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The Role Of Dıetary Tryptophan Intake In Fıbromyalgıa Syndrome

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---Beslenme ve Diyet Dergisi / J N u i r and Diet 32(l):61-65/2003

THE ROLE OF DIETARY TRYPTOPHAN INTAKE IN

FIBROMYALGIA SYNDROME

- Dr. Hakan GENÇ*, Dr. Meryem SARAÇOĞLU*, Dr. Burcu DUYUR*, Dr. H. Rana ERDEM*—1

A B S T R A C T

Fibrom yalgia Syndrom e (FS) is a common disea- se characterized by diffuse, w idespread pain and m ultiple tender points. Syndrome was sııbclassifı- ed as p r im a ıy fibrom ya lg ia (PFS) and secondaıy fib ro m yalgia (SFS). The a im o f this study was to e v a lu a te the role o f d ieta ry tryptophan in FS. Twenty fe m a le p a tie n ts w ith PFS, 20 with SFS and 20 fe m a le Controls, m atched by age and body m a ss index, p a r tic ip a te d in this study. D ietary tryptophan intakes o f the F S and control subjects were assessed with "total nutrition sc o re ” (TNS) prepared f o r this study. Average daily consumpti- on o f tıyptophan (ADCT) values were also calcu- lated b ased on this scoring system. A signifıcant difference w as obsen>ed between TNS and A D C T values o f F S p a tien ts and control subjects. TNS and AD CTs were signifıcantly lo\ver in botlı PFS and S F S groups. A s a result, tryptophan rich diet can be recom m ended to these p atients as a p a rt o f treatm ent regimen.

Key yvords: Fibromyalgia, diet, tryptophan Ö Z E T

F ibrom iyalji sendrom u (FS) diffüz, yaygın ağrı ve çok sayıda hassas noktalarla karakterize, sık gözlenen bir hastalıktır. Sendrom p rim e r F S ve seko n der F S olarak a lt gruplara ayrılmaktadır. Bu çalışm an ın am acı d iyet triptofan içeriğinin F S ’daki rolünü araştırm aktır. Yaşları ve beden kitle indeksleri açısından eşleştirilmiş 20 primer, 20 sekonder kadın F S hastası ve 20 kadın kontrol birey çalışm aya alınmıştır. Fibrom iyaljik hasta­ * M in is tr y o f H e a lth , A n k a ra E d u c a tio n a n d R e s e a r c h H o sp ital

2 n d D e p a r tm e n t o f P h y s ic a l M e d ic in e a n d R e h a b ilita tio n , A n k a r a - T U R K E Y

lar ve kontrol bireylerinin diyetlerinin triptofan i- çerikleri, bu çalışma için hazırlanmış olan “total beslenm e s k o r u ” (TBS) ile değerlendirilm iştir. Ortalama günlük triptofan alımları (OGTA) yine bu skorlama sistemi baz alınarak hesaplanmıştır. F S hastası ve kontrol bireyleri arasında TBS ve OGTA açısından anlamlı fa rk lılık gözlenmiştir. TBS ve OGTA prim er ve sekonder F S hastaların­ da kontrol bireylerine oranla belirgin olarak dü­ şük bulunmuştur. Sonuç olarak F S hastalarına, tedavi rejiminin bir parçası olarak triptofandan zengin diyet önerilmesinin yararlı olacağı belir­ lenmiştir.

Anahtar kelimeler: Fibromiyalji, triptofan, diyet

IN T R O D U C T IO N

Fibromyalgia Syndrome (FS) is a common disea- se characterised by widespread m usculosceletal pain and tendemess on palpation o f spesific ten- dinomusculoskeletal sites, called “tender points . FS was subclassifıed as prim ary fibrom yalgia (PFS) and secondary fibromyalgia (SFS). Patient with prim ary fibromyalgia have diffuse, wides- pread pain and multiple tender points in the ab- sence o f underlying, cau sativ e, or sig n ifıcan t concomitant condition. In the presence o f these conditions it is classifıed as secondary fibromyal­ gia. Studies have shown that the clinical charac- teristics o f FS in these patients are not signifı- cantly different from those o f primary fibromyal­ gia (1,2).

The most common characteristics o f the syndro­ me are nonrestorative sleep, tensiontype headac- he, subjective soft tissue swelling, m om ing stiff- ness and paresthesias. In addition anxiety,

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dep-62 G E N Ç H., SA R A Ç O Ğ L U M ., D U Y U R B ., E R D E M R.

ression, dysm enorrhea, irritable bowel syndrome, S icca sy n d ro m e, R a y n a u d ’s p henom enon and w om an urethral syndrom e m ay be seen in fıb- ro m y alg ia. C hronic fatique syndrom e, restless legs syndrom e, hypermobility, noctum al myoclo- nus, psychogenic pain are conditions sim ilar or related to fıbromyalgia (1,3).

One o f the most important pathophysiologic the- ories o f FS is combination o f Central and perip- heral m echanism s based on “central neurohormo- n al d y s fu n c tio n ” . D e c re a se d se ro to n in level w h ich m ay be trig gered by nonspesifıc stress from traum a, viral infection or mental stress is thought to be a causative factor (3).

The aim o f this study was to evaluate the role of dietary tryptophan which is a precursor o f seroto­ nin in FS. We also assessed the most common characteristics o f FS in our patients.

MATERIALS AND METHODS

Tvventy female patients vvith PFS, 20 with SFS (due to type2 diabetes m ellitus (DM )) and 20 woman Controls, matched by age and body mass index (BMI), participated in the study. Ali pati­ ents fulfilled the classifıcation criteria for fib- rom y alg ia pro posed by A m erican C o llege o f Rheumatology (ACR) (4). First, demographic fe- atures o f the patients were noted and clinical cha­ racteristics o f FS such as nonrestorative sleep, tensiontype headache, m om ing stiffness, subjec- tive sofit tissue swelling and paresthesias were as- ked. Then ali patients undenvent detailed loco- motor and systemic examination.

Tender point (TP) and control point (CP) exami- nations w ere perform ed w ith F is c h e r’s tissue compliancemeter which may be used as a pressu- re pain algom eter (5-7). Eighteen TP and 4 CP (mid forearm and thumbnail on the left and right sides o f the body) (8) were evaluated respecti- vely. Compliancemeter was applied to these spe- sifıc points and the amount o f pressure causing pain (pain pressure treshold PPT) were recorded as kg/cm 2 . Points that vvere painful w ith less than 4 kg/cm2 pressure vvere accepted as tender

points. Severity o f fıb ro m y a lg ia w as a sse sse d vvith total myalgic score (TM S) and control point score (CPS). The sum o f the PPTs o f 22 points (1 8 T P a n d 4 C P ) w e re c a l c u l a t e d a s T M S (kg/cm2) and the sum o f the PPTs o f the control points were recorded as CPS (kg/cm 2) (6,7). We used “total nutrition score (T N S)” , prepared for th is study, fo r th e a s s e s s m e n t o f d ie ta ry tryptophan intakes o f the FS and control subjects. Tryptophan rich fo od in tak e (an im al p ro te in s; meat, egg, offal, m ilk, cheese, vegetable proteins; dry beans, chickpeas, lentils, oily seeds; sesam - me, black cumin, sunflow er seed, pum pkin seed, almond, walnut, peanut, flour; bread and choco- late) (9) was scored 0 to 4 according to consum p- tion frequency o f each food (0: none or rare, 1: once a mounth, 2: once a w eek, 3: m ore than ön­ ce a week, 4: everyday; at least for one m eal). The sum o f the scores w ere calculated as TN S. Average daily consum ption o f tryptophan values (ADCT) o f FS patients and control subjects also calculated according to co n su m p tio n freq uen cy and am ount o f each food based on this scoring system. The am ount o f tryptophan w hich w as ta- ken with food for 30 days w as calculated and di- vided to 30. Final value w as recorded as A D C T (g/day).

SPSS 10.0 for w indow s w as used for statistical analysis. C hisquare an d onevvay A N O V A tests vvere selected for analysis and po sth o c analysis were perform ed vvith B o n ferro n i test. P values less than 0.05 were accepted as significant.

RESULTS

The m ean age o f the 20 fem ales w ith PFS w as 51.25 ± 8.82 years (betw een 34-70), 20 fem ales with SFS vvas 55.65 ± 11.06 years (betvveen 36- 78) and 20 female control w as 51.40 ± 7.68 years (betvveen 40-65). D em o g rap h ic fea tu re s o f fıb- rom yalgia and control groups and m ean disease durations are given in Table 1. T here w as no sta- tistic a lly sig n ific a n t d iffe re n c e betvveen th e 3 groups vvith respect to m ean age, height, vveight, body m ass in d ex a n d d u ra tio n o f th e d is e a s e (p>0.05). The m ean DM duration vvas 9.8 ± 5.27

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T h e R o le o f D ietary T ry p to p h a n in ta k e in F ib ro m y alg ia S y ndrom e 63

y ears and m ean fasting blood glucose level was 193.5 ± 63.42 m g/dL in SFS group.

P a tie n ts w ith PFS w ere not differen t than SFS g roup in any o f clinical param eters (p>0.05). N o n rc s to ra tiv e sleep, su b jective jo in t svvelling, m o rn in g stiffn e ss and p a re sth esias w ere found m o re in P F S a n d SF S g ro u p s th a n C ontrols (p< 0.001).

N u m b e r o f t e n d e r p o in ts w a s f o u n d h ig h e r (p < 0 .0 0 1 , p < 0 .0 1 ) and total m yalgic score and co n tro l point scores w ere low er (p<0.001) in PFS and SFS g roup s than in control subjects (Table

2).

A s ig n ifıc a n t d ifferen ce w as o bserved betw een to ta l n u tritio n sc o re s (T N S ) and av erage daily co n su m p tio n o f tryptophan (A D C T) values o f FS patien ts an d control subjects. TN S was found to be s ig n ific a n tly lo w e r in PFS and SFS groups (p< 0 .05 , p<0.01 respectively) than control group. A D C T w as fo u n d to be sig n ifican tly low er in PFS and SFS g roups too (p<0.05, p<0.01 respec­ tively). M ean T N S and A D TC values and statis- tical a n a ly sis are show n in Table 3.

D IS C U S S IO N

P a th o p h y sio lo g ic th eories o f FS can be divided into the three groups b ased on the follow ing pro- p o s e d m e c h a n is m s . (1) P rim arily Central: This th e o r y b a s e d on c o m o rb id ity o f fib ro m y a lg ia w ith m a jö r dep ressio n , m igraine, irritable bowel s y n d ro m e , c h ro n ic fatiq u e syndrom e, panic di- s o rd e rs an d the a lp h a e le c tro e n c ep h a lo g ra p h ic sle e p an o m aly . (2) C o m b in atio n o f Central and p e rip h e ra l m ech an ism s based on “central neuro- h o n n o n a l d y sfu n c tio n ” . D ecreased serotonin le­ vel w h ic h m ay be triggered by nonspesifıc stress fro m traum a, viral infection or m ental stress is o- ne o f the po ssible m echanism s. (3) Prim arily pe­ ripheral: T h is theory focused on localised ische- m ia due to distu rb ed m icrocirculation that causes m u sc le pain. To explain w idespread pain at rest, c h a ra c te ristic o f FS, this theory invokes disturbed p a in m o d u la tio n in the cen tral nerv o us system

(CNS) (3).

One o f the A C R criterion for the diagnosis o f FS is the existence o f “sensitive points”. W hile for- m er data indicated pain only in these described points, recent studies have shown an increase in the sensitivity throughout the body (10). M oreo- ver, it is stated in the recent studies that a central hyperexcitability exists in FS patients and as a consequance o f this, the afferent input originated from periphery is am plifıed and continued by the central nervous system (11-13).

Tryptophan, which is an amino acid and a precur- sor o f serotonin, not only inhibits the descending pain pathw ays, but also is an im portant neurot- ransm itter in stage 4 sleep. D ecrease in restorati- ve nonREM sleep, occurence o f somatic com pla- ints, depression and an increase in the perceived pain ensues as a consequence o f its decrease in the brain. Decreased serotonin level is one o f the most studied m echanism s in the etiopathogenesis o f fibromyalgia (13,14). 5 Hydroxy-L-tryptophan is used per oral in the treatment o f patients w ith fib ro m y a lg ia and is rep o rted to have su c ce ss (15).

A num ber o f studies have reported the effects o f diet on the symptom s o f rheum atic disease, but alm ost ali have dealt with rheumatoid arthrıtıs, so very little inform ation on fibrom yalgia is avai- lable (16,17). K aartinen et al.(17), assessed the effect o f uncooked vegan diet on symptoms in 18 FS patients. They concluded that vegan diet had benefıcial effects on fibrom yalgia symptom s. Vi­ tamin B6 plays a role in the synthesis o f seroto­ nin from try p to p h an . T ry p to p h a n m e ta b o lism was altered, with urinary excretions o f xanthure- nic acid after tryptophan loading. Pyridoxine rep- letion corrected ali o f the ab norm alities noted. Vitamin B6 in natural foods w as as available as crystalline pyridoxine (18). Futher studies w ere n ecessary ab o u t this issue. M ark u s et al. also show ed the effects o f w hey p ro tein on plasm a tryptophan levels. They reported that w hey prote­ in rich in ? la c ta lb u m in in c re a se d the ıa tio o f plasm a tryptophan to the sum o f other large

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neut-Table 1. D em ographic featu res o f FS and control groups and mean disease dıırations

6 4 G E N Ç H., S A R A Ç O Ğ L U M ., D U Y U R B., E R D E M R.

Age (year) H eight (m) W eight (kg) BMI (kg/m 2) D uration o f FS(year)

PFS 51.25±8.82 1.60±0.06 72.05±10.71 28.09±4.97 4 .0 0 İ2 .7 3

SFS (Type-2 DM) 55.65±11.06 1.56±0.07 73.55±10.87 30.1 2 i4 .4 3 4 .4 5 İ2 .3 7

Control 5 1.40±7.68 1.58±0.05 7 5 .5 0 il0 .6 9 30.00±4.39

P >0.05 >0.05 >0.05 >0.05 >0.05

FS: Fibrom yalgia, PFS: Prim ary Fibrom yalgia, SFS: Secondary Fibrom yalgia, DM : D iabetes M ellitus, BM I: Body Mass Index

Table 2. Clinical featu res o f prim ary, secondary F S and control groups.

P rim a ry FS S eco n d ary FS P P rim a ry FS C o n tro l P S e c o n d ary FS C o n tro l P (n:20) (% ) (n:20) (% ) (n:20) (% ) (n:20) (% ) (n :2 0 ) (% ) (n :2 0 ) (% ) NRS 16 (80) 18 (90) >0.05 16 (80) 6 (30) <0.001 18 (90) 6 (30) <0.001 SJS 19 (95) 15 (75) >0.05 19 (95) 9 (45) <0.001 15 (75) 9 (45) <0.05 MS 18 (90) 18 (90) >0.05 18 (90) 7 (35) <0.001 18 (90) 7 (35) <0.001 Paresthesia 15 (75) 16 (80) >0.05 15 (75) 5 (25) <0.001 16 (80) 5 (25) <0.001 Headache 18 (80) 18 (90) >0.05 18 (80) 17 (85) >0.05 18 (90) 17 (85) >0.05 NTP 14.70±2.27 14.65±1.87 >0.05 14.70±2.27 4.75±2.79 <0.001 14.65±1.87 4 .7 5 i2 .7 9 <0.01 TMS (kg/cm 2) 71.50±4.53 70.15±4.75 >0.05 71.50±4.53 102.30±4.34 <0.001 7 0 .1 5 i4 .7 5 1 0 2 .3 0 i4 .3 4 <0.001 CPS (kg/cm*) 14.78±2.60 14.93±2.14 >0.05 14.78±2.60 23.77±3.26 <0.001 1 4 .93i2.14 2 3 .7 7 i3 .2 6 <0.05

FS: F ıb ro m y alg ia, N R S: N o n -R esto rativ e Sleep, SJS: S u b jectiv e Jo in t Svvelling, M S: M o m in g StifTness, N T P : N u m b e r o f T e n d e r P o in ts , T M S : T otal M yalgic S core, C PS: C o n tro l P o in t S core,

Table 3. Total nutrition scores (TNS) and average daily consumption o f tryptophan (ADCT) values o f p rim a ry fibrom yalgia (PFS), secondary fıbrom yalgia (SFS) patients and control group.

P rim ary FS Secondary FS P P rim a ry FS C o n tro l P S e c o n d a ry FS C o n tro l P

(n:20) (n:20) (n:20) (n:20) (n :2 0 ) (n :2 0 )

TNS 15.40±2.95 ADTC (g/day) 1.06i0.39

14.15i3.46 0.98İ0.58 >0.05 >0.05 15.40i2.95 1.06i0.39 17.60±3.35 1.25*0.96 <0.05 <0.05 1 4 .15i3.46 0 .9 8 i0 .5 8 17 .60i3.35 1.25±0.96 <0.01 <0.01

mance in stressvulnerable subjects (19).

This is the fırst study to investigating the role o f dietary tryptophan intake in FS using TNS vvhich is prepared for this study. TNS is a simple and u- seful scoring system under lim ited laboratory conditions. We found using this scoring system that our patients vvith PFS and SFS had lovver di­ etary tryptophan intake as compared to the con­ trol group. We also found that our patients vvith PFS and SFS had lower average daily consumpti­ on o f tryptophan values (1.06±0.39 g/day and 0.98±0.58 g/day respectively) as com pared to control subjects. These values also lovver than the average daily consumption o f tryptophan in USA (1.2 g/day)(20).

M ultiple theories about the pathogenesis o f this disease dictates various therapy regimens. As the

diffıcult, current therapeutical ap p roaches seem to be inadequate. L edingham et al. (21) vvere re- ceived sev en ty tw o p a tie n ts vvith PFS in th e ir study and they reported a poor prognosis charac- terised by a high degree o f f'unctional im pairm ent and persistence o f symptom s.

In conclusion, considering the central hyperexci- tab ility exists in FS p a tie n ts, try p to p h a n m ay play an important role in fibrom yalgia as a cau- sative factor and also plays a role in persistence o f fibromyalgia symptom s. Thus tryptophan rich diet (for exam ple ineluding w hey proteins, m ilk, meat, vegetable proteins, chocolate ete.) can be recom mended to these patients. The am ount and frequency o f dietary triptophan intake and also the effect o f tryptophan on sym ptom s in FS p ati­ ents should be confırm ed vvith further studies.

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T h e R o le o f D ictary T ry p to p h a n In tak e in F ib ro m y alg ia S yndrom e 65

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