Therapeutic lifestyle change intervention improved metabolic syndrome criteria and is complementary to amlodipine/atorvastatin.

AIMS: To examine whether addition of amlodipine (5 mg)/atorvastatin (10 mg) A/A to Therapeutic Lifestyle change intervention (TLC) would beneficially modulate Metabolic Syndrome (MetS) and oxidized low-density lipoprotein (Ox-LDL) levels. METHODS: Patients with MetS (n = 53) were randomized to TLC + placebo or TLC + A/A for 12 months. Anthropometric measurements, blood pressure (BP), lipid profile, plasma Ox-LDL, and area under the curve of free fatty acid (AUCFFA) during oral glucose tolerance test, a marker of adipose tissue health, were assessed before and after the intervention. RESULTS: Twenty-six patients completed the study with an overall improvement of MetS (p = 0.02). TLC + placebo was beneficial in reversing MetS comparable to TLC + A/A (54% vs. 39%; p = 0.08). Both treatments decreased systolic BP (p ≤ 0.01). TLC + A/A also decreased diastolic BP and triglyceride levels. The changes in Ox-LDL levels directly correlated with changes in weight in the TLC-placebo group (r = 0.64; p = 0.04). AUCFFA determined the loss of fat mass (r = 0.472, p = 0.03). CONCLUSIONS: 1) Addition of A/A has the advantage of improving the lipid profile and BP; but TLC alone was comparable to TLC + A/A in improving MetS; 2) weight change determines the TLC-associated change in Ox-LDL levels; and 3) AT metabolic health is a significant predictor of TLC-associated loss of body fat mass.

Folate Insufficiency Due to Celiac Disease in a 49-Year-Old Woman of Southeast Asian-Indian Ethnicity.

The clinical presentation of celiac disease has evolved from chronic diarrhea and malnutrition to mild nutrient insufficiencies. Recently diagnosed adults with celiac disease should be assessed for micronutrient deficiencies because early institution of a gluten-free diet (GFD) prevents morbidity and reduces the incidence of gastrointestinal malignant neoplasms and osteoporosis. In this report, we present the case of a 49-year-old woman of Southeast Asian-Indian descent living in the United States who had folate insufficiency, as manifested by low serum and red blood cell (RBC) folate levels. Further investigation, including serologic testing and intestinal biopsy, confirmed a diagnosis of celiac disease and other nutrient deficiencies. Managing the condition of this patient with folate supplements and implementation of a recommended GFD reversed the folate insufficiency. In conclusion, when serum and/or RBC levels are low in a person of Southeast Asian-Indian descent living in a country with folate fortification of the grain supply, such as the United States, the medical team needs to look for an organic cause, as in our patient, to diagnose and manage celiac disease early and, hopefully, forestall complications.

Modulation of endothelial progenitor cell number and function with n-3 polyunsaturated fatty acids.

Endothelial dysfunction is pivotal in atherosclerosis. Endothelial progenitor cells (EPC) predict cardiovascular events and could serve as a cellular biomarker of endothelial function. Epidemiological studies suggest the benefits of omega 3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on cardiovascular health. However, there is a paucity of data on the effect of n-3 PUFA on EPC number and functionality. Incubation with DHA and EPA, either alone or in combination significantly increased the number of EPCs and colony forming units (CFU). In addition, co-incubation with DHA + EPA, significantly enhanced EPC migratory capacity, adhesive properties and greater incorporation into tubules. Thus, EPA + DHA are effective in improving EPC number and functionality in-vitro. Future studies will test the effect of n-3 PUFA supplementation on EPC number and function in-vivo and will elucidate plausible mechanisms.

Effects of Aloe vera supplementation in subjects with prediabetes/metabolic syndrome.

BACKGROUND: Metabolic syndrome affects 1 in 3 U.S. adults. The primary target of treatment of patients with metabolic syndrome is therapeutic lifestyle change. Numerous animal trials have reported positive effects of Aloe vera in in vivo models of diabetes, but there is a paucity of controlled clinical trials in patients with prediabetes. Thus, the objective of this pilot study was to examine the effect of aloe compared to placebo on fasting blood glucose, lipid profile, and oxidative stress in subjects with prediabetes/metabolic syndrome. METHODS: This was a double-blind, placebo-controlled Institutional Review Board (IRB)-approved pilot study of two aloe products (UP780 and AC952) in patients with prediabetes over an 8-week period. A total of 45 subjects with impaired fasting glucose or impaired glucose tolerance and having two other features of metabolic syndrome were recruited (n=15/group). Parameters of glycemia [fasting glucose, insulin, homeostasis model assessment (HOMA), glycosylated hemoglobin (HbA1c), fructosamine, and oral glucose tolerance test (OGTT)] and oxidative stress (urinary F2-isoprostanes) were measured along with lipid profile and high-sensitivity C-reactive protein (hsCRP) levels before and after supplementation. RESULTS: There were no significant baseline differences between groups. Compared to placebo, only the AC952 Aloe vera inner leaf gel powder resulted in significant reduction in total and low-density lipoprotein cholesterol (LDL-C) levels, glucose, and fructosamine. In the UP780 Aloe vera inner leaf gel powder standardized with 2% aloesin group, there were significant reductions in HbA1c, fructosamine, fasting glucose, insulin, and HOMA. Only the UP780 aloe group had a significant reduction in the F2-isoprostanes compared to placebo. CONCLUSIONS: Standardized aloe preparations offer an attractive adjunctive strategy to revert the impaired fasting glucose and impaired glucose tolerance observed in conditions of prediabetes/metabolic syndrome.

Effect of orange juice and beverage with phytosterols on cytokines and PAI-1 activity.

BACKGROUND & AIMS: Inflammation is pivotal in all phases of atherosclerosis. Dietary options which lower inflammatory biomarkers would be an attractive strategy to reduce risk from cardiovascular diseases and cancer. Indeed, fruit and vegetable intake or fruit juice consumption is associated with health and wellness. However, there is a paucity of data examining the effect of orange juice on biomarkers of inflammation in healthy volunteers. We have previously conducted the first placebo-controlled randomized studies examining the effect of sterol fortified orange juice or sterol fortified reduced calorie orange juice beverage supplementation (2 g sterols/day) compared to Placebo OJ or Placebo OJBev, and showed significant benefits on the lipid profile as well as significant reduction in hsCRP, the prototypic marker of inflammation and a cardiovascular risk marker. The aim of this study was to examine the effect of orange juice (OJ) or OJ beverage (Bev) alone and fortified with plant sterols (1g/240 ml juice or beverage twice a day) on pro-inflammatory cytokines and PAI-1, a marker of impaired fibrinolysis in healthy human volunteers. METHODS: In the first study, 72 healthy human volunteers received Placebo OJ or Sterol OJ and in the second study, 72 volunteers received OJBev or Sterol OJBev for 8 weeks and blood was drawn at baseline and following supplementation for 8 weeks. Biomarkers of Inflammation (IL-1b, IL-6, TNF, IL-8, IL-10) were assessed in serum using the BD Human Inflammatory Cytokine Cytometric Bead Array and PAI-1 activity was assessed in citrated plasma. RESULTS: OJ or OJBev alone failed to result in any significant effects on circulating cytokine levels or PAI-1 activity. There was a significant reduction in IL-1b with sterol fortified OJ (p < 0.05) compared to baseline. In addition, both sterol fortified OJ as well as sterol fortified OJBev resulted in significant reductions in serum IL-6 levels (p < 0.01). CONCLUSION: Thus, sterol fortified OJ and OJ Beverage are able to effectively lower biomarkers of inflammation in healthy human volunteers in addition to providing lipid profile benefits and may thus contribute to decreasing cardiovascular risk.

Management of hypertriglyceridemia in the diabetic patient.

The hypertriglyceridemia of diabetes can be classified into mild to moderate (triglycerides between 150-499 mg/dL) and severe hypertriglyceridemia (triglycerides > or =500 mg/dL). As in any other individuals with hypertriglyceridemia, secondary causes need to be excluded. The management of severe hypertriglyceridemia (chylomicronemia syndrome) includes aggressive reduction of triglycerides with intravenous insulin, fibrates, omega-3 fatty acids, and/or niacin therapy to avert the risk of pancreatitis. In patients with mild to moderate hypertriglyceridemia, the treatment of choice is statin therapy to achieve the low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL) target goals. The evidence base would favor niacin therapy in combination with statin therapy to achieve the goals pertaining to LDL cholesterol and non-HDL cholesterol. The data about the combination of fibrate therapy with statin therapy are disappointing.

Effects of epigallocatechin gallate on regulatory T cell number and function in obese v. lean volunteers.

Obesity predisposes to an increased incidence of diabetes and CVD. Also, obesity is a pro-inflammatory state. Regulatory T cells (Tregs) are essential negative regulators of inflammation and are down-regulated in pro-inflammatory states. Animal models of obesity are associated with decreased Tregs. The dietary modulation of Tregs could be used as a therapeutic strategy to control inflammation. Epigallocatechin gallate (EGCG) is a potent anti-inflammatory agent and an active ingredient of green tea and is suggested to have a role as a preventive agent in obesity, diabetes and CVD. The role of EGCG in the modulation of Tregs has, however, not been studied. Thus, the aim of the present study was to determine the effect of EGCG on the number and function of Tregs in obese and lean human subjects in vitro, and to delineate its specific regulation mechanisms. Tregs were isolated from normal-weight and obese subjects. Tregs were cultured in the absence or presence of EGCG (20 mum) for 24 h. Foxp3-expressing Tregs were enumerated using flow cytometry. Histone deacetylase (HDAC) activity and nuclear NF-kappaBp65 level were measured by ELISA and Western blots. Obese subjects had lower Tregs and IL-10 production than lean subjects. EGCG treatment significantly enhanced the number of Foxp3-expressing Tregs and IL-10 production in vitro (P < 0.05) in both groups. Also, EGCG decreased NF-kappaB activity and increased HDAC activity and HDAC-2 expression in Tregs (P < 0.05) in both groups. Thus, in part, EGCG enhances the functionality of Tregs, i.e. IL-10 production and number by suppressing the NF-kappaB signalling pathway via inducing epigenetic changes.

A randomized placebo-controlled crossover trial of aloe vera on bioavailability of vitamins C and B(12), blood glucose, and lipid profile in healthy human subjects.

Several factors limit the absorption and bioavailability of vitamins. Vitamin C, a commonly used water-soluble supplement reduces the risk of disease. Vitamin B(12) is necessary for the development of RBC, growth, and nervous system. Vitamin B(12) deficiency is common among elderly. Thus, agents that improve bioavailability of vitamin C and B(12), especially in older individuals would be important. Aloe Vera is a botanical with immunomodulatory properties. Aloe is processed using the hand-filleted technique or whole leaf procedure. The aim of this study is to examine the effect of two different aloe vera preparations (aloe inner leaf gel, [AG] and aloe whole leaf decolorized gel, [AL]) compared to placebo on the bioavailability of vitamins, C and B(12), in healthy human volunteers in a randomized crossover trial. Subjects (n = 15) received in a random fashion either aloe whole leaf extract (AL with vitamins B(12), 1 mg and vitamin C 500 mg) or aloe fillet gel (AG with B(12) 1 mg and vitamin C 500 mg) or water (with vitamin B(12) 1 mg and vitamin C 500 mg). Blood was obtained fasting, followed by 1, 2, 4, 6, 8, and 24 hours postingestion of aloe/water. When given with vitamins C and B(12), AG significantly increased plasma oxygen radical absorbance capacity (ORAC) at both 4 and 24 hours and AL at 4 hours compared to baseline and placebo. AG significantly increased plasma vitamin C at 4, 6, 8, and 24 hours and AL at 4 and 6 hours compared to baseline and placebo (p <.01). Also, both aloes significantly increased serum vitamin B(12) levels at 1 and 2 hours compared to baseline and placebo (p <.01). Thus, AG and AL preparations are safe, well tolerated, and enhance the bioavailability of vitamins C and B(12) and antioxidant potential.

Alpha-lipoic acid supplementation and diabetes.

Diabetes is a common metabolic disorder that is usually accompanied by increased production of reactive oxygen species or by impaired antioxidant defenses. Importantly, oxidative stress is particularly relevant to the risk of cardiovascular disease. Alpha-lipoic acid (LA), a naturally occurring dithiol compound, has long been known as an essential cofactor for mitochondrial bioenergetic enzymes. LA is a very important micronutrient with diverse pharmacologic and antioxidant properties. Pharmacologically, LA improves glycemic control and polyneuropathies associated with diabetes mellitus; it also effectively mitigates toxicities associated with heavy metal poisoning. As an antioxidant, LA directly terminates free radicals, chelates transition metal ions, increases cytosolic glutathione and vitamin C levels, and prevents toxicities associated with their loss. These diverse actions suggest that LA acts by multiple mechanisms both physiologically and pharmacologically. Its biosynthesis decreases as people age and is reduced in people with compromised health, thus suggesting a possible therapeutic role for LA in such cases. Reviewed here is the known efficacy of LA with particular reference to types 1 and 2 diabetes. Particular attention is paid to the potential benefits of LA with respect to glycemic control, improved insulin sensitivity, oxidative stress, and neuropathy in diabetic patients. It appears that the major benefit of LA supplementation is in patients with diabetic neuropathy.

A dose-response study on the effects of purified lycopene supplementation on biomarkers of oxidative stress.

OBJECTIVE: While tomato product supplementation, containing antioxidant carotenoids, including lycopene, decreases oxidative stress, the role of purified lycopene as an antioxidant remains unclear. Thus, we tested the effects of different doses of purified lycopene supplementation on biomarkers of oxidative stress in healthy volunteers. METHODS: This was a double-blind, randomized, placebo-controlled trial, examining the effects of 8-week supplementation of purified lycopene, on plasma lycopene levels, biomarkers of lipid peroxidation {LDL oxidizability, malondialdehyde & hydroxynonenals (MDA & HNE), urinary F(2)-isoprostanes}, and markers of DNA damage in urine and lymphocytes. Healthy adults (n = 77, age > or = 40 years), consumed a lycopene-restricted diet for 2 weeks, and were then randomized to receive 0, 6.5, 15, or 30 mg lycopene/day for 8 weeks, while on the lycopene-restricted diet. Blood and urine samples were collected at the beginning and end of Week 2 of lycopene-restricted diet, and at end of Week 10 of the study. RESULTS: Independent of the dose, plasma lycopene levels significantly increased in all lycopene supplemented groups versus placebo (p < 0.05). ANOVA revealed a significant decrease in DNA damage by the comet assay (p = 0.007), and a significant decrease in urinary 8-hydroxy deoxoguanosine (8-OHdG) at 8 weeks versus baseline (p = 0.0002), with 30 mg lycopene/day. No significant inter- or intra-group differences were noted for glucose, lipid profile, or other biomarkers of lipid peroxidation at any dose/time point. CONCLUSIONS: Thus, purified lycopene was bioavailable and was shown to decrease DNA oxidative damage and urinary 8-OHdG at the high dose.

Gamma-tocopherol supplementation alone and in combination with alpha-tocopherol alters biomarkers of oxidative stress and inflammation in subjects with metabolic syndrome.

Metabolic syndrome (MetS) is associated with increased incidence of diabetes and cardiovascular disease (CVD). Prospective clinical trials with alpha-tocopherol (AT) have not yielded positive results. Because AT supplementation decreases circulating gamma-tocopherol (GT), we evaluated supplementation with GT (800 mg/day), 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 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. Urinary alpha- and gamma-CEHC, metabolites of the respective Ts, also increased correspondingly, i.e., alpha-CEHC with AT and gamma-CEHC with GT supplementation, compared to placebo. HsCRP levels significantly decreased in the combined AT+GT group. LPS-activated whole blood release of IL-1 and IL-6 did not change. There was a significant decrease in TNF with AT alone or in combination with GT. Plasma MDA/HNE and lipid peroxides were significantly decreased with AT, GT, or in combination. Nitrotyrosine levels were significantly decreased only with GT or GT+AT but not with AT compared to placebo. Thus, 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.

BACKGROUND: Oxidative stress and inflammation are crucial in atherogenesis. alpha-Tocopherol is both an antioxidant and an antiinflammatory agent. OBJECTIVE: We evaluated the effect of RRR-alpha-tocopherol supplementation on carotid atherosclerosis in patients with stable coronary artery disease (CAD) on drug therapy. DESIGN: Randomized, controlled, double-blind trial compared RRR-alpha-tocopherol (1200 IU/d for 2 y) with placebo in 90 patients with CAD. Intimal medial thickness (IMT) of both carotid arteries was measured by high-resolution B-mode ultrasonography at 0, 1, 1.5, and 2 y. At 6-mo intervals, plasma alpha-tocopherol concentrations, C-reactive protein (CRP), LDL oxidation, monocyte function (superoxide anion release, cytokine release, and adhesion to endothelium), and urinary F(2)-isoprostanes were measured. RESULTS: 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). alpha-Tocopherol supplementation significantly reduced urinary F(2)-isoprostanes (P < 0.001) and monocyte superoxide anion and tumor necrosis factor release compared with baseline and placebo (P < 0.001). No significant difference was observed in the mean change in total carotid IMT in the placebo and alpha-tocopherol groups. In addition, no significant difference in cardiovascular events was observed (P = 0.21). CONCLUSIONS: 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 y.

Coenzyme Q10 supplementation and heart failure.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Western world. Oxidative stress appears to play a pivotal role in atherosclerosis. Coenzyme Q10 (CoQ10), one of the most important antioxidants, is synthesized de novo by every cell in the body. Its biosynthesis decreases with age and its deficit in tissues is associated with degenerative changes of aging, thus implicating a possible therapeutic role of CoQl0 in human diseases. There is evidence to support the therapeutic value of CoQ10 as an adjunct to standard medical therapy in congestive heart failure. However, much further research is required, especially in the use of state-of-the-art techniques to assess functional outcomes in patients with congestive heart failure.

High-dose alpha-tocopherol therapy does not affect HDL subfractions in patients with coronary artery disease on statin therapy.

BACKGROUND: Subfractions of HDL, particularly large HDL (HDL2), are inversely correlated with the severity of coronary artery disease (CAD). alpha-Tocopherol (AT) is the main lipid-soluble antioxidant in plasma. Results of a previous small study (n = 44) suggested that either a combination of an antioxidant cocktail [800 IU/day 2R,4'R,8'R-(RRR)-AT plus 1 g vitamin C, 25 mg beta-carotene, and 100 microg selenium] or individual antioxidant vitamins combined with simvastatin-niacin (S-N) therapy attenuated the protective increase in HDL2 seen with S-N alone. Few data are available on the effect of AT therapy alone on HDL subfractions, which we addressed in this study. METHODS: In a prospective placebo-controlled study, we randomized 127 patients with stable CAD to receive high-dose RRR-AT (1200 IU/day for 2 years) or placebo. HDL subfractions (small, medium, and large HDL particles) were analyzed by nuclear magnetic resonance spectroscopy. RESULTS: AT concentrations significantly increased in the AT arm but not with placebo. No differences were noted between AT and placebo groups in concentrations of total cholesterol, triglyceride, LDL-cholesterol, or HDL-cholesterol. AT therapy did not affect total, small, medium, or large HDL particles compared with baseline or placebo. Furthermore, serum apolipoprotein A1 concentrations did not change after 2 years AT therapy as compared with baseline. CONCLUSIONS: High-dose AT therapy administered for a 2-year period does not negatively affect either HDL subfractions or apolipoprotein A1 in patients with CAD on statin therapy. Thus the negative interaction previously proposed between antioxidant cocktail and statin therapy cannot be attributed to AT.

The effect of weight loss and dietary fatty acids on inflammation.

Inflammation plays a pivotal role in all stages of atherosclerosis. Weight loss appears to be the best nonpharmacologic modality to reduce inflammation. Intervention trials convincingly demonstrate that weight loss reduces biomarkers of inflammation, such as C-reactive protein. Limited studies have shown that certain dietary fatty acids (ie, oleic acid and alpha-linolenic acid) reduce biomarkers of inflammation. Most of the studies with fish oil supplementation have shown null effects, and conflicting results have been reported with saturated and trans fatty acids. Much further research is needed to define the role of individual dietary factors on the biomarkers of inflammation and the mechanism of the anti-inflammatory effects of weight loss.

Reduced-calorie orange juice beverage with plant sterols lowers C-reactive protein concentrations and improves the lipid profile in human volunteers.

BACKGROUND: Dietary plant sterols effectively reduce LDL cholesterol when incorporated into fat matrices. We showed previously that supplementation with orange juice containing plant sterols (2 g/d) significantly reduced LDL cholesterol. Inflammation is pivotal in atherosclerosis. High-sensitivity C-reactive protein (hs-CRP), the prototypic marker of inflammation, is a cardiovascular disease risk marker; however, there is a paucity of data on the effect of plant sterols on CRP concentrations. OBJECTIVE: The aim of this study was to examine whether plant sterols affect CRP concentrations and the lipoprotein profile when incorporated into a reduced-calorie (50 calories/240 mL) orange juice beverage. DESIGN: Seventy-two healthy subjects were randomly assigned to receive a reduced-calorie orange juice beverage either without (Placebo Bev) or with (1 g/240 mL; Sterol Bev) plant sterols twice a day with meals for 8 wk. Fasting blood was obtained at baseline and after 8 wk of Placebo Bev or Sterol Bev supplementation. RESULTS: Sterol Bev supplementation significantly reduced total cholesterol (5%; P < 0.01) and LDL cholesterol (9.4%; P < 0.001) compared with both baseline and Placebo Bev (P < 0.05). HDL cholesterol increased significantly with Sterol Bev (P < 0.02). No significant changes in triacylglycerol, glucose, or liver function tests were observed with Sterol Bev. Sterol Bev supplementation resulted in no significant change in vitamin E and carotenoid concentrations. Sterol Bev supplementation resulted in a significant reduction of CRP concentrations compared with baseline and Placebo Bev (median reduction: 12%; P < 0.005). CONCLUSION: Supplementation with a reduced-calorie orange juice beverage containing plant sterols is effective in reducing CRP and LDL cholesterol and could be incorporated into the dietary portion of therapeutic lifestyle changes.

The role of dietary supplementation with plant sterols and stanols in the prevention of cardiovascular disease.

Several studies have shown that increased levels of low-density lipoprotein (LDL) cholesterol predict cardiovascular events. The Adult Treatment Panel II (ATP II) introduced the principle of therapeutic lifestyle changes, including plant sterols/stanols for the management of LDL cholesterol. Plant sterols and stanols in fat matrices effectively lower LDL cholesterol levels in hypercholesterolemic, diabetic, and healthy human volunteers. Recent studies also show that sterols (2 g/d) lower LDL cholesterol even when incorporated in nonfat matrices. In addition, they may reduce biomarkers of oxidative stress and inflammation. Plant sterols and stanols exert their hypocholesterolemic effects possibly by interfering with the uptake of both dietary and biliary cholesterol from the intestinal tract. Present evidence is accumulating to promote their use for lowering LDL cholesterol levels, as a first line of therapy (as well as adjunctive therapy) in patients on statin therapy.

Dietary factors that promote or retard inflammation.

Inflammation plays a pivotal role in all stages of atherosclerosis. Cardiovascular risk factors and metabolic syndrome are typified by low-grade inflammation. Intervention trials convincingly demonstrate that weight loss reduces biomarkers of inflammation, such as C-reactive protein (CRP) and interleukin (IL)-6. Limited studies have shown that certain dietary factors; oleic acid, alpha-linolenic acid, and antioxidants RRR-alpha-alpha tocopherol, reduce biomarkers of inflammation. Most of the studies with fish oil supplementation have shown null effects, and conflicting results have been reported with saturated and trans fatty acids, cholesterol, and soy intake. Much further research is needed to define the role of individual dietary factors on the biomarkers of inflammation and the mechanism of the anti-inflammatory effects of weight loss.

Development of an in vitro screening assay to test the antiinflammatory properties of dietary supplements and pharmacologic agents.

BACKGROUND: Monocytes and macrophages are critical in atherosclerosis and on stimulation secrete proinflammatory, proatherogenic cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, which have been shown to be present in atherosclerotic lesions. The aim of this study was to develop a rapid in vitro screening assay to test the antiinflammatory effects of different compounds. METHODS AND RESULTS: THP-1 cells (human monocytic cell line) were stimulated with different concentrations of lipopolysaccharide (LPS; 0 to 1000 microg/L) and for different times (4, 12, and 24 h), and the secretion of proinflammatory cytokines (IL-1, IL-6, and TNF-alpha) was assessed. TNF-alpha secretion was maximum at the lowest LPS concentration (100 microg/L) and at shortest duration of incubation (4 h). Maximum secretion of IL-1beta and IL-6 was achieved at 24 h with higher doses of LPS. Treatment of THP-1 with various test compounds such as dietary supplements (alpha-tocopherol, N-acetylcysteine, catechin and epigallocatechin gallate) as well as pharmacologic agents (statins, peroxisome proliferator-activated receptor-gamma agonists, and an angiotensin II receptor blocker) significantly inhibited LPS-stimulated TNF-alpha release. CONCLUSIONS: The release of TNF-alpha after stimulation of THP-1 cells with LPS is a valid model system to test novel compounds for potential antiinflammatory effects.