Účinok koloidného zlata na kognitívne funkcie: pilotná štúdia

Guy E. Abraham MD, Souhaila A. McReynolds, Joel S. Dill PhD

Optimox Corporation, Torrance, CA, USA

Abstrakt

Štúdia zisťuje vplyv koloidného zlata na kognitívne funkcie. Štúdie sa zúčastnilo 5 osôb vo veku od 15 do 45 rokov. Účastníci vykonali prepracovaný súboru inteligenčných testov Wechsler Intelligence (WAIS-R) pred užívaním, po 4 týždňovom užívaní koloidného zlata v množstve 30 mg/deň a potom opäť po 1 až 3 mesiacoch od skončenia užívania. Celková hodnota WAIS-R testov (IQ) bola vyrátaná ako súčet skóre slovných testov a výkonových testov. Po 4 týždňoch užívania koloidného zlata bolo zaznamenané 20% zvýšenie hodnoty IQ s priemernou hodnotou + štandardnou chybou (SE): 112,8 + 2,3 pred a 137 + 3,8 po užívaní zlata (p <0,005). Oba testy, výkonový aj slovný sa rovnakou mierou podieľali na zvýšení hodnoty IQ. Účinky koloidného zlata pretrvali u 3 osôb po dobu 1 až 2 mesiacov od skončenia užívania zlata, u 2 osôb, ktoré vykonali testy až po 3 mesiacoch od skončenia užívania zlata, sa hodnota IQ vrátila späť k pôvodnej hodnote.

Úvod

Je všeobecne známe, že inteligencia, alebo kognitívne funkcie sú súhrnom mnohých duševných schopností. Z tohto dôvodu testy, ktoré boli vyvinuté na určovanie inteligenčného kvocientu (IQ) zahŕňajú viacero testov hodnotiacich niekoľko úrovní inteligencie. Z množstva dostupných IQ testov bol ako najvyhovujúcejší vybraný takzvaný „Full Scale I.Q.” test zo súboru Wechsler inteligenčných testov (WIS), ktorý sa vypočíta zo súčtu skóre 11 samostatných testov (6 verbálnych a 5 výkonnostných testov)(1). Upravená verzia týchto IQ testov (WAIS-R) sa používa vo veľkej miere na posúdenie vplyvu určitých živín(2,3) na duševné schopnosti v závislosti od pohlavia, rasy, veku a vzdelania(4-7).

Zlato je vzácny kov, ktorý patrí do skupiny prechodných prvkov I v periodickej tabuľke a v prírode existuje v dvoch základných formách: kovové zlato a soli zlata. Kovové zlato je ne-toxické, často používané v zubnom lekárstve a je široko dostupné v koloidnom stave ako doplnok stravy. Jeden z nás (GEA) pozoroval významné subjektívne zlepšenie duševného výkonu u 21 dospelých jedincov po užití koloidného zlata (Aurasol®) počas obdobia od 3 do 9 mesiacov v dennej dávke 15 mg zlata (nepublikované). Aby bolo možné popísať objektívne a štandardizované hodnotenie vplyvu koloidného zlata na duševnú výkonnosť, súbor testov WAIS-R(7) bol aplikovaný na 5 osobách (4 ženy, 1 muž) vo veku 15 - 45 rokov a to pred, počas a po mesiaci užívania rovnakého prípravku koloidného zlata v množstve 30 mg/deň. Výsledky naznačujú, že koloidné zlato pri užívaní 30 mg/deň významne zlepšilo úroveň IQ už po jednom mesiaci podávania.

Materiál a metódy

Koloidná disperzia zlata bola pripravená zmenou citrátu Frensovou redukčnou metódou. Koncentrácia zlata v tomto prípravku (Aurasol®) bola 1 mg / ml. Štúdie sa zúčastnilo 5 osôb (4 ženy a 1 muž) vo veku od 15 do 45 rokov. Osoby vykonávali testy WAIS-R(7). Boli vyrátané verbálne, výkonnostné a celkové výsledky (IQ) pre každú osobu. Každá osoba vykonala testy WAIS-R pred začiatkom podávania koloidného zlata, po podaní 30 mg koloidného zlata denne počas 1 mesiaca, a opäť po 1 až 3 mesiacoch od skončenia podávania koloidného zlata. Štatistická významnosť údajov bola hodnotená párovým t-testom(9).

Výsledky

Skupinu verbálnych testov sa nie je možné a teda nie je významne ovplyvnená opakovaním. Výkonnostné testy sa môžu zlepšiť opakovaním a to je potrebné zohľadniť pri vyhodnocovaní výsledkov v Tabuľke I. Priemerné hodnoty + štandardná chyba (SE) boli nasledovné (pred- a po- užívaní): verbálne 61,4 + 2,4 a 75,4 + 4,5 (p<0,005); výkonnostné 51,4 + 0,83 a 61,6 + 1,9 (p<0,01); celková úroveň (IQ) 112,8 + 2,3 a 137 + 3,8 (p<0,005). Oboje, verbálne (ne-naučené) aj výkonnostné (možné sa naučiť) výsledky prispeli rovnakou mierou na zvýšenie celkovej úrovne IQ po podávaní koloidného zlata. Zvýšenie celkovej hodnoty IQ teda nie je možné pripísať len naučením sa správnych odpovedí opakovaním v druhom súbore testov.

Je zaujímavé, že u dvoch osôb (#1 and #2), ktoré opakovali skupinu testov po 3 mesiacoch od skončenia podávania koloidného zlata, celková úroveň IQ sa vrátila takmer na úroveň prvých testov pred začiatkom podávania, zatiaľ čo u 2 osôb, ktoré opakovali testy po 1 mesiaci od skončenia podávania zlata, (#3 and #5) a u jednej osoby (#4), ktorá opakovala testy po 2 mesiacoch od skončenia podávania, celková úroveň IQ bola stále nad úrovňou prvých testov. To naznačuje, že efekt zlata na duševnú výkonnosť trvá aj po dobu jedného až dvoch mesiacov po ukončení užívania koloidného zlata.

Diskusia

Skupina WIS testov je výborný ukazovateľ duševných schopností(1). V skutočnosti, podľa Lezaka(10), priemerná úroveň WIS testov poskytuje minimálne toľko informácií, ako priemerná hodnota na školskom vysvedčení. Spozorovali sme významné zvýšenie (20%) priemernej úrovne IQ u 5 osôb vo veku od 15 do 45 rokov po iba mesačnom užívaní koloidného zlata pri dávkovaní 30 mg/deň. Tento efekt pretrvával až 2 mesiace po ukončení podávania prípravku zlata. Pokiaľ je nám známe, je to prvá štúdia skúmajúca efekt koloidného zlata na duševné schopnosti. Preto možné mechanizmy pôsobenia koloidného zlata sú zatiaľ len špekulatívne. Avšak potenciálne využitie ne-toxických koloidných prvkov s výrazným a rýchlym pozitívnym vplyvom na duševnú výkonnosť majú nepochybne veľmi praktickú hodnotu, a to nielen v školách, ale aj na pracoviskách.

Povzbudivé výsledky tejto pilotnej štúdie si zaslúžia ďalšie skúmanie účinkov koloidného zlata na väčšiu skupinu osôb v rôznych vekových skupinách. Testovanie rôzneho množstva zlata by pomohlo pri stanovení výsledkov IQ testov v závislosti na množstve užitého zlata, aby sa zistil vzťah dávkovanie / výsledky. Zistenie najmenšieho množstva koloidného zlata, ktoré už má za následok žiaduce účinky na duševnú výkonnosť, by pomohlo udržať náklady takéhoto programu čo najnižšie.

Odkazy

  1. Lezak, M.D., In: Neuropsychological Assessment. New York, Oxford University Press; 1995:690.
  2. Goodwin, J.S., Goodwin, J.M., Garry, P.J. Association between nutritional status and cognitive functioning in a healthy elderly population. J Amer. Med. Assoc., 1983; 249:2917-2921.
  3. Southon, S., Wright, A.J., Finglas, P.M., Bailey, A.L., et. al. Dietary intake and micronutrient status of adolescents: effect of vitamin and trace element supplementation on indices of status and performance in tests of verbal and non-verbal intelligence. Br. J. Nutr., 1994; 71:897-918.
  4. Kaufman, A.S., McLean, J.E., Reynolds, C.R. Sex, race, residence, region, and education differences on the 11 WAIS-R subtests. J. Clin. Psychology, 1988; 44:231-248.
  5. Kaufman, A.S., McLean, J., Reynolds, C. Analysis of WAIS-R factor patterns sex and race. J. Clin. Psychology, 1991; 47:548-557.
  6. Kaufman, A.S., Reynolds, C.R., McLean, J.E. Age and WAIS-R intelligence in a national sample of adults in the 20 to 74 year age range: A cross-sectional analysis with educational level controlled. Intelligence, 1989; 13:235-253.
  7. Kaufman, A.S. Assessing adolescent and adult intelligence. Boston, Allyn and Bacon Inc.; 1990.
  8. Abraham, G.E., Himmel, P.B. Management of Rheumatoid Arthritis: Rationale for the Use of Colloidal Metallic Gold. In Press, J. Nutr. Med., 1997.
  9. Huntsberger, D.V., Leaverton, P.E., In: Statistical Inference in the Biomedical Sciences. Boston, Allyn and Bacon Inc.; 1970:135.
  10. Lezak, M.D., In: Neuropsychological Assessment. New York, Oxford University Press;1995:691.

Koloidné zlato v liečbe reumatickej artritídy (RA)

Peter B. Himmel, Jorge D. Flechas, Guy E. Abraham


Užívanie preparátov solí zlata (aurotiomalátov) ako hlavnej terapie pri liečbe RA sa v posledných rokoch znížilo v dôsledku zjavne chýbajúcej dlhodobej efektívnosti, toxických vedľajších účinkov a oneskorenému nástupu pôsobenia. Jeden z nás (GEA) predpokladal, že aktívnou zložkou aurotiomalátu je koloidné zlato vytvárané in vivo ako dôsledok nerovnováhy a následného zhlukovania monoatomárneho zlata a že vedľajšie účinky boli spôsobené samotnými aurotiomalátmi a trojmocnými katiónmi zlata generovanými touto nerovnováhou. Ak je tento predpoklad správny, je možné očakávať, že koloidné zlato má terapeutické účinky pri RA a je zároveň bez vedľajších účinkov.

Metódy

10 pacientov (6 žien, 4 muži; priemerný vek 50 +/- 3,16 (štandardná chyba) s dlhotrvajúcou RA (9 z 10 seropozitívny) dostávalo orálne dávku koloidného zlata (Aurasol®) v množstve od 30 do 60 mg na deň počas jedného mesiaca. Klinické testy boli prevádzané každý týždeň a laboratórne testy v týždňoch 1, 2 a 4. Možnosť toxicity zlatom bola zisťovaná dotazovaním pacientov na prítomnosť svrbenia, vyrážok, vredov v ústach, kovovú chuť, poruchy trávenia. Bola sledovaná krv na pokles WBC, Hb, krvných doštičiek, BUN, nárast kreatínu alebo eozinofilov; a moč na proteinúriu. Účinnosť terapie bola hodnotená pomocou bodovania „86 Joint Count Index” na bolestivosť a opuch kĺbov: AM stuhnutosť; modifikovaného dotazníka zdravotného stavu (MHAQII) od T. Pincusa a ESR.

Výsledky

Štatisticky významné zlepšenia boli zaznamenané každý týždeň pri testoch na bolestivosť a opuch kĺbov. Už prvý týždeň bolo zlepšenie z 58,8 na 18,2 (p<0,01) u bolesti a zo 42,5 na 15,9 (p<0,01) u opuchov. Opuchy kĺbov sa ďalej znižovali až na hodnotu 13,0 (p<0,001) v 4. týždni. Únava pacientov klesla z 5,32 na 3,35 (p<0,05) behom mesiaca a pocit spokojnosti pri výkone aktivít bol zrejmý po prvom týždni, z 3,1 na 2,5 (p<0,01) a ďalej pretrvával. Žiadne laboratórne vyšetrenia nezaznamenali toxicitu zlatom. Jeden pacient mal 2 tvrdé vredy, ktoré sa vyčistili počas tejto terapie, 8 z 10 pacientov reagovalo na koloidné zlato.

Záver

V tejto pilotnej štúdii sa zistilo, že koloidné zlato (Aurasol®) rýchlo pôsobilo (v priebehu jedného týždňa) na zníženie bolestivosti a opuchov kĺbov bez vedľajších účinkov, zvýšilo pocit spokojnosti pri výkone aktivít a znížilo únavu u 8 z 10 pacientov trpiacich na dlhotrvajúcu RA. Štúdia bude pokračovať po dobu jedného roka. Mali by nasledovať viac kontrolované štúdie skúmajúce koloidné zlato.

Poznámky

Štúdia už ukončila svoj ôsmy mesiac so stále všetkými pôvodnými desiatimi pacientmi. Pacienti sa stále majú dobre a neboli zaznamená žiadne podstatné vedľajšie účinky. Sumarizujú sa získané údaje, aby ich bolo možné publikovať.

Management of Rheumatoid Arthritis (RA): Rationale for the Use of Colloidal Metallic Gold

Guy E. Abraham MD FACN 1 and Peter B. Himmel MD 2

1 Optimox Corporation, Torrance, CA, USA
2 Himmel Health, Wakefield, RI, USA

In Press - Journal of Nutritional & Environmental Medicine (Dec. 1997)

Abstract

Gold salts of monovalent gold (AU I) with a gold-sulfur ligand (aurothiolates) are the only form of gold currently in use for the management of Rheumatoid Arthritis (RA). Aurothiolates have limited success and are associated with a high incidence of side effects. Metallic gold (AUo) is non-toxic and used extensively in dentistry. Monoatomic metallic gold is generated in vivo from AUI salts, during oxidation to AU III. Monoatomic gold tends to form clusters of colloid particles. It is postulated that the active ingredient in aurotherapy is AUo and the side effects are caused by AU III. To test this postulate, 10 RA patients with long standing erosive bone disease not responding to previous treatment, were recruited from a private practice. Clinical and laboratory evaluation were performed prior to oral administration of 30 mg of colloidal metallic gold daily, and thereafter weekly for 4 weeks and monthly for additional 5 months. There was no clinical or laboratory evidence of toxicity in any of the patients.

The effects of the colloidal gold on tenderness and swelling of joints were rapid and dramatic, with a significant decrease in both parameters after the first week, which persisted during the study period. The mean scores for tenderness and swelling were respectively for the pre-and post- 1 week = 58,8 and 18,2 (p<0,01); and 42,5 and 15,9 (p<0,01).

By 24 weeks of gold administration, the mean scores were 10 times lower than pre-treatment levels being respectively 5,4 and 3,3 for tenderness and swelling. As a group, there was a significant improvement of functional status after 24 weeks of gold therapy: 3 patients were in clinical remission and one patients status improved from totally disabled to full-time work. Evaluated individually, 9 of 10 patients improved markedly after 24 weeks of colloidal gold at 30 mg/day. Cytokines interleukin-6 (IL-6) and Tumor necrosis factor (TNFa) were significantly suppressed by the colloidal gold with pre- and post-24 week mean values of 270 and 104 (p<0,05) for IL-6; and 207 and 74 (p<0,05) for TNFa. The results of this open trial in 10 patients with long standing erosive RA not responding to previous treatment support the postulate that colloidal gold is indeed the active ingredient in aurothiolate therapy, and that the side effects are mainly due to the trivalent gold (AU III) generated by oxidation of AU I. Colloidal metallic gold could become an effective and safe alternative to the aurothiolates in the management of RA patients. Keywords: rheumatoid arthritis, colloidal metallic gold.

Introduction

Aurothiolates have been used in the treatment of rheumatoid arthritis (RA) since their introduction by Forestier in 1929(1). In a follow-up publication, Forestier reported that the only forms of gold effective in the management of RA were organic compounds containing monovalent cathionic gold (AU I) covalently bound to a sulfur moiety (aurothiolates), and given by weekly intramuscular injection to achieve a total cumulative dose of 2,5 to 3 gm(2). He stated that colloidal gold was ineffective, but did not mention the dosage, the form of colloidal gold, whether metallic or cathionic, neither the method of administration. Several subsequent reports by various investigators have confirmed the short term efficacy of the parenteral forms of aurothiolates in RA(3), but in more recently published clinical studies with the parenteral aurothiolates, several side effects were reported: Pulmonary damage(4-7), myelotoxicity, leukopenia, thrombocytopenia, and anemia(8-12). In a recent longitudinal study of 822 RA patients receiving parenteral aurothiolate therapy over a 5 year period(13), no statistical improvement was observed in two outcome variables evaluated: functional assessment and number of painful joints. In an attempt to minimize the side effects of injectable gold complexes, an oral preparation was introduced in 1976(14). However, this preparation caused diarrhea/loose stools in 50% of the patients, was less effective than the parenteral forms of aurothiolates and produced the same side effects as the injectable forms of gold salts although to a lesser extent.

Since chemical complexes of monovalent gold readily disproportionate in solution with formation of metallic monoatomic gold and trivalent gold according to the reaction: 3AU+ --> 2AUo + AU+++(15), it would be expected that monovalent gold organocomplexes, such as the aurothiolates if administered orally or parenterally, would disproportionate in vivo with formation of metallic monoatomic gold and trivalent gold (AU III). In vivo clustering of metallic gold atoms would eventually form colloidal particles of gold. One of us (GEA) postulated that the active ingredient in aurothiolate therapy is colloidal metallic gold generated by in vivo disproportionation with subsequent clustering of monoatomic metallic gold to form colloidal gold; and that the side effects were due mainly to the trivalent gold (AU III) generated from disproportionation (Fig 1). If this postulate is valid, one would expect colloidal metallic gold to have therapeutic effects in RA and devoid of side effects. Metallic gold is non-toxic, used extensively in dentistry and is widely available in colloidal form as a nutritional supplement for human consumption. The above postulate was tested in 10 patients with long standing erosive RA with minimal to no response to previous treatment. The results obtained support the postulate that colloidal metallic gold is indeed the active ingredient in aurothiolate therapy and offer a more effective and safer alternative to aurothiolate therapy in RA patients.

Materials and Methods

A. Colloidal metallic gold:

Aqueous dispersions of colloidal gold (Aurasol®) were prepared by one of us (GEA) at a final concentration of 1000 mg/l, (1000 PPM) by the citrate method of Maclagan(16) and Frens(17), with several proprietary modifications. The sizes of the colloid particles were less than 20 nm in several batches, confirmed by quantitative recovery after passing through a 20 nm filter. Accelerated shelf-life studies proved the stability of the aqueous dispersion for up to 2 years at ambient temperature. The following metals were measured in the aqueous colloidal gold dispersion and were undetectable at 0,5 PPM (<0,5 mg/l): Antimony, arsenic, barium, beryllium, cadmium, chromium, cobalt, copper, lead, mercury, molybdenum, nickel, selenium, silver, thallium, vanadium, and zinc. Lead levels were measured again in a more sensitive assay and were undetectable at 50 PPB (<0,05 mg/l). Sterilization was achieved by microfiltration through 100 nm pore size and sodium benzoate was used as anti-microbial preservative.

B. RA Patients:

In order to minimize the placebo effect, the 10 worse cases (9 of 10 seropositive) with long standing (7-40 years duration) erosive RA with minimal to no response to previous treatment, were recruited from the private practice of one of us (PBH). Nine of 10 patients received previously aurothiolate therapy without effect and 5 of the 9 experienced side effects of skin rash, stomatitis and proteinuria. The clinical data on these patients are displayed in Table I. Six of the ten patients were totally work-disabled. After informed consent was obtained, the patients underwent complete clinical and laboratory evaluations before and weekly afterward for 4 weeks and monthly for an additional 5 months of oral colloidal gold administration. The inflammatory cytokines, tumor necrosis factor a (TNFa) and interleukin-6 (IL-6) were evaluated prior to and 24 weeks following gold administration (Immunoscience Lab, Beverly Hills, CA). Paired data analysis was used for the evaluation of response to colloidal gold(18).

Performance parameters were assessed by the method of Pincus, et. al.,(19). The severity of swelling and tenderness was assessed for 86 joints, based on the quantitation of Lansbury(20), and the classification described in the Dictionary of the Rheumatic Diseases(21). The American Rheumatology Association (ARA) functional class by Steinbrocker, et al.,(22) was used to evaluate functional status: Class I: Complete functional capacity with ability to carry on all usual duties without handicaps; Class II: Functional capacity adequate to conduct normal activities despite handicap or discomfort or limited mobility of one or more joints; Class III: Functional capacity adequate to perform only few or none of the duties of usual occupation or self care; Class IV: Largely or wholly incapacitated with patient bed ridden or confined to wheel chair, permitting little or no self care.

Since preliminary data by one of us (GEA) suggested that amounts up to 15 mg/day of colloidal gold was without clinical effect in RA, patients 1 through 5 received 30 mg/day for the first week and 60 mg/day for the second week, whereas patients 6 through 10 received 60mg/day for the first week and 30 mg/day for the second week. Except for one patient, no significant difference was found between these two amounts on the clinical parameters evaluated. The patients were therefore continued on the trial at 30 mg/day for a duration of 24 weeks.

Results

The effects of the colloidal gold (Aurasol®) on tenderness and swelling of joints were rapid and dramatic, with a significant decrease in both parameters after the first week, which persisted during the study period. The mean scores for tenderness and swelling were respectively for the pre- and post- 1 week = 58,8 and 18,2 (p<0,01); and 42,5 and 15,9 (p<0,01). By 24 weeks of gold administration, the mean scores were 10 times lower than pre-treatment levels being respectively 5,4 and 3,3 for tenderness and swelling. Duration of AM joint stiffness (in hours) showed a decreasing trend that reached statistical significance with pre-and post 24 week mean scores of 2,8 and 0,4 respectively (p<0,01).

The mean body weight after 24 weeks on colloidal gold was not significantly different from the pre-treatment mean value. As a group, there were significant changes in ARA functional class, and physician's estimate of disease activity. Pre- and post- 24 week mean values were 2,9 and 2,3 (p<0,05) for ARA functional class; and 3,1 and 1,5 (p<0,01) for physician's estimate of disease activity. After 24 weeks on colloidal gold, 3 patients (#5, #6, #7) were in clinical remission. Work status improved in 3 patients (#3, #5, #6), with the most impressive results in patient #6, who changed from totally disabled to full time work, and ARA class IV to class I. The inflammatory cytokines IL-6 and TNFa were significantly suppressed by the colloidal gold with pre- and post-24 week mean values of 270 and 104 (p<0,05) for IL-6; and 207 and 74 (p<0,05) for TNFa.

There was no clinical or laboratory evidence of toxicity in the patients. Specifically no change was observed in subsets of white blood cells and platelets in the RA patients, supporting the absence of cytotoxicity from colloidal gold. There was no significant change in hemoglobin, hematocrit, liver function tests, BUN, serum creatinine and urinalysis in the RA patients and the levels of these parameters remained within normal limits during the study period. Clinically, there were no reports or signs of skin rashes, stomatitis, gastrointestinal disturbances, vasomotor reactions, myalgias, arthralgias, pruritus, headache or metallic taste. Evaluated individually, 9 of 10 patients improved markedly after 24 weeks of colloidal gold at 30 mg/day.

Discussion

In studies performed in vitro(23) and in vivo(24), administered metallic colloidal gold particles are ultimately sequestered within lysosomes of phagocytes, visible under electron microscopy (EM). After administration of aurothiolates to RA patients, gold particles visible under EM selectively accumulate in the lysosomes of synovial cells and macrophages(25). It is believed that stabilization of lysosomes by these gold particles plays a role in their therapeutic actions(26). Electron probe x-ray analysis of lysosomes revealed that the form of gold present in lysosomes obtained from patients receiving aurothiolates is devoid of sulfur atoms and therefore cannot be in the form of aurothiolates(26). Since disproportionation of aurothiolates generate monoatomic metallic gold with a diameter of 0,28 nm, a size below the resolution of EM, the only way the gold particles in the lysosomes could be visible under EM is by clustering of metallic monoatomic gold to form colloidal gold particles. These results are consistent with the postulate that the gold in lysosomes is in the form of colloid particles of metallic gold. Therefore, the argument that colloidal metallic gold is the active ingredient from aurotherapy seems very plausible.

The results of this open trial in 10 patients with long standing erosive RA not responding to previous treatment support the postulate that colloidal gold is indeed the active ingredient in aurothiolate therapy, and that the side effects are mainly due to the trivalent gold (AU III) generated by in vivo disproportionation. Common sense would favor the active ingredient in its pure state over a precursor that generates both the active form and another form causing side effects. The most prevalent side effects of aurotherapy are skin rash and diarrhea. Trivalent gold cause contact dermatitis and skin rash(27). The diarrheogenic action of aurothiolates can be explained by their ability to stimulate intestinal secretion in vitro, an effect shared by trivalent gold(28). Aurothiolates cause adverse immune reactions in up to one third of RA patients(29-31). Some of these side effects can be reproduced in susceptible mouse strains following long-term exposure to the aurothiolates: increased serum levels of IgM, IgG and IgE formation, of IgG antinuclear antibodies, and granular IgG deposits along the glomerular basement membrane(32-34). T-lymphocytes from susceptible mice fail to be sensitized to the aurothiolates but mount a secondary response to Au (III) salts, suggesting the adverse immune reactions to the aurothiolates are elicited by T cell sensitization to Au (III) formed in vivo through oxidation of Au (I)(35).

A placebo effect in these RA patients is very unlikely since their favorable clinical response was associated with the concurrent suppression of the inflammatory cytokines TNFa and IL-6. The powerful anti-inflammatory properties of colloidal gold while devoid of cytotoxicity and side effects could make it useful in other inflammatory and immune complexes diseases. Tissue levels of colloidal gold in the therapeutic ranges could be achieved rapidly with increased dosages without the risks of complications reported for the aurothiolates. Colloidal metallic gold could become an effective and safe alternative to the aurothiolates in the management of RA patients.

Since colloidal metallic gold catalyzes electron-transfer in oxidation reduction reactions(36), one possible mechanism of action of colloidal gold could be in potentiating the suppressive effect of antioxidants on free radical formation. The mechanisms of action of colloidal gold however remain speculative at this time, and we are currently investigating such mechanisms in animal models. Acknowledgements: The authors wish to thank Ralf Albrecht for useful discussions, and Pat Kellum for skillful secretarial assistance.

References

  1. Forestier, J: La Chrysotherapie dans les Rhumatismes Chroniques, Bull. et Mem. Soc. Med. des Hop. de Paris, 1929; 44: 323-329.
  2. Forestier, J: Rheumatoid Arthritis and its Treatment by Gold Salts, J. Lab. Clin. Med., 1935; 20: 827-840.
  3. Empire Rheumatism Council: Gold Therapy in Rheumatoid Arthritis. Final Report of a Multicenter Controlled Trial. Ann. Rheum. Dis., 1961; 20: 315-324.
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