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Online Library: Inflammations

The following pages provide an overview of the most recent research and clinical studies about the health benefits of micronutrients in fighting inflammations. This collection of scientific facts proves that anyone who privately or publicly questions the health value of micronutrients does not serve YOUR health, or the health of the people, but rather the multi-billion dollar investment 'business with disease' based on patented pharmaceutical drugs.

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A multi-nutrient supplement reduced markers of inflammation and improved physical performance in active individuals of middle to older age: a randomized, double-blind, placebo-controlled study.

Source: Nutrition journal 2011; 10(1):90.

Author: Dunn-Lewis C, Kraemer WJ, Kupchak BR, Kelly NA, Creighton BA, Luk HY, Ballard KD, Comstock BA, Szivak TK, Hooper DR, Denegar CR, Volek JS.

Affiliation: Human Performance Laboratory, Department of Kinesiology, University of Connecticut, Storrs, CT, 06269, USA.

Abstract: While exercise acts to combat inflammation and aging, the ability to exercise may itself be compromised by inflammation and inflammation's impact on muscle recovery and joint inflammation. A number of nutritional supplements have been shown to reduce inflammation and improve recovery. The purpose of the current investigation was to examine the effect of a multi-nutrient supplement containing branched chain amino acids, taurine, anti-inflammatory plant extracts, and B vitamins on inflammatory status, endothelial function, physical function, and mood in middle-aged individuals. 31 healthy and active men and women participated in this investigation. Subjects completed one 28 day cycle of placebo supplementation and one 28 day cycle of multi-nutrient supplementation (separated by a one week washout period) in a balanced, randomized, double-blind, cross-over design. Testing consisted of brachial artery flow mediated dilation (FMD), blood measures, and physical performance on vertical jump, handgrip strength, and balance (dispersion from center of pressure). Conclusions: A multi-nutrient supplement is effective in improving inflammatory status in both men and women, markers of pain, joint pain, strength, and power in men only, and both anxiety and balance (a risk factor for hip fracture) in women. Therefore, a multi-nutrient supplement may help middle-aged individuals to prolong physical function and maintain a healthy, active lifestyle.

A multi-nutrient supplement reduced markers of inflammation and improved physical performance in active individuals of middle to older age: a randomized, double-blind, placebo-controlled study

Source: Nutrition Journal 2011, 10:90 doi:10.1186/1475-2891-10-90

Author: Dunn-Lewis C, Kraemer WJ, Kupchak BR, Kelly NA, et al.

Affiliation: Human Performance Laboratory, Department of Kinesiology, University of Connecticut, Storrs, CT, 06269, USA

Abstract: While exercise acts to combat inflammation and aging, the ability to exercise may itself be compromised by inflammation and inflammation's impact on muscle recovery and joint inflammation. A number of nutritional supplements have been shown to reduce inflammation and improve recovery. The purpose of the current investigation was to examine the effect of a multi-nutrient supplement containing branched chain amino acids, taurine, anti-inflammatory plant extracts, and B vitamins on inflammatory status, endothelial function, physical function, and mood in middle-aged individuals. Thirty-one healthy and active men and women participated in this investigation. Subjects completed one 28 day cycle of placebo supplementation and one 28 day cycle of multi-nutrient supplementation (separated by a one week washout period) in a balanced, randomized, double-blind, cross-over design. Subjects completed weekly perceptual logs and pre- and post- testing around the supplementation period. Testing consisted of brachial artery flow mediated dilation (FMD), blood measures, and physical performance on vertical jump, handgrip strength, and balance (dispersion from centre of pressure). Significance for the investigation was p ≤ 0.05. Perceived energy improved for both men and women. General pain, and joint pain decreased in men only, while anxiety and balance improved in women only. Men showed increased performance in vertical jump power and grip strength. Conclusions: A multi-nutrient supplement is effective in improving inflammatory status in both men and women, markers of pain, joint pain, strength, and power in men only, and both anxiety and balance (a risk factor for hip fracture) in women. Therefore, a multi-nutrient supplement may help middle-aged individuals to prolong physical function and maintain a healthy, active lifestyle.

Association of serum n-3 polyunsaturated fatty acids with C-reactive protein in men.

Source: European Journal of Clinical Nutrition 2011 Nov 23. doi: 10.1038/ejcn.2011.195. [Epub ahead of print]

Author: Reinders I, Virtanen JK, Brouwer IA, Tuomainen TP.

Affiliation: Department of Health Sciences and the EMGO Institute for Health Care Research, VU University Amsterdam, Amsterdam, The Netherlands.

Abstract: N-3 polyunsaturated fatty acids (PUFAs) have been associated with reduced inflammation. The authors tested the hypothesis that high serum concentrations of the n-3 PUFAs are associated with lower serum C-reactive protein (CRP) concentrations in healthy middle-aged Finnish men. They also examined whether exposure to mercury, an environmental contaminant in fish, which is also a major source of long-chain n-3 PUFA, was associated with CRP. Data from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study were analyzed cross-sectionally to determine the associations between serum n-3 PUFAs, hair mercury and serum CRP in 1395 healthy men, aged 42-60 years. Linear regression analyses were performed to analyze the associations. Conclusions: Serum n-3 PUFAs and especially the long-chain n-3 PUFA concentration, a marker of fish or fish oil consumption, were inversely associated with serum CRP in men. Exposure to mercury was not associated with serum CRP.

Oral green tea catechin metabolites are incorporated into human skin and protect against UV radiation-induced cutaneous inflammation in association with reduced production of pro-inflammatory eicosanoid 12-hydroxyeicosatetraenoic acid.

Source: Br J Nutr. 2013 Jan 28:1-10.

Author: Rhodes LE, Darby G, Massey KA, Clarke KA, Dew TP, Farrar MD, Bennett S, Watson RE, Williamson G, Nicolaou A.

Affiliation: Photobiology Unit, Dermatology Centre, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Hospital, Manchester M6 8HD, UK.

Abstract: Green tea catechins (GTC) reduce UV radiation (UVR)-induced inflammation in experimental models, but human studies are scarce and their cutaneous bioavailability and mechanism of photoprotection are unknown. The authors aimed to examine oral GTC cutaneous uptake, ability to protect human skin against erythema induced by a UVR dose range and impact on potent cyclo-oxygenase- and lipoxygenase-produced mediators of UVR inflammation, PGE2 and 12-hydroxyeicosatetraenoic acid (12-HETE), respectively. In an open oral intervention study, 16 healthy human subjects were given low-dose GTC (540 mg) with vitamin C (50 mg) daily for 12 weeks. Pre- and post-supplementation, the buttock skin was exposed to UVR and the resultant erythema quantified. Skin blister fluid and biopsies were taken from the unexposed and the UVR-exposed skin 24 hours after a pro-inflammatory UVR challenge (3 minimal erythema doses). Urine, skin tissue and fluid were analysed for catechin content and skin fluid for PGE2 and 12-HETE by liquid chromatography coupled to tandem MS. A total of fourteen completing subjects were supplement compliant (twelve female, median 42•5 years, range 29-59 years). Benzoic acid levels were increased in skin fluid post-supplementation (P= 0•03), and methylated gallic acid and several intact catechins and hydroxyphenyl-valerolactones were detected in the skin tissue and fluid. AUC analysis for UVR erythema revealed reduced response post-GTC (P= 0•037). Pre-supplementation, PGE2 and 12-HETE were UVR induced (P= 0•003, 0•0001). After GTC, UVR-induced 12-HETE reduced from mean 64 (sd 42) to 41 (sd 32) pg/ěl (P= 0•01), while PGE2 was unaltered. Conclusion: GTC intake results in the incorporation of catechin metabolites into human skin associated with abrogated UVR-induced 12-HETE; this may contribute to protection against sunburn inflammation and potentially longer-term UVR-mediated damage.


Antioxidant and anti-inflammatory properties of curcumin.

Source: Advances in experimental medicine and biology 2007; 595:105-25

Author: Menon VP, Sudheer AR.

Affiliation: Department of Biochemistry & Center for Micronutrient Research, Annamalai University, Tamilnadu, India.

Abstract: Curcumin, a yellow pigment from Curcuma longa, is a major component of turmeric and is commonly used as a spice and food-coloring agent. It is also used as a cosmetic and in some medical preparations. The desirable preventive or putative therapeutic properties of curcumin have also been considered to be associated with its antioxidant and anti-inflammatory properties. Because free-radical-mediated peroxidation of membrane lipids and oxidative damage of DNA and proteins are believed to be associated with a variety of chronic pathological complications such as cancer, atherosclerosis, and neurodegenerative diseases, curcumin is thought to play a vital role against these pathological conditions. Because inflammation is closely linked to tumor promotion, curcumin with its potent anti-inflammatory property is anticipated to exert chemopreventive effects on carcinogenesis. Hence, the past few decades have witnessed intense research devoted to the antioxidant and anti-inflammatory properties of curcumin. In this review, the authors describe both antioxidant and anti-inflammatory properties of curcumin, the mode of action of curcumin, and its therapeutic usage against different pathological conditions.

Suppression of NF-kappaB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: Implications for the treatment of osteoarthritis.

Source: Biochemical pharmacolog 2007; 73(9): 1434-45

Author: Shakibaei M, John T, Schulze-Tanzil G, Lehmann I, Mobasheri A.

Affiliation: Institute of Anatomy, Ludwig-Maximilians-University Munich, Germany.

Abstract: Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) play a key role in the pathogenesis of osteoarthritis (OA). Anti-inflammatory agents capable of suppressing the production and catabolic actions of these cytokines may have therapeutic potential in the treatment of OA and a range of other osteoarticular disorders. The purpose of this study was to examine the effects of curcumin (diferuloylmethane), a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signaling pathways in human articular chondrocytes maintained in vitro. The effects of curcumin were studied in cultures of human articular chondrocytes treated with IL-1beta and TNF-alpha for up to 72h. Expression of collagen type II, integrin beta1, cyclo-oxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) was monitored by western blotting. The effects of curcumin on the expression, phosphorylation and nuclear translocation of protein components of the NF-kappaB system were studied by western blotting and immunofluorescence, respectively. Treatment of chondrocytes with curcumin suppressed IL-1beta-induced NF-kappaB activation via inhibition of IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation and p65 nuclear translocation. Curcumin inhibited the IL-1beta-induced stimulation of up-stream protein kinase B Akt. These events correlated with down-regulation of NF-kappaB targets including COX-2 and MMP-9. Similar results were obtained in chondrocytes stimulated with TNF-alpha. Curcumin also reversed the IL-1beta-induced down-regulation of collagen type II and beta1-integrin receptor expression. These results indicate that curcumin has nutritional potential as a naturally occurring anti-inflammatory agent for treating OA through suppression of NF-kappaB mediated IL-1beta/TNF-alpha catabolic signalling pathways in chondrocytes.

Curcumin Modulates Nuclear Factor {kappa}B (NF-{kappa}B)-mediated Inflammation in Human Tenocytes in Vitro: ROLE OF THE PHOSPHATIDYLINOSITOL 3-KINASE/Akt PATHWAY.

Source: The Journal of biological chemistry 2011; 286(32): 28556-66

Author: Buhrmann C, Mobasheri A, Busch F, Aldinger C, Stahlmann R, Montaseri A, Shakibaei M.

Affiliation: From the Musculoskeletal Research Group, Institute of Anatomy, Ludwig-Maximilian-University Munich, Germany.

Abstract: Inflammatory processes play essential roles in the pathogenesis of tendinitis and tendinopathy. These events are accompanied by catabolic processes initiated by pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Pharmacological treatments for tendinitis are restricted to the use of non-steroidal anti-inflammatory drugs. Recent studies in various cell models have demonstrated that curcumin targets the NF-κB* signaling pathway. However, its potential for the treatment of tendinitis has not been explored. Herein, we used an in vitro model of human tenocytes to study the mechanism of curcumin action on IL-1β-mediated inflammatory signaling. Curcumin at concentrations of 5-20 μm inhibited IL-1β-induced inflammation and apoptosis in cultures of human tenocytes. The anti-inflammatory effects of curcumin included down-regulation of gene products that mediate matrix degradation (matrix metalloproteinase-1, -9, and -13), prostanoid production (cyclooxygenase-2), apoptosis (Bax and activated caspase-3), and stimulation of cell survival (Bcl-2), all known to be regulated by NF-κB. Furthermore, curcumin suppressed IL-1β-induced NF-κB activation via inhibition of phosphorylation and degradation of inhibitor of κBα, inhibition of inhibitor of κB-kinase activity, and inhibition of nuclear translocation of NF-κB. Furthermore, the effects of IL-1β were abrogated by wortmannin, suggesting a role for the phosphatidylinositol 3-kinase (PI-3K) pathway in IL-1β signaling. Curcumin suppressed IL-1β-induced PI-3K p85/Akt activation and its association with IKK. These results demonstrate, for the first time, a potential role for curcumin in treating tendon inflammation through modulation of NF-κB signaling, which involves PI-3K/Akt* and the tendon-specific transcription factor scleraxis* in tenocytes.

• NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls the transcription of DNA. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection (kappa light chains are critical components of immunoglobulins). Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development.

• Phosphatidylinositol 3-kinases (PI 3-kinases or PI3Ks) are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.

• The scleraxis protein is a member of the basic-helix-loop-helix (bHLH) superfamily of transcription factors. It is thought that early scleraxis expressing progenitor cells lead to the eventual formation of tendon tissue and other muscle attachments.

Biological actions of curcumin on articular chondrocytes.

Source: Osteoarthritis and cartilage 2010; 18(2): 141-9

Author: Henrotin Y, Clutterbuck AL, Allaway D, Lodwig EM, Harris P, Mathy-Hartert M, Shakibaei M, Mobasheri A.

Affiliation: University of Ličge, Institute of Pathology, Sart-Tilman, Ličge, Belgium.

Abstract: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. The authors highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). They also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signaling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA.

A pilot study of the antioxidant effect of curcumin in tropical pancreatitis

Source: The Indian journal of medical research 2005; 122(4):315-8

Author: Durgaprasad S, Pai CG, Vasanthkumar, Alvres JF, Namitha S.

Affiliation: Department of Pharmacology, Kasturba Medical College, Manipal, India.

Abstract: Oxidative stress occurs in association with painful exacerbations of chronic pancreatitis and antioxidant supplementation appears to benefit this condition. Curcumin, the active constituent of turmeric, is known to exhibit antioxidant activity. This pilot study was therefore undertaken to evaluate the effect of oral curcumin with piperine* on the pain, and the markers of oxidative stress in patients with tropical pancreatitis (TP). Twenty consecutive patients with tropical pancreatitis were randomized to receive 500 mg of curcumin with 5 mg of piperine, or placebo for 6 wk, and the effects on the pattern of pain, and on red blood cell levels of malonyldialdehyde* (MDA) and glutathione (GSH) were assessed. There was a significant reduction in the erythrocyte MDA levels following curcumin therapy compared with placebo; with a significant increase in GSH levels. There was no corresponding improvement in pain. Conclusion: Oral curcumin with piperine reversed lipid peroxidation in patients with tropical pancreatitis. Further studies with large sample are needed to define its effect on the pain and other manifestations of tropical pancreatitis.

* Piperine is the alkaloid responsible for the pungency of black pepper and long pepper.
* Malonyldialdehyde (MDA) is a product of fatty acid peroxidation (the oxidative degradation of lipids).


Neutrophil Restraint by Green Tea: Inhibition of Inflammations, Associated Angiogenesis, and Pulmonary Fibrosis

Source: The Journal of Immunology 2003; 170: 4335–4341

Author: Massimo Dona1, Isabella Dell’Aica1, Fiorella Calabrese2, Roberto Benelli2, Monica Morini2, Adriana Albini2, and Spiridione Garbisa1

Affiliation: Departments of Experimental Biomedical Sciences and Pathology, Medical School of Padova, Padova, Italy1 and Molecular Biology Laboratory, National Institute for Research on Cancer, Genova, Italy2

Abstract: Green tea has been claimed to exert anti-inflammatory properties through unknown molecular mechanisms. The researchers have previously documented that the most abundant catechin of green tea, epigallocatechin-3-gallate (EGCG), strongly inhibits neutrophil elastase. The presented study shows that 1) micromolar EGCG represses reactive oxygen species activity and inhibits apoptosis of activated neutrophils, and 2) dramatically inhibits chemokine-induced neutrophil chemotaxis in vitro; 3) both oral EGCG and green tea extract block neutrophil-mediated angiogenesis in vivo in an inflammatory angiogenesis model, and 4) oral administration of green tea extract enhances resolution in a pulmonary inflammation model, significantly reducing consequent fibrosis. These results provide molecular and cellular insights into the claimed beneficial properties of green tea and indicate that EGCG is a potent anti-inflammatory compound with therapeutic potential.

EGCG and Polyphenon E Attenuate Inflammation-Related Mouse Colon Carcinogenesis Induced by AOM Plus DDS

Source: Molecular Medicine Reports 2008; 1(3): 355–361

Author: Yohei Shirakami, Masahito Shimizu, Hisashi Tsurumi, Yukihiko Hara, Takuji Tanaka, Hisakata Moriwaki

Affiliation: Department of Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan

Abstract: This study investigated whether epigallocatechin gallate (EGCG), a candidate chemopreventive agent and major biologically-active component of green tea, and Polyphenon E (Poly E), a mixture of GTCs, suppress inflammation-related colon carcinogenesis induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) in mice. At week 17, treatment with EGCG or Poly E had significantly suppressed the multiplicity and volume of colonic neoplasms as compared to the AOM/DSS group, and had resulted in a lesser degree of malignancy. In addition, treatment with EGCG or Poly E decreased the protein and mRNA expression levels of Cyclooxygenase (COX)-2 and the mRNA expression of inflammatory cytokines (TNF-α, IFN-γ, IL-6, IL-12 and IL-18) in the colonic mucosa. These findings provide evidence that tea catechins are beneficial to the suppression of cancer development in the inflamed colon.

Epigallocatechin Gallate Inhibits Endothelial Exocytosis

Source: Biological Chemistry 2008; 389(7): 935–941

Author: Munekazu Yamakuchi1, Clare Bao1, Marcella Ferlito1, Charles J. Lowenstein1,2

Affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA1 and Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA2

Abstract: This study hypothesized that epigallocatechin gallate (EGCG), the most abundant polyphenol in tea, inhibits endothelial exocytosis, the initial step in leukocyte trafficking and vascular inflammation. This study found that EGCG indeed decreases endothelial exocytosis in a concentration-dependent manner, with the effects most prominent after 4 h of treatment. Other catechin polyphenols had no effect on endothelial cells. The study data suggest that polyphenols can decrease vascular inflammation by increasing the synthesis of NO, which blocks endothelial exocytosis.

New Research Identifies Possible Mechanism for Green Tea's Anti-Cancer Effects: [EGCG] Modulates Cellular Signaling Involved in Chronic Inflammation

Source: Oncology Times 2005; : 27(17): 45

Author: Eastman, Peggy


Abstract: This study highlighted the ability of some phytochemicals, including EGCG, to modulate the cellular signaling involved in chronic inflammation that may be linked to an increased risk of cancer. EGCG is known to interact with NfkB, a key regulator of immune and inflammatory responses. Inflammation has long been suspected to contribute to carcinogenesis, noted Young-Joon Surh, PhD, Professor and Chief of the National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University in Seoul. A new horizon in chemoprevention research is the recent discovery of molecular links between inflammation and cancer, he added.

Folic Acid

Folic Acid, Inflammation, and Atherosclerosis : False Hopes or the Need for Better Trials?

Source: Clinica Chimica Acta 2006; 367(1-2): 11-19

Author: Mangoni Arduino A.


Abstract: The B-vitamin folic acid has recently gained attention because of its potential to provide beneficial effects on surrogate end-points, such as endothelial function, in patients at high cardiovascular risk. However, the role of folic acid in mitigating the pro-inflammatory state associated with atherosclerosis is controversial. This review considers the current evidence supporting the role of some well-established inflammatory markers in predicting cardiovascular outcomes, the mechanisms by which folic acid might exert anti-inflammatory effects, the epidemiological data relating folic acid concentrations with inflammatory markers, the published interventional studies on the effects of folic acid supplementation on these markers, and the factors that need to be considered in designing future trials.

Folic Acid Protects Motor Neurons Against the Increased Homocysteine, Inflammation and Apoptosis in SOD1 G93A Transgenic Mice

Source: Neuropharmacology 2008; 54(7): 1112-9

Author: Zhang X, Chen S, Li L, Wang Q, Le W.

Affiliation: Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, PR China.

Abstract: Using SOD1(G93A) mice model of ALS, this study demonstrated that mutation in SOD1 caused a significant increase in the level of plasma homocysteine (Hcy). The results showed FA or FA+B12 treatment significantly delayed the disease onset and prolonged the lifespan, accompanied by the significant reduction of motor neuron loss. Moreover, FA or FA+B12 treatment decreased the levels of cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP) but up-regulated the level of anti-apoptotic protein Bcl-2. These results provide evidence to demonstrate that elevated Hcy is involved in the pathogenesis of fALS and FA therapy may have therapeutic potential for the treatment of the disease.


Effect of a High Dose of glucosamine on systemic and tissue inflammation in an experimental model of atherosclerosis aggravated by chronic arthritis

Source: American Journal of Physiology – Heart and Circulatory Physiology 2009; 297: H268-H276.

Author: Raquel Largo,1 María José Martínez-Calatrava,1 Olga Sánchez-Pernaute,1 M. Esther Marcos,1 Juan Moreno-Rubio,1 César Aparicio,2 Jesús Egido,3 and Gabriel Herrero-Beaumont1

Affiliation: Joint and Bone Research Unit1 and Department of Vascular Surgery2, Vascular Research Laboratory, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain3

Abstract: This study set out to explore the effect of glucosamine (GS) administration on markers of systemic and local inflammation in rabbits with atherosclerosis aggravated by chronic arthritis. A group of these rabbits was treated prophylactically with oral GS (500 mg·kg–1·day–1), and, when the animals were killed, serum was extracted and peripheral blood mononuclear cells (PBMC) were isolated. The results of this study show that in a combined rabbit model of chronic arthritis and atherosclerosis, orally administered GS reduced the markers of inflammation in peripheral blood, as well as the femoral and synovial membrane lesions. GS also prevented the development of inflammation-associated aortic lesions. These results suggest an atheroprotective effect of GS.

Green Tea

Green Tea Increases Anti-Inflammatory Tristetraprolin and Decreases Pro-Inflammatory Tumor Necrosis Factor mRNA Levels in Rats

Source: Journal of Inflammation 2007; 4:1

Author: Heping Cao,1 Meghan A. Kelly,1 Frank Kari,2 Harry D. Dawson,1 Joseph F. Urban Jr,1 Sara Coves,3 Anne M. Roussel4 and Richard A. Anderson1

Affiliation: Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Building 307C, BARC-East, 10300 Baltimore Avenue, Beltsville, MD 20705, USA;1 Office of Clinical Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA;2 Unilever France, F92842 Rueil Malmaison, France;3 Laboratoire de NVMC (Nutrition, Vieillissement et Maladies Cardiovasculaires), Faculte de Pharmacie, Joseph Fourier University, Domaine de la Merci, 38700 La Tronche, France4

Abstract: Tea has anti-inflammatory properties but the molecular mechanisms have not been completely elucidated. This study hypothesized that TTP and/or its homologues might contribute to the beneficial effects of tea as an anti-inflammatory product. Quantitative real-time PCR was used to investigate the effects of green tea (0, 1, and 2 g solid extract/kg diet) on the expression of Ttp family genes (Ttp/Tis11/Zfp36, Zfp36l1/Tis11b, Zfp36l2/Tis11d, Zfp36l3), pro-inflammatory genes (Tnf, Csf2/Gm-csf, Ptgs2/Cox2), andElavl1/Hua/Hur andVegf genes in liver and muscle of rats fed a high-fructose diet known to induce insulin resistance, oxidative stress, inflammation, and TNF-alpha levels. The results show that tea can modulate Ttp mRNA levels in animals and suggest that a post-transcriptional mechanism through TTP could partially account for tea's anti-inflammatory properties. The results also suggest that drinking adequate amounts of green tea may play a role in the prevention of inflammation-related diseases.

Effect of Green Tea Consumption on Inflammation, Insulin Resistance and Pulse Wave Velocity in Type 2 Diabetes Patients

Source: Diabetes Research and Clinical Practice 2006; 71(3): 356–358

Author: O.H. Ryu,1 J. Lee,2 K.W. Lee,1 H.Y. Kim,1 J.A. Seo,1 N.H. Kim,1 S.H. Baik,1 D.S. Choi,1 K.M. Choi1

Affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, 80 Guro-Dong, Guro-Gu, Seoul 152-050, South Korea;1 Department of Preventive Medicine, Korea University, Seoul, South Korea2

Abstract: This study examined the effects of green tea on  inflammation and arterial stiffnea nin type 2 diabets pawtients. As results, inflammatory markers, such as hsCRP and IL-6, were unchanged after green tea consumption, and neither were blood glucose, lipid profiles, insulin resistance, or serum adiponectin levels. Furthermore, tea consumption did not improve baPWV. These results suggest that the above-described mechanisms are unlikely to explain the cardiovascular risk reduction by tea consumption observed in epidemiological studies.

Effect of Green Tea Polyphenols on Chronic Inflammation-Induced Bone Loss in Female Rats

Source: The FASEB Journal, 2008; 22:314.3.

Author: Chwan-Li Shen,1 James K. Yeh,2 Xiao-Qing Liu,2 Dale M Dunn,1 Barbara J Stoecker,3 Piwen Wang,4 Yuntian Tang41 and Jia-Sheng Wang4

Affiliation: Pathology, Texas Tech University Health Sciences Center, Lubbock, TX;1 Medicine, Winthrop-University Hospital, Mineola, NY;2 Nutritional Sciences, Oklahoma State University, Stillwater, OK;3 Environmental Toxicology, The Institute Enviornmental & Human Health, Lubbock, TX4

Abstract: This study further examines effects of GTPs on chronic-inflammation-induced bone loss of female rats. A 2 (placebo vs. lipopolysaccharide, LPS) x 2 (no GTPs vs. 0.5% GTPs in drinking water) factorial design using 40 female rats (3-month-old) assigned to 4 groups (n=10/group): placebo (P, placebo implantation), LPS implantation (L), P+0.5% GTP (PG), and LPS+0.5% GTP (LG) for 12 wks. After 12 weeks, LPS resulted in a significant increase in inflammation index based on white blood cell count (WBC), accompanied by a significant decrease in bone mineral density (BMD). Supplementation of GTP significantly lowered the WBC and increased BMD. This study suggests a potentially significant prophylactic role of green tea in bone health of women with chronic inflammation-induced bone loss.


Effectiveness of Carbocysteine Lysine Salt Monohydrate on Models of Airway Inflammation and Hyperresponsiveness

Source: Pharmacological Research 1995; 31(6): 387-392

Author: C. Asti,1 G. Melillo,1 G. F. Caselli,1 L. Daffonchio,1 G. Clavenna,1 C. Omini1 and A. Hernandez2

Affiliation: Dompe' S.p.A., Department of Pharmacology, L'Aquila, Italy;1 Institute of Pharmacological Sciences, University of Milan, Italy2

Abstract: This study investigated the possible effects of the mucoactive drug Carbocysteine lysine salt monohydrate (CLS.H2O) on experimentally-induced airway inflammation and hyperresponsiveness. CLS.H2O given by the oral route (300 mg kg−1 significantly reduced neutrophil infiltration into the airway lumen induced by intratracheal injection of IL-1β in rats. In addition, CLS.H2O inhibited dose-dependently (100–300 mg kg−1 p.o.) the formation of pleural exudate and leukocyte recruitment induced by intrapleural injection of carrageenan in rats. These results suggest that CLS.H2O can exert an anti-inflammatory action in addition to its mucoregulatory activity. The anti-inflammatory and anti-hyperreactivity effect of the drug within the airways may be of advantage in the treatment of inflammatory lung diseases where mucus secretion together with airway inflammation and hyperreactivity contribute to airway obstruction.

Role of the Lysine-Specific Demethylase 1 in the Proinflammatory Phenotype of Vascular Smooth Muscle Cells of Diabetic Mice

Source: Circulation Research 2008; 103(6): 615-623

Author: Reddy Marpadga A.;1 Villeneuve Louisa M.;1,2 Mei Wang;1 Lating Linda;1 Nataraja Rama1,2

Affiliation: Department of Diabetes, Beckman Research Institute of City of Hope, Duarte, CA;1 Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA2

Abstract: Insulin resistance and type 2 diabetes are major risk factors for vascular complications. Vascular smooth muscle cells (VSMCs) derived from db/db mice, an established mouse model of type 2 diabetes, displayed enhanced inflammatory gene expression and proatherogenic responses. This study examined the hypothesis that aberrant epigenetic behavior and "memory" of the diabetic cells. Protein levels of lysine-specific chromatin events may the underlying mechanism for this persistent dysfunctional demethylasel (LSD1), which negatively regulates H3K4 methylation and its occupancy at these gene promoters, were significantly reduced in dbldb VSMCs. The results demonstrate novel functional roles for LSD1 and H3K4 methylation in VSMCs and inflammation.

Inhibitory Effects of Lysine Analogue Tranexamic Acid on Collagen Degradation in Inflamed Gingival Tissue

Source: Fragr Journal 2004;.32(7): 26-31

Author: Kigawa Mari, Kataoka Shinsuke


Abstract: This study evaluated the effect of the lysine analogue tranexamic acid (TXA), an inhibitor of plasmin, on gingival inflammation. This study applied a hamster gingival inflammation model to investigate collagen degradation and plasmin localization in gingiva. TXA (15 mg/body) or placebo was administered orally once daily for 3 weeks. Upregulation of MMP activity was observed in the inflamed gingival tissue. Although plasmin was strongly stained in the all sections of inflamed gingival tissue in the placebo group, plasmin was localized around vessels in the TXA group. In addition, we also found that TXA reduced the fMLP-induced neutrophil chemotaxis in a dose-dependent manner. The results suggest that TXA inhibits the collagen degradation of inflamed gingiva by controlling the plasmin related MMP activation pathways and prevents gingival inflammation by reducing the neutrophil migration rate.

Omega 3 Fatty Acids

Omega-3 Fatty Acids and Inflammation

Source: Curr Atheroscler Rep 2004; 6(6): 461-7

Author: Mori T.A., Beilin L.J.

Affiliation: School of Medicine and Pharmacology--Royal Perth Hospital Unit, The University of Western Australia, Medical Research Foundation Building, Perth, Western Australia 6847, Australia.

Abstract: Dietary omega-3 (n-3) fatty acids have a variety of anti-inflammatory and immune-modulating effects that may be of relevance to atherosclerosis and its clinical manifestations of myocardial infarction, sudden death, and stroke. Epidemiologic studies provide evidence for a beneficial effect of n-3 fatty acids on manifestations of coronary heart disease and ischemic stroke, whereas randomized, controlled, clinical feeding trials support this, particularly with respect to sudden cardiac death in patients with established disease. Clinically important anti-inflammatory effects in man are further suggested by trials demonstrating benefits of n-3 fatty acids in rheumatoid arthritis, psoriasis, asthma, and inflammatory bowel disorders. Given the evidence relating progression of atherosclerosis to chronic inflammation, the n-3 fatty acids may play an important role via modulation of the inflammatory processes.

Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases

Source: J Am Coll Nutr 2002; 21(6): 495-505.

Author: Simopoulos A.P.

Affiliation: The Center for Genetics, Nutrition and Health, Washington, DC 20009, USA

Abstract: Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn's disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB(4) produced by omega-6 fatty acids. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.

Dietary Modification of Inflammation with Lipids

Source: Proc Nutr Soc 2002; 61(3): 345-58

Author: Calder P.C.

Affiliation: Institute of Human Nutrition, University of Southampton, Bassett Crescent East, UK

Abstract: Animal and human studies have shown that dietary fish oil results in suppressed production of pro-inflammatory cytokines and can decrease adhesion molecule expression. These effects occur at the level of altered gene expression. Recent studies have shown that n-3 PUFA can down regulate the activity of the nuclear transcription factor NFB. Fish oil feeding has been shown to ameliorate the symptoms in some animal models of chronic inflammatory disease and to protect against the effects of endotoxin and similar inflammatory challenges. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some patients with asthma, supporting the idea that the n-3 PUFA in fish oil are anti-inflammatory. There are indications that inclusion of n-3 PUFA in enteral and parenteral formulas might be beneficial to patients in intensive care or post-surgery.

Fatty Acids, the Immune Response, and Autoimmunity: a Question of n-6 Essentiality and the Balance Between n-6 and n-3

Source: Lipids 2003; 38(4): 323-41

Author: Harbige L.S.

Affiliation: School of Chemical and Life Sciences, University of Greenwich at Medway, Chatham Maritime, Kent ME4 4TB, United Kingdom

Abstract: Low intakes of long-chain n-3 fatty acids (fish oils) enhance certain immune functions, whereas high intakes are inhibitory on a wide range of functions, e.g., antigen presentation, adhesion molecule expression, Th1 and Th2 responses, proinflammatory cytokine and eicosanoid production, and they induce lymphocyte apoptosis. The effect of dietary fatty acids on animal autoimmune disease models depends on both the autoimmune model and the amount and type of fatty acids fed. Diets low in fat, essential fatty acid deficient (EFAD), or high in long-chain n-3 PUFA from fish oils increase survival and reduce disease severity in spontaneous autoantibody-mediated disease, whereas high-fat LA-rich diets increase disease severity. Finally, the view that all n-6 PUFA are proinflammatory requires revision, in part, and their essential regulatory and developmental role in the immune system warrants appreciation.

Beneficial Effect(s) of n-3 Fatty Acids in [Inflammations] in Cardiovascular Diseases: But, Why and How?

Source: Prostaglandins Leukot Essent Fatty Acids 2000; 63(6): 351-62

Author: Das U.N.

Affiliation: EFA Sciences LLC, 1420 Providence Highway, Norwood, MA 02062, USA

Abstract: Low rates of coronary heart disease was found in Greenland Eskimos and Japanese who are exposed to a diet rich in fish oil. Suggested mechanisms for this cardio-protective effect focused on the effects of n-3 fatty acids on eicosanoid metabolism, inflammation, beta oxidation, endothelial dysfunction, cytokine growth factors, and gene expression of adhesion molecules; But, none of these mechanisms could adequately explain the beneficial actions of n-3 fatty acids. It is suggested that the principle mechanism of cardioprotective and neuroprotective action(s) of n-3 fatty acids can be due to the suppression of TNFalpha and IL synthesis and release, modulation of hypothalamic-pituitary-adrenal anti-inflammatory responses, and an increase in acetylcholine release, the vagal neurotransmitter.

Omega-3 Fatty Acids and Inflammation: Novel Interactions Reveal a New Step in Neutrophil Recruitment

Source: PLoS Biol 2009; 7(8): e1000177

Author: Samantha P. Tull,1 Clara M. Yates,1 Benjamin H. Maskrey,2 Valerie B. O'Donnell,2 Jackie Madden,3 Robert F. Grimble,3 Philip C. Calder,3 Gerard B. Nash,1 G. Ed. Rainger1

Affiliation: Centre for Cardiovascular Sciences, School of Clinical and Experimental Medicine, The Medical School, The University of Birmingham, Birmingham, United Kingdom,1 Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, United Kingdom,2 Institute of Human Nutrition, School of Medicine, University of Southampton, Southampton, United Kingdom3

Abstract: Inflammation is a physiological response to tissue trauma or infection, but leukocytes, which are the effector cells of the inflammatory process, have powerful tissue remodelling capabilities. This study describes a new step in the neutrophil recruitment process that relies upon a lipid-mediated signal to regulate the migration of neutrophils across endothelial cells. Importantly, the ability of the dietary n-3-PUFA, EPA, to inhibit this process not only revealed an unsuspected level of regulation in the migration of inflammatory leukocytes, it also contributes to our understanding of the interactions of this bioactive lipid with the inflammatory system. Moreover, it indicates the potential for novel therapeutics that target the inflammatory system with greater affinity and/or specificity than supplementing the diet with n-3-PUFAs.

Polyunsaturated fatty acids and inflammation.

Source: Biochem Soc Trans. 2005;33:423-427

Author: Calder PC.

Affiliation: Institute of Human Nutrition, School of Medicine, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.

Abstract: The n-6 polyunsaturated fatty acid, arachidonic acid, is a precursor of prostaglandins, leukotrienes and related compounds that have important roles as mediators and regulators of inflammation. Consuming increased amounts of long chain n-3 polyunsaturated fatty acids (found in oily fish and fish oils) results in a partial replacement of the arachidonic acid in cell membranes by eicosapentaenoic and docosahexaenoic acids. This leads to decreased production of arachidonic acid-derived mediators. This alone is a potentially beneficial anti-inflammatory effect of n-3 fatty acids. However, n-3 fatty acids have a number of other effects that might occur downstream of altered eicosanoid production or are independent of this. For example, they result in suppressed production of pro-inflammatory cytokines and can modulate adhesion molecule expression. These effects occur at the level of altered gene expression.

N-3 polyunsaturated fatty acids and inflammation: from molecular biology to the clinic.

Source: Lipids. 2003;38(4):343-352

Author: Calder PC.

Affiliation: Institute of Human Nutrition, School of Medicine, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, United Kingdom.

Abstract: The immune system is involved in host defense against infectious agents, tumor cells, and environmental insults. Inflammation is an important component of the early immunologic response. Inappropriate or dysfunctional immune responses underlie acute and chronic inflammatory diseases. The n-6 PUFA arachidonic acid (AA) is the precursor of prostaglandins, leukotrienes, and related compounds that have important roles in inflammation and in the regulation of immunity. Feeding fish oil results in partial replacement of AA in cell membranes by EPA. This leads to decreased production of AA-derived mediators, through several mechanisms, including decreased availability of AA, competition for cyclooxygenase (COX) and lipoxygenase (LOX) enzymes, and decreased expression of COX-2 and 5-LOX. This alone is a potentially beneficial anti-inflammatory effect of n-3 FA. However, n-3 FA have a number of other effects that might occur downstream of altered eicosanoid production or might be independent of this effect. For example, dietary fish oil results in suppressed production of proinflammatory cytokines and can modulate adhesion molecule expression. These effects occur at the level of altered gene expression. Fish oil feeding has been shown to ameliorate the symptoms of some animal models of autoimmune disease and to protect against the effects of endotoxin. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some asthmatics, supporting the idea that the n-3 FA in fish oil are anti-inflammatory. There are indications that the inclusion of fish oil in enteral and parenteral formulae is beneficial to patients.

Modulation of human immune and inflammatory responses by dietary fatty acids.

Source: Nutrition. 2001 Jul-Aug;17(7-8):669-673

Author: Kelley DS.

Affiliation: Western Human Nutrition Research Center, ARS/USDA, and the Department of Nutrition, University of California at Davis, Davis, California, USA.

Abstract: I review the effects of the amount and composition of dietary fat on indices of human immune and inflammatory responses. A reduction in the amount of fat intake enhanced several indices of immune response, including lymphocyte proliferation, natural-killer-cell activity, cytokine production, and delayed-type hypersensitivity. When total fat intake was held constant, an increase in the intake of linoleic acid (18:2 omega-6) or arachidonic acid (20:4 omega-6) by healthy human volunteers did not inhibit many indices of immune response tested but did increase the production of inflammatory eicosanoids (prostaglandin E2 and leukotriene B4). Supplementation of human diets with omega-3 fatty acids reduced several aspects of neutrophil, monocyte, and lymphocyte functions, including the production of inflammatory mediators. Most of the studies have indicated reductions in these functions, with a minimum of 1.2 g/d of supplementation with eicosapentaenoic acid and docosahexaenoic acid for 6 wk. However, other studies concomitantly supplementing with 205 mg/d of vitamin E did not find inhibition of immune-cell functions, even with larger amounts and longer durations of supplementation with these fatty acids. One study reported that supplementation with docosahexaenoic acid selectively inhibits inflammatory responses without inhibiting T- and B-cell functions. Despite some discrepancies, fish oils have been used successfully in the management of several inflammatory and autoimmune diseases. The potential for the use of fish oils in the management of these diseases is tremendous, even though further studies are needed to establish safe and adequate intake levels of omega-3 fatty acids.


Effect of the Flavonoid Quercetin on Inflammation and Lipid Peroxidation Induced by Helicobacter Pylori in Gastric Mucosa of Guinea Pig

Source: J Gastroenterol 2008; 43(6): 441-7

Author: González-Segovia R, Quintanar JL, Salinas E, Ceballos-Salazar R, Aviles-Jiménez F, Torres-López J.

Affiliation: Department of Microbiology, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Ciudad Universitaria, Av. Universidad 940., C.P. 20100, Aguascalientes Ags, México.

Abstract: The aim of this study was to analyze the effect of oral administration of pure quercetin on inflammation and lipid peroxidation induced by H. pylori in the gastric mucosa of the guinea pig. Sixty days after oral infection with H. pylori guinea pigs received 200 mg/kg of quercetin daily by mouth for 15 days. Quercetin significantly reduced the infiltration index of mononuclear cell and bacterial colonization in the pyloric antrum and corpus. In the antrum of infected quercetin-treated animals, a significant diminution of neutrophil leukocyte infiltration was observed compared with the infected nonquercetin-treated animals. The results indicate that in vivo oral quercetin administration decreases H. pylori infection in the gastric mucosa and reduces both the inflammatory response and lipid peroxidation.

Quercetin Prevents Lipopolysaccharide-Induced HMGB1 Release and Proinflammatory Function

Source: Am. J. Respir. Cell Mol. Biol. 2009; doi:10.1165/rcmb.2008-0119OC

Author: Daolin Tang,1 Rui Kang,2 Weimin Xiao,3 Huali Zhang,4 Michael T Lotze,5 Haichao Wang,6 and Xianzhong Xiao7

Affiliation: Department of Pathophysiology, Central South University, Xiangya School of Medicine, Laboratory of Shock, Changsha, China; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States;1 Department of Pediatrics, Central South University, Xiangya Hospital, Changsha, China; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States;2 Department of Pathophysiology, Central South University, Xiangya School of Medicine, Laboratory of Shock, Changsha, China; College of Optometry, University of Houston, Houston, Texas, United States;3 Department of Pathophysiology, Central South University, Xiangya School of Medicine, Laboratory of Shock , Changsha, China;4 Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States;5 Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, New York, United States;6 Department of Pathophysiology, Central South University, Xiangya School of Medicine, Laboratory of Shock, Changsha, China7

Abstract: This study reports that quercetin attenuates lethal systemic inflammation caused by endotoxemia even if treatment is begun following the early TNF response. Quercetin treatment reduced circulating levels of HMGB1 in animals with established endotoxemia. In macrophage cultures, quercetin inhibited release as well as the cytokine activities of HMGB1. Quercetin and autophagic inhibitor wortmannin inhibited LPS-induced type II LC3 production and aggregation as well as HMGB1 translocation and release, suggesting a potential association between autophagy and HMGB1 release. Quercetin delivery, a strategy to pharmacologically inhibit HMGB1 release that is effective at clinically achievable concentrations, now warrants further evaluation in sepsis and other systemic inflammatory disorders.

Dietary Vitamin E and Quercetin Modulate Inflammatory Responses of Collagen-Induced Arthritis in Mice

Source: Journal of Medicinal Food 2009, 12(4): 770–775

Author: Eun-Jin Choi,1 Sang-Cheol Bae,2 Rina Yu,3 Jeehee Youn,4 Mi-Kyung Sung1

Affiliation: Department of Food and Nutrition, Sookmyung Women's University, Seoul, Republic of Korea;1 Department of Food Science and Nutrition, University of Ulsan, Ulsan, Republic of Korea;2 Department of Rheumatology, The Hospital for Rheumatic Diseases, Hanyang University, Seoul, Republic of Korea;3 Major in Anatomy & Cell Biology, College of Medicine, Hanyang University, Seoul, Republic of Korea4

Abstract: Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial joints. This study investigated whether or not a diet deficient in vitamin E is a possible risk factor in the development of RA and evaluated the efficacy of antioxidant supplementation. The mice in the control group were subdivided into the control group (C/C), the 0.05% α-tocopherol-supplemented group (C/+VE), and the 0.5% quercetin-supplemented group (C/+Q). Study results indicate that the −VE/−VE group showed higher joint tissue tumor necrosis factor-α and interleukin-1β mRNA expressions, whereas α-tocopherol or quercetin supplementation reduced tissue cytokine mRNA levels to values comparable to those of the C/C group.

Daily Quercetin Supplementation Dose-Dependently Increases Plasma Quercetin Concentrations in Healthy Humans

Source: The Journal of Nutrition 2008; 138(9): 1615-1621 

Author: Egert Sarah;1 Wolffram Siegfried;2 Bosy-Westphal Anja;1 Boesh-Saadatmandi Christine;1 Eva Wagner Anika;1 Frank Jan;1 Rimbach Gerald;1 Mueller Manfred James1

Affiliation: Institute of Human Nutrition and Food Science, Physiology and Metabolism, Christian-Albrechts-University Kiel, 24105 Kiel, Germany;1  Institute of Animal Nutrition, Physiology and Metabolism, Christian-Albrechts-University Kiel, 24105 Kiel, Germany2

Abstract: The aim of this study was to investigate the effects of an oral supplementation of quercetin at 3 different doses on plasma concentrations of quercetin, parameters of oxidant/antioxidant status, inflammation, and metabolism. To this end, 35 healthy volunteers were randomly assigned to take 50, 100, or 150 mg/d (group Q50-Q150) quercetin for 2 weeks. Pharmacokinetics of quercetin were investigated in a subgroup of 15 volunteers. The areas under the plasma concentration-time curves ranged from 76.1 μmol·min·L-1 to 305.8 μmol·min·L-1 (50- and 150-mg dosages, respectively). Median maximum plasma concentrations of quercetin (431 nmol/L) were observed 360 min after intake of 150 mg quercetin. In conclusion, daily supplementation of healthy humans with graded concentrations of quercetin for 2 weeks dose-dependently increased plasma quercetin concentrations but did not affect antioxidant status, oxidized LDL, inflammation, or metabolism.


Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice.

Source: Eur J Pharmacol. 2010;633(1-3):78-84.

Author: Sánchez-Fidalgo S, Cárdeno A, Villegas I, Talero E, de la Lastra CA.

Affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, Spain.

Abstract: Ulcerative colitis is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and upregulation of inflammatory mediators. Resveratrol is a polyphenolic compound found in grapes and wine, with multiple pharmacological actions, mainly anti-inflammatory, antioxidant, antitumour and immunomodulatory activities. The aim of this study was to investigate the effect of dietary resveratrol on chronic dextran sulphate sodium (DSS)-induced colitis. The authors conclude that resveratrol diet represents a novel approach to the treatment of chronic intestinal inflammation.

Anti-inflammatory effect of resveratrol on adipokine expression and secretion in human adipose tissue explants.

Source: Int J Obes (Lond). 2010;34(10):1546-53

Author: Olholm J, Paulsen SK, Cullberg KB, Richelsen B, Pedersen SB.

Affiliation: Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus C, Denmark.

Abstract: Human obesity is closely associated with a state of chronic low-grade inflammation, which also involves the adipose tissue with enhanced production of bioactive substances (adipokines). Calorie restriction (CR) reduces adipocytokine production and improves metabolic profile in rodents. Some of these effects are mediated through activation of the sirtuin 1 (Sirt1) enzyme, and in this study, we investigate whether the natural phytoalexin, resveratrol (RSV), which is a potent Sirt1 activator, has anti-inflammatory effects in human adipose tissue explants. This study is the first to show anti-inflammatory effects of RSV on adipokine expression and secretion in human adipose tissue in vitro through the SIRT1 pathway. Thus, RSV is hypothesized to possess beneficial effects and might improve the metabolic profile in human obesity.

An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol.

Source: J Clin Endocrinol Metab. 2010;95(9):E1-8

Author: Ghanim H, Sia CL, Abuaysheh S, Korzeniewski K, Patnaik P, Marumganti A, Chaudhuri A, Dandona P.

Affiliation: Division of Endocrinology, Diabetes, and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209, USA.

Abstract: Resveratrol have been shown to exert an antiinflammatory and antiaging effects in vitro and in animal models. The objective of the study was to investigate the effect of a Polygonum cuspidatum extract (PCE) containing resveratrol on oxidative and inflammatory stress in normal subjects. Results: the PCE-containing resveratrol has a comprehensive suppressive effect on oxidative and inflammatory stress.

Vitamin B6

Inflammation Causes Tissue-Specific Depletion of Vitamin B6

Source: Arthritis Research & Therapy 2005; 7: R1254-R1262

Author: En-Pei Chiang,1 Donald E. Smith,2 Jacob Selhub,3 Gerard Dallal,4 Yi-Cheng Wang1 and Ronenn Roubenoff5

Affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan;1 Comparative Biology Unit, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA;2 Vitamin Metabolism and Aging Laboratory (JS), New England Medical Center, Boston, MA, USA;3 Biostatistics Unit (GD), New England Medical Center, Boston, MA, USA;4 Nutrition, Exercise Physiology, and Sarcopenia Laboratory, New England Medical Center, Boston, MA, USA5

Abstract: The study indicates strong and consistent associations between vitamin B6 status and several indicators of inflammation in patients with rheumatoid arthritis. Clinical indicators, including the disability score, the length of morning stiffness, and the degree of pain, and biochemical markers, including the erythrocyte sedimentation rate and C-reactive protein levels, were found to be inversely correlated with circulating vitamin B6 levels. Such strong associations imply that impaired vitamin B6 status in these patients results from inflammation. The study examined whether inflammation directly alters vitamin B6 tissue contents and its excretion in vivo.

Inflammation, Homocysteine, and Vitamin B6 Status After Ischemic Stroke

Source: Stroke 2004; 35(1): 12-5

Author: Kelly P.J., Kistler J.P., Shih V.E., Mandell R., Atassi N., Barron M., Lee H., Silveira S., Furie K.L.

Affiliation: Stroke Service, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Fruit St, Boston, Mass 02114, USA

Abstract: This study investigated vitamin B6 status, tHcy, and inflammation (measured by C-reactive protein [CRP]) in patients with stroke and controls. Consecutive cases with new ischemic stroke were compared with matched controls. Fasting tHcy, PLP, and CRP were measured. RESULTS: The adjusted odds ratio of low PLP in the highest compared with the lowest CRP quartile was 16.6 (2, 139.9, P=0.01). Age, CRP, supplemental vitamin use, and albumin were independent predictors of PLP (P<0.05 for all). No relationship was observed between CRP and tHcy. The study concludes that the relationship between inflammation and low B6 status may partially explain the findings of previous epidemiological studies.

Vitamin B6 Serum Level and Inflammation and in the InChianti Study

Source: Journal of Thrombosis and Haemostasis 2005; Volume 3, Supplement1: OR128

Author: Gori A.M, Corsi A.M, Bandinelli S, Giusti B, Lapini I, Lauretani F, Pepe G, Ferrucci L, Abbate R, Gensini G.F.


Abstract: This study aimed at determining the relationship between vitamin B6 serum levels, vitamin status and inflammatory markers in a population-based study which sampled people living in two sites in the surrounding of Florence (Italy), the InChianti Study. To evaluate the relationship between circulating vitamin B6 levels, the nutrient intakes, and the inflammatory markers this study stratified the study participants by tertiles of circulating vitamin B6 levels. According to vitamin B6 tertiles, folate, vitamin B12, alpha-tocopherol and albumin levels were significantly higher and conversely CRP, IL-6, IL-6r levels and whole blood cell count were significantly lower in the highest tertile than in the lowest tertiles. The results demonstrated that vitamin B6 levels, independently of the dietary intake and smoking habit, are predicted by pro-inflammatory markers CRP, IL-6R and by anti-oxidant vitamins.

Vitamin C

Essential Nutrients [Including Vitamin C] Suppress Inflammation by Modulating Key Inflammatory Gene Expression

Source: Published in: Inflammation Research, Volume 56, supplement 3, June 2007, p. S471 Poster #P12.05

Author: V. Ivanov, J. Cha, S. Ivanova, M.W.Roomi, A. Niedzwiecki, M.Rath.

Affiliation: Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050

Abstract: “The process of inflammation accompanies the progression and aggravates the outcome of all modern human chronic pathological conditions. This study investigated whether supplementation with a mixture of selected essential nutrients (NM) consisting of ascorbate, green tea catechins, citrus flavanoids hesperidin, naringenin and quercetin, lysine, proline, arginine and cysteine would be beneficial in bacterial liposaccharide (LPS)-induced systemic inflammation in mice. Two-week supplementation with 250 mg NM/kg body weight prior to LPS challenge provided protection significantly greater than the reference supplementation with ibuprofen. The induction of the two cytokines most responsive to LPS challenge, interleukin-6 (IL-6) and monocyte chemoattracting protein-1, was reduced in NM-supplemented animals by 58% and 86%, respectively, whereas corresponding reduction in ibuprofen group was 34% and 43%. mRNA levels for COX2 and inflammatory cytokines were also dramatically reduced. These results are significant since they illustrate the superior protective anti-inflammatory effect of supplementation with the non-toxic nutrient mixture over the commonly used drug ibuprofen with its adverse effects.”

Nutrient Mixture [Including Vitamin C] Prevents Hyper-Reactive Response of Bronchial Muscle to Inflammatory and Allergic Stimuli

Source: Published in: Journal of the American College of Nutrition, Vol. 24(5), Oct 2005, abstract #74

Author: Ivanov V., Roomi M.W., Niedzwiecki A., Rath M.

Affiliation: Matthias Rath Research Institute BV, Santa Clara, CA.

Abstract: “Asthma, a chronic pathological condition poorly managed by conventional treatment, is manifested by bronchial hyper-reactivity and bronchial spasm. Pathogenesis is linked to infection, inflammation, and allergic reaction to pollution. We investigated the effect of a nutrient mixture (NM) consisting of ascorbic acid, amino acids lysine, proline, arginine and cysteine, and polyphenols from green tea extract on bronchial smooth muscle cells (BrSMC) hyper-reactive response to pathogenic stimuli in vitro. Gel contraction was accelerated by K+, Ca2+ and Mg2+ ions and decreased by bivalent metal chelators, such as EDTA and heparin. Stimulation of BrSMC with inflammatory mediators as bacterial lipopolysaccharide (LPS) and endothelin-1 significantly increased collagen gel contraction. NM inhibited the hyper-reactive response of BrSMC to all tested pathogenic stimuli in a dose-dependent manner. The relaxation effect of NM was greater than the combined effect of its individual components. In conclusion, NM has therapeutic potential in safely and effectively controlling asthma. These data justify further in vivo experimental and clinical testing.”

A Nutrient Mixture Containing Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Green Tea Extract Suppresses Autocrine Inflammatory Response in Cultured Human Aortic Smooth Muscle Cells

Source: Research Communications in Molecular Pathology and Pharmacology 2004

Author: V. Ivanov, S. Ivanova, M.W. Roomi, T. Kalinovsky, A. Niedzwiecki, M. Rath

Affiliation: Matthias Rath Research, 1260 Memorex Drive, Santa Clara, California, 95050 USA

Abstract: “Recognition of the involvement of inflammatory processes in atherosclerotic lesion initiation and development of pathological consequences initiated a search for an effective inhibitor. This prompted us to investigate whether a unique nutrient mixture (NS), containing ascorbic acid, lysine, proline, arginine, N-acetyl cysteine and tea phenolics, could reduce an autocrine response of human aortic smooth muscle cell (SMC) to inflammatory stimuli. The results show 2.5-fold induction of interleukin-1alpha (IL-1_) content in cellular media was completely reversed in the presence of 20 _g/ml NS (containing 20 _M ascorbic acid). Secretion of pro-interleukin–1 beta (pro-IL-1_) and of its activator, caspase-1, was inhibited by 46% and 67%, respectively. This resulted in significant reduction of IL-1_ formation. Secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8) was also dramatically reduced. Anti-inflammatory effects of NS exceeded the sum of actions of its individual components. The study concludes that the mixture of ascorbic acid, tea phenolics, and selected amino acids tested has a strong potential against involvement of vascular cells into inflammatory response to pathogens.”

Down Regulation of MMP-2 Expression and Invasion Potential of Human Gingival Fibroblasts

Source: Published in: Conference proceedings, Abstract #37, pg 42

Author: M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath.

Affiliation: Matthias Rath Research., Cancer Research Division, Santa Clara, CA 95050

Abstract: Gingivitis, the earliest stage of gum disease, affects three out of four adults over the age of 35. Left untreated, it progresses to periodontitis, an advanced stage of gum disease characterized by additional destruction of gum tissue and progression to the bone. MMPs play a critical role in this process as they degrade the majority of the extracellular matrix components. This study examined the effect of a nutrient mixture (NM) of ascorbic acid, lysine, proline, and green tea extract on expression of MMPs by gingival fibroblasts in cell culture. NM significantly inhibited MMP-2 expression and invasion through Matrigel, suggesting NM has great potential as a therapeutic tool in prevention and treatment of gingivitis and its sequelae.

Vitamin C Treatment Reduces Elevated C–Reactive Proteins

Source: Free Radical Biology and Medicine 2009; 46(1): 70–77

Author: Block G, Jensen CD, Dalvi TB, Norkus EP, Hudes M, Crawford PB, Holland N, Fung EB, Schumacher L, Harmatz P

Affiliation: University of California, Berkeley, 94720, USA.

Abstract: The UC Berkeley-led study looked at the separate effects of two antioxidants: vitamin C and vitamin E. The researchers randomly divided 396 healthy, non-smoking adults from the San Francisco Bay Area into groups taking daily doses of either 1,000 milligrams of vitamin C, 800 international units of vitamin E or a placebo. They compared participants' baseline CRP levels with their levels two months later, at the end of the study. Participants who had baseline CRP levels less than 1 milligram per litre saw no significant effect on CRP levels after taking vitamin C supplements. However, those who started off with CRP levels of 1 milligram per litre or higher saw a 16.7 percent drop in levels after two months of treatment with vitamin C.The researchers found no significant results for those taking vitamin E. Although this study ended at two months, Block noted that there is no evidenc. “This finding of an effect of vitamin C is important because it shows in a carefully conducted randomized, controlled trial that for people with moderately elevated levels of inflammation, vitamin C may be able to reduce CRP as much as statins have done in other studies," said Block.

Vitamin C Intake and the Risk of Gout in Men

Source: Archives of Internal Medicine 2009; 169(5): 502-507.

Author: Hyon K. Choi,1,2 Xiang Gao,2,4 Gary Curhan2-4

Affiliation: Division of Rheumatology, Department of Medicine, Arthritis Research Centre of Canada, Vancouver General Hospital, University of British Columbia, Vancouver, Canada;1 Channing Laboratory2 and Renal Division, Department of Medicine,3 Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston.4 Dr Choi is now with the Rheumatology Section, Clinical Epidemiology Unit, Boston University School of Medicine, Boston.

Abstract: Division of Rheumatology, Department of Medicine, Arthritis Research Centre of Canada; Vancouver General Hospital, University of British Columbia, Vancouver, Canada (Dr. Choi); Channing Laboratory (Drs. Choi, Gao, and Curhan) and Renal Division, Department of Medicine (Dr. Curhan), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston (Drs. Gao and Curhan). This study prospectively examined the relation between vitamin C intake and risk of incident of gout (a painful inflammation of the big toe and foot) in 46 994 male participants with no history of gout at baseline. Vitamin C intake was assessed every 4 years through validated questionnaires. During the 20 years of follow-up, the researchers documented 1317 confirmed incident cases of gout. Compared with men with vitamin C intake less than 250 mg/d, the multivariate relative risk (RR) of gout was 0.83 (95% confidence interval [CI], 0.71-0.97) for total vitamin C intake of 500 to 999 mg/d, 0.66 (0.52-0.86) for 1000 to 1499 mg/d, and 0.55 (0.38-0.80) for 1500 mg/d or greater (P < .001 for trend). The multivariate RR per 500-mg increase in total daily vitamin C intake was 0.83 (95% CI, 0.77-0.90). This study concludes that higher vitamin C intake is independently associated with a lower risk of gout. Supplemental vitamin C intake may be beneficial in the prevention of gout.

Evidence for Anti-Inflammatory Effects of Combined Administration of Vitamin E and C in Older Persons with Impaired Fasting Glucose: Impact on Insulin Action

Source: Journal of the American College of Nutrition 2008; 27( 4): 505-511

Author: Maria Rosaria Rizzo, Angela Marie Abbatecola, Michelangela Barbieri, Maria Teresa Vietri, Michele Cioffi, Rodolfo Grella, AnnaMaria Molinari, Rosalyn Forsey, Jonathan Powell and Giuseppe Paolisso.

Affiliation: Department of Geriatric and Metabolic Diseases; Department of General Pathology II University of Naples, Italy; Unilever Corporate Research, Colworth Park, Sharnbrook, Beds, England

Abstract: The aim of this study was to investigate combined effect of vitamin E and C in elderly with Impaired Fasting Glucose (IFG) on insulin action and substrate oxidation. Controlled-trial administration of vitamin E (1000 mg/day) and vitamin C (1000 UI/day) was performed for four weeks in thirteen older men with IFG. Rise in plasma levels of vitamin C and E correlated with WBGD. The study concludes that combined administration of vitamin E and C lowered inflammation and improved insulin action through a rise in non-oxidative glucose metabolism.

Serum Vitamin C Concentration Is Low in Peripheral Arterial Disease and Is Associated With Inflammation and Severity of Atherosclerosis

Source: Journal of the American Heart Association 2001; 103(14): 1863-1868

Author: Langlois Michel;1 Duprez Daniel;2 Delanghe Joris;1 De Buyzere Marc;2 Clement Denis L.2

Affiliation: Departments of Clinical Chemistry1 and Cardiology2, Ghent University Hospital, Ghent, Belgium.

Abstract: This study examined whether inflammation is associated with antioxidant status in patients with intermittent claudication, and tested the hypothesis that vitamin C status might be low in PAD and that it correlates with measures of inflammation and functional status in patients with intermittent claudication. The researchers investigated 85 PAD patients (Fontaine stage II) who were regularly followed for at least 12 months at our department, 106 patients with essential hypertension without PAD (to account for the effect of pulse pressure), and 113 healthy volunteers of the same region. The study shows that vitamin C concentrations are low in PAD and are associated with inflammation and the patient's functional state. Low-grade inflammation in atherosclerosis may be associated with oxidative stress and the resultant decrease in antioxidants such as vitamin C. Future studies attempting to relate circulating vitamin C concentrations to disease occurrence should include in their analysis a marker of inflammatory response such as CRP.

Dietary Vitamin C Down-Regulates Inflammatory Gene Expression in ApoE4 Smokers

Source: Biochemical and Biophysical Research Communications 2005, 338(2): 951-955.

Author: Jonathan Majewicz, Gerald Rimbach, Anna R. Proteggente, John K. Lodge, Klaus Kraemer and Anne M. Minihane

Affiliation: Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, University of Reading, Whiteknights, Reading RG6 6AP, UK.; Christian Albrechts University, Institute of Human Nutrition and Food Science, Olshausentrasse 40, D-24118 Kiel, Germany; Centre for Nutrition and Food Safety, School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK; BASF Aktiengesellschaft, Fine Chemicals, 67056 Ludwigshafen, Germany.

Abstract: The deleterious impact of cigarette smoking on cardiovascular health may be in part attributable to a free radical mediated proinflammatory response in circulating monocytes. In the current investigation, the impact of vitamin C supplementation on monocyte gene expression was determined in apoE4 smokers versus non-smokers. A total of 10 smokers and 11 non-smokers consumed 60 mg/day of vitamin C for four weeks and a fasting blood sample was taken at baseline and post-intervention for the determination of plasma vitamin C and monocyte gene expression profiles using cDNA array and real time PCR. In apoE4 smokers, supplementation resulted in a 43% increase in plasma vitamin C concentrations. Furthermore, a number of genes were differentially expressed more than 2-fold in response to treatment, including a downregulation of the proinflammatory mediators tumor necrosis factor (TNF) β, TNF receptor, neurotrophin-3 growth factor receptor, and monocyte chemoattractant protein 1 receptor. The study has identified a number of molecular mechanisms underlying the benefit of vitamin C supplementation in smokers.

Associations of Vitamin C Status, Fruit and Vegetable Intakes, and Markers of Inflammation and Hemostasis

Source: American Journal of Clinical Nutrition 2006; 83: 567–74.

Author: Wannamethee S.G., Lowe G.D.O., Rumley A., Bruckdorfer K.R., Whincup P.H.

Affiliation: Departments of Primary Care and Population Sciences (SGW) and of Biochemistry and Molecular Biology (KRB), Royal Free and University College Medical School, London, United Kingdom; the University Department of Medicine, Royal Infirmary, Glasgow, United Kingdom (GDOL and AR); and the Department of Community Health Sciences, St George's, University of London, London, United Kingdom (PHW)

Abstract: The objective was to examine the associations between dietary and plasma vitamin C concentrations, fruit and vegetable intakes, and markers of inflammation and hemostasis associated with cardiovascular disease in older men free of cardiovascular disease. This cross-sectional study examined 3258 men aged 60–79 years with no physician diagnosis of myocardial infarction, stroke, or diabetes and who were drawn from general practices in 24 British owns. Plasma vitaminC, fruit intake, and dietary vitaminCintake were significantly and inversely associated with mean concentra- ions of C-reactive protein, an acute phase reactant, and tissue plas-minogen activator (t-PA) antigen, a marker of endothelial dysfunction, even after adjustment for confounders. Vegetable intake was correlated significantly (inversely) only with t-PA. The study concludes that the findings suggest that vitamin C has antiinflammaory effects and is associated with lower endothelial dysfunction in men with no history of cardiovascular disease or diabetes.

Effects of Oral Vitamin C Supplementation on Oxidative Stress and Inflammation Status in Haemodialysis Patients

Source: Nephrology Dialysis Transplantation 2005; 20(9): 1874-1879

Author: Christine Fumeron1, Thao Nguyen-Khoa2,3, Claudine Saltiel1, Messeret Kebede2, Claude Buisson1, Tilman B. Drüeke3, Bernard Lacour2 and Ziad A. Massy4

Affiliation: AURA Centre Henri Küntziger,1 Biochemistry A Laboratory2 and INSERM U507, Necker Hospital, Paris,3 Divisions of Clinical Pharmacology and Nephrology, INSERM ERI-12, Amiens University Hospital and University of Picardie, Amiens, France.4

Abstract: There is increasing evidence for the presence of oxidative stress and vitamin C deficiency in dialysis patients. Limited data, however, are available regarding the effects of vitamin C supplementation on oxidative stress and inflammation markers in such patients. The objective of this randomized, open-label trial was to assess the effects of oral vitamin C supplementation (250 mg three times per week) for 2 months on well-defined oxidative and inflammatory markers in 33 chronic haemodialysis (HD) patients. This study concludes that short-term oral vitamin C supplementation did not modify well-defined oxidative/antioxidative stress and inflammation markers in HD patients. Whether a higher oral dose or the intravenous route can modify these markers remains to be determined.

Vitamin C and the Risk of Developing Inflammatory Polyarthritis: Prospective Nested Case-Control Study

Source: Annals of the Rheumatic Diseases 2004; 63: 843-847

Author: D.J. Pattison, A.J., Silman, N.J. Goodson, M. Lunt, D. Bunn, R. Luben, A. Welch, S. Bingham, K-T Khaw, N. Day, D.P.M. Symmons

Affiliation: Arthritis Research Campaign (arc) Epidemiology Unit, University of Manchester, Oxford Road, Manchester M13 9PT, UK.; Norfolk Arthritis Register, Norfolk & Norwich University Hospital, Colney Lane, Norwich NR4 7UZ, UK.; Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK.; MRC Dunn Human Nutrition Unit, Welcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, UK.

Abstract: The aim of this study was to investigate whether there is an association between consumption of fruit and vegetables and dietary antioxidants and the risk of developing inflammatory polyarthritis (IP). In a prospective, population based, nested case-control study of residents of Norfolk, UK, men and women aged 45–74 years were recruited, between 1993 and 1997 through general practice age-sex registers to the Norfolk arm of the European Prospective Investigation of Cancer (EPIC-Norfolk). Dietary intake was assessed at baseline using 7 day diet diaries. Lower intakes of fruit and vegetables, and vitamin C were associated with an increased risk of developing IP. Those in the lowest category of vitamin C intake, compared with the highest, increased their risk of developing IP more than threefold, adjusted odds ratio (OR) with 95% confidence intervals (CI) 3.3 (95% CI 1.4 to 7.9). This study concludes that Patients with IP (cases) consumed less fruit and vitamin C than matched controls, which appeared to increase their risk of developing IP.

Vitamin D

Higher Serum Vitamin D Concentrations are Associated with Longer Leukocyte Telomere Length in Women; Boosting Vitamin D May Have Long-Term Benefits For Inflammation and Aging

Source: American Journal of Clinical Nutrition 2007; 86(5): 1420-1425

Author: Richards J.B.,1 Valdes AM,1 Gardner J.P.,2 Paximadas D,1 Kimura M.,2 Nessa A., Lu X.,2 Surdulescu G.L.,1 Swaminathan R.,3 Spector T.D.,1 Aviv A.2

Affiliation: Twin Research and Genetic Epidemiology, St Thomas' Hospital, King's College, London School of Medicine, London, United Kingdom;1 the Center of Human Development and Aging, University of Medicine and Dentistry of New Jersey, Newark, NJ;2 and the Department of Chemical Pathology, St Thomas' Hospital, London, United Kingdom3

Abstract: The objective of this study was to examine whether vitamin D concentrations would attenuate the rate of telomere attrition in leukocytes, such that higher vitamin D concentrations would be associated with longer LTL.  Serum vitamin D concentrations were measured in 2160 women aged 18-79 y (mean age: 49.4) from a large population-based cohort of twins. LTL was measured by using the Southern blot method.  Using a genetic marker called leukocyte telomere length (LTL), the researchers found those with the highest vitamin D levels had longer LTL, indicating lower levels of inflammation and body stress. The telomere difference between those with the highest and lowest vitamin D levels was equivalent to 5 years of aging. These findings suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging, age-related diseases and inflammations. Previous research has found that shortened LTL is linked to risk for heart disease and could be an indication of chronic inflammation -- a key determinant in the biology of aging.

Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women

Source: Journal of Inflammation 2008; 5: 10

Author: Catherine A. Peterson; Mary E. Heffernan

Affiliation: Department of Nutritional Sciences, University of Missouri-Columbia, Columbia, MO, 65211, USA

Abstract: A University of Missouri nutritional sciences researcher has found that vitamin D deficiency is associated with inflammation, a negative response of the immune system, in healthy women. Increased concentrations of serum TNF-α, an inflammatory marker, were found in women who had insufficient vitamin D levels. This study is the first to find an inverse relationship between vitamin D levels and concentrations of TNF-α in a healthy, non-diseased population. This may explain the vitamin's role in the prevention and treatment of inflammatory diseases, including heart disease, multiple sclerosis and rheumatoid arthritis. "The findings reveal that low vitamin D levels negatively impact inflammation and immune response, even in healthy women," said Catherine Peterson, assistant professor in the MU College of Human Environmental Sciences.

The Association Between Vitamin D and Inflammation with the 6-Minute Walk and Frailty in Patients with Heart Failure

Source: Journal of the American Geriatrics Society 2008; 56( 3): 454-461

Author: Rebecca S. Boxer, MD, Deborah A. Dauser, MPH, Stephen J. Walsh, ScD, W. David Hager, MD, and Anne M. Kenny, MD

Affiliation: Departments of Family Medicine and Internal Medicine, Case Western University Hospital, Cleveland, Ohio;  General Clinical Research Center, Farmington, Connecticut;  Division of Epidemiology and Biostatistics, Department of Community Medicine and Health Care, Farmington, Connecticut;  Division of Cardiology, Department of Internal Medicine and  Center on Aging, Farmington, Connecticut; Department of Internal Medicine, University of Connecticut Health Center, Farmington, Connecticut.

Abstract: The objective of this study was to identify relationships between anabolic hormones, inflammatory markers, and physical function in sixty patients with an ejection fraction of 40% or less. The 6-minute walk distance and frailty phenotype were measured. The relationship between physical measures of hormones and inflammatory mediators were examined. Longer 6-minute walk distance was correlated with higher 25-hydroxyvitamin D (25OHD) level, and a shorter walk was correlated with higher cortisol: dehydroepiandrosterone sulphate (DHEAS) ratio, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), and intact parathyroid hormone (PTH) This study concludes that twenty-five-hydroxyvitamin D and hsCRP levels may contribute to lower aerobic capacity and frailty in patients with heart failure. A longitudinal study will further define the role of 25OHD and hsCRP on muscle strength and functional decline.

Alfacalcidol Versus Plain Vitamin D in Inflammation Induced Bone Loss

Source: The Journal of Rheumatology 2005, 76: 26-32

Author: Stephan H. Scharla, Erich Schacht, and Uta G. Lempert

Affiliation: Medizinische Fakultät, Ludwig-Maximilians-University, Munich, Germany.

Abstract: Disturbances of vitamin D metabolism play an important role in the development of inflammation induced osteoporosis. This article reviews the interaction between inflammatory disease and vitamin D metabolism, summarizes the rationale for the therapeutic use of alfacalcidol, and provides recent data from controlled clinical trials comparing the effect of alfacalcidol versus plain vitamin D in secondary osteoporosis. D-hormone analogs offer an important treatment option. One explanation is that animals and humans with inflammatory diseases exhibit markedly reduced circulating concentrations of D-hormone, partly the result of inhibition of renal 1-alpha-hydroxylase by TNF-alpha. In addition, the number of vitamin D receptors is reduced by glucocorticoids. D-hormone inhibits the release of cytokines (IL-1, IL-6, TNF-alpha) from macrophages and stimulates osteoprotegerin secretion in vitro and improves arthritis in animal models.

A Role of Vitamin D in Low-Intensity Chronic Inflammation and Insulin Resistance in Type 2 Diabetes Mellitus?

Source: Nutrition Research Reviews 2005; 18(2): 175-182

Author: Mario Flores

Affiliation: Centro de Investigacio 'n en Nutricio 'n y Salud, Instituto Nacional de Salud Publica (National Institute of Public Health), Cuernavaca, Mexico.

Abstract: Evidence from different directions, including observational and experimental studies, points to a role of vitamin D status in low-intensity chronic inflammation and insulin resistance in type 2diabetes mellitus (T2DM). It has been recognized that insulin resistance and low-intensity chronic inflammation are risk factors for T2DM. It is suggested that the relationship between vitamin D and low-intensity chronic inflammation and insulin resistance in T2DM can be mediated in part by the immune-modulating properties of the active form of vitamin D (1-a,25-dihydroxyvitamin D3; 1,25(OH)2D3), which is able to down regulate the production of pro-inflammatory cytokines ?particularly TNF-a, and IL-6.  It is to be noted that an inverse association between vitamin D status and insulin resistance has been observed in a sample of adult participants in the NHANES, which persisted after controlling for BMI (Scragg et al. 2004). More studies are needed to clarify these issues.

Anti-inflammatory effect of vitamin D on gingivitis: a dose response randomized controlled trial.


Author: Hiremath VP, Rao CB, Naiak V, Prasad KV.

Affiliation: Department of Public Health Dentistry, Maratha Mandal Dental College, Belgaum, India

Abstract: In a randomized controlled trial, a daily Oral Vitamin D supplementation was given in dose of 2000 IU for Group A, 1000 IU for Group B , 500 IU for Group C and placebo for Group D over 3 months period to assess the anti-inflammatory effect of vitamin D on gingivitis at various doses. The changes in gingival scores were measured at the period of 1 st , 2 nd and 3 rd month. Gingivitis score changed in direct proportion to the dose of vitamin D supplementation. Group A mean gingival scores were 2.4 (baseline); 1.7 (1 st month), 0.8 (2 nd month) and 0.3 (3 rd month). The group B the mean baseline gingival score from 2.3 reduced to 2.0 (month), 1.1 (two months) and 0.5 (third month). Group C had baseline gingival scores of 2.2 and 1.9 (1 st month), 1.4 (2 nd month) and 0.8 (last visit). Conclusion: Comparing baseline gingivitis scores with later visit score by Wilcoxon paired test, the anti-inflammatory effect was significantly seen in group A after one month itself, group B at two months and group C at 3 rd month after oral vitamin D supplementation. However, Group D did not show any significant anti-inflammatory effect.

Vitamin E

Dietary Vitamin E and Quercetin Modulate Inflammatory Responses of Collagen-Induced Arthritis in Mice

Source: Journal of Medicinal Food 2009; 12(4): 770-5.

Author: Choi E.J., Bae S.C., Yu R., Youn J., Sung M.K.

Affiliation: Department of Food and Nutrition, Sookmyung Women's University, Seoul, Republic of Korea.

Abstract: This study investigated whether or not a diet deficient in vitamin E is a possible risk factor in the development of RA and evaluated the efficacy of antioxidant supplementation. Male DBA/1J mice were maintained on either a control diet (C) or a vitamin E-depleted (-VE) diet for 4 weeks before arthritis induction. The mice in the control group were subdivided into the control group (C/C), the 0.05% alpha-tocopherol-supplemented group (C/+VE), and the 0.5% quercetin-supplemented group (C/+Q). Study results indicate that the -VE/-VE group showed higher joint tissue tumor necrosis factor-alpha and interleukin-1beta mRNA expressions, whereas alpha-tocopherol or quercetin supplementation reduced tissue cytokine mRNA levels to values comparable to those of the C/C group. Supplementation with alpha-tocopherol or quercetin in mice fed -VE diet decreased these markers similar to those of the mice in the C/C group. These results suggest that dietary deficiency of vitamin E increases inflammatory responses and that antioxidants successfully suppress the inflammatory responses. However, significant clinical improvement may require longer observation.

In Vivo Vitamin E Administration Attenuates Interleukin-6 and Interleukin-1Beta Responses to an Acute Inflammatory Insult in Mouse Skeletal and Cardiac Muscle

Source: Experimental Physiology 2008; 93(12): 1263-72

Author: Huey K.A., Fiscus G., Richwine A.F., Johnson R.W., Meador B.M.

Affiliation: Department of Kinesiology, University of Illinois at Urbana-Champaign, 120 Freer Hall, 906 South Goodwin Avenue, Urbana, IL 61801, USA.

Abstract: These experiments tested the hypothesis that vitamin E administration attenuates nuclear factor kappaB (NF-kappaB), IL-6, IL-1beta and tumour necrosis factor alpha (TNFalpha) responses in skeletal and cardiac muscle to an inflammatory challenge induced by systemic lipopolysaccharide (LPS). The researchers compared IL-6, IL-1beta and TNFalpha mRNA and protein, activated NF-kappaB and total oxidized proteins in skeletal and cardiac muscle 4 or 24 h after saline or LPS injection in mice receiving vitamin E or placebo for 3 days prior to the insult. The study concludes that vitamin E decreased LPS-induced increases in plasma IL-1beta but not IL-6 compared with placebo. The major results provide the first in vivo evidence that short-term vitamin E administration reduces IL-6 and IL-1beta responses to LPS in skeletal and cardiac muscle and prevents LPS-induced increases in NF-kappaB activation and total oxidized proteins.

Modulation of Inflammation by Vitamin E and C Supplementation Prior to Anterior Cruciate Ligament Surgery

Source: Free Radical Biology & Medicine 2009; 46(5): 599-606

Author: Barker T, Leonard SW, Trawick RH, Martins TB, Kjeldsberg CR, Hill HR, Traber MG.

Affiliation: The Orthopedic Specialty Hospital, Murray, UT 84107, USA

Abstract: The purpose of this study was to evaluate the influence of prior antioxidant (AO) supplementation on circulating cytokines following anterior cruciate ligament (ACL) surgery. A randomized, double-blind, placebo-controlled trial was conducted in men undergoing ACL surgery, who were randomly assigned to either: (1) AO (200 IU of vitamin E (50% d-alpha-tocopheryl acetate and 50% d-alpha-tocopherol) and 500 mg ascorbic acid), or (2) matching placebos (PL). Subjects took supplements twice daily for 2 weeks prior to and up to 12 weeks after surgery. Following surgery, inflammation and muscle damage increased in both groups, as assessed by increased circulating IL-6, C-reactive protein, and creatine kinase. During AO supplementation, plasma alpha-T and AA increased while gamma-T concentrations decreased significantly (P< 0.05). At 90 min the AO group displayed a significant decrease in AA, an inverse correlation between AA and (interleukin) IL-8 (r(2)= 0.50, P< 0.05), and a significantly lower IL-10 response than that of the PL group. IL-10 was significantly elevated at 90 min and 72 h in the PL group. In summary, these findings show that circulating inflammatory cytokines increase and AO supplementation attenuated the increase in IL-10 in patients post-ACL surgery.

Elevated Plasma Gamma-Tocopherol and Decreased Alpha-Tocopherol in Men are Associated with Inflammatory Markers and Decreased Plasma 25-OH Vitamin D

Source: Nutrition and Cancer 2008; 60 Suppl 1: 21-9

Author: Cooney R.V., Franke A.A., Wilkens L.R., Gill J., Kolonel L.N.

Affiliation: University of Hawaii at Manoa, Honolulu, Hawaii 96813, USA

Abstract: Chronic inflammation is a risk factor for many diseases of aging. Using stored plasma samples from 657 male control subjects in a previous study of prostate cancer, this study have analyzed associations of the tocopherols, inflammation markers, and 25-hydroxy (OH) vitamin D. Plasma alpha-Toc and gamma-Toc were inversely correlated, whereas delta-Toc and alpha-Toc levels were positively correlated, suggesting a unique regulatory mechanism. gamma-Toc levels were positively and alpha-Toc negatively associated with plasma C-reactive protein (CRP) and urinary isoprostane F(2t), which are markers of inflammation and oxidation. In these data, all-cause mortality appeared to be positively associated with CRP and inversely with 25-OH vitamin D. We hypothesize that plasma levels of tocopherols may serve as markers of systemic inflammation, complicating epidemiologic assessment of their role in cancer etiology.

Evidence for Anti-Inflammatory Effects of Combined Administration of Vitamin E and C in Older Persons with Impaired Fasting Glucose: Impact on Insulin Action

Source: Journal of the American College of Nutrition 2008; 27(4): 505-11.

Author: Rizzo MR, Abbatecola AM, Barbieri M, Vietri MT, Cioffi M, Grella R, Molinari A, Forsey R, Powell J, Paolisso G.

Affiliation: Second University of Naples, Department of Geriatric Medicine and Metabolic Diseases, Naples, Italy.

Abstract: Vitamin E and C given separately improve insulin sensitivity due to an inhibitory effect on oxidative stress and inflammation, however their combined effect on glucose control and inflammation is unknown. This study investigated combined effect of vitamin E and C in elderly with Impaired Fasting Glucose (IFG) on insulin action and substrate oxidation. Controlled-trial administration of Vitamin E (1000 mg/day) and Vitamin C (1000 UI/day) were provided for four weeks. Vitamin administration reduced insulin, glucose, lipid, TNF-alpha and [8-]isoprostane levels. Rise in plasma levels of Vitamin C and E correlated with whole body glucose disposal (WBGD). The study concludes that combined administration of vitamin E and C lowered inflammation and improved insulin action through a rise in non-oxidative glucose metabolism.

Age-Associated Changes in Immune and Inflammatory Responses: Impact of Vitamin E Intervention

Source: Journal of Leukocyte Biology 2008; 84(4): 900-14

Author: Wu D., Meydani S.N.

Affiliation: Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.

Abstract: Aging is associated with dysregulated immune and inflammatory responses. Declining T cell function is the most significant and best-characterized feature of immunosenescence. Intrinsic changes within T cells and extrinsic factors contribute to the age-associated decline in T cell function. T cell defect seen in aging involves multiple stages from early receptor activation events to clonal expansion. Among extrinsic factors, increased production of T cell-suppressive factor PGE(2) by macrophages (Mphi) is most recognized. Vitamin E reverses an age-associated defect in T cells, particularly naïve T cells. This effect of vitamin E is also reflected in a reduced rate of upper respiratory tract infection in the elderly and enhanced clearance of influenza infection in a rodent model. This review discusses age-related immune and inflammatory changes and the effect of vitamin E as nutritional intervention with a focus on the work conducted in university laboratory.

Severe Vitamin E Deficiency Exacerbates Acute Hyperoxic Lung Injury Associated with Increased Oxidative Stress and Inflammation

Source: Free Radical Research 2008; 42(6): 602-12

Author: Yamaoka S., Kim H.S., Ogihara T., Oue S., Takitani K., Yoshida Y., Tamai H.

Affiliation: Department of Pediatrics, Perinatal Center, Osaka Medical College, Takatsuki, Osaka, Japan.

Abstract: Hyperoxia causes acute lung injury along with an increase of oxidative stress and inflammation. It was hypothesized that vitamin E deficiency might exacerbate acute hyperoxic lung injury. This study used alpha-tocopherol transfer protein knockout (alpha-TTP KO) mice fed a vitamin E-deficient diet (KO E(-) mice) as a model of severe vitamin E deficiency. Compared with wild-type (WT) mice, KO E(-) mice showed a significantly lower survival rate during hyperoxia. After 72 h of hyperoxia, KO E(-) mice had more severe histologic lung damage and higher values of the total cell count and the protein content of bronchoalveolar lavage fluid (BALF) than WT mice. IL-6 mRNA expression in lung tissue and the levels of 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) in both lungs and BALF were higher in KO E(-) mice than in WT mice. It was concluded that severe vitamin E deficiency exacerbates acute hyperoxic lung injury associated with increased oxidative stress or inflammation.

Gamma-Tocopherol Supplementation Alone and in Combination with Alpha-Tocopherol Alters Biomarkers of Oxidative Stress and Inflammation in Subjects with Metabolic Syndrome

Source: Free Radical Biology & Medicine 2008; 44(6): 1203-8

Author: Devaraj S., Leonard S., Traber M.G., Jialal I.

Affiliation: Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, CA 95817, USA.

Abstract: This study evaluated supplementation with gamma–tocopherol (GT) (800 mg/day), alpha–tocopherol (AT) (800 mg/day), the combination or placebo for 6 weeks alone AT and GT concentrations, biomarkers of oxidative stress, and inflammation in subjects with metabolic syndrome (MetS) (n=20/group). Plasma AT and GT levels increased following supplementation with AT alone or GT alone or in combination. AT supplementation significantly decreased GT levels. HsCRP levels significantly decreased in the combined AT+GT group. LPS-activated whole blood release of IL-1 and IL-6 did not change. The study concludes that the combination of AT and GT supplementation appears to be superior to either supplementation alone on biomarkers of oxidative stress and inflammation and needs to be tested in prospective clinical trials to elucidate its utility in CVD prevention.

Effect of High-Dose Alpha-Tocopherol Supplementation on Biomarkers of Oxidative Stress and Inflammation and Carotid Atherosclerosis in Patients with Coronary Artery Disease

Source: The American Journal of Clinical Nutrition 2007; 86(5): 1392-8

Author: Devaraj S, Tang R, Adams-Huet B, Harris A, Seenivasan T, de Lemos JA, Jialal I.

Affiliation: University of Texas Southwestern Medical Center, Dallas, TX, USA.

Abstract: Oxidative stress and inflammation are crucial in atherogenesis. Alpha-Tocopherol is both an antioxidant and an antiinflammatory agent. This study evaluated the effect of RRR-alpha-tocopherol supplementation on carotid atherosclerosis in patients with stable coronary artery disease (CAD) on drug therapy. This randomized, controlled, double-blind trial compared RRR-alpha-tocopherol (1200 IU/d for 2 y) with placebo in 90 patients with CAD. This study shows that alpha-Tocopherol concentrations were significantly higher in the alpha-tocopherol group but not in the placebo group. High-sensitivity CRP concentrations were significantly lowered with alpha-tocopherol supplementation than with placebo (32%; P < 0.001). The study concludes that high-dose RRR-alpha-tocopherol supplementation in patients with CAD was safe and significantly reduced plasma biomarkers of oxidative stress and inflammation but had no significant effect on carotid IMT during 2 years.

Alpha Tocopherol Supplementation Decreases Serum C-Reactive Protein and Monocyte Interleukin-6 Levels in Normal Volunteers and Type 2 Diabetic Patients

Source: Free Radical Biology and Medicine, October 15, 2000, Volume 29, Issue 8, pp. 790-792

Author: Sridevi Devara, Ishwarlal Jialal

Affiliation: Departments of Pathology University of Texas Southwestern Medical Center, Dallas, TX, USA, Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

Abstract: The aim of the study was to test the effect of RRR-AT supplementation (1200 IU/d) on plasma C-reactive protein (CRP) and interleukin-6 (IL-6) release from activated monocyte in Type 2 diabetic patients with and without macrovascular complications compared to matched controls. Plasma high sensitive CRP (Hs-CRP) and Monocyte IL-6 were assayed at baseline, following 3 months of supplementation and following a 2 month washout phase. DM2-MV subjects have elevated HsCRP and monocyte IL-6 compared to controls. Alpha tocopherol (AT) supplementation significantly lowered levels of C-reactive protein and monocyte interleukin-6 in all three groups. In conclusion, AT therapy decreases inflammation in diabetic patients and controls and could be an adjunctive therapy in the prevention of atherosclerosis.

Cosupplementation with Vitamin E and Coenzyme Q10 Reduces Circulating Markers of Inflammation in Baboons

Source: The American Journal of Clinical Nutrition 2004; 80(3): pp. 649–655.

Author: Xing Li Wang,1,2 David L Rainwater,1 Michael C Mahaney,1,3 and Roland Stocker4

Affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX;1 the Division of Cardiothoracic Surgery, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston;2 the Southwest National Primate Research Center, San Antonio, TX;3 the Centre for Vascular Research, School of Medical Sciences, University of New South Wales, and the Department of Haematology, Prince of Wales Hospital, Sydney, Australia4

Abstract: This study explored the effects of a high-fat, high-cholesterol (HFHC) diet on vascular responses in baboons and the potential response-attenuating effects of vitamin E and coenzyme Q10 (CoQ10) supplementation. After being maintained for 3 months on a baseline diet (low in fat and cholesterol), 21 baboons were challenged with an HFHC diet for 7 weeks. Subsequent supplementation of the HFHC diet with the antioxidant vitamin E (250, 500, or 1000 IU/kg diet) for 2 wk reduced serum CRP concentrations from 0.91 ± 0.02 to 0.43 ± 0.06 mg/dL. Additional supplementation with CoQ10 (2 g/kg diet) further reduced serum CRP to ≈30% of baseline (0.28 ± 0.03 mg/dL; P = 0.036 compared with the HFHC diet). The study concludes that dietary supplementation with vitamin E alone reduces the baseline inflammatory status that is indicated by the CRP concentration in healthy adult baboons. Cosupplementation with CoQ10, however, significantly enhances this antiinflammatory effect of vitamin E.

Vitamin K

Vitamin K and Vitamin D Status: Associations with Inflammatory Markers in the Framingham Offspring Study

Source: American Journal of Epidemiology 2008; 167(3): 313-320

Author: M. Kyla Shea1, Sarah L. Booth1, Joseph M. Massaro2,3,4, Paul F. Jacques1, Ralph B. D'Agostino, Sr3,4, Bess Dawson-Hughes1, José M. Ordovas1, Christopher J. O'Donnell4,5, Sekar Kathiresan5, John F. Keaney, Jr6, Ramachandran S. Vasan4,6,7 and Emelia J. Benjamin4,6,7,8

Affiliation: USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA;1 Department of Biostatistics, School of Public Health, Boston University, Boston, MA;2 Department of Mathematics and Statistics, Boston University, Boston, MA;3 Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA;4 Department of Medicine, Massachusetts General Hospital, Harvard University, Boston, MA;5 Whitaker Cardiovascular Institute, Boston University Medical Center, Boston, MA;6 Cardiology and Preventive Medicine Sections, Department of Medicine, School of Medicine, Boston University, Boston, MA;7 Department of Epidemiology, School of Public Health, Boston University, Boston, MA8

Abstract: This study examined associations between vitamins K and D and inflammation in vivo. The authors used multiple linear regression analyses, adjusted for age, sex, body mass index, triglyceride concentrations, use of aspirin, use of lipid-lowering medication, season, menopausal status, and hormone replacement therapy. Vitamin K status, measured by plasma phylloquinone concentration and phylloquinone intake, was inversely associated with circulating inflammatory markers as a group and with several individual inflammatory biomarkers (p < 0.01). Percentage of undercarboxylated osteocalcin, a functional measure of vitamin K status, was not associated with overall inflammation but was associated with C-reactive protein (p < 0.01). Although plasma 25-hydroxyvitamin D was inversely associated with urinary isoprostane concentration, an indicator of oxidative stress (p < 0.01), overall associations between vitamin D status and inflammation were inconsistent. The observation that high vitamin K status was associated with lower concentrations of inflammatory markers suggests that a possible protective role for vitamin K in inflammation merits further investigation.

Vitamin K Circulating Cytokines and Bone Mineral Density in Older Men and Women

Source: The American Journal of Clinical Nutrition 2008; 88: 356-63

Author: Shea, K., Dallal, G., Dawson-Hughes, B., Ordovas, J.M., O'Donnell, C., Gundberg, C., Peterson, J., Booth, S.L.

Affiliation: USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA; Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA Department of Medicine, Massachusetts General Hospital, Harvard University, Boston, MA; NIH-NHLBI; Yale University.

Abstract: Limited data from cell studies suggest that vitamin K can modulate inflammation, and the results from one population study support this. To better understand the influence of vitamin K on inflammation in older adults, 379 men and women (60-80y) were randomized to receive a multi-vitamin with vitamin K or a multi-vitamin without vitamin K for 3 years. Measures of inflammation, as well as bone mineral density, were done at baseline and after 3 years of follow-up. Although vitamin K status, as measured by blood concentrations of vitamin K, was inversely associated with inflammation at baseline, there was no difference in the change in inflammation between those who received the vitamin K supplement and those who did not. This study concludes that vitamin K status may be associated with lower inflammation, but supplementation with vitamin K for 3 years did not influence change in inflammation in generally healthy older men and women.

Vitamin K Can Suppress the Inflammation Induced by Lipopolysaccharide Administration

Source: The Journal of Hard Tissue Biology 2005; 14(2): 284-285

Author: Shirakawa Hitoshi, Ohsaki Yusuke, Hiwatashi Kazuyuki, Furukawa Yuji, Mizutani Takeo, Komai Michio.

Affiliation: Tohoku University., Sendai, Japan; Ala Res. Center, Yokohama, Japan

Abstract: In this study the researchers used DNA microarray techniques to identify the effect of K status on gene expression in rat liver. Expression of genes involved in the acute inflammation response was enhanced in rats fed a K-deficient diet relative to control and K1-supplemented diet groups. Moreover, dietary supplementation with K1 suppressed inflammation induced by LPS administration. These results indicate that orally administrated K1 suppresses inflammation in the rat. However, the physiological role of K in these varied organs is not yet fully understood. It is likely that vitamin K has functions in addition to its role as a cofactor of protein g-glutamyl carboxylation.


Zinc: Role in Immunity, Oxidative Stress and Chronic Inflammation

Source: Current Opinion in Clinical Nutrition and Metabolic Care 2009; 12(6): 646-652

Author: Prasad A.S.

Affiliation: Department of Internal Medicine, Division of Hematology/Oncology, Wayne State University, School of Medicine, Detroit, Michigan, USA.

Abstract: Zinc is essential for multiple cellular functions including immunity. In this review, recent findings of zinc supplementation in various diseases have been presented. Zinc supplementation was effective in decreasing incidences of infections in the elderly, in patients with sickle cell disease (SCD) and decreasing incidences of respiratory tract infections in children. Zinc supplementation has prevented blindness in 25% of the elderly individuals with dry type of AMD. Zinc supplementation was effective in decreasing oxidative stress and generation of inflammatory cytokines such as TNF-alpha and IL-1beta in elderly individuals and patients with SCD. Zinc supplementation has been successfully used as a therapeutic and preventive agent for many conditions. Zinc functions as an intracellular signal molecule for immune cells.

Zinc and Micronutrient Combinations to Combat Gastrointestinal Inflammation

Source: Current Opinion in Clinical Nutrition and Metabolic Care 2009; 12(6): 653-660

Author: Scrimgeour A.G., Condlin M.L.

Affiliation: Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA.

Abstract: This study has examined current evidence for dietary supplementation with zinc and other micronutrients for primary prevention of multiple micronutrient deficiencies that are known to result from therapies used in the treatment of gastrointestinal inflammatory disorders. Epidemiological observations and clinical findings have strengthened the concept that both nutritional deficiencies and nutritional excesses impair the gastrointestinal response(s) and alter susceptibility to inflammation and other diseases. The interaction of micronutrient intake, biochemical indicators of nutritional status, and four specific gastrointestinal inflammation states have been reviewed. The study concludes that for each inflammation 'state', enhancement of micronutrient status can improve immunocompetance and for improve immunocompetance that minimize therapeutic side-effects.

Effects of Zinc Supplementation on Serum Zinc and C-Reactive Protein Concentrations in Hemodialysis Patients

Source: Journal of Renal Nutrition 2009;19(6): 475-8

Author: Rashidi A.A., Salehi M., Piroozmand A., Sagheb M.M.

Affiliation: School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.

Abstract: This randomized, double-blinded, placebo-controlled clinical study examined the effects of zinc supplementation on serum zinc and C-reactive protein concentrations in hemodialysis patients. Fifty-five hemodialysis patients (32 men and 23 women) participated after meeting the following criteria: zinc deficiency, treated for a minimum of 6 months; no record of hospitalizations in the preceding 3 months; and hemodialysis treatment 2 to 3 times per week. Patients were randomly divided into two groups. The zinc supplementation group (n=28) received a 220-mg zinc sulfate capsule, and the control group (n=27) received a placebo capsule (220mg corn starch), for 42 days. A progressive decrease in serum C-reactive protein concentrations was observed in the zinc-supplemented group from the beginning (13.5+/-3.8mg/L SEM) to the end (10.5+/-3.5mg/L SEM) of the study, but this event was not significant. This study shows that zinc supplementation intake may cause an increase in serum zinc concentrations, leading to a decrease of inflammation in hemodialysis patients.

Distinctive Modulation of Inflammatory and Metabolic Parameters in Relation to Zinc Nutritional Status in Adult Overweight/Obese Subjects

Source: The Journal of Nutritional Biochemistry 2009; May 6 [Epub ahead of print]

Author: Costarelli L., Muti E., Malavolta M., Cipriano C., Giacconi R., Tesei S., Piacenza F., Pierpaoli S., Gasparini N., Faloia E., Tirabassi G., Boscaro M., Polito A., Mauro B., Maiani F., Raguzzini A., Marcellini F., Giuli C., Papa R., Emanuelli M., Lattanzio F., Mocchegiani E.

Affiliation: Laboratory of Nutrigenomic and Immunosenescence, Research Department, Italian National Research Centres on Ageing (INRCA), 60121 Ancona, Italy.

Abstract: Considering the potential interactions among zinc nutritional status, inflammation, overweight/obesity and insulin secretion, the aim of the present work was to clarify the influence of zinc dietary intake on some metabolic, inflammatory and zinc status parameters in adult overweight/obese subjects. In particular, subjects with a lower zinc dietary intake displayed a deeper inflammatory status, general impairment of the zinc status, an altered lipid profile and increased insulin production with respect to obese subjects with normal zinc dietary intake. Moreover, in the presence of low dietary zinc intake, the obese subjects are less capable to respond to oxidative stress and to inflammation leading to the development of obesity or to a worsening of already preexisting obesity status. In conclusion, a possible zinc supplementation in obese subjects with a deeper inflammatory status and more altered zinc profile may be suggested in order to limit or reduce the inflammation, taking also into account that zinc supplementation normalizes "inflammaging" as well as zinc profile leading to a correct intra- and extracellular zinc homeostasis.

Zinc Deficiency Induces Vascular Pro-Inflammatory Parameters Associated with NF-kappaB and PPAR Signaling

Source: Journal of the American College of Nutrition 2008; 27(5): 577-87

Author: Shen H., Oesterling E., Stromberg A., Toborek M., MacDonald R., Hennig B.

Affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA.

Abstract: Marginal intake of dietary zinc can be associated with increased risk of cardiovascular diseases. The current study hypothesized that vascular dysfunction and associated inflammatory events are activated during a zinc deficient state. The researchers tested this hypothesis using both vascular endothelial cells and mice lacking the functional LDL-receptor gene. The results show that zinc deficiency increased oxidative stress and NF-kappaB DNA binding activity, and induced COX-2 and E-selectin gene expression, as well as monocyte adhesion in cultured endothelial cells. Finally, plasma data from LDL-R-deficient mice suggest an overall pro-inflammatory environment during zinc deficiency and support the concept that zinc is required for proper anti-inflammatory or protective functions of PPAR. This study suggests that zinc nutrition can markedly modulate mechanisms of the pathology of inflammatory diseases such as atherosclerosis.

Zinc Supplementation Decreases Oxidative Stress, Incidence of Infection, and Generation of Inflammatory Cytokines in Sickle Cell Disease Patients

Source: Translational Research 2008; 152(2): 67-80.

Author: Bao B., Prasad A.S., Beck F.W., Snell D., Suneja A., Sarkar F.H., Doshi N., Fitzgerald J.T., Swerdlow P.

Affiliation: Department of Internal Medicine, Division of Hematology/Oncology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.

Abstract: Previous studies demonstrated that zinc supplementation to adult SCD patients decreased the incidences of infections and hospital admissions. This study hypothesized that zinc supplementation improves T-helper cell function and decreases vascular endothelial cell activation, oxidative stress, and nuclear factor-kappa B (NF-kappaB)-DNA binding in mononuclear cells (MNCs) in SCD patients. To test this hypothesis, 36 SCD patients were recruited and randomly divided into 2 groups. One group (n = 18) received 25-mg zinc orally thrice a day for 3 months. The other group (n = 18) received placebo. The results indicate that the zinc-supplemented group had decreased incidence of infections compared with the placebo group. Zinc supplementation also increased relative levels of IL-2 and IL-2Ralpha mRNAs in phytohemagglutinin-p-stimulated MNCs. These results suggest that zinc supplementation may be beneficial to SCD patients.

Zinc Supplementation in the Elderly Reduces Spontaneous Inflammatory Cytokine Release and Restores T Cell Functions

Source: Rejuvenation Res. February, 2008; 11(1): pp.227-37

Author: Kahmann L., Uciechowski P., Warmuth S., Plumakers B., Gressner A.M., Malavolta M., Mocchegiani E., Rink L.

Affiliation: Institute of Immunology, RWTH Aachen University Hospital, Aachen, Germany.

Abstract: Aging is associated with low-grade inflammation on the one hand and mild zinc deficiency on the other. These conditions contribute to decreased immune functions, resulting in increased incidences of infections and autoimmune diseases. The aim of this study was to give more insight into the question, to what extent is low-grade inflammation caused by zinc deficient status. The study reports the effect of improved intracellular zinc status on low-grade inflammatory activity in 19 healthy elderly subjects. The study shows that adjustment of labile zinc by moderate zinc supplementation reduces spontaneous cytokine release and defects in termination of inflammatory activity. This results in reduced amounts of unspecific preactivated T cells and leads to improved T cell response upon mitogenic stimulation. Therefore, in contrast to other anti-inflammatory drugs, zinc does not suppress, but improves immune reaction upon pathogen invasion. These results suggest that mildly zinc-deficient, healthy elderly subjects might benefit from moderate zinc supplementation due to a more balanced immune response with reduced incidences of infections and autoimmune diseases.