Cardiovascular Disease (CVD) - Plasma/Serum Lycopene and Disease Risk

Critical Findings

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	G.Tom +, N,	P.Tom +, N,	F.Tom +, N, -	Lyco +, N,	Other +, N,
Heart	Farwell WR	The relationship between total plasma carotenoids and risk factors for chronic disease among middle-aged and older men. Farwell WR, Michael Gaziano J, Norkus EP, Sesso HD. Br J Nutr. 2008 Oct;100(4):883-9. Epub 2008 Mar 12.	2008	Individual plasma carotenoids have been associated with various chronic diseases but little is known about the relationship between total plasma carotenoids and risk factors for chronic diseases. In the Physicians' Health Study, we examined 492 men free of CVD and cancer for the relationship between total plasma carotenoids (the sum of alpha-carotene, beta-carotene, lycopene, zeaxanthin, lutein and beta-cryptoxanthin) and a wide variety of factors that predict chronic disease. Multivariate linear and logistic regression was performed to calculate parameter estimates (95% CI) and OR (95% CI) for total plasma carotenoids. In linear regression models, BMI, hypertension, alcohol intake and plasma levels of each lipid parameter and a-tocopherol significantly predicted levels of total plasma carotenoids. Upon adjustment for multiple chronic disease risk factors, the OR for levels of total plasma carotenoids greater than or equal to the median (> or=1.301 micromol/l) was statistically significant for current smoking (OR 0.21; 95% CI 0.06, 0.77), weekly alcohol ingestion (OR 2.30; 95% CI 1.06, 4.99), daily alcohol ingestion (OR 2.46; 95% CI 1.29, 4.67), each 100 mg/l increase in total cholesterol (OR 0.73; 95% CI 0.58, 0.91), LDL-cholesterol (OR 1.48; 95% CI 1.17, 1.89) and HDL-cholesterol (OR 1.58; 95% CI 1.26, 1.99), each 100 mg/ml increase in intercellular adhesion molecule-1 (OR 0.70; 95% CI 0.53, 0.93) and each 10 micromol/l increase in alpha-tocopherol (OR 1.33; 95% CI 1.12, 1.57), using logistic regression. Few lifestyle and clinical risk factors appear to be related to levels of total plasma carotenoids; however, levels of biomarkers such as plasma lipids and alpha-tocopherol may be strongly related.	CS					N plasma [carotenoi ds] not related to lifestyle/cli nical risk factors
Heart: BP	Hozawa A	Circulating carotenoid concentrations and incident hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Hozawa A, Jacobs DR Jr, Steffes MW, Gross MD, Steffen LM, Lee DH. J Hypertens. 2009 Feb;27(2):237-42.	2009	BACKGROUND: Several epidemiological studies have demonstrated that carotenoid concentrations relate inversely to cardiovascular disease incidence. Thus, we examined the association of circulating carotenoids with hypertension, a major macrovascular disease risk factor. METHODS: Black and White men and women in the Coronary Artery Risk Development in Young Adults Study, aged 18-30 years at recruitment (1985-1986) from four US cities, were investigated over 20 years. At years 0, 7, and 15, we determined the relationships of the sum of four serum carotenoids (alpha-carotene, beta-carotene, lutein/zeaxanthin, cryptoxanthin) and of lycopene with incident hypertension using proportional hazards regression models. RESULTS: In 4412 participants, year 0 sum of four carotenoids was significantly inversely associated with 20-year hypertension incidence after adjustment for baseline systolic blood pressure and other confounding factors (relative hazard per SD increase of sum of four carotenoids: 0.91; 95% confidence interval = 0.84-0.99). The inverse relationships persisted in time-dependent models updating year 0 sum of four carotenoids with year 7 and year 15 values (relative hazard per SD increase of sum of four carotenoids: 0.84; 95% confidence interval = 0.77-0.92). Lycopene was unrelated to hypertension in any model. CONCLUSION: Those individuals with higher concentrations of sum of carotenoids, not including lycopene, generally had lower risk for future hypertension.	PC				N	BP

 

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	G.Tom +, N,	P.Tom +, N,	F.Tom +, N, -	Lyco +, N,	Other +, N,
Heart:inflam &endothelialfxn	van Herpen-Broekmans WM	Serum carotenoids and vitamins in relation tomarkers of endothelialfunction and inflammation. Van Herpen-Broekmans WM, Klopping-Ketelaars IA, Bots ML, Kluft C, Princen H, Hendriks HF, Tijburg LB, van Poppel G, Kardinaal AF. Eur J Epidemiol. 2004;19(10):915-21.	2004	BACKGROUND: Endothelial cell dysfunction may be related to an increase in cellular oxidative stress. Carotenoids and vitamins could have an antioxidant-mediated tempering influence on endothelial function and inflammation, thereby reducing the risk of atherosclerosis. METHODS: We measured serum carotenoids, alpha-tocopherol and Vitamin C concentrations in 379 subjects sampled from the general population. High-sensitive C-reactive protein (CRP), fibrinogen (Fbg) and leukocytes were measured as markers of inflammation. Furthermore, soluble intercellular adhesion molecule-1 (sICAM-1) and flow-mediated vasodilation (FMD; n= 165) were measured as markers of endothelial function. Relationships between serum carotenoids and vitamins and markers of endothelial function and inflammation were analysed after adjustment for confounding. RESULTS: In the total study group, lutein and lycopene were inversely related to sICAM-1 with regression-coefficients of -0.38+/-0.19 (p = 0.04) and -0.16+/-0.08 (p = 0.04) per 1 micromol/l, respectively. beta-Carotene was inverse related to leukocytes (-0.23+/-0.07; p = 0.007) and CRP (-1.09+/-0.30; p = 0.0003) per 1 micromol/l. Vitamin C was inverse related to CRP (-0.01+/-0.005; p = 0.04) per 1 micromol/l, whereas alpha-tocopherol was positively related to CRP (0.03+/-0.01; p = 0.02) per 1 micro/l. Zeaxanthin was inversely related to FMD (31.2+/-15.3; p = 0.04) per 1 micromol/l. CONCLUSION: The inverse relations between carotenoids, Vitamin C and sICAM-1, CRP and leukocytes may help to explain the possible protective effect of carotenoids and Vitamin C on atherosclerosis through an influence on inflammatory processes and endothelial function.	CS				(-)/N
Heart:inflam &endothelialfxn	Rowley K	Inflammation andvascular endothelialactivation in an Aboriginalpopulation: relationships to coronary disease risk factors and nutritional markers. Rowley K, Walker KZ, Cohen J, Jenkins AJ, O'Neal D, Su Q, Best JD, O'Dea K. Med J Aust. 2003 May 19;178(10):495-500.	2003	OBJECTIVE: To describe the levels of inflammation and vascular endothelial activation in an Aboriginal community, and the relationship of these factors to coronary heart disease (CHD) risk factors and markers of nutritional quality. DESIGN AND PARTICIPANTS: A cross-sectional survey of 95 women and 76 men participating in a chronic-disease prevention program. SETTING: A remote Aboriginal community in Western Australia in 1996. MAIN OUTCOME MEASURES: Concentrations of markers of inflammation (C-reactive protein [CRP]) and vascular endothelial activation (soluble E-selectin [sE-selectin]); presence of metabolic syndrome; concentrations of diet-derived antioxidants. RESULTS: Participants exhibited very high plasma concentrations of CRP (mean, 5.4 mg/L; 95% CI, 4.6-6.3 mg/L) and sE-selectin (mean, 119 ng/mL; 95% CI, 111-128 ng/mL). Both CRP and sE-selectin concentrations were significantly higher in the presence of the metabolic syndrome. There were significant inverse linear relationships between concentrations of CRP and plasma concentrations of the antioxidants lycopene, beta-carotene, cryptoxanthin and retinol. Even stronger inverse associations were evident between concentrations of sE-selectin and lycopene, beta-carotene, cryptoxanthin and lutein. CONCLUSIONS: Vascular inflammation and endothelial activation may be important mediators of elevated CHD risk in Aboriginal people. Inadequate nutrition and physical inactivity may contribute to this process.	CS				(-)

 

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	G.Tom +, N,	P.Tom +, N,	F.Tom +, N, -	Lyco +, N,	Other +, N,
Heart: oxidation	Sesso HD	Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in women. Sesso HD, Buring JE, Norkus EP, Gaziano JM. Am J Clin Nutr. 2004 Jan;79(1):47-53.	2004	BACKGROUND: Growing evidence suggests that lycopene has significant in vitro antioxidant potential. Lycopene has rarely been tested in prospective studies for its role in cardiovascular disease (CVD) prevention. OBJECTIVE: We examined the association between plasma lycopene and the risk of CVD in middle-aged and elderly women. DESIGN: A prospective, nested, case-control study was conducted in 39 876 women initially free of CVD and cancer in the Women's Health Study. Baseline blood samples were collected from 28 345 (71%) of the women. During a mean of 4.8 y of f ollow-up, we identified 483 CVD cases and 483 control subjects matched by age, smoking status, and follow-up time. Plasma lycopene, other carotenoids, retinol, and total cholesterol were measured. RESULTS: In analyses matched for age and smoking, with adjustment for plasma cholesterol, the relative risks (RRs) and 95% CIs of CVD in increasing quartiles of plasma lycopene were 1.00 (referent), 0.78 (95% CI: 0.55, 1.11), 0.56 (0.39, 0.82), and 0.62 (0.43, 0.90). In multivariate models, the RRs were 1.00 (referent), 0.94 (0.60, 1.49), 0.62 (0.39, 1.00), and 0.67 (0.41, 1.11); those in the upper compared with the lower half of plasma lycopene had an RR of 0.66 (0.47, 0.95). For CVD, exclusive of angina, women in the upper 3 quartiles had a significant multivariate 50% risk reduction compared with those in the lowest quartile. The stepwise addition of individual plasma carotenoids did not affect the RRs. CONCLUSIONS: Higher plasma lycopene concentrations are associated with a lower risk of CVD in women. These findings require confirmation in other cohorts, and the determinants of plasma lycopene concentrations need to be better understood.	CC nested				(-)W	Ox
Heart: oxidation	Sesso HD	Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in men. Sesso HD, Buring JE, Norkus EP, Gaziano JM. Am J Clin Nutr. 2005 May;81(5):990-7.	2005	BACKGROUND: Emerging evidence suggests a possible role of lycopene in the primary prevention of cardiovascular disease (CVD). OBJECTIVE: We examined whether plasma lycopene concentrations in the Physicians' Health Study were associated with CVD in a prospective, nested, case-control design. DESIGN: Baseline blood samples were collected starting in 1996. During a mean follow-up of 2.1 y, we identified 499 cases of CVD (confirmed myocardial infarction, stroke, CVD death, or revascularization procedures) and an equal number of men free of CVD and matched for age (x: 69.7 y), follow-up time, and smoking status. We collected self-reported coronary disease risk factors and measured plasma carotenoids, retinol, lipids, and C-reactive protein. RESULTS: In matched analyses with additional adjustment for plasma total cholesterol and randomized treatment, the relative risks (RRs) of CVD for men in the lowest to highest quartiles of plasma lycopene were 1.00 (reference), 0.92, 1.04, and 0.95 (P for linear trend = 0.93). With multivariate adjustment, the RRs of total CVD were 1.00 (reference), 1.08, 0.94, and 1.03 (P for linear trend = 0.98). For important vascular events (241 cases), excluding revascularization procedures, the multivariate RRs remained nonsignificant (P for linear trend = 0.50). Adding plasma carotenoids, lipids, or C-reactive protein to multivariate models had a minimal effect on the RRs of total CVD for plasma lycopene. Compared with lycopene, higher concentrations of plasma lutein/zeaxanthin and retinol suggested a moderate increase in CVD risk, whereas no association was found for beta-cryptoxanthin, alpha-carotene, and beta-carotene. CONCLUSIONS: Higher plasma lycopene concentrations were not associated with the risk of CVD in this study of older men. Further evaluation in diverse populations is necessary.	CC nested				NM	Ox

 

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	G.Tom +, N,	P.Tom +, N,	F.Tom +, N, -	Lyco +, N,	Other +, N,
Heart: oxidation	Karppi J	Lycopene, lutein and beta-carotene as determinants of LDL conjugated dienes in serum. Karppi J, Nurmi T, Kurl S, Rissanen TH, Nyyssönen K. Atherosclerosis. 2009 Oct 13. [Epub ahead of print]	2009	Oxidative modification of low-density lipoprotein (LDL) in the vascular endothelium is considered to be important in the development of early atherosclerosis. The aim of this study was to investigate the main determinants of serum LDL conjugated dienes in women (n=124) and men (n=225). We focused on the influence of fat-soluble vitamins and carotenoids on the concentration of conjugated dienes in LDL. In multivariate linear regression models, including age, body mass index, diastolic blood pressure, symptomatic ischaemic heart disease (IHD) or IHD history, statin medication, leukocytes and serum triglycerides as covariates, plasma lycopene (standardized beta=-0.33; P=0.002) and lutein (standardized beta=-0.22; P=0.027) concentrations were the strongest determinants of serum LDL conjugated dienes in women, whereas plasma beta-carotene (standardized beta=-0.23; P=0.002) was the most important factor in men. Furthermore, statin medication, diastolic blood pressure, age and serum triglycerides were significant determinants of LDL conjugated dienes. The regression model with lycopene contributed to 29% in women and 15% in men with beta-carotene of the variation of serum LDL conjugated dienes. Results of the present study suggest that plasma lycopene, lutein and beta-carotene are the most powerful antioxidants for explaining the content of in vivo oxidatively modified LDL in serum.	CS				(-) for W	LDLox B-carot for M
Heart: oxidation inflammat ion, endotheli al	Kim OY	Independent inverse relationship between serum lycopene concentration and arterial stiffness. Kim OY, Yoe HY, Kim HJ, Park JY, Kim JY, Lee SH, Lee JH, Lee KP, Jang Y, Lee JH Atherosclerosis. 2009 Aug 13. [Epub ahead of print]	2009	OBJECTIVE: Emerging evidence suggests a role of lycopene in the primary prevention of cardiovascular disease. This study aimed to investigate the association of serum lycopene concentration with brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness and markers of oxidative stress and inflammation. METHODS: healthy women (n=264, 31-75 yrs) were classified into tertiles according to serum lycopene concentration. Multivariate linear regression analyses were used to assess the relationship between serum lycopene and baPWV. RESULTS: Subjects in middle tertile (T2) and upper tertile (T3) had lower baPWV (1263+/-23 and 1265+/-14cm/s vs. 1338+/-21cm/s; p=0.009) and lower oxidized LDL (oxLDL) (53+/-3 and 55+/-3U/L vs. 66+/-3U/L; p<0.001) than those in lowertertile (T1). Subjects in T3 showed higher LDL particle size (24.3+/-0.08nm vs. 24.0+/-0.07nm, p=0.005) and lower C-reactive protein (hs-CRP) (0.80+/-0.25mg/dL vs. 1.27+/-0.24mg/dL, p=0.015), compared with those in T1. Logistic regression analysis showed that baPWV decreased with the increment of lycopene concentration; log baPWV decreased by 0.21cm/s (95% CI -0.168;-0.045, p=0.001) per unit change in lycopene. After adjustment for age, BMI, smoking, drinking, menopause and blood pressure, the estimated effect was attenuated by 35%, but remained statistically significant [-0.13cm/s (95% CI -0.112;-0.018, p=0.006)]. Further adjustment for beta-carotene, alpha-tocopherol, oxLDL, LDL particle size, and hs-CRP increased the strength of the association [beta=-0.221 (95% CI -0.215;-0.012, p=0.029)]. CONCLUSION: This study supports the presence of an independent inverse relationship between circulating lycopene and baPWV. Additionally, reduced oxidative modification of LDL may be one of mediators on the mechanisms how lycopene reduces arterial stiffness.	CS				(-)	CRP baPWV size LDL LDLox

 

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	G.Tom +, N,	P.Tom +, N,	F.Tom +, N, -	Lyco +, N,	Other +, N,
Heart: stroke	Ito Y	Cardiovascular disease mortality and serum carotenoid levels: a Japanese population-based follow-up study. Ito Y, Kurata M, Suzuki K, Hamajima N, Hishida H, Aoki K. J Epidemiol. 2006 Jul;16(4):154-60.	2006	BACKGROUND: Some observational epidemiologic studies suggest that dietary and serum carotenoids are associated with reduced cardiovascular disease mortality. METHODS: Three thousand and sixty-one subjects (1,190 males and 1,871 females), aged 39 to 80 years, were recruited from residents of Hokkaido, Japan who had attended comprehensive health check-up programs from 1988 through 1995. Serum levels of alpha-carotene, beta-carotene, and lycopene were separately determined by high-performance liquid chromatography. Serum levels of total carotene consisted of the sum of alpha-carotene, beta-carotene, and lycopene levels. Each serum level of alpha-carotene, beta-carotene, lycopene, total carotene, triglyceride, and alanine transaminase (ALT) activity was transformed logarithmically. The hazard ratios of serum alpha- and beta-carotenes, lycopene, and total carotene values were estimated by the Cox proportional hazard model after adjusting for sex, age, and other potential confounding factors. RESULTS: During the 11.9-year follow-up period, 80 deaths (49 males and 31 females) from cardiovascular disease, 40 deaths from heart disease, and 37 deaths from stroke were identified among the cohort subjects. High serum values of carotenoids such as alpha- and beta-carotenes, and lycopene were found to be significantly associated with low hazard ratios for cardiovascular disease mortality. However, a significant inverse association between high serum lycopene value and the risk for stroke mortality was not always observed. CONCLUSIONS: High serum levels of total carotene, comprising alpha- and beta-carotenes and lycopene, may reduce the risk for cardiovascular disease mortality among the Japanese population.	PC				(-)/N
Heart: IMT	Rissanen T	Serum lycopene concentrations and carotid atherosclerosis: the Kuopio Ischaemic Heart Disease Risk Factor Study. Rissanen TH, Voutilainen S, Nyyssonen K, Salonen R, Kaplan GA, Salonen JT. Am J Clin Nutr. 2003 Jan;77(1):133-8.	2003	BACKGROUND: Interest in lycopene is growing rapidly following the recent publication of epidemiologic studies in which high circulating lycopene concentrations were associated with reductions in cardiovascular disease. Lycopene is one of the major carotenoids in the Western diet and is probably one of the protective factors in a vegetable-rich diet. OBJECTIVE: We studied the hypothesis that the intima-media thickness of the common carotid artery (CCA-IMT) would be greater in men with low serum lycopene concentrations. DESIGN: We investigated the relation between serum lycopene concentration and CCA-IMT in 1028 middle-aged men (aged 46-64 y) in eastern Finland who were participants in the Kuopio Ischaemic Heart Disease Risk Factor study and who were examined in 1991-1993. The subjects were classified into quarters according to serum lycopene concentration. RESULTS: In a covariance analysis with adjustment for covariates, the men in the lowest quarter of serum lycopene concentration had a significantly higher mean CCA-IMT and maximal CCA-IMT (P = 0.005 and P = 0.001 for the difference, respectively) than did the other men. The mean and maximal CCA-IMT increased linearly across the quarters of serum lycopene concentration. CONCLUSIONS: A low serum lycopene concentration is associated with a higher CCA-IMT in middle-aged men from eastern Finland. This finding suggests that the serum lycopene concentration may play a role in the early stages of atherosclerosis. Increased thickness of the intima-media has been shown to predict coronary events; thus, lycopene intakes and serum concentrations may have clinical and public health relevance.	CC				(-) IMT

 

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	G.Tom +, N,	P.Tom +, N,	F.Tom +, N, -	Lyco +, N,	Other +, N,
Heart: IMT	Riccioni G	Relationship between plasma antioxidant concentrations and carotid intima-media thickness: the Asymptomatic Carotid Atherosclerotic Disease In Manfredonia Study Riccioni G, D'Orazio N, Palumbo N, Bucciarelli V, Ilio E, Bazzano LA, Bucciarelli T Eur J Cardiovasc Prev Rehabil. 2009 Jun;16(3):351-7.	2009	BACKGROUND: Few studies have examined the relationship among carotid atherosclerosis, vascular risk factors, and antioxidant plasma concentrations, and those that have reported conflicting results. The aim of this study was to assess the relationship between asymptomatic carotid atherosclerosis, as defined by carotid intima-media thickness (CIMT), and inflammatory markers, plasma lipids and serum antioxidant vitamins. METHODS AND RESULTS: We examined baseline characteristics of the 640 participants in the Asymptomatic Carotid Atherosclerotic Disease In Manfredonia Study. All participants were asymptomatic with respect to carotid artery disease in 2006-2007 and underwent physical examination with carotid ultrasound investigation, the collection of medical history and laboratory data. Analysis of variance methods were used to examine differences between participants by category of CIMT. Of the 640 participants, 291 did not have evidence of carotid atherosclerosis (CIMT<0.8 mm), 232 were found to have some atherosclerosis (0.8 mm< or =CIMT<1.2 mm), and 117 were found to have extensive atherosclerosis (CIMT>1.2 mm). Among participants with CIMT> or =0.8 mm, body mass index, blood pressures, total cholesterol, LDL cholesterol, triglycerides, uric acid, C-reactive protein, and fibrinogen were significantly higher, whereas concentrations of vitamin A, vitamin E, lycopene, and beta-carotene were all significantly lower when compared with participants who did not show evidence of carotid atherosclerosis (P<0.001). CONCLUSION: The optimal control of hypertension, diabetes, and dyslipidemia, in addition to smoking cessation and an adequate intake of antioxidant micronutrients from foods represent a key for the prevention of atherosclerotic disease.	CS				(-) IMT in indiv w/ evidence of carotid athero
Heart: IMT	Rissanen T	Lycopene, atherosclerosis, and coronary heart disease. Rissanen T, Voutilainen S, Nyyssonen K, Salonen JT. Exp Biol Med (Maywood). 2002 Nov;227(10):900-7.	2002	Diets rich in fruits and vegetables containing carotenoids have been of interest because of their potential health benefit against chronic diseases such as cardiovascular diseases (CVD) and cancer. Interest particularly in lycopene is growing rapidly following the recent publication of epidemiological studies that have associated high lycopene levels with reductions in CVD incidence. Two studies were conducted. In the first one, we examined the role of lycopene as a risk-lowering factor with regard to acute coronary events and stroke in the prospective Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study. The subjects were 725 middle-aged men free of coronary heart disease and stroke at the study baseline. In a Cox's proportional hazards' model adjusting for covariates, men in the lowest quartile of serum levels of lycopene had a 3.3-fold (P < 0.001) risk of the acute coronary event or stroke as compared with others. In the second study, we assessed the association between plasma concentration of lycopene and intima-media thickness of the common carotid artery wall (CCA-IMT) in a cross-sectional analysis of the Antioxidant Supplementation in the Atherosclerosis Prevention (ASAP) study data in 520 asymptomatic men and women. In a covariance analysis adjusting for common cardiovascular risk factors, low plasma levels of lycopene were associated with an 18% increase of IMT in men as compared with men in whom plasma levels were higher than median (P = 0.003 for difference). In women, the difference did not remain significant after the adjustments. On the basis of these works, it is evident that the circulating levels of lycopene play some role with regard to cardiovascular health in Finland, at least in men. We conclude that circulating levels of lycopene, a biomarker of tomato-rich food, may play a role in early stages of atherogenesis and may have clinical and public health relevance.	CS and PC				(-) (-) men IMT

 

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	G.Tom +, N,	P.Tom +, N,	F.Tom +, N, -	Lyco +, N,	Other +, N,
Heart: IMT, inflammat ion	Riccioni G	Plasma antioxidants and asymptomatic carotid atherosclerotic disease. Riccioni G, Bucciarelli T, D'Orazio N, Palumbo N, di Ilio E, Corradi F, Pennelli A, Bazzano LA. Ann Nutr Metab. 2008;53(2):86-90. Epub 2008 Oct 21. Compound (MeSH Keyword),.	2008	BACKGROUND: Atherosclerosis remains clinically mute for a long time and frequently manifests itself with an acute cardiovascular event. The possibility of detecting this disease in a subclinical phase and reducing or reversing its progression is an issue of relevance. Published studies on the association between antioxidant vitamins and carotenoids and carotid intima-media thickness (CIMT) have been inconclusive. METHODS: We enrolled 220 consecutive, asymptomatic participants. After carotid ultrasound investigation, a medical history was taken, a physical examination was performed and venous blood samples were collected. Venous blood samples were analyzed for concentrations of antioxidant vitamins and carotenoids. RESULTS: Low concentrations of vitamin A (p < 0.01), vitamin E (p < 0.001), lycopene (p < 0.01) and beta-carotene (p < 0.001) were significantly associated with carotid atherosclerosis (CIMT > or = 0.8 mm). In addition, marginally higher body mass index, plasma haemoglobin and high-density lipoprotein cholesterol were also associated with carotid atherosclerosis, while other laboratory parameters considered in this study (total cholesterol, low-density lipoprotein cholesterol, triglycerides and C-reactive protein) were not significantly associated with carotid atherosclerosis. CONCLUSIONS: Low plasma concentrations of antioxidant vitamins (A, E, beta-carotene) and lycopene were associated with early carotid atherosclerotic lesions as measured by CIMT. Regular intake of foods rich in lycopene and antioxidant vitamins may slow the progression of atherosclerosis.	CS				(-)/N (-) ↓ [lyco] = ↑ athero lesions (IMT) ~~~~~ N CRP Lipids	N CRP TG LDL TC

 

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	G.Tom +, N,	P.Tom +, N,	F.Tom +, N, -	Lyco +, N,	Other +, N,
Heart: inflammat ion	Lidebjer C	Low plasma levels of oxygenated carotenoids in patients with coronary artery disease. Lidebjer C, Leanderson P, Ernerudh J, Jonasson L. Nutr Metab Cardiovasc Dis. 2007 Jul;17(6):44856.	2007	BACKGROUND AND AIMS: Low circulating levels of carotenoids have been associated with cardiovascular disease. The distribution of different carotenoids in blood may have an impact on the cardioprotective capacity. The aim of the present study was to determine the plasma levels of 6 major carotenoids in patients with coronary artery disease (CAD) and relate the findings to clinical, metabolic and immune parameters. METHODS AND RESULTS: Plasma levels of oxygenated carotenoids (lutein, zeaxanthin, beta-cryptoxanthin) and hydrocarbon carotenoids (alpha-carotene, beta-carotene, lycopene) were determined in 39 patients with acute coronary syndrome, 50 patients with stable CAD and 50 controls. Serological assays for inflammatory activity and flow cytometrical analysis of lymphocyte subsets were performed. Both patient groups had significantly lower plasma levels of oxygenated carotenoids, in particular lutein+zeaxanthin, compared to controls. Low levels of oxygenated carotenoids were associated with smoking, high body mass index (BMI), low high density lipoprotein (HDL) cholesterol and, to a minor degree, inflammatory activity. Plasma levels of lutein+zeaxanthin were independently associated with the proportions of natural killer (NK) cells, but not with other lymphocytes, in blood. CONCLUSION: Among carotenoids, lutein+zeaxanthin and beta-cryptoxanthin were significantly reduced in CAD patients independent of clinical setting. The levels were correlated to a number of established cardiovascular risk factors. In addition, the relationship between NK cells and lutein+zeaxanthin may indicate a particular role for certain carotenoids in the immunological scenario of CAD.	CC				N
Heart: MI	Kohlmeier L	Lycopene and myocardial infarction risk in the EURAMIC Study. Kohlmeier L, Kark JD, Gomez-Gracia E, Martin BC, Steck SE, Kardinaal AF, Ringstad J, Thamm M, Masaev V, Riemersma R, Martin-Moreno JM, Huttunen JK, Kok FJ. Am J Epidemiol. 1997 Oct 15;146(8):61826.	1997	A multicenter case-control study was conducted to evaluate the relations between antioxidant status assessed by biomarkers and acute myocardial infarction. Incidence cases and frequency matched controls were recruited from 10 European countries to maximize the variance in exposure within the study. Adipose tissue needle aspiration biopsies were taken shortly after the infarction and analyzed for levels of carotenoids and tocopherols. An examination of colinearity including all covariates and the three carotenoids, alpha-carotene, beta-carotene, and lycopene, showed that the variables were sufficiently independent to model simultaneously. When examined singularly, each of the carotenoids appeared to be protective. Upon simultaneous analyses of the carotenoids, however, using conditional logistic regression models that controlled for age, body mass index, socioeconomic status, smoking, hypertension, and maternal and paternal history of disease, lycopene remained independently protective, with an odds ratio of 0.52 for the contrast of the 10th and 90th percentiles (95% confidence interval 0.33-0.82, p = 0.005). The associations for alpha- and beta-carotene were largely eliminated. We conclude that lycopene, or some substance highly correlated which is in a common food source, may contribute to the protective effect of vegetable consumption on myocardial infarction risk.	CC				(-)	Adipose tissue biopsy

 

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	G.Tom +, N,	P.Tom +, N,	F.Tom +, N, -	Lyco +, N,	Other +, N,
Heart: oxidation	Shin MJ	Plasma levels of leptin are associated with the plasma levels of LDL conjugated dienes in children. Shin MJ, Park E. Ann Nutr Metab. 2007;51(1):1-6. Epub 2007 Jan 24.	2007	BACKGROUND: Plasma leptin has been suggested to be involved in the proatherogenic process by increasing oxidative stress. We investigated the relationship between leptin and plasma conjugated diene formation, a measure of LDL oxidation in vivo in schoolchildren. METHODS: We measured blood lipid profiles, plasma antioxidant vitamins, leptin and diene conjugation in LDL of 118 Korean children (35 overweight-obese vs. 83 normal weight children). RESULTS: The overweight-obese children showed significantly higher levels of leptin (p < 0.0001), conjugated dienes (p = 0.02), total cholesterol (p < 0.05), triglyceride (p < 0.005) and LDL cholesterol (p < 0.01) and a significantly lower level of plasma lycopene (p < 0.0001) compared with the normal weight children. When all the subjects were classified into the three groups by tertiles of leptin levels, significant differences in circulating conjugated dienes (p < 0.05), lipid-corrected lycopene (p < 0.05), total cholesterol (p < 0.05), triglyceride (p < 0.05) and LDL cholesterol (p < 0.05) were found among the three groups. CONCLUSION: Our results showed that leptin was positively associated with the LDL conjugated diene formation, which might be related to the proatherogenic process in schoolchildren.	CS				(-) ↑ LDLox (CD assay) with ↓ plasma [lyco] inverse relationshi p in OB children
Heart: oxidation	Watters JL	Associations of antioxidant nutrients and oxidative DNA damage in healthy African-American and White adults. Watters JL, Satia JA, Kupper LL, Swenberg JA, Schroeder JC, Switzer BR. Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1428-36.	2007	High antioxidant intake has been shown to reduce cancer risk and may also mitigate the effects of oxidative DNA damage, which is hypothesized to be causally linked to carcinogenesis. This study examined potential racial differences in (a) dietary intakes and plasma concentrations of vitamin C, vitamin E, and carotenoids and oxidative DNA damage and (b) associations between plasma antioxidants and oxidative DNA damage. Data were from a cross-sectional study of 164 generally healthy nonsmoking African-Americans and Whites in North Carolina, ages 20 to 45 years, equally distributed by race and sex. Participants completed a demographic and health questionnaire, four 24-h dietary recalls, and a dietary supplement inventory; had height and weight measured; and provided a semifasting blood sample. African-Americans had statistically significantly lower plasma concentrations of vitamin E, alpha-carotene, beta-carotene, and lutein + zeaxanthin than Whites, as well as lower self-reported intake of most antioxidants. Levels of oxidative DNA damage, measured using the alkaline comet assay, were lower in African-Americans than Whites. An inverse association between lycopene and oxidative DNA damage (r = -0.20; P = 0.03) was found in the combined study population after adjusting for sex, age, body mass index, passive smoke exposure, physical activity, education, income, and alcohol intake. There was also a positive association of vitamin E with oxidative DNA damage in the total population (r = 0.21; P = 0.02) and in African-American men (r = 0.63; P = 0.01) after adjusting for covariates. This study is among the first to examine these associations in a sample of healthy adults with an adequate representation of African-Americans.	CS				(-) ↓ oxDNA damage

 

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	G.Tom +, N,	P.Tom +, N,	F.Tom +, N, -	Lyco +, N,	Other +, N,
Heart: oxidation, inflammat ion	Wang L	Associations of plasma carotenoids with risk factors and biomarkers related to cardiovascular disease in middle-aged and older women. Wang L, Gaziano JM, Norkus EP, Buring JE, Sesso HD. Am J Clin Nutr. 2008 Sep;88(3):747-54.	2008	BACKGROUND: Cardiovascular disease (CVD) risk factors may potentially influence plasma concentrations of carotenoids. However, data on the association of plasma carotenoids with CVD related biomarkers are only limited. OBJECTIVE: We examined the cross-sectional association of plasma carotenoids with blood lipids, glycated hemoglobin (Hb A(1c)), and C-reactive protein (CRP) in middle-aged and older women initially free of CVD and cancer. DESIGN: Participants from 3 nested case-control studies in the Women's Health Study were pooled. Baseline plasma carotenoids, including alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein-zeaxanthin, blood lipids, Hb A(1c), and CRP were available for 2895 women. RESULTS: Women who were current smokers or obese had lower plasma concentrations of most carotenoids expect for lycopene. After adjusting for age, race, lifestyle factors, clinical factors, plasma total cholesterol, and dietary carotenoids, an increase of 30 mg/dL in LDL cholesterol was associated with a 17% increase in alpha-carotene, a 16% increase in beta-carotene, and an 8.5% increase in lycopene; an increase of 10 mg/dL in HDL cholesterol was associated with a 5.3% decrease in lycopene; an increase of 0.3% in Hb A(1c) was associated with a 1.4% increase in lycopene; and an increase of 2 mg/L in CRP was associated with a 1.3% decrease in beta-carotene (all P < 0.01). CONCLUSIONS: In middle-aged and older women free of CVD and cancer, plasma carotenoids were associated with smoking, obesity, LDL cholesterol, HDL cholesterol, Hb A(1c), and CRP. The associations differ among individual carotenoids, possibly reflecting metabolic effects of lifestyle and physiologic factors on plasma carotenoids, and may partially explain the inverse association of plasma carotenoids with CVD outcomes observed in epidemiologic studies.	CS				(+) ↑ lyco: ↑ LDL ↑ HbA(1c):↑ lyco ↓ HDL:↓lyc o ~~~~~ N lyco:BW and CRP
Heart: oxidation, inflammat ion, endotheli al	Hozawa A	Relationships of circulating carotenoid concentrations with several markers of inflammation, oxidative stress, and endothelial dysfunction: the Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) study. Hozawa A, Jacobs DR Jr, Steffes MW, Gross MD, Steffen LM, Lee DH. Clin Chem. 2007 Mar;53(3):447-55. Epub 2007 Jan 18.	2007	BACKGROUND: Serum carotenoid concentrations relate inversely to cardiovascular disease incidence. To clarify the effect of carotenoids on atherosclerotic risk factors, we examined the association of circulating carotenoids with inflammation, oxidative stress, endothelial dysfunction, and smoking. METHODS: Black and white men and women in the Coronary Artery Risk Development in Young Adults study, ages 18 to 30 years at recruitment (1985-1986) from 4 US cities, were investigated over 15 years. We included 2048 to 4580 participants in analyses of the sum of serum alpha-carotene, beta-carotene, zeaxanthin/lutein, and beta-cryptoxanthin concentrations and of lycopene at year 0 and at year 7. RESULTS: The year 0 sum of 4 carotenoids was inversely associated (all P <0.05) with year 0 leukocyte count (slope per sum carotenoid SD, -0.17); year 7 fibrinogen (slope, -0.10); year 7 and year 15 C-reactive protein (slope, -0.12 and -0.09); and year 15 F(2)-isoprostanes (slope, -13.0), soluble P-selectin (slope, -0.48), and soluble intercellular adhesion molecule-1 (sICAM1; slope, -5.1). Leukocyte counts and sICAM1 and F(2)-isoprostane concentrations had stronger associations in smokers than in nonsmokers, and sICAM1 concentrations were higher in the highest carotenoid quartile in smokers than in the lowest carotenoid quartile in nonsmokers. Superoxide dismutase was positively associated with the sum of 4 carotenoids (slope, 0.12; P <0.01). Lycopene was inversely associated only with sICAM1. The year 7 carotenoid associations with these markers were mostly similar to those at year 0. CONCLUSIONS: Circulating serum carotenoids were associated, some interactively with smoking, in apparently beneficial directions with markers of inflammation, oxidative stress, and endothelial dysfunction.	PC				(-)/N	N CRP P-selectin isoPros ~~~~ (-) ICAM