Antioxidants, diet and rheumatoid arthritis.

I also have an information sheet on Juvenile Rheumatoid Arthritis from the National institute of arthritis and Musculoskeletal & Skin Diseases. It's too long to put here, but if you contact me I can mail or e-mail you a copy.

1. Vitamins (alone and in combination),
2.  Minerals 
3. Essential Fatty Acids.

Z Rheumatol 1998 Aug;57(4):215-21

[Effectiveness of vitamin E in comparison with diclofenac sodium in treatment of
patients with chronic polyarthritis].

[Article in German]

Wittenborg A, Petersen G, Lorkowski G, Brabant T

Rheumazentrum Ruhrgebiet St. Josefs-Krankenhaus, Herne.

In a randomized, double blind parallel group comparison the antiphlogistic and
analgetic efficacy of high-dosed vitamin E (3 x 400 mg
RRR-alpha-Tocopherolacetat/d) versus diclofenac-sodium has been investigated in
hospitalized patients with established chronic rheumatoid arthritis. After 3
weeks of treatment the vitamin E group (n = 42) as well as the diclofenac group
(n = 43) showed a significant improvement of all assessed clinical parameters.
Duration of morning stiffness could be reduced under vitamin E treatment from 90
min to 68 min and under diclofenac treatment from 68 min to 30 min. The joint
index according to Richie declined from 56 to 46 (vitamin E) and 49 to 34
(diclofenac). Grip strength increased in the vitamin E group as well as in the
diclofenac group. In addition, the degree of pain, assessed by a 10 cm visual
analogue scale, reduced significantly under vitamin E as well as under
diclofenac. Regarding the therapeutical result both, physicians and patients,
considered both drugs to be similarly effective. Especially regarding the risk
profile of NSAR in long-term treatment of chronic rheumatoid arthritis intake of
high-dosed vitamin E is a possible alternative in the treatment of inflammatory
rheumatoid diseases.

Clin Sci (Colch) 1992 Dec;83(6):657-64

Alpha-tocopherol, lipids and lipoproteins in knee-joint synovial fluid and serum
from patients with inflammatory joint disease.

Fairburn K, Grootveld M, Ward RJ, Abiuka C, Kus M, Williams RB, Winyard PG,
Blake DR

Inflammation Research Group, London Hospital Medical College, U.K.

1. We have determined the antioxidant status of synovial fluid and serum of
patients with inflammatory joint disease in terms of the biologically active
lipid-soluble antioxidant, alpha-tocopherol. Synovial fluid concentrations of
alpha-tocopherol were significantly lower relative to those of paired serum
samples (P < 0.001). Serum levels of alpha-tocopherol in these patients did not
differ significantly from those in control serum. 2. Lower concentrations of
cholesterol, triacylglycerol and low-density lipoprotein were also observed in
patients' synovial fluid compared with matched serum samples. However, multiple
regression analysis of the data indicated that there remained a significant
depletion of alpha-tocopherol, which was largely independent of these
co-variables, in inflammatory synovial fluid. These findings are consistent with
the consumption of alpha-tocopherol within the inflamed joint via its role in
terminating the process of lipid peroxidation. 3. Nuclear magnetic resonance
spectroscopic analysis of matched inflammatory synovial fluid and serum
confirmed lower concentrations of triacylglycerol in synovial fluid together
with evidence of a shortened mean triacylglycerol chain length. The latter
metabolic difference suggests an increased utilization of triacylglycerols for
energy within the inflamed joint.

This paper indicates that low levels of vitamin E (alpha tocopherol) and vitamin A (beta carotene and retinol) are present in rheumatoid arthritis sufferers well before the appearance of disease symptoms.  Could supplementation with these vitamins have a preventative effect?

Ann Rheum Dis 1997 May;56(5):323-5

Serum concentrations of alpha tocopherol, beta carotene, and retinol preceding
the diagnosis of rheumatoid arthritis and systemic lupus erythematosus.

Comstock GW, Burke AE, Hoffman SC, Helzlsouer KJ, Bendich A, Masi AT, Norkus EP,
Malamet RL, Gershwin ME

Department of Epidemiology, School of Hygiene and Public Health, Johns Hopkins
University, Baltimore, Maryland, USA.

OBJECTIVES: Because oxidative damage has been implicated in the pathogenesis of
rheumatoid arthritis and systemic lupus erythematosus, this study was designed
to see if serum concentrations of alpha tocopherol, beta carotene, and retinol,
substances believed to be involved in the prevention or repair of oxidative
damage, might be lower among persons who develop rheumatoid arthritis or
systemic lupus erythematosus than among those who do not. METHODS: For this
prospective case-control study, persons with rheumatoid arthritis and systemic
lupus erythematosus that developed two to 15 years after donating blood for a
serum bank in 1974 were designated as cases. For each case, four controls were
selected from the serum bank donors, matched for race, sex, and age. Stored
serum samples from cases and controls were assayed for alpha tocopherol, beta
carotene, and retinol. RESULTS: Cases of both diseases had lower serum
concentrations of alpha tocopherol, beta carotene, and retinol in 1974 than
their matched controls. For rheumatoid arthritis, the difference for beta
carotene (-29%) was statistically significant. CONCLUSIONS: These findings
support those of a previous study that low antioxidant status is a risk factor
for rheumatoid arthritis. They suggest a similar association for systemic lupus
erythematosus.

Ann Rheum Dis 1994 Jan;53(1):51-3

Serum antioxidants and risk of rheumatoid arthritis.

Heliovaara M, Knekt P, Aho K, Aaran RK, Alfthan G, Aromaa A

Social Insurance Institution, Helsinki, Finland.

OBJECTIVES--Oxygen free radicals have been implicated as mediators of tissue
damage in patients with rheumatoid arthritis (RA). Thus it is possible that
several micronutrients acting as antioxidants and free radical scavengers
provide protection against RA. Serum alpha-tocopherol, beta-carotene, and
selenium were studied for their associations with the risk of RA. METHODS--A
case control study was nested within a Finnish cohort of 1419 adult men and
women. During a median follow up of 20 years, 14 individuals initially free of
arthritis developed RA. Two controls per each incident case were individually
matched for sex, age, and municipality. Serum alpha-tocopherol, beta-carotene
and selenium concentrations were measured from stored serum samples. An
antioxidant index was calculated as the product of the molar concentrations of
these three micronutrients. RESULTS--Elevated risks of RA were observed at low
levels of alpha-tocopherol, beta-carotene and selenium, but none of the
associations were statistically significant. A significant association, however,
was observed with a low antioxidant index (p for trend = 0.03), the relative
risk of RA between the lowest tertile and the higher tertiles of its
distribution being 8.3 (95% confidence interval 1.0-71.0). CONCLUSIONS--The
results of the present study are in line with the hypothesis that a low
antioxidant level is a risk factor for RA.

Biofactors 1998;8(1-2):155-9

Oxidant-antioxidant imbalance in blood of children with juvenile rheumatoid
arthritis.

Araujo V, Arnal C, Boronat M, Ruiz E, Dominguez C

Centre d'Investigacions en Bioquimica i Biologia Molecular, Hospital
Materno-Infantil Vall d'Hebron, Barcelona, Spain.

Juvenile rheumatoid arthritis (JRA) is the most commonly diagnosed rheumatic
disease in children and may represent not a single disease, but rather a
syndrome of diverse aetiologies in which inflammation is an exceedingly complex
process. Oxidative free radical production at inflammation sites contributes to
tissue damage and could also play a significant role in the pathogenesis of JRA.
The aim of this study was to evaluate the antioxidant status and lipid
peroxidation parameters related to the clinical form of JRA. Plasma
malondialdehyde and hydroperoxide concentrations in children with polyarticular
and systemic JRA subtypes were significantly higher than in controls. Plasma
vitamin E and beta-carotene levels of the JRA children were lower in the three
forms compared with healthy children. Patients with JRA present an imbalance in
the oxidant-antioxidant system that manifests clearly in the polyarticular and
systemic forms through an increase in lipoperoxidation products and significant
decrease in the lipid-soluble antioxidants vitamin E and beta-carotene.

Analyst 1998 Jan;123(1):3-6

Rheumatoid arthritis and metal compounds--perspectives on the role of oxygen
radical detoxification.

Aaseth J, Haugen M, Forre O

Medical Department, Kongsvinger Hospital, Norway.

Rheumatoid arthritis (RA) is characterised by migration of activated phagocytes
and other leukocytes into synovial and periarticular tissue. Activated oxygen
species and other mediating substances from triggered phagocytes appear to
exacerbate and perpetuate the rheumatoid condition. Iron excesses are capable of
aggravating the arthritic inflammation, probably through their pro-oxidant
potentials. In contrast, therapeutically given gold salts, through a lysosomal
loading of the metal, inhibit the triggered cells, thereby reducing the toxic
oxygen production. Pharmacological doses of zinc also may immobilise
macrophages. Furthermore, the copper-zinc-containing enzyme SOD (superoxide
dismutase) can act as a scavenger of toxic oxygen in the tissues. Therapeutic
remission of RA has been obtained following intraarticular administration of
SOD. Intramuscular administration of copper complexes has induced remission in
about 60% of RA patients in open studies. Another drug, penicillamine, that
protects cellular membranes against toxic oxygen in vitro, is presumed to act as
an antirheumatic via the SOD mimetic activity of its copper complex. Thiomalate
and other thiols may possess similar activities. Selenium compounds also may act
as oxygen radical scavengers. A significant alleviation of articular pain and
morning stiffness was obtained following selenium and vitamin E supplementation
in a double-blind study on RA patients. The observations reviewed here indicate
that metal compounds and other antioxidants can reduce the rheumatic
inflammation by reducing the cellular production and/or concentration of toxic
oxygen species.

Inflammation 1993 Jun;17(3):283-94

Copper-dependent antioxidase defenses in inflammatory and autoimmune rheumatic
diseases.

Miesel R, Zuber M

Deutsches Rheumaforschungszentrum, Berlin, Germany.

Gel-filtered sera of patients with various inflammatory and autoimmune rheumatic
diseases (N = 354) were screened for the presence of the inflammation marker
Cu-thionein. The concentrations of Cu-thionein were significantly diminished in
patients with connective tissue diseases (P < 0.001). Sera of patients suffering
from inflammatory rheumatic diseases were almost totally depleted of this
low-molecular-weight copper protein that exerts pronounced superoxide dismutase
activity and scavenges effectively hydroxyl radicals and singlet oxygen.
Cortisone treatment of patients with rheumatoid arthritis, systemic lupus
erythematosus, and polymyalgia rheumatica replenished impressively the serum
concentration of Cu-thionein. The partial oxidation of the EPR-silent
Cu(I)-chromophore to Cu(II)/Cu(I)-thionein, which is essential for the catalytic
dismutation of superoxide, was monitored by electron paramagnetic resonance in
the presence of activated neutrophils and monocytes. Release of Cu-thionein
during the oxidative burst of peripheral blood monocytes was demonstrated in
vitro. The role of prooxidant-antioxidant imbalances in the pathogenesis of
rheumatic diseases is discussed.

Analyst 1998 Jan;123(1):3-6

Rheumatoid arthritis and metal compounds--perspectives on the role of oxygen
radical detoxification.

Aaseth J, Haugen M, Forre O

Medical Department, Kongsvinger Hospital, Norway.

Rheumatoid arthritis (RA) is characterised by migration of activated phagocytes
and other leukocytes into synovial and periarticular tissue. Activated oxygen
species and other mediating substances from triggered phagocytes appear to
exacerbate and perpetuate the rheumatoid condition. Iron excesses are capable of
aggravating the arthritic inflammation, probably through their pro-oxidant
potentials. In contrast, therapeutically given gold salts, through a lysosomal
loading of the metal, inhibit the triggered cells, thereby reducing the toxic
oxygen production. Pharmacological doses of zinc also may immobilise
macrophages. Furthermore, the copper-zinc-containing enzyme SOD (superoxide
dismutase) can act as a scavenger of toxic oxygen in the tissues. Therapeutic
remission of RA has been obtained following intraarticular administration of
SOD. Intramuscular administration of copper complexes has induced remission in
about 60% of RA patients in open studies. Another drug, penicillamine, that
protects cellular membranes against toxic oxygen in vitro, is presumed to act as
an antirheumatic via the SOD mimetic activity of its copper complex. Thiomalate
and other thiols may possess similar activities. Selenium compounds also may act
as oxygen radical scavengers. A significant alleviation of articular pain and
morning stiffness was obtained following selenium and vitamin E supplementation
in a double-blind study on RA patients. The observations reviewed here indicate
that metal compounds and other antioxidants can reduce the rheumatic
inflammation by reducing the cellular production and/or concentration of toxic
oxygen species.

Med Klin 1997 Sep 15;92 Suppl 3:29-31

[Selenium concentration in erythrocytes of patients with rheumatoid arthritis.
Clinical and laboratory chemistry infection markers during administration of
selenium].

[Article in German]

Heinle K, Adam A, Gradl M, Wiseman M, Adam O

Rheumaeinheit der Ludwig-Maximilians-Universitat, Staatliche Orthopadische
Klinik, Munchen.

PATIENTS AND METHODS: Seventy patients with definitive rheumatoid arthritis were
matched to built 2 groups, which were double-blind and randomized allocated to
supplementation with sodium-selenit 200 micrograms/d or placebo for 3 months,
each. Both groups were given fish oil fatty acids (30 mg/kg body weight), DMARDS
were continued throughout the study, while variations in steroids or NSAD were
admitted. RESULTS: Selenium concentrations in erythrocytes of patients with
rheumatoid arthritis were 85.1 +/- 26 micrograms/l, and significantly lower than
found in an average German population (123 +/- 23 micrograms/l). During the
observation period of 3 months normal selenium concentrations were not restored,
despite supplementation higher than RDA. At the end of the experimental period
the selenium supplemented group showed less tender or swollen joints, and
morning stiffness. Selenium-supplemented patients needed less cortisone and NSAD
than controls. In accordance with clinical improvement we found a decrease of
laboratory indicators of inflammation (C-reactive protein, alpha 2-globuline,
prostaglandin E2). CONCLUSION: No side effects of supplementation with selenium
were noted, which can be considered as adjuvant therapy in patients with
rheumatoid arthritis.

Scand J Rheumatol 1996;25(5):325-30

Nutritional status of Danish rheumatoid arthritis patients and effects of a diet
adjusted in energy intake, fish-meal, and antioxidants.

Hansen GV, Nielsen L, Kluger E, Thysen M, Emmertsen H, Stengaard-Pedersen K,
Hansen EL, Unger B, Andersen PW

Department of Rheumatology, King Christian X's Hospital, Graasten, Denmark.

This study deals with the nutritional status of Danish RA patients and address
the question of whether or not RA can be directly influenced by dietary
manipulation. In a prospective, single-blinded study of 6 months duration, 109
patients with active RA were randomly assigned to either treatment with or
without a specialized diet. The energy consumption was adjusted to normal
standards of body weights and the intake of fish meals and antioxidants were
increased. A daily food diary was completed by the patients, and the total
intake of 47 different food-elements was calculated. Nutritional status together
with disease activity parameters were recorded. At baseline, the Danish
RA-patients had neglected food habits with a significant reduction in intake of
total energy, of D-vitamin and of E-vitamin. A very low intake of n-3 fatty
acids was also found. During the study, 28 of the 109 patients dropped out,
introducing a confounding effect on the overall result. In the remaining 81,
those following the diet demonstrated a significant improvement in the duration
of morning stiffness, number of swollen joints, pain status, and reduced cost of
medicine, while doctors global assessment, laboratory data, X-ray, and daily
activities were unaltered. In conclusion, dietary analysis and appropriate,
corrective advice should be offered to Danish RA patients.

Am J Clin Nutr 1999 Dec;70(6):1077-82

Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables?

Linos A, Kaklamani VG, Kaklamani E, Koumantaki Y, Giziaki E, Papazoglou S,
Mantzoros CS

Department of Epidemiology, University of Athens Medical School, Greece.

BACKGROUND: Although several studies showed that risk of rheumatoid arthritis
(RA) is inversely associated with consumption of n-3 fatty acids, the one study
showing that olive oil may have a protective role has not yet been confirmed.
OBJECTIVE: We examined the relation between dietary factors and risk of RA in
persons from southern Greece. DESIGN: We studied 145 RA patients and 188 control
subjects who provided information on demographic and socioeconomic variables,
prior medical and family history, and present disease status. Subjects responded
to an interviewer-administered, validated, food-frequency questionnaire that
assessed the consumption of >100 food items. We calculated chi-square statistics
for linear trend and odds ratios (ORs) for the development of RA in relation to
the consumption of olive oil, fish, vegetables, and a series of food groups
classified in quartiles. RESULTS: Risk of developing RA was inversely and
significantly associated only with cooked vegetables (OR: 0.39) and olive oil
(OR: 0.39) by univariate analysis. A significant trend was observed with
increasing olive oil (chi-square: 4.28; P = 0.03) and cooked vegetable
(chi-square: 10. 48; P = 0.001) consumption. Multiple logistic regression
analysis models confirmed the independent and inverse association between olive
oil or cooked vegetable consumption and risk of RA (OR: 0.38 and 0.24,
respectively). CONCLUSIONS: Consumption of both cooked vegetables and olive oil
was inversely and independently associated with risk of RA in this population.
Further research is needed to elucidate the underlying mechanisms of this
finding, which may include the antioxidant properties or the high n-9 fatty acid
content of the olive oil.