would
trigger unpleasant symptoms in aspartame reactors.
This means that the biochemical data and the voluminous case reports
about aspartame toxicty are indeed relevant to making sound judgements
about the safety of neotame. Neotame must be put to the test, and by
independent researchers, given the necessary support to complete fully
competent, definitive studies."
I appreciate any information, testimony, or research references.
In mutual service, Rich Murray
*******************************************************************
|
|
|
| | |
|
 |
