linoleic-acid and Arthritis--Rheumatoid

An expert workshop reviewed the health effects of n-3 polyunsaturated fatty acids (PUFA), and came to the following conclusions. 1. Consumption of fish may reduce the risk of coronary heart disease (CHD). People at risk for CHD are therefore advised to eat fish once a week. The n-3 PUFA in fish are probably the active agents. People who do not eat fish should consider obtaining 200 mg of very long chain n-3 PUFA daily from other sources. 2. Marine n-3 PUFA somewhat alleviate the symptoms of rheumatoid arthritis. 3. There is incomplete but growing evidence that consumption of the plant n-3 PUFA, alpha-linolenic acid, reduces the risk of CHD. An intake of 2 g/d or 1% of energy of alpha-linolenic acid appears prudent. 4. The ratio of total n-3 over n-6 PUFA (linoleic acid) is not useful for characterising foods or diets because plant and marine n-3 PUFA show different effects, and because a decrease in n-6 PUFA intake does not produce the same effects as an increase in n-3 PUFA intake. Separate recommendations for alpha-linolenic acid, marine n-3 PUFA and linoleic acid are preferred.

Topics: alpha-Linolenic Acid; Animals; Arthritis, Rheumatoid; Coronary Disease; Fatty Acids, Omega-3; Fishes; Health Promotion; Humans; Linoleic Acid; Nutrition Policy; Plants, Edible

Ten patients with chronic rheumatic diseases were treated either with sunflower oil (linoleic acid 66%; n = 6) or with olive oil (linoleic acid 4%; n = 4) for 21 days. Sunflower oil but not olive oil increased the serum concentrations of linoleic acid in all fractions studied. In cholesteryl esters, both arachidonic acid and dihomo-gamma-linolenic acid concentrations were slightly diminished. The changes in all these fatty acids were already seen on the first days of treatment. Plasma arachidonic acid metabolites showed no uniform changes during the treatment. Excretions of the main metabolite of prostacyclin (6-keto-PGF1 alpha) and thromboxane B2 into urine were slightly increased in most patients on sunflower oil. No marked improvement was seen in the clinical or conventional laboratory parameters in either treatment.

Topics: Arachidonic Acids; Arthritis, Rheumatoid; Clinical Trials as Topic; Fatty Acids; Female; Humans; Linoleic Acid; Linoleic Acids; Male; Time Factors

Munziq Balgam (MBm) is a classic preparation of a traditional Uyghur medicine used for many years to treat abnormal body fluid diseases. The formula, as an in-hospital preparation, has already been used in the Hospital of Xinjiang Traditional Uyghur Medicine to treat rheumatoid arthritis (RA) with significant clinical effects.. This study intends to reveal the intervention effect of MBm on collagen-induced arthritis (CIA) rats, discover the potential biomarkers with efficacy, and explore the mechanisms of metabolic regulation by using metabolomics method.. Sprague Dawley (SD) rats were randomly divided into five groups: blank group, CIA model group, Munziq Balgam nomal-dosage, Munziq Balgam high-dosage group and control group. Body weight, paw swelling, arthritis index, immune indices and histopathological experiments were carried out. Plasma from rats were detected by UPLC-MS/MS. Metabolomics of plasma was performed to analyze metabolic profiles, potential biomarkers, and metabolic pathways of MBm for CIA rats. The main metabolic result of Uyghur medicine MBm was compared with that of Zhuang medicine Longzuantongbi granules (LZTBG) to explore the characteristics of two ethnic medicines from different regions for RA.. MBm could significantly alleviate symptoms of CIA rats by relieving arthritis symptoms on paw redness and swelling, inflammatory cell infiltration, synovial hyperplasia, pannus, cartilage and bone tissue destruction, as well as inhibiting the expression of IL-1β, IL-6, TNF-α, UA and ALP. Linoleic acid, alpha-linolenic acid, pantothenate and CoA biosynthesis, achidonic acid, gycerophospholipid, sphingolipid metabolism, primary bile acid biosynthesis, porphyrin and chlorophyll metabolism and fatty acid degradation served as the main nine pathways of the interventional effect of MBm on CIA rats. Twenty-three different metabolites were screened out and strongly associated with the indicator makes of RA. Eight potential efficacy-related biomarkers were finally discovered in metabolic pathway network (phosphatidylcholine, bilirubin, sphinganine 1-phosphate, phytosphingosine, SM (d18:1/16:0), pantothenic acid, l-palmitoylcarnitine, chenodeoxycholate). Three metabolites (chenodeoxycholate, hyodeoxycholic acid and O-palmitoleoylcarnitine) were changed in both the metabolic study of MBm and LZTBG intervention effects on CIA rats. Additionally, MBm and LZTBG shared the same 6 metabolic pathways including linoleic acid, alpha-linolenic acid, pantothenate and CoA biosynthesis, achidonic acid, gycerophospholipid, and primary bile acid biosynthesis.. The study suggested that MBm may effectively alleviate RA by regulating inflammation, immunity-related pathways and multiple targets. Metabolomics analysis showed that MBm (Xinjiang, the north of China) and LZTBG (Guangxi, the south of China), two ethnic medicines from different regions in China, share common metabolites and pathways but also have distinct differences in their interventions for RA.

Topics: alpha-Linolenic Acid; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Bile Acids and Salts; Biomarkers; China; Chromatography, High Pressure Liquid; Chromatography, Liquid; Edema; Linoleic Acid; Metabolomics; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

Obesity-in which free fatty acid (FFA) levels are chronically elevated-is a known risk factor for different rheumatic diseases, and obese patients are more likely to develop osteoarthritis (OA) also in non-weight-bearing joints. These findings suggest that FFA may also play a role in inflammation-related joint damage and bone loss in rheumatoid arthritis (RA) and OA. Therefore, the objective of this study was to analyze if and how FFA influence cells of bone metabolism in rheumatic diseases. When stimulated with FFA, osteoblasts from RA and OA patients secreted higher amounts of the proinflammatory cytokine interleukin (IL)-6 and the chemokines IL-8, growth-related oncogene α, and monocyte chemotactic protein 1. Receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin, and osteoblast differentiation markers were not influenced by FFA. Mineralization activity of osteoblasts correlated inversely with the level of FFA-induced IL-6 secretion. Expression of the Wnt signaling molecules, axin-2 and β-catenin, was not changed by palmitic acid (PA) or linoleic acid (LA), suggesting no involvement of the Wnt signaling pathway in FFA signaling for osteoblasts. On the other hand, Toll-like receptor 4 blockade significantly reduced PA-induced IL-8 secretion by osteoblasts, while blocking Toll-like receptor 2 had no effect. In osteoclasts, IL-8 secretion was enhanced by PA and LA particularly at the earliest time point of differentiation. Differences were observed between the responses of RA and OA osteoclasts. FFA might therefore represent a new molecular factor by which adipose tissue contributes to subchondral bone damage in RA and OA. In this context, their mechanisms of action appear to be dependent on inflammation and innate immune system rather than Wnt-RANKL pathways.

Topics: Aged; Animals; Arthritis, Rheumatoid; Cells, Cultured; Female; Humans; Interleukin-8; Leukocytes, Mononuclear; Linoleic Acid; Male; Mice, Inbred C57BL; Middle Aged; Osteoarthritis; Osteoblasts; Osteoclasts; Palmitic Acid

Topics: Adult; Aged; Aged, 80 and over; Aging; Arteriosclerosis; Arthritis, Rheumatoid; Humans; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipid Peroxidation; Lipoproteins, LDL; Middle Aged

9-Hydroxy-10,12-octadecadienoic acid (9-HODE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODE) are accumulated in the low density lipoproteins of patients suffering from rheumatoid arthritis for a factor of 20-50 compared to healthy individuals of the same age. Both acids, derived by lipid peroxidation of linoleic acid, induce the release of interleukin 1 beta. The latter induces bone degression. The genesis of 9- and 13-HODE seems therefore to be an important factor in the development and progression of rheuma; in addition 9-HODE was reported to be a stimulus of inflammation, comparable to leukotrienes.

Topics: Adult; Aged; Aldehydes; Arthritis, Rheumatoid; Chromatography, Gas; Female; Humans; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipid Peroxidation; Lipid Peroxides; Lipoproteins, LDL; Male; Mass Spectrometry; Middle Aged

Prostaglandins (PG) and related eicosanoids which derive from essential fatty acids are important mediators and modulators of inflammation. Macrophages (M phi), which derive from peripheral blood monocytes (PBM), are prominent cells in the synovium of patients with rheumatoid arthritis (RA), and are a major source of synovial PGE2. In addition, fresh and cultured PBM from RA patients produce more PG than normal control cells. When allowed to mature in culture PBM exhibit many characteristics of macrophages (M-M phi). We examined uptake by M-M phi of eicosanoid precursor fatty acids (FA), their incorporation into cellular phospholipid (PL), and mobilization of FA after cell stimulation. Cultured M-M phi from treated and untreated RA patients (RA M-M phi) took up significantly more linoleic acid (LA), dihomogammalinolenic acid (DHLA) and arachidonic acid (AA) than M-M phi from normal volunteers (N M-M phi). The enhanced uptake of FA observed in 12-day cultures of RA M-M phi was similar to uptake seen in normal human peritoneal macrophages (PM phi). After uptake FA were incorporated mainly into phosphatidylcholine (PC). M-M phi from untreated RA patients incorporated a smaller proportion of [14C]LA into PC (37.0 +/- 12.7% of total PL label) than normal cells (86.0 +/- 4.2%), and a greater proportion of [3H]AA into PC (57.1 +/- 7.1%) than normals (23.9 +/- 6.9%). Stimulation of M-M phi with calcium ionophore A23187 resulted in significantly greater hydrolysis of LA and AA from PC in RA M-M phi from both treated and untreated patients than from PC in N M-M phi. The data indicate that M-M phi from RA patients mature more rapidly in vitro than M-M phi from controls as uptake of FA by RA M-M phi increases with duration of culture and by 12 days in culture equals uptake by normal human peritoneal M phi. Also, RA M-M phi exhibit differences from N M-M phi in uptake, PL distribution, and hydrolysis of eicosanoid precursor FA. Such changes in FA metabolism might influence cell function and inflammatory responses.

Topics: 8,11,14-Eicosatrienoic Acid; alpha-Linolenic Acid; Arachidonic Acid; Arachidonic Acids; Arthritis, Rheumatoid; Calcimycin; Cell Differentiation; Cells, Cultured; Fatty Acids; Humans; Kinetics; Linoleic Acid; Linoleic Acids; Linolenic Acids; Macrophages; Membrane Lipids; Monocytes; Palmitic Acid; Palmitic Acids; Phospholipids; Prostaglandins