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HOT TOPICS is a review  of  the  medical  literature  on  a  topic  of  
current interest.  The  articles are taken from the MEDLINE online database 
produced by the National Library of Medicine,  as well as  many  other  
online  sources  of information.  

This  listing  is  NOT a complete review,  but represents a selection.  
Further information may be obtained from campus  libraries  (including  the  
Biomedical Library),  or  from your local library.  Many of the articles will 
be available in the Biomedical Library.  We will be happy to assist  you  in  
locating  them during  our  regular hours.  If you have any questions please 
leave a message.  I welcome any suggestions for further HOT  TOPICS, and will 
be happy to answer any questions regarding this section. -- Steve Clancy, 
Biomedical Library, UCI.  


KEY TO HOT TOPICS REFERENCES 

3. France C; Ditto B.                                    <AUTHOR(S)>
     Cardiovascular responses to occupational stress and caffeine in
   telemarketing employees.                              <ARTICLE TITLE>
     Psychosomatic Medicine, 1989 Mar-Apr, 51(2):145-51. <JOURNAL TITLE>
More <[Y],N,C,A>!                   
Abstract: Cardiovascular responses to the combination of caffeine and a
    challenging occupational activity were examined using a within-subject,
    double-blind design. Seventeen female and 11 male telemarketing employees
    received drinks that did and did not contain 250 mg of caffeine on two


NUTRASWEET: ADVERSE EFFECTS


1. Dailey JW; Lasley SM; Mishra PK; Bettendorf AF; Burger RL; Jobe PC.
     Aspartame fails to facilitate pentylenetetrazol-induced convulsions in
   CD-1 mice.
     Toxicology and Applied Pharmacology, 1989 May, 98(3):475-86.

Abstract: Concentrations of plasma amino acids and brain monoamines as well as
    pentylenetetrazol-induced seizures were monitored in CD-1 mice treated with
    aspartame in acute oral doses from 0 to 2500 mg/kg. One hour after
    administration aspartame produced increases in plasma concentrations of
    phenylalanine and tyrosine and modest reductions in concentrations of brain
    serotonin and 5-hydroxyindole acetic acid. However, these effects of the
    sweetener had no influence on the convulsive dose fifty (CD50) of
    pentylenetetrazol. Moreover, aspartame failed to alter the percentage of
    mice exhibiting seizures when exposed to an approximate CD50 of
More <[Y],N,C,A>!                       pentylenetetrazol. Finally, aspartame had no effect on brain norepinephrine
    or dopamine concentrations. In sharp contrast to previously reported
    studies, these observations suggest that aspartame, given in heroic doses,
    does not alter the propensity to seizure activity in CD-1 mice. We conclude
    that changes in plasma amino acids and brain serotonin produced by large
    oral bolus doses of aspartame are insufficient to result in functional
    deficits which might have the capacity to facilitate
    pentylenetetrazol-induced seizures. 

2. Lipton RB; Newman LC; Cohen JS; Solomon S.
     Aspartame as a dietary trigger of headache.
     Headache, 1989 Feb, 29(2):90-2.

Abstract: Many dietary factors have been implicated as possible precipitants of
    headache. There have been recent differences of opinion with regard to the
    effect of the artificial sweetener aspartame as a precipitant of headache.
    To assess the importance of aspartame as a dietary factor in headache, 190
    consecutive patients of the Montefiore Medical Center Headache Unit were
    questioned about the effect of alcohol, carbohydrates and aspartame in
    triggering their headaches. Of the 171 patients who fully completed the
    survey, 49.7 percent reported alcohol as a precipitating factor, compared
    to 8.2 percent reporting aspartame and 2.3 percent reporting carbohydrates.
    Patients with migraine were significantly more likely to report alcohol as
    a triggering factor and also reported aspartame as a precipitant three
More <[Y],N,C,A>!                       times more often than those having other types of headache. The conflicting
    results of two recent placebo-control studies of aspartame and headache are
    discussed. We conclude that aspartame may be an important dietary trigger
    of headache in some people. 

3. Yost DA.
     Clinical safety of aspartame.
     American Family Physician, 1989 Feb, 39(2):201-6.

Abstract: Aspartame is a synthetic sweetener commonly used in soft drinks and
    many foods. Even with high doses, the metabolites of this sweetener do not
    accumulate in toxic amounts. To date, no definite symptom complex has been
    connected with aspartame, and it is considered safe for use in all
    populations, including diabetics, phenylketonuric heterozygotes and
    pregnant women. 

4. Tollefson L.
     Monitoring adverse reactions to food additives in the U.S. Food and Drug
   Administration.
     Regulatory Toxicology and Pharmacology, 1988 Dec, 8(4):438-46.

Abstract: Technological advances in food science have resulted in the
    development of numerous food additives, most of which require premarket
    approval by the Food and Drug Administration (FDA). Concomitant with the
More <[Y],N,C,A>!                       benefits of these additives, such as extending the shelf life of certain
    food commodities, is the potential for various risks. These potential risks
    include the possibility of the consumer experiencing an adverse reaction to
    the additive. In order to ascertain the character and the gravity of
    alleged adverse reactions to food products which it regulates, the FDA's
    Center for Food Safety and Applied Nutrition has developed the Adverse
    Reaction Monitoring System (ARMS). This postmarketing surveillance system
    for food additives is designed to analyze consumer reports of adverse
    reactions in order to alert FDA officials about any potential public health
    hazard associated with an approved food additive, and to delineate specific
    syndromes which may lead to focused clinical investigations. To date, among
    the products routinely monitored in the ARMS, sulfiting agents and the
    artificial sweetener aspartame have generated the largest volume of
    consumer reports describing adverse reactions. An overview of the analyses
    of the sulfite and aspartame adverse reaction reports is presented, along
    with a description of the mechanics of the postmarketing surveillance
    system, and a detailed discussion of its limitations. 

5. Fountain SB; Hennes SK; Teyler TJ.
     Aspartame exposure and in vitro hippocampal slice excitability and
   plasticity.
     Fundamental and Applied Toxicology, 1988 Aug, 11(2):221-8.

Abstract: Aspartame (APM) is a low-calorie sweetener recently approved and
More <[Y],N,C,A>!                       released for widespread use in the United States. However, concerns still
    exist that APM consumption may be responsible for adverse neurological and
    psychological effects in some people. In addition, recent reports indicate
    that APM exposure may alter regional brain neurotransmitter levels. The
    present study assessed the effects of APM and its amino acid moieties on
    rat hippocampal slice excitability and plasticity. Specifically, tests of
    excitatory systems, inhibitory systems, and synaptic plasticity (induction
    of long-term potentiation--LTP) were administered postexposure. Exposures
    of 0.01, 0.1, 1, and 10 mM APM potentiated the response of hippocampal CA1
    pyramidal cells, but had no apparent effect on local inhibitory systems.
    APM exposure did not block the establishment of LTP at any dose despite the
    potentiation of pyramidal cell response observed postexposure. In addition,
    0.1 mM phenylalanine (PHE) produced a greater increase in excitability than
    that produced by an equivalent dose of APM, 0.1 mM aspartic acid (ASP) and
    0.1 mM phenylalanine methyl ester (PM) produced effects comparable to those
    produced a smaller, but reliable, change in hippocampal CA1 excitability
    relative to baseline. Like APM, none of the amino acids produced detectable
    changes in inhibitory systems or neuronal plasticity. 

6. Stegink LD; Filer LJ Jr; Baker GL; Bell EF; Ziegler EE; Brummel MC; Krause
   WL.
     Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino
   acid concentrations in individuals heterozygous for phenylketonuria.
     Metabolism: Clinical and Experimental, 1989 Jan, 38(1):78-84.
More <[Y],N,C,A>!                   
Abstract: It has been suggested that excessive use of aspartame (APM)
    (N-L-alpha-aspartyl-L-phenylalanine methyl ester) might grossly elevate
    plasma aspartate and phenylalanine concentrations in individuals
    heterozygous for phenylketonuria (PKUH). In study 1 six adult PKUH (three
    males; three females) ingested three successive 12-oz servings of beverage
    at 2-h intervals. The study was carried out in two parts in a randomized
    crossover design. In one arm the beverage was not sweetened. In the other
    the beverage provided 10 mg APM/kg body weight per serving. The addition of
    APM to the beverage did not significantly increase plasma aspartate
    concentration but did increase plasma phenylalanine levels 2.3 to 4.1
    mumol/dL above baseline values 30 to 45 min after each dose. The high mean
    plasma phenylalanine level after repeated APM dosing (13.9 +/- 2.15
    mumol/dL) was slightly, but not significantly, above the normal
    postprandial range for PKUH (12.6 +/- 2.11 mumol/dL). In study 2 six
    different adult PKUH ingested beverage providing 30 mg APM/kg body weight
    as a single bolus. The high mean plasma phenylalanine concentration and the
    phenylalanine to large neutral amino acid ratio were significantly higher
    when APM was ingested as a single bolus than when ingested as a divided
    dose. 

7. Garriga MM; Metcalfe DD.
     Aspartame intolerance.
     Annals of Allergy, 1988 Dec, 61(6 Pt 2):63-9.
More <[Y],N,C,A>!                   
Abstract: Aspartame is a food additive marketed under the brand name
    Nutrasweet. Aspartame is a white, odorless, crystalline powder and consists
    of two amino acids, L-aspartic acid and L-phenylalanine. It is 180 times as
    sweet as sugar. The Food and Drug Administration (FDA) first allowed its
    use in dry foods in July 1981 and then approved its use in carbonated
    beverages in July 1983. It has subsequently been approved for use in a
    number of materials including multivitamins, fruit juices, stick-type
    confections, breath mints, and iced tea. The FDA requires the statement
    "phenylketonurics: contains phenylalanine" on labels of food products
    containing aspartame because individuals with phenylketonuria (PKU) must
    restrict their intake of phenylalanine. Aspartame is judged to be free of
    long-term cancer risks. Aspartame is not stable under certain conditions
    including baking and cooking, and prolonged exposure to acid conditions. In
    such situations it loses its sweetness. Products formed from aspartame
    include its component amino acids (phenylalanine and aspartic acid),
    methanol, and diketopiperazine (DKP). Animal studies show DKP to be
    nontoxic. Methanol occurs in small amounts and does not exceed that formed
    during consumption of many foods including fresh fruits and vegetables.
    FDA's Center for Food Safety and Applied Nutrition (CFSAN) monitors
    aspartame's safety in part through reports of adverse reactions. After
    aspartame was approved for use in carbonated beverages, the FDA received an
    increased number of reports concerning adverse reactions related to
    aspartame. The Centers for Disease Control (CDC) reviewed these reports,
More <[Y],N,C,A>!                       which included complaints of neurologic, gastrointestinal, andallergic
    reactions.(ABSTRACT TRUNCATED AT 250 WORDS) 

8. Guiso G; Caccia S; Vezzani A; Stasi MA; Salmona M; Romano M; Garattini S.
     Effect of aspartame on seizures in various models of experimental
   epilepsy.
     Toxicology and Applied Pharmacology, 1988 Dec, 96(3):485-93.

Abstract: We investigated in rats whether aspartame intake affected the
    susceptibility to seizures induced chemically (metrazol, quinolinic acid)
    or electrically (electroshock). Aspartame (0.75-1.0 g/kg), given orally as
    a single bolus to 16-hr fasted animals 60 min before metrazol,
    significantly increased the number of animals showing clonic-tonic
    seizures. At 1.0 g/kg the ED50 for clonic-tonic convulsions was lowered by
    23%. A similar increase in seizure susceptibility was observed with
    0.25-0.5 g/kg of the aspartame's metabolite phenylalanine. When aspartame
    was administered to fasted rats in three divided doses (0.33 g/kg) over 120
    min or to fed animals after a meal, or overnight with the diet, no
    significant changes in the incidence of animals showing seizures was
    observed. One gram per kilogram aspartame and 0.5 g/kg phenylalanine did
    not modify the CC50 (mA) for tonic hindlimb extension induced by
    electroshock and the electroencephalographic seizures caused by
    intrahippocampal injection of 120 nmol quinolinic acid. Plasma and brain
    levels of phenylalanine and tyrosine significantly raised after both 1 g/kg
More <[Y],N,C,A>!                       aspartame as a single bolus (plasma: Phe 285%, Tyr 288%; brain: Phe 146%,
    Tyr 192%; above controls) or in three divided doses (plasma: Phe 207%, Tyr
    315%; brain Phe 103%, Tyr 211%; above controls) and 0.5 g/kg phenylalanine
    (plasma: Phe 339%, Tyr 410%; brain: Phe 219%, Tyr 192%; above controls),
    but the ratio Phe/Tyr was not modified. Our data indicate that aspartame
    cannot be regarded as a general proconvulsant agent. The mechanisms of
    potentiation of seizures induced by metrazol after the administration of
    the sweetner in a single rapid intake will be discussed. 

9. Nabors LO.
     Saccharin and aspartame: are they safe to consume during pregnancy?
   [latter].
     Journal of Reproductive Medicine, 1988 Aug, 33(8):102.

10. Copestake P.
      Aspartame--a bit of a headache?
      Food and Chemical Toxicology, 1988 Jun, 26(6):571.

11. Janssen PJ; van der Heijden CA.
      Aspartame: review of recent experimental and observational data.
      Toxicology, 1988 Jun, 50(1):1-26.

Abstract: In this report the neurotoxicity of aspartame and its constituent
    amino acids aspartic acid and phenylalanine is reviewed. The adverse
More <[Y],N,C,A>!                       reactions ascribed to the consumption of aspartame-containing products, as
    reported in the U.S.A., are discussed and placed in perspective with the
    results of recent behavioural studies in humans and animals. The issue of
    common intake levels associated with proposed uses of aspartame is
    addressed. In brief, the following conclusions can be drawn: When aspartame
    is consumed at levels within the ADI-limit of 40 mg/kg body wt, there is no
    significant risk for an aspartate-induced neurotoxic effect in the brain.
    When aspartame is consumed at levels within the ADI-limit by normal
    subjects or persons heterozygous for phenylketonuria (PKU) the resultant
    plasma phenylalanine concentrations are practically always within the
    normal postprandial range; elevation to plasma concentrations commonly
    associated with adverse effects has not been observed. Persons suffering
    from phenylketonuria (PKU-homozygotes) on a phenylalanine-restricted diet
    should avoid consumption of aspartame. PKU-homozygotes on the (less strict)
    phenylalanine-liberalized diet should be made aware of the phenylalanine
    content of aspartame. In the available behavioural studies in humans with
    acute dosing, no adverse effects were observed. Long-term studies on
    behaviour and cognitive function in (sensitive) humans are lacking.
    Analyses of adverse reaction reports made by consumers in the U.S.A. have
    not yielded a specific constellation of symptoms clearly related to
    aspartame that would suggest a widespread public health hazard associated
    with aspartame use. Focussed clinical studies are now being carried out in
    the U.S.A.; the results should provide additional evidence concerning the
    interpretation of the reports on adverse reactions ascribed to aspartame.
More <[Y],N,C,A>!                       In the regulation of admitted uses for aspartame the possibility of intake
    levels exceeding the ADI-limit in some groups of consumers should be a
    point of attention.

12. Schiffman SS.
      Aspartame and headache [letter].
      Headache, 1988 Jun, 28(5):370-2.

13. Aspartame and headache [letter].
      New England Journal of Medicine, 1988 May 5, 318(18):1200-2.

14. Koehler SM; Glaros A.
      The effect of aspartame on migraine headache.
      Headache, 1988 Feb, 28(1):10-4.

15. Edmeads J.
      Aspartame and headache.
      Headache, 1988 Feb, 28(1):64-5.

16. London RS.
      Saccharin and aspartame. Are they safe to consume during pregnancy?
      Journal of Reproductive Medicine, 1988 Jan, 33(1):17-21.

Abstract: Saccharin and aspartame are commonly used artificial sweeteners. Some
More <[Y],N,C,A>!                       of the currently available information on their safety in pregnancy was
    reviewed, with recommendations formulated on their use in the
    periconceptional period and pregnancy.

17. Pinto JM; Maher TJ.
      Administration of aspartame potentiates pentylenetetrazole- and
    fluorothyl-induced seizures in mice.
      Neuropharmacology, 1988 Jan, 27(1):51-5.

Abstract: An association has recently been proposed between the incidence of
    seizures and prolonged consumption of the phenylalanine-containing
    artificial sweetener, aspartame. Since consumption of aspartame, unlike
    dietary protein, can elevate phenylalanine in brain, and thereby inhibit
    the synthesis and release of neurotransmitters known to protect against
    seizure activity, the effect of oral doses of aspartame on the sensitivity
    of mice to the proconvulsant agents, pentylenetetrazole and fluorothyl was
    studied. Doses of aspartame were used which increased phenylalanine more
    than tyrosine in brain, as occurs in humans after the consumption of any
    dose of aspartame. Pretreatment with aspartame significantly increased the
    percentage of animals convulsing after administration of pentylenetetrazole
    and significantly lowered the CD50 for this convulsant. The average time to
    onset of seizures induced by fluorothyl in control mice was 510 sec;
    pretreatment with oral doses of 1000, 1500 and 2000 mg/kg of aspartame 1 hr
    earlier significantly reduced the time required to elicit seizures (394,
More <[Y],N,C,A>!                       381 and 339 sec, respectively). The seizure-promoting effect of aspartame
    could be demonstrated 30, 60 or 120 min after the 1000 mg/kg dose. The
    seizures induced by either convulsant were potentiated by equimolar amounts
    of phenylalanine, a major endogenous metabolite of aspartame, while the
    other metabolites, aspartic acid and methanol, were without effect.
    Administration together with aspartame of the large neutral amino acid
    valine, which competes with phenylalanine for entry into the brain,
    completely abolished the seizure-promoting effect of aspartame.(ABSTRACT
    TRUNCATED AT 250 WORDS)

18. Lout RK; Messer LB; Soberay A; Kajander K; Rudney J.
      Cariogenicity of frequent aspartame and sorbitol rinsing in laboratory
    rats.
      Caries Research, 1988, 22(4):237-41.

Abstract: The cariogenicity of frequent rinsings with aspartame and sorbitol
    was studied in the rat caries model with animals randomly assigned to four
    oral rinse groups (16 rats/group): 0.05% aspartame, 20% sorbitol, deionized
    distilled water, and 20% sucrose; all solutions at pH 3.0. After rinsing
    five times daily for 21 days, mandibular molars were scored for caries.
    Smooth surface, proximal and morsal caries scores did not differ
    significantly between groups. Moderate dentinal sulcal caries for the
    sucrose group was significantly greater than in the aspartame, sorbitol,
    and water groups (p less than 0.05). Rinsing with 0.05% aspartame (similar
    in pH and concentration to that found in carbonated beverages) or sorbitol
    did not potentiate caries activity.

19. Position of the American Dietetic Association: appropriate use of nutritive
    and non-nutritive sweeteners.
      Journal of the American Dietetic Association, 1987 Dec, 87(12):1689-94.

Abstract: Moderation in the consumption of nutritive and non-nutritive
    sweeteners appears to be prudent advice for persons who choose to use
    sweeteners. The major benefit from use of sweeteners is a perceived
More <[Y],N,C,A>! c                       improvement in the quality of life. Some nutritive sweeteners also provide
    important textural properties to many foods. Sweeteners should be used in
    the context of an otherwise nutritious and well-balanced diet. Excessive
    intake of any sweetener requires nutrition counseling for basic nutrition
    reasons. An individual can minimize potential risks from any one sweetener
    by using a variety of available sweeteners, thus ingesting less of any
    specific sweetener. Research into possible risks of long-term uses of
    non-nutritive sweeteners, either alone or in combination, should continue.
    It is important that the public have a choice of various non-nutritive
    sweeteners, with safe and reasonable guidelines on how to use each. As new
    sweeteners become available, they must receive the same rigorous testing to
    which previously approved sweeteners have been subjected.

20. Schiffman SS; Buckley CE 3d; Sampson HA; Massey EW; Baraniuk JN; Follett
    JV; Warwick ZS.
      Aspartame and susceptibility to headache.
      New England Journal of Medicine, 1987 Nov 5, 317(19):1181-5.

Abstract: We performed a double-blind crossover trial of challenges with 30 mg
    of aspartame per kilogram of body weight or placebo in 40 subjects who
    reported having headaches repeatedly after consuming products containing
    aspartame. The incidence rate of headache after aspartame (35 percent) was
    not significantly different from that after placebo (45 percent) (P less
    than 0.50). No serious reactions were observed, and the incidence of
    symptoms other than headache following aspartame was also equivalent to
    that after placebo. No treatment-related effects were detected in vital
    signs, blood pressure, or plasma concentrations of cortisol, insulin,
    glucagon, histamine, epinephrine, or norepinephrine. Most of the subjects
    were well educated and overweight and had a family or personal history of
    allergic reactions. The subjects who had headaches had lower plasma
    concentrations of norepinephrine (P less than 0.0002) and epinephrine (P
    less than 0.02) just before the development of headache. We conclude that
    in this population, aspartame is no more likely to produce headache than
    placebo.

21. Maher TJ; Wurtman RJ.
      Possible neurologic effects of aspartame, a widely used food additive.
      Environmental Health Perspectives, 1987 Nov, 75:53-7.

Abstract: The artificial sweetener aspartame (L-aspartyl-L-phenylalanyl-methyl
    ester), is consumed, primarily in beverages, by a very large number of
    Americans, causing significant elevations in plasma and, probably, brain
    phenylalanine levels. Anecdotal reports suggest that some people suffer
    neurologic or behavioral reactions in association with aspartame
    consumption. Since phenylalanine can be neurotoxic and can affect the
    synthesis of inhibitory monoamine neurotransmitters, the phenylalanine in
    aspartame could conceiveably mediate neurologic effects. If mice are given
    aspartame in doses that elevate plasma phenylalanine levels more than those
    of tyrosine (which probably occurs after any aspartame dose in humans), the
    frequency of seizures following the administration of an epileptogenic
    drug, pentylenetetrazole, is enhanced. This effect is simulated by
    equimolar phenylalanine and blocked by concurrent administration of valine,
    which blocks phenylalanine's entry into the brain. Aspartame also
    potentiates the induction of seizures by inhaled fluorothyl or by
    electroconvulsive shock. Perhaps regulations concerning the sale of food
    additives should be modified to require the reporting of adverse reactions
    and the continuing conduct of mandated safety research.

22. Kruesi MJ; Rapoport JL; Cummings EM; Berg CJ; Ismond DR; Flament M; Yarrow
    M; Zahn-Waxler C.
      Effects of sugar and aspartame on aggression and activity in children.
      American Journal of Psychiatry, 1987 Nov, 144(11):1487-90.

Abstract: Habitual sugar consumption and behavior following challenge by sugar
    and aspartame were studied in 30 preschool boys. The 18 subjects whose
    parents considered them sugar reactive had more disruptive behavior
    problems at baseline than the other 12 subjects. Habitual sugar consumption
    correlated only with duration of aggression against property in alleged
    responders. Double-blind crossover challenges with aspartame, saccharin,
    sucrose, and glucose produced no significant effect on aggression or
    observers' ratings of behavior. Lower actometer counts followed the trials
    of aspartame, but the difference was not apparent to observers. It is
    unlikely that sugar and aspartame are clinically significant causes of
    disruptive behavior.

23. Alfin-Slater RB; Pi-Sunyer FX.
      Sugar and sugar substitutes. Comparisons and indications.
      Postgraduate Medicine, 1987 Aug, 82(2):46-50, 53-6.

Abstract: Public confusion and concern about the use of sugar and sugar
    substitutes are widespread. Physicians must be prepared to answer patients'
    inquiries about these substances. Some population groups should avoid
    certain sugar substitutes. In particular, pregnant women and young children
    should avoid saccharin, and phenylketonuric homozygous persons should avoid
    aspartame. In a varied, balanced diet, the use of aspartame and saccharin
    is one safe way for the general population to enjoy sweet foods with fewer
    calories and less cariogenic potential. Sugar substitutes may be helpful in
    dietary compliance for overweight and diabetic patients.

24. The safety of aspartame [letter].
      Jama, 1987 Jul 10, 258(2):205-6.

25. Stegink LD.
      The aspartame story: a model for the clinical testing of a food additive.
      American Journal of Clinical Nutrition, 1987 Jul, 46(1 Suppl):204-15.

Abstract: Toxicology is based on the premise that all compounds are toxic at
    some dose. Thus, it is not surprising that very large doses of aspartame
    (or its components--aspartate, phenylalanine, and methanol) produce
    deleterious effects in sensitive animal species. The critical question is
    whether aspartame ingestion is potentially harmful to humans at normal use
    and potential abuse levels. This paper reviews clinical studies testing the
    effects of various doses of aspartame upon blood levels of aspartate,
    phenylalanine, and methanol. These studies demonstrate that blood levels of
    these compounds are well below levels associated with adverse effects in
    sensitive animal species.

26. Dews PB.
      Summary report of an International Aspartame Workshop.
      Food and Chemical Toxicology, 1987 Jul, 25(7):549-52.

27. Zametkin AJ; Karoum F; Rapoport JL.
      Treatment of hyperactive children with D-phenylalanine.
      American Journal of Psychiatry, 1987 Jun, 144(6):792-4.

Abstract: Eleven hyperactive boys were treated for 2 weeks with D-phenylalanine
    (20 mg/kg per day) and for 2 weeks with placebo in a double-blind crossover
    study. Tests included parent and teacher behavior ratings, cognitive
    measures, and blood and urine measures of norepinephrine, amino acids, and
    trace amines. No significant improvement or deterioration in behavior and
    no side effects were noted, and only serum phenylalanine was increased by
    the active treatment phase. This provides reassurance about the toxicity of
    aspartame, a food additive that contains phenylalanine, but argues against
    precursor loading treatment of hyperactivity.

28. Freedman M.
      Consumption of aspartame by heterozygotes for phenylketonuria [letter].
      Journal of Pediatrics, 1987 Apr, 110(4):662-3.

29. Maher TJ.
      Natural food constituents and food additives: the pharmacologic
    connection.
      Journal of Allergy and Clinical Immunology, 1987 Mar, 79(3):413-22.


itory monoamine neurotransmitters, the phenylalanine in
    aspartame could conceiveably mediate neurologic effects. If mice are given
    aspartame in doses that elevate plasma phenylalanine levels more than those
    of tyrosine (which probably occurs after any aspartame dose in humans), the
    frequency of seizures following the administration of an epileptogenic
    drug, pentylenetetrazole, is enhanced. This effect is simulated by
    equimolar phenylalanine and blocked by concurrent administration of valine,
    which blocks phenylalanine's entry int