The Case for the Removal of the Ban on Tryptophan

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http://www.patrickholford.com/tryptophan/

 

The Case for the Removal of the Ban on Tryptophan supplements JoAnn Guest

Aug 03, 2003 11:02 PDT

 

THE CASE FOR THE REMOVAL OF THE BAN ON TRYPTOPHAN AS A FOOD SUPPLEMENT

A submission from the Institute for Optimum Nutrition Scientific

Committee on Tryptophan to the UK Food Standards Agency regarding the

removal of the ban on L-tryptophan food supplements specified in The

Tryptophan in Foods Regulations 1990 (Statutory Instrument 1990 No.

1728)

 

July 2002

 

Executive summary

Prior to the 1989/90 Eosinophilia Myalgia Syndrome (EMS) epidemic,

L-tryptophan was used extensively (by around 30 million consumers) with

very few cases of EMS or EMS-like symptoms ever reported (around 10).

After the removal of L-tryptophan from the market in 1990, isolated

idiopathic cases of EMS in individuals not taking L-tryptophan or 5HTP

continued, casting doubt on the relevance of pre-epidemic cases to

safety assessments of L-tryptophan.

 

Where L-tryptophan has been reintroduced, either as a POM (UK and

elsewhere) or an OTC food supplement (Belgium & Holland), considerable

vigilance and detailed surveillance have failed to record a single case

of EMS resulting from the supplementation of L-tryptophan.

 

Indeed, not one case of EMS has ever been traced to an uncontaminated

batch of L-tryptophan.

 

It is therefore asserted, and clear from the available evidence, that

the 1989/90 EMS epidemic was solely the result of L-tryptophan

containing a contaminant - 'peak E' - resulting from the production

processes at a single Japanese manufacturer, Showa Denko KK.

 

It is a misconception that L-tryptophan food supplements are still

banned in the US.

 

The continuing ban in the UK is clearly unwarranted, and this document

aims to provide the UK Food Standards Agency with the requested

'significant reassurances with regard to safety necessary if the

addition of Tryptophan to foods was to be permitted.'

 

A lifting of the UK ban is now, quite rightly, happening in the case of

Foods for a Particular Nutritional Use (PARNUTS), and should be extended

to OTC food supplements in the UK, as there is no good evidence to

support its continuing prohibition.

 

 

 

1.0 Introduction

Tryptophan is an essential amino acid used by the body in the

manufacture of other amino acids, niacin and the neurotransmitter

serotonin. It is the only essential amino acid not available OTC as a

food supplement in the UK.

 

The UK Food Standards Agency (FSA) view on Tryptophan at present is that

while uncertainty persists about the contamination problem and the exact

cause of EMS (which they assert also resulted from different batches of

Tryptophan than the one known to be contaminated) there is no good

reason to re-allow its free sale in the UK. The agency asserts, " The

continuing uncertainty means that significant reassurances with regard

to safety would be necessary if the addition of tryptophan to foods was

to be permitted. " 1

 

 

 

2.0 The need for tryptophan as a food supplement

 

2.1 Tryptophan is the least abundant amino acid in foods.

 

2 It has an unusual distribution in foods, and most dietary proteins are

deficient in this amino acid, so sub-clinical deficiency may be more

prevalent than is recognised.

 

A key role of L-tryptophan in the body is its conversion to the

neurotransmitter serotonin. Serotonin is associated with mood, sleep

patterns and dreaming.

 

It influences many physiological functions, including blood pressure,

digestion, body temperature and pain sensation.

 

Serotonin also affects mood and circadian rhythm.

 

2.2 Adequate levels of serotonin provide emotional and social stability,

while low levels of serotonin are associated with: depression; anxiety;

premenstrual syndrome (PMS); increased sexual drive; carbohydrate

cravings; sleep disturbances; increased sensitivity to pain; emotional

volatility, including violent behaviour against self and others;

obsessive thinking; alcohol and drug abuse; and suicide.

 

2.3 Research and clinical observations have identified specific times or

settings where serotonin is depleted and/or individual requirements may

be increased, such as during periods of growth, in sports people, in

those under stress, during winter, and in women, due to hormonal

influences on serotonin levels.

 

There is no good reason to deny individuals who may require more

Tryptophan than they can obtain in their diet access to over-the-counter

(OTC) L-tryptophan food supplements.

 

3.0 L-tryptophan was withdrawn in 1990

 

3.1 Tryptophan was implicated in a fatal 1989/90 outbreak of

Eosinophilia-Mayalgia Syndrome (EMS), a rare autoimmune disease marked

by severe muscle pain, spasms and weakness, swelling of the arms and

legs, numbness, fever and rashes.

 

In all, more than 1500 cases of EMS, including at least 37 deaths, were

reported to the US National Centres for Disease Control. On March 22,

1990, the FDA imposed an import alert prohibiting the importation of

manufactured L-tryptophan, except for special dietary purposes.

 

Because all of the L-tryptophan sold in the US at that time was

imported, the net effect of the recall and import alert was the removal

of L-tryptophan from the US market.

 

In the UK, The Tryptophan in Foods Regulations 1990 (Statutory

Instrument 1990 No. 1728) removed L-tryptophan food supplements from the

UK market. These actions were entirely appropriate until more was known

about why a previously safe food supplement was now causing these

reactions.

 

Ultimately, the evidence pointed squarely to major contamination in a

new processing method developed by one Japanese manufacturer, Showa

Denko KK.

 

 

 

4.0 Incidence of EMS prior to the epidemic of 1989/90

 

 

4.1 Prior to the epidemic of 1989/90, Tryptophan had been supplemented

for more than 30 years by some 30 million people in the US and around

the world.

 

3 Given that just 8-12 cases of EMS-like symptoms were reported during

this time it is inappropriate to deem L-tryptophan unsafe on the basis

of this very small number of cases,

 

most of which were 5HTP not Tryptophan,

 

and none of which were actually confirmed as EMS, but rather individual

symptoms that are also present in EMS.

 

4.2 Cases of EMS or EMS-like symptoms have been noted in individuals who

have not used L-tryptophan food supplements, demonstrating that many

cases of EMS or EMS-like symptoms are idiopathic and have nothing to do

with Tryptophan.

 

A nationwide survey in Canada in 1992/3 found 19 definite and 25

possible EMS cases in people not using L-tryptophan or

5-Hydroxy-L-tryptophan, and the author asserted that " it's continuing

occurrence in Canada [after the withdrawal] brings causal

interpretations of earlier studies into question. " 4

 

 

 

5.0 No EMS cases where L-tryptophan has been reintroduced since the

epidemic

 

5.1 Since 1994, L-tryptophan has been sold in the UK as a

prescription-only-medicine (POM), manufactured by Merck Pharmaceuticals

and sold under the name 'Optimax'.

 

Over these eight years Merck reports many thousands of prescriptions of

Optimax - 500mg tablets taken in doses of 2-4 tablets, 3 times daily, ie

3-6g/day. Merck is required to monitor each patient (around 700 at any

one time) every 3 to 6 months to ensure they are having no adverse

reactions,5 and this extensive surveillance program has not recorded a

single case of EMS resulting from this level of tryptophan during this

time.6 There was one case of EMS reported by a doctor to Merck and the

MCA, though this was found to be an erroneous diagnosis. Side-effects of

sleepiness or nausea are infrequently reported.

 

5.2 We understand that other European countries, similarly to the UK -

including Italy, Spain, France and Germany - also make L-tryptophan

available as a POM, and no cases of EMS have been reported. Strict

guidelines are used to ensure the purity and safety of L-tryptophan.7

 

5.3 L-tryptophan is sold freely as a food supplement OTC in Belgium and

Holland, having recalled it in 1990 and reintroduced it when it became

apparent that the problem was one of contamination from a single

manufacturer.

 

No cases of Tryptophan-implicated EMS have been reported in either

country since this re-introduction.

 

It is freely sold OTC as a food supplement - 500mg per capsule to a

maximum of 6g per day.

 

5.4 L-tryptophan as an OTC food supplement is not banned in the United

States.

The commonly held view that it is banned in the US is a misconception,

reinforced by the continuing import alert on L-tryptophan being shipped

into the US.

 

The US Dietary Supplement Health and Education Act (DSHEA) of 1994

specifies that a dietary ingredient may be marketed as long as it does

not present a significant or unreasonable risk of harm, or the FDA has

instituted administrative proceedings to ban the ingredient. In regards

to the latter, the FDA has never attempted to ban L-tryptophan, nor has

it taken any regulatory action against a company that is marketing

L-tryptophan dietary supplements in the United States since the

enactment of DSHEA.

 

This is confirmed by the FDA Information Paper on L-tryptophan and

5-hydroxy-L-tryptophan, February 2001:

 

" Although FDA continues to enunciate its concern about the safety of

dietary supplements containing L-tryptophan and related compounds such

as L-5-hydroxytryptophan, this does not mean that FDA prohibits the

marketing of dietary supplements that contain L-tryptophan.

 

Under the Food, Drug and Cosmetic Act (the Act), as amended by the

Dietary Supplement Health and Education Act of 1994 (DSHEA), the

manufacturer is responsible for ensuring that its products are safe.

 

A firm is not required to obtain premarket review or approval from the

FDA of its products before marketing them as dietary supplements.

Moreover, a firm is not required to submit scientific evidence to FDA of

the safety of its products or ingredients.

 

While we are unaware of conclusive scientific data that would establish

that a dietary supplement L-tryptophan would be safe, if a firm has

information that it believes establishes that a product containing

L-tryptophan is safe within the meaning of the Act, it could market such

a product as a dietary supplement. The burden and responsibility for

assuring that such a product is not adulterated under the Act is with

the firm and not FDA. " 8

 

 

 

6.0 Confirmation that contamination of Showa Denko's L-tryptophan was

the only cause of the 1989/90 EMS epidemic.

 

6.1 Not one case of EMS has ever been traced to use of L-tryptophan

uncontaminated with peak E.9

 

6.2 A reappraisal of the evidence at a national symposium in Washington

DC, published in the Journal of Rheumatology in 1996, confirmed that the

problem was not with L-tryptophan itself, but due to contamination

resulting from changes the company made to its fermentation and

filtration process.10

 

Between December 1988 and June 1989, a number of alterations in

L-tryptophan production were instituted by Showa Denko.

 

These included the use of a new bacterial strain (strain V) of bacillus

amyloliquefaciens that had been genetically manipulated to produce

L-tryptophan with a high yield, bypass of the reverse-osmosis filtration

step, and reduction in the amount of powdered activated carbon used for

purification.

 

Multivariate analysis of the manufacturing conditions showed a

significant correlation between the reduction of the amount of powdered

activated carbon and the development of the EMS.11

 

6.3 On May 25, 2000, Gerald J Gleich, MD with the Allergic Diseases

Research Laboratory, Departments of Immunology and Medicine, Mayo Clinic

and Foundation, and a leading expert on this issue, stated

 

" Tryptophan itself clearly is not the cause of EMS in that individuals

who consumed product from companies other than Showa Denko did not

develop EMS.

 

The evidence points to Showa Denko product as the culprit and to the

contaminants as the cause. " 12

 

6.4 The UK FSA toxicology division asserts that 3-5% of the EMS cases

were not associated with the product of the manufacturer concerned.13

This implies that the products were known to be from other

manufacturers, though this is not the case. The FSA cites the US FDA as

the source for this data.

 

6.4.1 The US FDA Office of Health Affairs 'Dear Colleague' letter (Sept

3, 1992)14 cited by the UK FSA states that " more than 95% of the cases

of EMS were traced to one company, Showa Denko....No other company's

product has been definitely linked to EMS, in some instances the source

could not be fully ascertained " .

 

" However " , it continues, 3 observations " have caused the FDA not to

eliminate other brands of Tryptophan, or Tryptophan itself, as causal or

contributing to the development of EMS " . These 3 observations are

addressed in turn.

 

" 1. 3-5% of EMS cases have not been definitively linked to Showa Denko's

product. "

 

6.4.2 The 3% figure represents a single case of EMS in one study of 30

cases (ie 3%) in which the Tryptophan used by this patient could not be

traced to Showa Denko.15 Despite this, the authors concluded " The

outbreak of EMS in 1989 resulted from the ingestion of a chemical

constituent (peak E) that was associated with specific

tryptophan-manufacturing conditions at one company. "

 

The 5% comes from a statement in the FDA 'Dear Colleague' letter

observing that in 'multiple epidemiologic studies, more than 95% of the

cases of EMS were traced to Showa Denko'.

 

The remaining cases were not able to be traced to any specific

manufacturer, though as Showa Denko supplied 50-60 per cent of the

tryptophan on the US market it's quite likely that these cases did

involve Showa Denko products, though this could not be confirmed by the

physician involved.

 

" 2. At least eight cases with EMS-like symptoms have been associated

with 5-hydroxytryptophan, a compound related to tryptophan, but produced

from botanical sources. "

 

6.4.3 This assertion is irrelevant. It refers to 'EMS-like symptoms',

not EMS. It refers to 5-hydroxytryptophan, not L-tryptophan.

 

And the links between 5HTP and these cases is by no means clear (see

sections 4.1, 4.2).

 

" 3. Surveillance for EMS has demonstrated that 'non-epidemic' cases were

occurring prior to the epidemic in 1989/90. "

 

6.4.4 It is also the case that idiopathic non-epidemic cases have

continued since the ban, in people who had not used L-tryptophan or

5-hydroxy-L-tryptophan food supplements. See section 4.0. In light of

these post-epidemic cases not associated with L-tryptophan or 5HTP,

these pre-epidemic cases may have had nothing to do with the consumption

of L-tryptophan or 5HTP by these individuals either, and certainly don't

constitute evidence against L-tryptophan's safety.

 

6.5 The UK FSA cites four references pertaining to " Cases not linked to

Showa Denko " 16 These references are considered in turn:

 

6.5.1 Belongia EA et al, 1990, NEJM 323(6), p357-65

 

The authors conclude " The outbreak of EMS in 1989 resulted from the

ingestion of a chemical constituent [peak E] that was associated with

specific Tryptophan-manufacturing conditions at one company " , and thus

this paper does not support the assertion that the problem was anything

other than one of contamination.

 

6.5.2 Hamilton, 1991, Ann Rheum Dis 50, p55-6

 

The manufacturer is stated to be Energen of Norwalk, California, USA.

Joe Bensler of Energen was involved with the recall and dealt with the

FDA inspectors at the time. He says " Although we were mentioned in

several litigations, we were absolved in each case.

 

Where a plaintiff had a bottle of our tryptophan in their medicine

cabinet, they also apparently had other tryptophan products.

 

We have never used Showa Denko material in our products and the test

made by the lawyers verified this fact. The Showa Denko material was off

color and, although quite cheap, was unsatisfactory from our

standpoint. " (personal communications 10.07.02 Joseph Bensler

<ener-

 

6.5.3 Kamb ML et al., 1992, JAMA 267(1), P77-82.

 

This study investigated the links between EMS incidence at one

psychiatric practice in South Carolina and patients using L-tryptophan

during 1989. Four unspecified brands were implicated, the vast majority

involving 'Brand A' (45 of 47 definite cases), though Brands B, C & D

were also implicated in 2 definite and 32 possible cases.

 

Just six manufacturers produced powdered bulk L-tyrptophan at the time,

which is then packaged into hundreds of brands.

 

17 At the outbreak of the epidemic, almost 200 different brands of

L-tryptophan-containing products were in use by individuals who

developed the syndrome.

18 Because Showa Denko supplied 50-60% of the entire US L-tryptophan

market at that time, it is entirely possible that these unspecified

brands also contained Showa Denko product or the patients involved had

previously taken contaminated Showa Denko L-tryptophan.

 

6.5.4 Roufs, 1992, J Am Diet Assoc 92, p844-50.

 

Roufs' (1992) review traces implicated L-tryptophan containing products

to one raw-material manufacturer.

 

 

 

6.6 Young SN, in Richardson MA, 1990, 'Amino Acids in Psychiatric

Disease', Washington DC, American Psychiatric Press, p51-75; MMWR (1990)

39, p326-7; Cited in Roufs, 1992, J Am Diet Assoc 92, p844-50.

 

This review of research on Tryptophan up to 1989 concludes that 'The

side effects of Tryptophan are mild.

 

The ones most commonly observed are nausea, dizziness, headache and

drowsiness. In many of the clinical studies no side effects were

reported, even when doses were as high as 9.6g/day and 20g/day. In

double-blind, placebo-controlled studies, which included a comparison of

the side effects of Tryptophan and placebo, no significant differences

were seen.' No case of EMS is reported.

 

 

 

6.7 A review of the latest research on Tryptophan published in 1996

observed " It seems also noteworthy that in a large number of patients

treated over a long period of time by using uncontaminated

L-tryptophan... EMS was never provoked.

This result seems to represent a further support to the hypothesis that

EMS is caused by contaminated Tryptophan, as stressed by other

authors: " 19

 

Mayeno AN et al, 1992, Mayo Cli Proc 67(12), p1134.

 

Silver RM, 1992, Curr Opin Rheumatol 4(6), p851.

 

Varga J et al, 1993, J Invest Dermatol 100(1): 97S.

 

Adachi Jet al, 1993, Arch Toxicol 67(4), p284.

 

Kurihara N et al., 1993, Toxicol Lett 66(3), p231.

 

Philen RM et al., 1993, Am J Epidemiol 138(3), p154.

 

Taylor R & McNeil JJ, 1993, Med J Aust 158(1), p51.

 

Donofrio PD et al., 1992, Muscle nerve 15(7), p796.

 

 

 

6.8 A review conducted by scientists at the Centres for Disease Control

(CDC) led by Edwin Kilbourne examined all of the available evidence in

1996.

 

They concluded that the cause of the EMS epidemic could be traced back

to batches of L-tryptophan that were produced between October 1988 and

July 1989 by Showa Denko, who supplied between 50 and 60 percent of all

the L-tryptophan sold in the US.20

 

6.9 A similar review of cases in Germany reported that all 105 cases

recorded were associated with formulators that had used raw materials

from Showa Denko, and the study

 

" supports the patho-physiologic role of a contaminant in L-tryptophan in

the occurrence of cases of EMS in Germany. " 21

 

6.10 That a contaminant was the causative agent is supported by a report

of a patient who developed manifestations of acute EMS on two separate

occasions following ingestion of L-tryptophan originating from Showa

Denko, but who tolerated L-tryptophan-containing preparations produced

by a non-implicated manufacturer.22

 

 

 

7 In the UK, L-tryptophan is now being brought back in foods for

particular nutritional uses (PARNUTS)

7.1 A draft proposal from the FSA Food Labelling and Standards Division

responding to EU developments, is expected to come into action in June

2002, that will allow Tryptophan to be added to Foods for Particular

Nutritional Uses ('PNU foods', sometimes referred to as PARNUTS) -

 

specifically slimming foods, sports foods, and foods for diabetics, and

it's already allowed in infant and baby foods.

 

7.2 This is entirely appropriate and demonstrates a European

acknowledgement of the necessity of L-tryptophan and the absence of any

over-riding safety concerns.

The FSA asserts that this reintroduction is sufficiently safeguarded -

only authorised products are allowed to use it and there is a

notification arrangement of any adverse reactions - if there are any

problems it will be easy to trace and/or recall.

 

Further, if a manufacturer submits an application to market a food under

this legislation, they are required to convince the FSA sufficiently of

the safety of the Tryptophan they're using.

 

8 What objections remain to the return of L-tryptophan as an OTC food

supplement in the UK?

 

8.1 Future contamination concerns

Adequate controls are entirely feasible, and indeed are already required

in pharmaceutical grade L-tryptophan, L-trytpophan food supplement

manufacturers, and by manufacturers of PARNUTS foods containing

L-tryptophan.

According to one such manufacturer, the thorough testing of

L-Tryptophan for purity should include tests for EBT (peak E),

3-phenylamino-L-alanine, bacitracin, organic volatile impurities, heavy

metals, and pyrogens.23

 

8.2 Tracability concerns

As Merck pharmaceuticals have been marketing L-tryptophan as Optimax for

the past 8 years in the UK with not one single resulting case of EMS

emerging from their extensive surveillance program, and L-tryptophan

food supplements have been freely sold OTC in Holland and Belgium for at

least 10 years with also no reported cases of EMS, it would not appear

necessary to continue this degree of vigilance. If, however, full

tracability was deemed necessary, this is not beyond the capabilities of

the food supplement industry. For example it could be made available by

mail-order only, with records kept as to who was using it, so that

communications of changes to the regulatory situation, safety concerns,

or monitoring of effects could be easily conducted if need be. This

committee does not consider this necessary, though it is possible if the

FSA disagreed.

 

The purity and tracability requirements upon the newly re-allowed

PARNUTS foods containing L-tryptophan may be equally applicable to the

reintroduction on L-tryptophan food supplements.

 

9 Conclusion

It is widely agreed that L-tryptophan itself was not implicated in the

1989/90 EMS epidemic, that the ban was appropriate at the time until the

cause was known, but is wholly inappropriate now.

 

The problem was solely due to contamination of SD products in 1989 and

1990, and the " significant reassurances with regard to

safety...necessary [for] the addition of foods to be permitted " have

evidently been provided for it to be allowed in PARNUTS foods, and we

hope this document allows the further lifting of this unwarranted ban, a

ban that does not persist even in the US where the vast majority of

cases and deaths occurred.

 

We consider that the availability of L-tryptophan in OTC food

supplements is very much in the public interest to help those whose

needs may be higher than average.

 

This includes those under prolonged stress, women with post-menopausal

oestrogen deficiency and those prone to Seasonal Affective Disorder, all

conditions that are known to deplete serotonin and increase L-tryptophan

needs.

 

The benefit for these people significantly outweighs any perceived risk

which we consider to be non-existent.

 

-------------------

 

Scientific Advisory Committee

 

Patrick Holford BSc DipION, founder of the Institute for Optimum

Nutrition

 

Shane Heaton BSc DipION, clinical nutritionist

 

Dr Hyla Cass MD, assistant clinical professor at UCLA School of Medicine

 

Professor John Henry FRCP, FFAEM, clinical toxicologist at Imperial

College School of Medicine

 

Professor Arnold Beckett OBE, DSc, PhD, FRPharmS, medicinal chemist and

clinical pharmacologist

 

Professor Philip Cowen, MD, FRCPsych, professor of psychopharmacology

 

 

 

1 Letter from Cath Mulholland, FSA Toxicology division, 18th Dec 2001

 

2 Braverman ER et al., 1997, 'The Healing Nutrients Within', Keats

Publishers, USA.

 

3 Murray M, 1998, '5HTP', Bantam Books, US

 

4 Spitzer WO, 1995, 'Continuing occurrence of eosinophilia-myalgia

syndrome in Canada', Brit J Rheum 34, p246-51.

 

5 See Merck Pharmaceuticals website

http://emc.vhn.net/emc/assets/c/html/displaydoc.asp?documentid=1155 for

details of prescription and surveillance requirements

 

6 The Optimax Information and Clinical Support (OPTICS) Unit (0845

7626902), Merck Pharmaceuticals.

 

7 Steinhart H et al., 1996, 'Synthesis and analysis of contaminants in

EMS-related tryptophan', Experimental Biology and Medicine 398, p667-75.

 

8 http://www.cfsan.fda.gov/~dms/ds-tryp1.html

 

9Nicolodi M & Sicuteri F, 1996, 'Eosinophilia-myalgia syndrome: The role

of contaminants, the role of serotonergic setup', Experimental Biology

and Medicine 398, p351-7.

 

10 " Proceedings: Eosinophilia Myalgia Syndrome: Review and Reappraisal

of Clinical, Epidemiologic and Animal Studies Symposium, Washington DC,

December 7-8, 1994 " , J Rheum 46 suppl, 1996, 1-110.

 

11 Varga J et al., 1992, 'The cause and pathogenesis of the

Eosinophilia-Myalgia Syndrome', J Am Coll Phys 116(2), p140-7.

 

12 www.nemsn.org/what%20caused%20EMS.htm

 

13Letter from Cath Mulholland, FSA Toxicology division, 18th Dec 2001

 

14 www.cfsan.fda.gov/~dms/ds-ltr3.html

 

15 Belongia EA et al., 1990, 'An investigation of the cause of the

eosinophilia-myalgia syndrome associated with tryptophan use', N Eng J

Med 323(6), p357-65.

 

16 Email from Cath Mulholland, subject " Re: tryptophan/EMS " , June 12,

2002.

 

17 Slutsker L et al., 1990, 'EMS associated with exposure to tryptophan

from a single manufacturer', JAMA 264, P213-7.

 

18 Varga J et al., 1992, 'The cause and pathogenesis of the

Eosinophilia-Myalgia Syndrome', J Am Coll Phys 116(2), p140-7.

 

19 Nicolodi M & Sicuteri F, 1996, in Graziella Allegri Filippini et al.,

'Recent Advances in Tryptophan Research', Plenum press, New York.

 

20 Kilbourne EM et al., 1996, 'Tryptophan produced by Showa Denko and

epidemic eosinophilia-myalgia syndrome', J Rheum 46, p81-88

 

21 Carr L et al., 1994, 'EMS in Germany: An Epidemiologic Review " , Mayo

Clin Proc 69, p620-5.

 

22 Goronzy JJ & Weyand CM, 1990, 'Eosinophilia, myopathy, and neuropathy

in a patient with repeated use of L-tryptophan', Klin Wochenschr 68,

p1757-63.

 

23 Bios, manufacturer of pharmaceutical grade L-Tryptophan- see

www.biochemicals.com/faqs.php3

 

 

http://www.patrickholford.com/tryptophan/

 

 

JoAnn Guest

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