| Page 1 | Page 2 | Page 3 |
Special Interest
Special interest studies are those that were reviewed, are related to the topic area and considered of “interest” but do not specifically associate tomato or lycopene with a disease risk outcome in humans. These studies are generally older publications and focus on fruit and vegetable intake on disease risk; or in the case of newer investigations focus on mechanism of action in in vivo animal or in vitro models.
| 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, - |
|---|---|---|---|---|---|---|---|---|---|---|
| Bioavail- ability |
O'Neill ME | Intestinal absorption of beta-carotene, lycopene and lutein in men and women following a standard meal: response curves in the triacylglycerol-rich lipoprotein fraction. O'Neill ME, Thurnham DI. Br J Nutr. 1998 Feb;79(2):149-59. | 1998 | A high intake of fruit and vegetables is believed to be protective against heart disease and cancer. beta-Carotene has been closely examined for evidence of these protective properties but evidence is still conflicting and there are many other carotenoids in plant foods which deserve attention. This paper reports studies on the concentrations of lutein and lycopene in the triacylglycerol-rich lipoprotein (TRL) fraction of plasma in comparison with beta-carotene following a large dose of the respective carotenoids fed with a standard meal after an overnight fast. beta-Carotene (40 mg) was given to twelve volunteers (six men and six women) and six of the same volunteers (three men and three women) also received 31.2 mg lutein or 38 mg lycopene. Plasma was collected at hourly intervals for 8 h and the TRL fraction was separated and subsequently analysed for the respective carotenoids and retinyl palmitate in the case of beta-carotene. Intestinal uptake of the three carotenoids was estimated using the 'area under the curve' method and apparent absorption was calculated from these results. The response curves in the TRL fraction for beta-carotene and retinyl palmitate occurred maximally over the fourth to fifth hour postprandially. There was a correlation between the TRL concentrations of beta-carotene and retinyl palmitate (males r 0.62, P < 0.001; females r 0.52, P < 0.001) and there was no significant difference between men and women either in the total amount of beta-carotene appearing in the TRL fraction or in the amount converted to retinol. On estimation, approximately 1.4 mg of the 40 mg beta-carotene dose was absorbed and this was not significantly different from the amount of lycopene (1.0 mg) but significantly different (P < 0.05) from the amount of lutein (0.8 mg) absorbed, after correction for the smaller doses administered. There was approximately a twofold difference between subjects in the uptake of beta-carotene into the TRL fraction, a two- to threefold variation in lycopene and a two- to threefold variation in lutein. Despite these inter-subject differences, in three volunteers between whom there was a threefold difference in beta-carotene in the TRL fraction and a twofold difference in retinol formation, repeat experiments with beta-carotene 4 months later found differences of only 3-6% in the TRL beta-carotene content and 4-9% for the TRL retinol formed. In conclusion, large inter-subject variation in TRL carotene uptake precluded any differences between sexes but surprising intra-subject consistency was observed in TRL beta-carotene uptake of three subjects. | Interv | (+) [lyco] | TRL fractions | |||
| Bioavail- ability |
Boileau TWM | Boileau TW, Boileau AC, Erdman JW Jr. Bioavailability of all-trans and cis-isomers of lycopene. Exp Biol Med (Maywood). 2002 Nov;227(10):914-9. | 2002 | Lycopene, the predominant carotenoid in tomatoes, is among the major carotenoids in serum and tissues of Americans. Although about 90% of the lycopene in dietary sources is found in the linear, all-trans conformation, human tissues contain mainly cis-isomers. Several research groups have suggested that cis-isomers of lycopene are better absorbed than the all-trans form because of the shorter length of the cis-isomer, the greater solubility of cis-isomers in mixed micelles, and/or as a result of the lower tendency of cis-isomers to aggregate. Work with ferrets, a species that absorbs carotenoids intact, has demonstrated that whereas a lycopene dose, stomach, and intestinal contents contained 6-18% cis-lycopene, the mesenteric lymph secretions contained 77%-cis isomers. The ferret studies support the hypotheses that cis-isomers are substantially more bioavailable then all-trans lycopene. In vitro studies suggest that cis-isomers are more soluble in bile acid micelles and may be preferentially incorporated into chylomicrons. The implications of these findings are not yet clear. Rats appear to accumulate lycopene in tissues within the ranges reported for humans, suggesting that they can be used to study effects of lycopene isomers on disease processes. Investigations are underway to determine whether there are biological differences between all-trans and various cis-isomers of lycopene regarding its antioxidant properties or other biological functions. | Review |
| 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, - |
|---|---|---|---|---|---|---|---|---|---|---|
| Bioavail- ability |
Reboul E | Bioaccessibility of carotenoids and vitamin E from their main dietary sources. Reboul E, Richelle M, Perrot E, Desmoulins-Malezet C, Pirisi V, Borel P. J Agric Food Chem. 2006 Nov 15;54(23):8749-55. | 2006 | Vitamin E and carotenoids are fat-soluble microconstituents that may exert beneficial effects in humans, including protection against cancer, cardiovascular diseases, and age-related eye diseases. Their bioavailability is influenced by various factors including food matrix, formulation, and food processing. Since human studies are labor-intensive, time-consuming, and expensive, the in vitro model used in this study is increasingly being used to estimate bioaccessibility of these microconstituents. However, the ability of this model to predict bioavailability in a healthy human population has not yet been verified. The first aim of this study was to validate this model by comparing model-derived bioaccessibility data with (i) human-derived bioaccessibility data and (ii) published mean bioavailability data reported in studies involving healthy humans. The second aim was to use it to measure alpha- and gamma-tocopherol, beta-carotene, lycopene, and lutein bioaccessibility from their main dietary sources. Bioaccessibility as assessed with the in vitro model was well correlated with human-derived bioaccessibility values (r = 0.90, p < 0.05), as well as relative mean bioavailability values reported in healthy human groups (r = 0.98, p < 0.001). The bioaccessibility of carotenoids and vitamin E from the main dietary sources was highly variable, ranging from less than 0.1% (beta-carotene from raw tomato) to almost 100% (alpha-tocopherol from white bread). Bioaccessibility was dependent on (i) microconstituent species (lutein > beta-carotene and alpha-carotene > lycopene and alpha-tocopherol generally > gamma-tocopherol), (ii) food matrix, and (iii) food processing. | In vitro | N lyco about in the middle of carotenoids for bioavailability in invitro model |
||||
| Bone | Keen RW | Can biochemical markers predict bone loss at the hip and spine?: a 4-year prospective study of 141 early postmenopausal women. Keen RW, Nguyen T, Sobnack R, Perry LA, Thompson PW, Spector TD. Osteoporos Int. 1996;6(5):399-406. | 1996 | A number of recent studies have suggested that non-invasive measures of bone turnover are associated with bone loss at the forearm in postmenopausal women. Whether bone turnover markers are predictive of bone loss from the clinically important sites of lumbar spine and femoral neck remain unclear, and was the aim of this 4-year prospective study. One hundred and forty-one normal, postmenopausal women (mean age 52.0 +/- 3.3 years, mean menopause duration 20.4 +/- 5.7 months) were recruited for the study in 1988. Fasting early morning samples of blood and urine were collected at the baseline visit and stored at -20 degrees C prior to analysis. Serum was assayed for osteocalcin, oestradiol, oestrone, oestrone sulphate, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate and total alkaline phosphatase. Urine was assayed for calcium, hydroxyproline, oestrone glucuronide and the collagen cross-links pyridinoline and deoxypyridinoline using high-performance liquid chromatography. Bone density was measured at the lumbar spine and femoral neck using dual photon absorptiometry at time 0, 12, 24 and 48 months. The mean annual percentage change in bone density (SE) was -1.41% (0.18) at the lumbar spine and -0.86% (0.22) at the femoral neck. There was no evidence of bimodality or a fast loser subgroup as the rates of change were normally distributed. Both simple and multiple stepwise regression analyses revealed no significant correlation between the rates of change in bone density with any biochemical marker, either individually or in combination, despite the study having sufficient power (80%) to detect a correlation of 0.5 between any biochemical marker levels and bone loss. We conclude that single measurements of these markers of bone turnover and endogenous sex hormones appear unlikely to be clinically useful in predicting early postmenopausal bone loss from either the spine or the hip. | PC | N markers of TO ≠ bone loss of hip & bone |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Bone | Greenspan SL | Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial. Greenspan SL, Parker RA, Ferguson L, Rosen HN, Maitland-Ramsey L, Karpf DB. J Bone Miner Res. 1998 Sep;13(9):1431-8. | 1998 | Although the antiresorptive agent alendronate has been shown to increase bone mineral density (BMD) at the hip and spine and decrease the incidence of osteoporotic fractures in older women, few data are available regarding early prediction of long-term response to therapy, particularly with regard to increases in hip BMD. Examining short-term changes in biochemical markers incorporates physiologic response with therapeutic compliance and should provide useful prognostic information for patients. The objective of this study was to examine whether early changes in biochemical markers of bone turnover predict long-term changes in hip BMD in elderly women. The study was a double-blind, placebo-controlled, randomized clinical trial which took place in a community-based academic hospital. One hundred and twenty community-dwelling, ambulatory women 65 years of age and older participated in the study. Intervention consisted of alendronate versus placebo for 2.5 years. All patients received appropriate calcium and vitamin D supplementation. The principal outcome measures included BMD of the hip(total hip, femoral neck, trochanter, and intertrochanter), spine (posteroanterior [PA] and lateral), total body, and radius. Biochemical markers of bone resorption included urinary N-telopeptide cross-linked collagen type I and free deoxypyridinoline; markers of bone formation included serum osteocalcin and bone-specific alkaline phosphatase. Long-term alendronate therapy was associated with increased BMD at the total hip (4.0%), femoral neck (3.1%), trochanter (5.5%), intertrochanter (3.8%), PA spine (7.8%), lateral spine (10.6%), total body (2.2%), and one-third distal radius (1.3%) in elderly women (all p < 0.01). In the placebo group, bone density increased 1.9-2.1% at the spine (p < 0.05) and remained stable at all other sites. At 6 months, there were significant decreases in all markers of bone turnover (-10% to -53%, p < 0.01) in women on alendronate. The changes in urinary cross-linked collagen at 6 months correlated with long-term bone density changes at the hip (r = -0.35, p < 0.01), trochanter (r = -0.36, p < 0.01), PA spine (r = -0.41, p < 0.01), and total body (r = -0.34, p < 0.05). At 6 months, patients with the greatest drop in urinary cross-linked collagen (65% or more) demonstrated the greatest gains in total hip, trochanteric, and vertebral bone density (all p < 0.05). A 30% decrease in urinary cross-linked collagen at 6 months predicted a bone density increase of 2.8-4.1% for the hip regions and 5.8-6.9% for the spine views at the 2.5-year time point (p < 0.05). There were no substantive associations between changes in biochemical markers and bone density in the placebo group. Alendronate therapy was associated with significant long-term gains in BMD at all clinically relevant sites, including the hip, in elderly women. Moreover, these improvements were associated with early decreases in biochemical markers of bone turnover. Early dynamic decreases in urinary cross-linked collagen can be used to monitor and predict long-term response to bisphosphonate therapy in elderly women. Future studies are needed to determine if early assessment improves long-term patient compliance or uncovers poor compliance, thereby aiding the physician in maximizing the benefits of therapy. | n= 120 based on alendronate | CT/RCT | ||||
| Bone | Melhus H | Smoking, antioxidant vitamins, and the risk of hip fracture. Melhus H, Michaëlsson K, Holmberg L, Wolk A, Ljunghall S. J Bone Miner Res. 1999 Jan;14(1):129-35. | 1999 | Smoking increases the concentrations of free radicals, which have been suggested to be involved in bone resorption. We examined whether the dietary intake of antioxidant vitamins may modify the increased hip fracture risk associated with smoking. We prospectively studied 66,651 women who were 40-76 years of age. Forty-four of the cohort members who sustained a first hip fracture within 2-64 months of follow-up (n = 247) and 93 out of 873 age-matched controls were current smokers. Information on diet was obtained by a validated food-frequency questionnaire. The relative risk of hip fracture for current versus never smokers was analyzed in relation to the dietary intake of antioxidant vitamins stratified into two categories (low/high), where median intakes among the controls were used as cut-off points. After adjustment for major osteoporosis risk factors, the odds ratio (OR) for hip fracture among current smokers with a low intake of vitamin E was 3.0 (95% confidence interval 1.6-5.4) and of vitamin C 3.0 (1.6-5.6). In contrast, the OR decreased to 1.1 (0.5-2.4) and 1.4 (0.7-3.0) with high intakes of vitamin E and C, respectively. This effect was not seen for beta-carotene, selenium, calcium, or vitamin B6. In current smokers with a low intake of both vitamins E and C, the OR increased to 4.9 (2.2-11.0). The influence of the intake of these two antioxidant vitamins on hip fracture risk was less pronounced in former smokers. Our results suggest a role for oxidant stress in the adverse effects on the skeleton of smoking, and that an insufficient dietary intake of vitamin E and C may substantially increase the risk of hip fracture in current smokers, whereas a more adequate intake seems to be protective. | PC | (-) ↓ Vit C ↑ risk of hip fracture in smokers |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Bone | Sellmeyer DE | Potassium citrate prevents increased urine calcium excretion and bone resorption induced by a high sodium chloride diet. Sellmeyer DE, Schloetter M, Sebastian A. J Clin Endocrinol Metab. 2002 May;87(5):2008-12. | 2002 | The amount of sodium chloride in the diet of industrialized nations far exceeds physiological requirements. The impact of abundant dietary salt on skeletal health has yet to be established, but is potentially detrimental through increased urinary calcium losses. We examined the effect of increased dietary sodium chloride on urine calcium excretion and bone turnover markers in postmenopausal women and, further, whether potassium citrate attenuates the effects of increased dietary salt. Postmenopausal women (n = 60) were adapted to a low-salt (87 mmol/d sodium) diet for 3 wk, then randomized to a high-salt (225 mmol/d sodium) diet plus potassium citrate (90 mmol/d) or a high-salt diet plus placebo for 4 wk. Urine calcium, urine N-telopeptide, urine cAMP, serum osteocalcin, and fasting serum PTH were measured at the end of the low- and high-salt diets. On the high salt plus placebo diet, urine calcium increased 42 +/- 12 mg/d (mean +/- SEM), but decreased 8 +/- 14 mg/d in the high salt plus potassium citrate group (P = 0.008, potassium citrate vs. placebo, unpaired t test). N-telopeptide increased 6.4 +/- 1.4 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus placebo group and 2.0 +/- 1.7 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus potassium citrate group (P < 0.05, potassium citrate vs. placebo, unpaired t test). Osteocalcin, PTH, and cAMP were not significantly altered. The addition of oral potassium citrate to a high-salt diet prevented the increased excretion of urine calcium and the bone resorption marker caused by a high salt intake. Increased intake of dietary sources of potassium alkaline salts, namely fruit and vegetables, may be beneficial for postmenopausal women at risk for osteoporosis, particularly those consuming a diet generous in sodium chloride. | CT/RCT | (-) | No Lyco Na, K | |||
| Bone | Kim L | Lycopene II--effect on osteoblasts: the carotenoid lycopene stimulates cell proliferation and alkaline phosphatase activity of SaOS-2 cells. Kim L, Rao AV, Rao LG. J Med Food. 2003 Summer;6(2):79-86. | 2003 | We explored the possibility that lycopene, a carotenoid that is abundant in tomatoes, has effects on proliferation and differentiation of osteoblasts, the cells responsible for bone formation. Human osteoblast-like osteosarcoma SaOS-2 cells were cultured for 24 hours, after which varying doses of a water-dispersible microemulsion preparation of lycopene or vehicle of the same dilution were added. The cells were further cultured for 24 to 144 hours, and then the cell numbers were counted. Lycopene at 10(-6) and 10(-5) M had significant stimulatory effects on cell numbers, compared with the corresponding vehicle treatment, at all time points from 24 to 144 hours. The effects of lycopene on activity of the differentiation marker alkaline phosphatase activity in the absence or presence of dexamethasone were shown to be dependent on the stage of cell differentiation. This is the first report on the effects of lycopene on osteoblasts of human origin; the results may have important applications in the prevention of osteoporosis. | Cell culture | (-) affected alkaline phosphat ase activity, indep of cell stage |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Bone | Maggio D | Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study. Maggio D, Barabani M, Pierandrei M, Polidori MC, Catani M, Mecocci P, Senin U, Pacifici R, Cherubini A. J Clin Endocrinol Metab. 2003 Apr;88(4):1523-7. | 2003 | Although recent epidemiological studies found a positive correlation between dietary vitamin C intake and bone mineral density, data on plasma levels of vitamin C or other antioxidants in osteoporotic subjects are scanty. The aim of this study was to evaluate whether antioxidant defenses are decreased in elderly osteoporotic women and, if this is the case, to understand whether osteoporosis is a condition characterized by increased oxidative stress. To answer these questions, plasma vitamins C, E, and A; uric acid; and the enzymatic activities of superoxide dismutase in plasma and erythrocytes and of glutathione peroxidase in plasma were measured in 75 subjects with osteoporosis and 75 controls. Dietary and endogenous antioxidants were consistently lower in osteoporotic than in control subjects. On the other hand, plasma levels of malondialdehyde, a byproduct of lipid peroxidation, did not differ between groups. Our results reveal that antioxidant defenses are markedly decreased in osteoporotic women. The mechanisms underlying antioxidant depletion and its relevance to the pathogenesis of osteoporosis deserve further investigation. | CC | (-) ↓ anti-ox defense in osteo women vs non-osteo No Lyco | ||||
| Bone | Zhang J | Antioxidant intake and risk of osteoporotic hip fracture in Utah: an effect modified by smoking status. Zhang J, Munger RG, West NA, Cutler DR, Wengreen HJ, Corcoran CD. Am J Epidemiol. 2006 Jan 1;163(1):9-17. Epub 2005 Nov 23. | 2006 | The role of antioxidant intake in osteoporotic hip fracture risk is uncertain and may be modified by smoking. In the Utah Study of Nutrition and Bone Health, a statewide, population-based case-control study, the authors investigated whether antioxidant intake was associated with risk of osteoporotic hip fracture and whether this association was modified by smoking status. The analyses included data on 1,215 male and female cases aged > or = 50 years who incurred a hip fracture during 1997-2001 and 1,349 age- and sex-matched controls. Diet was assessed by food frequency questionnaire. Among ever smokers, participants in the highest quintile of vitamin E intake (vs. the lowest) had a lower risk of hip fracture after adjustment for confounders (odds ratio = 0.29, 95% confidence interval (CI): 0.16, 0.52; p-trend < 0.0001). The corresponding odds ratio for beta-carotene intake was 0.39 (95% CI: 0.23, 0.68; p-trend = 0.0004), and for selenium intake it was 0.27 (95% CI: 0.12, 0.58; p-trend = 0.0003). Vitamin C intake did not have a significant graded association with hip fracture risk among ever smokers. Similar findings were obtained when an overall antioxidant intake score was used (odds ratio = 0.19, 95% CI: 0.10, 0.37; p-trend < 0.0001). No similar associations were found in never smokers. Antioxidant intake was associated with reduced risk of osteoporotic hip fracture in these elderly subjects, and the effect was strongly modified by smoking status. | CC | (-) anti-ox status on hip fracture risk |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Bone | Rao LG | Lycopene consumption decreases oxidative stress and bone resorption markers in postmenopausal women. Rao LG, Mackinnon EF, Josse RG, Murray TM, Strauss A, Rao AV. Osteoporoos Int. 2007 Jan;18(1):109-15. | 2007 | INTRODUCTION: Oxidative stress induced by reactive oxygen species (ROS) is associated with the risk of osteoporosis, and can be reduced by certain dietary antioxidants. Lycopene is an antioxidant known to decrease the risk of age-related chronic diseases, such as cancer. However, the role of lycopene in osteoporosis has not yet been investigated. MATERIALS AND METHODS: In a cross-sectional study, 33 postmenopausal women aged 50-60 years provided seven-day dietary records and blood samples. Serum samples were used to measure serum lycopene, lipid peroxidation, protein thiols, bone alkaline phosphatase (BAP), and cross-linked N-telopeptides of type I collagen (NTx). The serum lycopene per kilogram body weight of the participants was grouped into quartiles and associated with the above serum parameters using one-way ANOVA and the Newman-Keuls post-test. RESULTS: The results showed that groups with higher lycopene intake, as determined from the dietary records, had higher serum lycopene (p<0.02). A higher serum lycopene was found to be associated with a low NTx (p<0.005). Similarly, groups with higher serum lycopene had lower protein oxidation (p<0.05). DISCUSSION: In conclusion, these results suggest that the dietary antioxidant lycopene reduces oxidative stress and the levels of bone turnover markers in postmenopausal women, and may be beneficial in reducing the risk of osteoporosis. | CS | (-) | ||||
| Bone MOA | Kim L | Lycopene effect on osteoblasts: the carotenoid lycopene stimulates cell proliferation and alkaline phosphatase activity of SaOS-2 cells. Kim L, Rao AV, Rao LG. J Med Food 2003;6:79–86. | 2003 | We explored the possibility that lycopene, a carotenoid that is abundant in tomatoes, has effects on proliferation and differentiation of osteoblasts, the cells responsible for bone formation. Human osteoblast-like osteosarcoma SaOS-2 cells were cultured for 24 hours, after which varying doses of a water-dispersible microemulsion preparation of lycopene or vehicle of the same dilution were added. The cells were further cultured for 24 to 144 hours, and then the cell numbers were counted. Lycopene at 10-6 and 10-5 M had significant stimulatory effects on cell numbers, compared with the corresponding vehicle treatment, at all time points from 24 to 144 hours. The effects of lycopene on activity of the differentiation marker alkaline phosphatase activity in the absence or presence of dexamethasone were shown to be dependent on the stage of cell differentiation. This is the first report on the effects of lycopene on osteoblasts of human origin; the results may have important applications in the prevention of osteoporosis. | Cell culture: human | (-) ↑ ALP in more differnetia ted osteoblast s (bone builders) |
| Disease type | First Author |
Study Title and Complete Citation |
Date | Abstract | Study Type |
G.Tom +, N, |
P.Tom +, N, |
F.Tom |
Lyco +, N, |
Other +, N, |
|---|---|---|---|---|---|---|---|---|---|---|
| Bone MOA | Rao LG | Lycopene I—Effect on Osteoclasts: Lycopene Inhibits Basal and Parathyroid Hormone-Stimulated Osteoclast Formation and Mineral Resorption Mediated by Reactive Oxygen Species in Rat Bone Marrow Cultures Rao LG, Krishnadev N, Banasikowska K, Rao AV Journal of Medicinal Food. July 2003, Vol. 6, No. 2: 69-78 | 2003 | Osteoclasts have been shown to produce reactive oxygen species (ROS) that can stimulate bone resorption. We explored the hypothesis that lycopene, the antioxidant carotenoid from tomatoes, can inhibit mineral resorption by inhibiting osteoclast formation and the production of ROS. Cells from bone marrow prepared from rat femur were plated into 16-well calciumphosphate–coated Osteologic Multi-test Slides and cultured in a-minimal essential medium supplemented with dexamethasone, b-glycerophosphate, and ascorbic acid. The cells were treated with varying doses of lycopene in the absence or presence of parathyroid hormone (PTH) at the start of culture and at each medium change (i.e., every 48 hours). On day 8, mineral resorption pits were quantitated. Similar, parallel experiments were carried out in 12–well plastic dishes to assess tartrate-resistant acid phosphatase (TRAP) activity. Results showed that lycopene inhibited TRAP1 formation of multinucleated cells in both vehicleand PTH-treated cultures. Osteoclasts reduced nitroblue tetrazolium (NBT) to purple-colored formazan, indicating the presence of ROS in these cells. The formazan-staining cells were decreased by treatment with 10-5M lycopene, indicating that lycopene inhibited the formation of ROS-secreting osteoclasts. In conclusion, we have shown that lycopene inhibits basal and PTH-stimulated osteoclastic mineral resorption and formation of TRAP1 multinucleated osteoclasts, as well as the ROS produced by osteoclasts. These findings are novel and may be important in the pathogenesis, treatment, and prevention of osteoporosis | Cell culture: rat | (-) ↓ osteoclast formation | ||||
| Brain | Craft NE | Carotenoid, tocopherol, and retinol concentrations in elderly human brain. Craft NE, Haitema TB, Garnett KM, Fitch KA, Dorey CK. J Nutr Health Aging. 2004;8(3):156-62. | 2004 | BACKGROUND: Antioxidants, such as tocopherols and carotenoids, have been implicated in the prevention of degenerative diseases. Although correlations have been made between diseases and tissue levels of antioxidants, to date there are no reports of individual carotenoid concentrations in human brain. OBJECTIVE: To measure the major carotenoids, tocopherols, and retinol in frontal and occipital regions of human brain. DESIGN: Ten samples of brain tissue from frontal lobe cortex and occipital cortex of five cadavers were examined. Sections were dissected into gray and white matter, extracted with organic solvents, and analyzed by HPLC. RESULTS: At least 16 carotenoids, 3 tocopherols, and retinol were present in human brain. Major carotenoids were identified as lutein, zeaxanthin, anhydrolutein, alpha- cryptoxanthin, beta- cryptoxanthin, alpha-carotene, cis- and trans-betacarotene, and cis- and trans-lycopene. Xanthophylls (oxygenated carotenoids) accounted for 66-77% of total carotenoids in all brain regions examined. Similar to neural retina, the ratio of zeaxanthin to lutein was high and these two xanthophylls were significantly correlated (p <0.0001). The tocopherol isomers occurred in the brain over a wider range of mean concentrations (0.11-17.9 nmol/g) than either retinol (87.8 - 163.3 pmol/g) or the identified carotenoids (1.8-23.0 pmol/g). CONCLUSIONS: The frontal cortex, generally vulnerable in Alzheimer's disease, had higher concentrations of all analytes than the occipital cortex which is generally unaffected. Moreover, frontal lobes, but not occipital lobes, exhibited an age-related decline in retinol, total tocopherols, total xanthophylls and total carotenoids. The importance of these differences and the role(s) of these antioxidants in the brain remain to be determined. Article not avail online | ↓ total carotenoi ds found in frontal cortex of cadavers |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Brain | Youm JW | Transgenic tomatoes expressing human betaamyloid for use as a vaccine against Alzheimer's disease. Youm JW, Jeon JH, Kim H, Kim YH, Ko K, Joung H, Kim H. Biotechnol Lett. 2008 Oct;30(10):1839-45. Epub 2008 Jul 5. | 2008 | Human beta-amyloid (Abeta) is believed to be one of the main components of Alzheimer's disease, so reduction of Abeta is considered a key therapeutic target. Using Agrobacterium-mediated nuclear transformation, we generated transgenic tomatoes for Abeta with tandem repeats. Integration of the human Abeta gene into the tomato genome and its transcription were detected by PCR and Northern blot, respectively. Expression of the Abeta protein was confirmed by western blot and ELISA, and then the transgenic tomato line expressing the highest protein level was selected for vaccination. Mice immunized orally with total soluble extracts from the transgenic tomato plants elicited an immune response after receiving a booster. The results indicate that tomato plants may provide a useful system for the production of human Abeta antigen. | ||||||
| Brain | Kumar P | Lycopene modulates nitric oxide pathways against 3-nitropropionic acid-induced neurotoxicity. Kumar P, Kalonia H, Kumar A. Life Sci. 2009 Nov 4;85(19-20):711-8. Epub 2009 Oct 12. | 2009 | AIM: The present study has been designed to investigate the involvement of the nitric oxide mechanism in the protective effect of lycopene against 3-nitropropionic acid-induced Huntington's disease-like symptoms in rats. MAIN METHODS: The present experimental protocol design includes systemic 3-nitropropionic acid (10mg/kg i.p) treatment for 14 days. Lycopene (2.5, 5 and 10mg/kg) was given orally, once a day, 1h before 3-nitropropionic acid treatment for 14 days. Body weight and behavioral parameters (locomotor and rotarod activity) were assessed on 1st, 5th, 10th and 15th day post-3-nitropropionic acid administration. Malondialdehyde, nitrite concentration, superoxide dismutase and catalase levels were measured on the 15th day in the striatum, cortex and hippocampus. Mitochondrial enzyme complexes were also assessed in these brain areas. Systemic 3-nitropropionic acid treatment significantly reduced body weight, locomotor activity and oxidative defense. The mitochondrial enzyme activities were also significantly impaired in he examined brain regions in 3-nitropropionic acid-treated animals. KEY FINDINGS: Lycopene (2.5, 5 and 10mg/kg) treatment significantly attenuated the impairment in behavioral, biochemical and mitochondrial enzyme activities as compared to the 3-nitropropionic acid-treated group. l-arginine (50mg/kg) pretreatment with a sub-effective dose of lycopene (5mg/kg) significantly attenuated the protective effect of lycopene. Furthermore, L-NAME (10mg/kg) pretreatment with a sub-effective dose of lycopene (5mg/kg) for 14 days significantly potentiated the protective effect. SIGNIFICANCE: The results of the present study suggest that the nitric oxide modulation is involved in the protective effect of lycopene against 3-NP-induced behavioral, biochemical and cellular alterations in rats. | Rat | (-) attenuate d behaviora l, biochem, and cellular response to 3nitropropi onic acid |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Brain | Kumar P | Effect of lycopene and epigallocatechin-3-gallate against 3-nitropropionic acid induced cognitive dysfunction and glutathione depletion in rat: a novel nitric oxide mechanism. Kumar P, Kumar A. Food Chem Toxicol. 2009 Oct;47(10):252230. Epub 2009 Jul 17 | 2009 | Huntington's disease is a neurodegenerative disorder characterized by symptoms like chorea and dementia. There is no exact therapeutic agent available to manage and cure this disease. 3-Nitropropionic acid, a neurotoxin causes gait and memory impairment which leads to oxidative damage and upsets glutathione defense in animals. 3-NP model is a useful tool to develop suitable therapeutic agent in the treatment of Huntington's disease. Present study compares the effects of lycopene and epigallocatechin-3-gallate (EGCG) on memory impairment and disturbs glutathione system against 3-NP treatment. 3-NP treatment significantly impaired memory as assessed in Morris water maze and elevated plus maze tasks. On the 15 day, the levels of reduced glutathione, total glutathione and glutathione-S-transferase were also significantly decreased in the striatum, hippocampus and cortex areas of the brain. The treatment with lycopene (2.5, 5 and 10mg/kg) and EGCG (10, 20 and 40 mg/kg) significantly improved memory and restored glutathione system functioning. Further, L-arginine and L-NAME pretreatment with the sub effective dose of lycopene (5mg/kg) and EGCG (20mg/kg) reversed and potentiate their protective effects respectively. In conclusion, lycopene and EGCG could be used to mange 3-NP induced behavioral and biochemical alterations by involving nitric oxide pathways. | Rat | (-) improved memory and glutothion e system function in response to 3nitropropi onic acid | ||||
| Brain | Wang W | Nutritional biomarkers in Alzheimer's disease: the association between carotenoids, n-3 fatty acids, and dementia severity. Wang W, Shinto L, Connor WE, Quinn JF. J Alzheimers Dis. 2008 Feb;13(1):31-8. | 2008 | Carotenoids are fat-soluble antioxidants that may protect polyunsaturated fatty acids, such as n-3 fatty acids from oxidation, and are potentially important for Alzheimer's disease (AD) prevention and treatment. Fasting plasma carotenoids were measured in 36 AD subjects and 10 control subjects by HPLC. Correlations between plasma carotenoid levels, red blood cell (RBC) n-3 fatty acids, and dementia severity were examined in AD patients. Moderately severe AD patients (MMSE=16-19) had much lower plasma levels of two major carotenoids: lutein and beta-carotene, compared to mild AD patients (MMSE=24-27) or controls. Among AD patients, variables (lutein, beta-carotene, RBC docosahexaenoic acid (DHA) and LDL-cholesterol) were significantly correlated with MMSE. A lower MMSE score was associated with lower lutein, beta-carotene and RBC DHA levels, and a higher LDL-cholesterol level. These variables explained the majority of variation in dementia severity (55% of variance in MMSE). Lutein, beta-carotene and beta-cryptoxanthin were positively correlated with RBC DHA in AD patients. The association between higher carotenoids levels and DHA and higher MMSE scores, supports a protective role of both types of nutrients in AD. These findings suggest targeting multiple specific nutrients, lutein, beta-carotene, and DHA in strategies to slow the rate of cognitive decline. | CC | Lutein, b-carotene |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| BW | Kaufmann NA | Eating habits and opinions of teen-agers on nutrition and obesity. Kaufmann NA, Poznanski R, Guggenheim K. J Am Diet Assoc. 1975 Mar;66(3):264-8. | 1975 | Opinions about good nutrition, causes of obesity and its prevention, as well as certain eating habits, were studied in 482 Israeli children (251 boys and 231 girls), thirteen to fourteen years old. Height, weight, and triceps skinfolds were measured. Mean relative weight and relative logarithmic skinfold thickness were close to standard, although 8 per cent of the boys and 9 per cent of the girls weighed more than 120 per cent of standard weight for their age and sex.Weight was closely associated with skinfold thickness. Over two-thirds of both boys and girls believed that daily consumption of milk, bread, fruits, eggs, cheese, meat, and tomatoes is desirable, and about two-thirds stated that overeating is a cause of obesity. More overweight than thin and normal-weight children indicated that, to prevent obesity, all kinds of food are permissible, but only in limited amounts. Most children believed in the fattening value of cakes, sweets, fried and fatty food, potatoes, bread, and nuts. The belief in the fattening value of potatoes, bread, and nuts was shared by a higher percentage of overweight than of under-and normal-weight children. Overweight children, particularly girls, reported eating less bread, cake, and cream, adding less sugar to beverages, and eating sweets and ice cream less frequently than thin and normal-weight children. A higher percentage of the obese group reported skipping one meal and eating no snack at school. Overweight teen-agers appear to be more conscious of their food intake than under- and normal-weight children. | CS | (+) Children believe ↑ tomato intake = good eating habits | ||||
| BW | Guggenheim K | Attitudes of adolescents to their body build and the problem of juvenile obesity. Guggenheim K, Poznanski R, Kaufmann NA. Int J Obes. 1977;1(2):135-49. | 1977 | Prevalence of obesity, attitude to body weight and dimensions, eating habits, opinions on good nutrition and on the causes and prevention of obesity were studied in two groups of Israeli children, each comprising about 500 boys and girls, 13--14 years old. Mean relative weight was close to median weight for height, although 9 per cent of both boys and girls weighed more than 120 per cent of median weight. Weight was closely related to triceps skinfold thickness. Twenty-six per cent of the boys and 15 per cent of the girls rated themselves as thin, 61 per cent of children of both sexes as medium, and 13 per cent of the boys and 25 per cent of the girls as obese. Self-perception of body build was more closely related to weight than to skinfold thickness. Two-thirds of the boys and over one-half of the girls were satisfied with their weight, but dissatisfaction with size and shape was often expressed. Boys wished to have larger muscles and chest circumference and many girls, even when not obese, wanted to be smaller in size and shape. Most of the obese children wanted to lose weight. Of 499 children examined, 16 boys (7 per cent of the sample) and 58 (21 per cent) girls reported for dietary therapy. While most of these children were obese, by either subjective or objective criteria, an appreciable number of nonobese children were also dieting. The children's own perception of their body build seemed to be a strong motivation to diet for weight control. Most of the dieters did not receive any dietary advice from professional people. Over two-thirds of both boys and girls believed that daily consumption of milk, bread, fruits, eggs, cheese, meat, and tomatoes is desirable. More overweight than thin and normal-weight children indicated that, to prevent obesity, all kinds of food are permissible, but only in limited amounts. Most children believed in the fattening value of cakes, sweets, fried and fatty foods, potatoes, bread and nuts. Overweight children, particularly girls, reported eating less bread, cake and cream, adding less sugar to beverages, and eating sweets and ice cream less frequently than thin and normal-weight children. Overweight teen-agers appear to be more conscious of their food intake than under- and normal-weight children. | CS | (+) Children believe ↑ tomato intake = good eating habits |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| BW | Nolan LJ | Elevated plasma cholecystokinin and appetitive ratings after consumption of a liquid meal in humans. Nolan LJ, Guss JL, Liddle RA, Pi-Sunyer FX, Kissileff HR. Nutrition. 2003 Jun;19(6):553-7. | 2003 | OBJECTIVE: This study had two objectives. The first was to evaluate the possibility that, in a previous study, a soup preload augmented the reduction of food intake in a test meal induced by an exogenous infusion of cholecystokinin (CCK) because the soup also endogenously released CCK. The second was to compare CCK release by soup between men and women to determine whether the increased satiating effectiveness of soup in women as opposed to men could have been partly attributable to differences in CCK release. METHODS: By using a bioassay that measures all of its known isoforms, we determined plasma CCK levels at baseline and at several times postprandially in eight healthy, non-obese men and women (four of each sex). Each subject ingested 800 g of tomato soup, which was followed 30 min later by 300 g of a yogurt shake. Appetitive ratings were also collected and related to CCK levels. RESULTS: Ingestion of tomato soup significantly increased plasma CCK levels by 3.81 pmol/L (+/- 1.21 standard error, P = 0.016) over baseline within 30 min in all subjects combined. When CCK concentrations at 5 min after soup and 5 min after yogurt were averaged, the women's mean averaged concentration was 5.58 pmol/L (+/- 1.994, t = 2.80, P = 0.0073) higher than the men's. The elevated levels persisted but did not rise further upon consumption of the yogurt shake. Hunger ratings declined and fullness ratings increased after eating, although patterns of ratings did not match exactly patterns of CCK release. CONCLUSIONS: A large quantity of tomato soup stimulates significant CCK release; therefore, some of the satiating effects of soup preloads could have been mediated by an elevation in endogenous CCK. | RCT | (+) ↑CCK= ↑satiety | ||||
| BW | Cullen KW | Validity and reliability of a behavior-based food coding system for measuring fruit, 100% fruit juice, vegetable, and sweetened beverage consumption: results from the Girls Health Enrichment Multisite Studies. Cullen KW, Himes JH, Baranowski T, Pettit J, Stevens M, Slawson DL, Obarzanek E, Murtaugh M, Matheson D, Sun W, Rochon J. Prev Med. 2004 May;38 Suppl:S24-33. | 2004 | BACKGROUND: This paper presents the rationale, reliability, and validity of a behavior-based food coding system for measuring fruit (F), juice (J), vegetable (V), sweetened beverage, and water consumption in children. METHODS: Coding algorithms for FJV, sweetened beverages, and water were developed for use with the Nutrition Data System for Research (NDS-R). Two hundred and ten 8- to 10-year-old African American girls at four field centers completed two 24-h dietary recalls at baseline and at 12 weeks follow-up after a weight gain prevention intervention. Differences in mean baseline consumption of selected food variables and other selected nutrients across the four field centers were analyzed. Intraclass correlation coefficients (ICCs) for reliability across 2 days of food recalls and 12-week test-retest reliability correlations were calculated. For the purposes of this paper, nutrient intake estimates were considered construct validators of food intake, and validity was assessed by correlating the coded food variable servings with nutrient intake. RESULTS: ICCs varied from zero (0.001 for beta carotene equivalents) to moderate (0.44 for sucrose), indicating substantial instability in consumption or reporting. Twelve-week test-retest correlations were slight to moderate (0.09 for lycopene to 0.49 for folate). FJV consumption was negatively related to percent energy from fat (r = -0.28; P = 0.001) and positively related to other nutrients. Sweetened beverage consumption was positively related to energy, sucrose, fructose, and vitamin C consumption. CONCLUSIONS: This behavior-based food coding system demonstrated construct validity among 8- to 10-year-old African American girls and can measure the desired food groups. | Interv | N | Methods validation test-retest |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Cancer | Bossola M | Taste intensity and hedonic responses to simple beverages in gastrointestinal cancer patients. Bossola M, Cadoni G, Bellantone R, Carriero C, Carriero E, Ottaviani F, Borzomati D, Tortorelli A, Doglietto GB. J Pain Symptom Manage. 2007 Nov;34(5):505-12. Epub 2007 Jul 5. | 2007 | Changes in the taste of food have been implicated as a potential cause of reduced dietary intake among cancer patients. However, data on intensity and hedonic responses to the four basic tastes in cancer are scanty and contradictory. The present study aimed at evaluating taste intensity and hedonic responses to simple beverages in 47 anorectic patients affected by gastrointestinal cancer and in 55 healthy subjects. Five suprathreshold concentrations of each of the four test substances (sucrose in black current drinks, citric acid in lemonade, NaCl in unsalted tomato juice, and urea in tonic water) were used. Patients were invited to express a judgment of intensity and pleasantness ranging from 0 to 10. Mean intensity scores directly correlated with concentrations of sour, salty, bitter, and sweet stimuli, in both normals and those with cancer. Intensity judgments were higher in cancer patients with respect to sweet (for median and high concentrations, P<0.05), salty (for all concentrations, P<0.05), and bitter tastes (for median concentration, P<0.01). Hedonic function increased with the increase of the stimuli only for the sweet taste. A negative linear correlation was found between sour, bitter, and salty concentrations and hedonic score. Both in cancer patients and in healthy subjects, hedonic judgments increased with the increase of the stimulus for the sweet taste (r=0.978 and r=0.985, P=0.004 and P=0.002, respectively), and decreased for the salty (r=-0.827 and r=-0.884, P=0.084 and P=0.047, respectively) and bitter tastes (r=-0.990 and r=-0.962, P=0.009 and P=0.001, respectively). For the sour taste, the hedonic scores remained stable with the increase of the stimulus in noncancer controls (r=-0.785, P=0.115) and decreased in cancer patients (r=-0.996, P=0.0001). The hedonic scores for the sweet taste and the bitter taste were similar in cancer patients and healthy subjects, and these scores were significantly higher in cancer patients than in healthy subjects for most of the concentrations of the salty taste and all the concentrations of the sour taste. The present study suggests that cancer patients, compared to healthy individuals, have a normal sensitivity, a normal liking for pleasant stimuli, and a decreased dislike for unpleasant stimuli. Moreover, when compared to controls, they show higher hedonic scores for middle and high concentrations of the salty taste and for all concentrations of the sour taste. Further studies are needed to evaluate whether these changes observed in cancer patients translate into any alteration in dietary behavior and/or food preferences. | CS | cancer patients had higher like of salty flavor | ||||
| Cancer MOA | Huang CS | Lycopene inhibits matrix metalloproteinase-9 expression and down-regulates the binding activity of nuclear factor-kappa B and stimulatory protein-1. Huang CS, Fan YE, Lin CY, Hu ML. J Nutr Biochem. 2007 Jul;18(7):449-56. Epub 2006 Oct 17. | 2007 | The carotenoid lycopene has been associated with decreased risks of several types of cancer, such as hepatoma. Although lycopene has been shown to inhibit metastasis, its mechanism of action is poorly understood. Here, we used SK-Hep-1 cells (from a human hepatoma) to test whether lycopene exerts its anti-invasion activity via down-regulation of the expression of matrix metalloproteinase (MMP)-9, an important enzyme in the degradation of basement membrane in cancer invasion. The activity and expressions of MMP-9 protein and mRNA were detected by gelatin zymography, Western blotting and RT-PCR, respectively. The binding abilities of nuclear factor-kappa B (NF-kappaB), activator protein-1 and stimulatory protein-1 (Sp1) to the binding sites in the MMP-9 promoter were measured by the electrophoretic mobility shift assay. We showed that lycopene (1-10 microM) significantly inhibited SK-Hep-1 invasion (P<.05) and that this effect correlated with the inhibition of MMP-9 at the levels of enzyme activity (r(2)=.94, P<.001), protein expression (r(2)=.80, P=.007) and mRNA expression (r(2)=.94, P<.001). Lycopene also significantly inhibited the binding abilities of NF-kappaB and Sp1 and decreased, to some extent, the expression of insulin-like growth factor-1 receptor (IGF-1R) and the intracellular level of reactive oxygen species (P<.05). The antioxidant effect of lycopene appeared to play a minor role in its inhibition of MMP-9 and invasion activity of SK-Hep-1 cells because coincubation of cells with lycopene plus hydrogen peroxide abolished the antioxidant effect but did not significantly affect the anti-invasion ability of lycopene. Thus, lycopene decreases the invasive ability of SK-Hep-1 cells by inhibiting MMP-9 expression and suppressing the binding activity of NF-kappaB and Sp1. These effects of lycopene may be related to the down-regulation of IGF-1R, while the antioxidant activity of lycopene appears to play a minor role. | Cell culture | (-) ↓ MMP-9 expressio n ↓ NFkB , activator protein-1 and Sp1 binding to MMP-9 promoter ↓ IGF-1R |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Cancer: breast | Ewertz M | Dietary factors and breast-cancer risk in Denmark. Ewertz M, Gill C. Int J Cancer. 1990 Nov 15;46(5):779-84. | 1990 | The influence of dietary factors, in particular the intake of fat and beta-carotene, on breast-cancer risk was evaluated in a case-control study including 1,486 breast cancer cases diagnosed over a 1 year period in Denmark. The control group was an age-stratified random sample of 1,336 women from the general population. Data on usual diet prior to the breast cancer diagnosis were collected by self-administered questionnaires of the semi-quantitative food frequency type. A highly significant trend (p less than 0.001) of increasing risk was observed with increasing fat intake, the RR for the highest quartile being 1.45 (95% Cl 1.17-1.80) compared with the lowest. However, information was not available to allow adjustment for the possible confounding effect of energy intake. The risk of breast cancer was not associated with consumption of vegetables rich in beta-carotene, multi-vitamin tablets or other dietary supplements, coffee, tea, sugar or artificial sweeteners. | CC | N Veg | ||||
| Cancer: breast | Graham S | Nutritional epidemiology of postmenopausal breast cancer in western New York. Graham S, Hellmann R, Marshall J, Freudenheim J, Vena J, Swanson M, Zielezny M, Nemoto T, Stubbe N, Raimondo T. Am J Epidemiol. 1991 Sep 15;134(6):552-66. | 1991 | The authors studied 439 postmenopausal breast cancer cases, identified in hospitals throughout western New York, with an interview schedule that considered frequency and amount ingested of 172 foods and provided data for an estimate of total calories ingested. These were compared with age-matched controls comprising a random sample of the same communities as the cases. The extensive interviews, requiring 2.0 hours on average to administer, also covered alcohol ingestion, Quetelet index, and a wide variety of reproductive factors. The authors found, as have most investigators over the past 25 years, that risk increased with increases in age at first pregnancy, decreased with increases in numbers of children and pregnancies, and increased in those with history of benign breast disease and in those with female relatives previously affected with breast cancer. Risk adjusted for potential confounders was highest among women with the lowest ingestion of carotene or a substance correlated with its ingestion. Risk was not associated with retinol ingestion. It increased with increases in Quetelet index. Fat intake, whether studied in terms of quantity or the proportion of total calories derived from fat, was not associated with risk of breast cancer. Our analyses of these factors were adjusted for age, education, and the reproductive history traits described above. | CC | N retinol (-) carotene |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Cancer: breast | Potischman N | Effects of breast cancer treatments on plasma nutrient levels: implications for epidemiological studies. Potischman N, Byers T, Houghton L, Root M, Nemoto T, Campbell TC. Cancer Epidemiol Biomarkers Prev. 1992 Nov-Dec;1(7):555-9. | 1992 | The interpretation of case-control studies in which blood nutrient levels are examined as etiological factors in cancer is complicated by the possibility that either the disease or its treatment may alter these levels. Circulating levels of selected nutrients were examined prior to diagnostic biopsy and compared with levels 3 to 4 months after diagnosis among 71 women with breast cancer and 95 women with benign breast disease. Among women with benign breast disease or women with breast cancer who were not given postsurgical adjuvant drug therapy, levels of alpha-carotene, lycopene, alpha-tocopherol, cholesterol, and triglycerides did not change over time. In contrast, women who received chemotherapy had increased levels of cholesterol, retinol, and alpha- and gamma-tocopherol, and women on antiestrogen therapy showed increased levels of triglycerides and alpha-tocopherol. Overall, the concentrations of carotenoids (lycopene, alpha-carotene, and beta-carotene) did not change in breast cancer cases, although subgroup analyses showed increased levels of beta-carotene among cases not receiving drug treatment and decreased levels among those receiving antiestrogens. In summary, blood levels of some nutrients did not appear to be affected by breast cancer or its treatments, but changes were noted for levels of plasma lipids, tocopherols, retinol, and beta-carotene. Those investigating the etiological relationship between breast cancer and circulating nutrients need to consider these effects in designing and interpreting epidemiological studies. | CC | |||||
| Cancer: breast | Levi F | Dietary factors and breast cancer risk in Vaud, Switzerland. Levi F, La Vecchia C, Gulie C, Negri E. Nutr Cancer. 1993; 19(3):327-35. | 1993 | The relationship between dietary factors and the risk of breast cancer was investigated in a case-control study conducted in the Canton of Vaud, Switzerland as a pilot phase for a larger cooperative study within the SEARCH Programme of the International Agency for Research on Cancer (Lyon, France). A total of 107 incident, histologically confirmed cases of breast cancer and 318 controls admitted to hospital for acute, nonhormone-related, gynecological, metabolic, or neoplastic disorders were interviewed. Significant direct trends in risk were observed with total energy intake [relative risk (RR) for highest vs. lowest intake tertile = 1.9] and, after allowance for energy intake, with frequency of consumption of various types of meat (RR = 2.1 for the highest tertile), cheese (RR = 2.7), and alcohol (RR = 2.1). Significant protections, on the order of 40-60% reductions for the highest vs. lowest consumption tertile, were conferred by total green vegetable consumption, selected types of vegetables and fruits (cucumbers, onions, pears), and a summary index of beta-carotene intake (RR = 0.4 for highest consumption tertile). Thus the present study confirmed the existence of an unfavorable dietary pattern for breast cancer risk (characterized by high-calorie, selected sources of animal fat and alcohol intake). Moreover, a significant protection could be gained by consuming a diet rich in vegetables and perhaps fruits. | CC | (-) |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Cancer: breast | Hernandez- Valero MA |
Comparison of baseline dietary intake of Hispanic and matched non-Hispanic white breast cancer survivors enrolled in the Women's Healthy Eating and Living study. Hernandez-Valero MA, Thomson CA, Hernandez M, Tran T, Detry MA, Theriault RL, Hajek RA, Pierce JP, Flatt SW, Caan BJ, Jones LA. J Am Diet Assoc. 2008 Aug;108(8):1323-9. | 2008 | OBJECTIVE: To assess the reported baseline dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women's Healthy Eating and Living study, a randomized plant-based dietary intervention clinical trial. DESIGN: Dietary data from 4 days repeated 24-hour recalls within 3 weeks included daily total intake of energy, protein, carbohydrates, cholesterol, total fat, monounsaturated fat, saturated fat, polyunsaturated fat, fruit/vegetable servings, carotenoids, alcohol, caffeine, and percentage of energy from protein, carbohydrates, alcohol, and fats. SUBJECTS: One hundred sixty-five Hispanic breast cancer survivors age-matched to 165 non-Hispanic white breast cancer survivors diagnosed with Stage I, II, or IIIA primary operable breast cancer. STATISTICAL ANALYSES: Two-sample t tests and Wilcoxon rank sum tests to compare dietary intake, and logistic and ordinal logistic regression analyses to examine the association between ethnicity, alcohol, and lycopene consumption, while controlling for place of birth, education, body mass index, and time since diagnosis. RESULTS: Hispanics were more likely to be foreign-born (P<0.001), less educated (P<0.0001) and to consume higher amounts of lycopene (P=0.029), while non-Hispanic whites were more likely to consume alcohol (P=0.001). However, no differences were observed in the average amounts of alcohol consumed or total percents of energy from alcohol. Both groups consumed more than five servings of fruits and vegetables daily. Being Hispanic remained a significant predictor of lower alcohol use (P=0.004) and higher lycopene consumption (P=0.005) after controlling for place of birth, education, body mass index, and time since diagnosis. CONCLUSIONS: There are more similarities than differences in the dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women's Healthy Eating and Living study. Further analysis is needed to determine if higher lycopene consumption shown among the Hispanic participants will translate to greater protection against breast cancer recurrence or increased survival. | CC | Hispanic women ↑ lyco | ||||
| Cancer: breast | Hernandez- Valero MA |
Comparison of baseline dietary intake of Hispanic and matched non-Hispanic white breast cancer survivors enrolled in the Women's Healthy Eating and Living study. Hernandez-Valero MA, Thomson CA, Hernandez M, Tran T, Detry MA, Theriault RL, Hajek RA, Pierce JP, Flatt SW, Caan BJ, Jones LA. J Am Diet Assoc. 2008 Aug;108(8):1323-9. | 2008 | OBJECTIVE: To assess the reported baseline dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women's Healthy Eating and Living study, a randomized plant-based dietary intervention clinical trial. DESIGN: Dietary data from 4 days repeated 24-hour recalls within 3 weeks included daily total intake of energy, protein, carbohydrates, cholesterol, total fat, monounsaturated fat, saturated fat, polyunsaturated fat, fruit/vegetable servings, carotenoids, alcohol, caffeine, and percentage of energy from protein, carbohydrates, alcohol, and fats. SUBJECTS: One hundred sixty-five Hispanic breast cancer survivors age-matched to 165 non-Hispanic white breast cancer survivors diagnosed with Stage I, II, or IIIA primary operable breast cancer. STATISTICAL ANALYSES: Two-sample t tests and Wilcoxon rank sum tests to compare dietary intake, and logistic and ordinal logistic regression analyses to examine the association between ethnicity, alcohol, and lycopene consumption, while controlling for place of birth, education, body mass index, and time since diagnosis. RESULTS: Hispanics were more likely to be foreign-born (P<0.001), less educated (P<0.0001) and to consume higher amounts of lycopene (P=0.029), while non-Hispanic whites were more likely to consume alcohol (P=0.001). However, no differences were observed in the average amounts of alcohol consumed or total percents of energy from alcohol. Both groups consumed more than five servings of fruits and vegetables daily. Being Hispanic remained a significant predictor of lower alcohol use (P=0.004) and higher lycopene consumption (P=0.005) after controlling for place of birth, education, body mass index, and time since diagnosis. CONCLUSIONS: There are more similarities than differences in the dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women's Healthy Eating and Living study. Further analysis is needed to determine if higher lycopene consumption shown among the Hispanic participants will translate to greater protection against breast cancer recurrence or increased survival. | CC | ↑ lyco intake in Hispanics vs whie survivors |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Cancer: cervical | Marshall JR | Diet and smoking in the epidemiology of cancer of the cervix. Marshall JR, Graham S, Byers T, Swanson M, Brasure J. J Natl Cancer Inst. 1983 May;70(5):847-51. | 1983 | This study of 513 white cervical cancer patients and 490 white hospitalized controls considered, with adjustment for marital history and parity, the effects of smoking and dietary characteristics on the relative risk of developing cervical cancer. Although smoking was shown to be positively associated with risk, no dose-response relationship was evident. The frequency of consumption of cruciferous vegetables was positively associated with risk. Respondent reports of the frequency of prior ingestion of several food items were used in constructing crude indices of exposure to basic nutrients; the index of beta-carotene exposure was negatively associated with risk, whereas the index of fat consumption was positively associated with risk. | CC | -carot (+) crucif | ||||
| Cancer: cervical | De Vet | The role of beta-carotene and other dietary factors in the aetiology of cervical dysplasia: results of a case-control study. de Vet HC, Knipschild PG, Grol ME, Schouten HJ, Sturmans F Int J Epidemiol. 1991 Sep;20(3):603-10. | 1991 | The effects of beta-carotene and several other dietary factors on the risk of cervical dysplasia were evaluated in a case-control study. Cases (n = 257) were the participants of a randomized trial assessing the effect of beta-carotene on cervical dysplasia. Controls (n = 705) were sampled from the general population. A postal questionnaire was used to obtain information about the frequency of consumption of several food items containing beta-carotene, retinol, vitamin C and dietary fibre. Information was also collected about other risk factors for cervical dysplasia, in order to adjust for possible confounding. To our surprise, we observed an increased risk of cervical dysplasia for women with a high intake of beta-carotene (odds ratio (OR) = 2.31; 95% confidence interval (CI): 1.27-4.19). No relationship was found with the intake of retinol, while both vitamin C and dietary fibre showed a weak and not statistically significant inverse relationship with cervical dysplasia. These findings do not support the hypothesis that beta-carotene protects against cervical dysplasia. | CC | (-) Vit C |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Cancer: cervical | Palan PR | Plasma concentrations of micronutrients during a nine-month clinical trial of beta-carotene in women with precursor cervical cancer lesions. Palan PR, Chang CJ, Mikhail MS, Ho GY, Basu J, Romney SL. Nutr Cancer. 1998; 30(1):46-52. | 1998 | The effects of oral supplementation of a 30-mg dose of beta-carotene on the plasma levels of carotenoids, tocopherols, and retinol were studied sequentially in 69 patients participating in a nine-month randomized placebo controlled trial conducted to examine efficacy of beta-carotene to induce regression of cervical intraepithelial neoplasia. At each visit (baseline and 1.5, 3, 6, 9, 10.5, and 15 mo), blood samples were collected and the levels of six micronutrients were determined by high-performance liquid chromatography. No limitations or changes were introduced in each participant's dietary habits. Cervico-vaginal lavage samples were also obtained at the same visit and assayed for the presence of human papillomavirus DNA by Southern blot hybridization and polymerase chain reaction. In the supplemented group, mean plasma beta-carotene levels were significantly higher (p = 0.0001) than baseline and remained markedly elevated for 15 months. In the longitudinal analysis of the placebo group, there were no variations among individual mean plasma levels of beta-carotene, alpha-carotene, lycopene, retinol, gamma-tocopherol, or alpha-tocopherol, suggesting absence of seasonal or dietary changes. In the placebo group, cigarette smoking and steroid contraceptive use were significantly associated with low levels of plasma beta-carotene (p = 0.05 and p = 0.012, respectively). However, in contrast, in the beta-carotene-supplemented group, steroid contraceptive use had no influence on the plasma beta-carotene levels. An additional noteworthy finding was that beta-carotene supplementation did not reverse the depletion effect in smokers. There was no association between the plasma levels of these six micronutrients in women with cervical intraepithelial neoplasia and persistent human papillomavirus infection status in the placebo or the supplemented groups. Functional sequential nutrient interactions with each other or with other essential micronutrients and possible long-term toxicity need to be addressed in clinical trials. | RCT | |||||
| Cancer: colorectal | Franceschi S | Food groups and risk of colorectal cancer in Italy. Franceschi S, Favero A, La Vecchia C, Negri E, Conti E, Montella M, Giacosa A, Nanni O, Decarli A. Int J Cancer. 1997 Jul 3;72(1):56-61. | 1997 | The proportion of colorectal cancer attributed to dietary habits is high, but several inconsistencies remain, especially with respect to the influence of some food groups. To further elucidate the role of dietary habits, 1,225 subjects with cancer of the colon, 728 with cancer of the rectum and 4,154 controls, hospitalized with acute non-neoplastic diseases, were interviewed between 1992 and 1996 in 6 different Italian areas. The validated food-frequency questionnaire included 79 questions on food items and recipes, categorised into 16 food groups. After allowance for non-dietary confounding factors and total energy intake, significant trends of increasing risk of colorectal cancer with increasing intake emerged for bread and cereal dishes (odds ratio [OR] in highest vs. lowest quintile = 1.7), potatoes (OR = 1.2), cakes and desserts (OR = 1.1), and refined sugar (OR = 1.4). Intakes of fish (OR = 0.7), raw and cooked vegetables (OR = 0.6 for both) and fruit other than citrus fruit (OR = 0.7) showed a negative association with risk. Consumption of eggs and meat (white, red or processed meats) seemed uninfluential. Most findings were similar for colon and rectum, but some negative associations (i.e., coffee and tea, and fish) appeared stronger for colon cancer. Our findings lead us to reconsider the role of starchy foods and refined sugar in light of recent knowledge on the digestive physiology of carbohydrates and the insulin/colon cancer hypothesis. The beneficial role of most vegetables is confirmed, with more than 20% reduction in risk of colorectal cancer from the addition of one daily serving. | CC | (-) |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Cancer: colorectal | La Vecchia C | Intake of selected micronutrients and risk of colorectal cancer. La Vecchia C, Braga C, Negri E, Franceschi S, Russo A, Conti E, Falcini F, Giacosa A, Montella M, Decarli A. Int J Cancer. 1997 Nov 14;73(4):525-30. | 1997 | The relationship between various micronutrients and colorectal cancer risk was investigated using data from a case-control study conducted between January 1992 and June 1996 in Italy. Cases were 1,953 incident, histologically confirmed colorectal cancers (1,225 of the colon and 728 of the rectum), admitted to the major teaching and general hospitals in the study areas, and 4,154 controls with no history of cancer, admitted to hospitals in the same catchment areas for acute, non-neoplastic diseases unrelated to the digestive tract and requiring no long-term modifications of the diet. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratio (ORs) were computed after allowance for age, sex and other potential confounding factors, including physical activity, total energy and fibre intake. For most micronutrients, ORs were below unity with increasing quintile of intake. The most consistent protective effects were for carotene, riboflavin and vitamin C (Multivariate ORs from the continuous model, with unit set as the difference between the upper cut-point of the 4th quintile and that of the 1st one, were 0.65, 0.73 and 0.80, respectively). Inverse relationships were observed also for calcium and vitamin D (ORs of 0.85 and 0.93, respectively). When the combined effect of calcium and vitamin D and selected anti-oxidants was considered, the OR reached 0.46 in subjects reporting high calcium/vitamin D and high anti-oxidant intake compared to those reporting low intake of both groups of micronutrients. Most results were apparently stronger for colon cancer and among females. Our results provide further support for a protective effect of several micronutrients on colorectal cancer risk and some indications for a specific and stronger effect of selected anti-oxidants. | CC | (-) carrot, ribo, Vit C |
||||
| Cancer: colorectal | Voorrips LE | Vegetable and fruit consumption and risks of colon and rectal cancer in a prospective cohort study: The Netherlands Cohort Study on Diet and Cancer. Voorrips LE, Goldbohm RA, van Poppel G, Sturmans F, Hermus RJ, van den Brandt PA. Am J Epidemiol. 2000 Dec 1;152(11):1081-92. | 2000 | The relation between vegetable and fruit consumption and colorectal cancer risk was comprehensively assessed in the Netherlands Cohort Study on Diet and Cancer using a validated 150-item food frequency questionnaire. After 6.3 years of follow-up (1986-1992), over 1,000 incident cases of colorectal cancer were registered. Using case-cohort analysis, the authors calculated rate ratios and 95% confidence intervals adjusted for age, alcohol intake, and family history of colorectal cancer. For colon cancer, no statistically significant associations with total vegetable intake or total fruit intake were found. However, among women, an inverse association was observed with vegetables and fruits combined (for the highest quintile vs. the lowest, the rate ratio was 0.66 (95% confidence interval: 0.44, 1.01)). Brassica vegetables and cooked leafy vegetables showed inverse associations for both men and women. Among women and, to a lesser extent, among men, inverse associations were stronger for distal colonic tumors than for proximal colonic tumors. For rectal cancer, no statistically significant associations were found for vegetable consumption or fruit consumption or for specific groups of vegetables and fruits; only Brassica vegetables showed a positive association in women. As in other cohort studies, the observed inverse relation between vegetable and fruit consumption and occurrence of colorectal cancer was less strong than relations reported in case-control studies. | PC | N F/V (-)W F/V |
| 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, |
|---|---|---|---|---|---|---|---|---|---|---|
| Cancer: colorectal | Seow A | Food groups and the risk of colorectal carcinoma in an Asian population. Seow A, Quah SR, Nyam D, Straughan PT, Chua T, Aw TC. Cancer. 2002 Dec 1;95(11):2390-6. | 2002 | BACKGROUND: Singapore Chinese have experienced a rapid transition toward a pattern of disease in which lifestyle-related, chronic, degenerative diseases are major public health concerns. The rates of colorectal carcinoma have increased 2-fold over the last 3 decades. It has long been known that dietary factors play a role in the risk of this disease, although studies in Asian populations, with their unique dietary intake, have been few. METHODS: The authors conducted a population-based case-control study that included 121 Chinese patients with colorectal carcinoma and 222 healthy control participants who provided information on usual intake of major food groups in the preceding 3 years, physical activity, family history of colorectal carcinoma, and demographic variables through an in-person questionnaire. RESULTS: High intake of red meat, but not other meats, indicated a predisposition to risk of colorectal carcinoma (adjusted odds ratio [OR] for the highest tertile vs. the lowest tertile, 2.2; 95% confidence interval [95%CI], 1.1-4.2). A low vegetable intake also was associated with a higher risk, and the combined effect appeared to be additive. Those in the highest tertile of meat intake and the lowest quartile of vegetable intake had an OR of 2.6 (95%CI, 1.0-6.7). The authors observed a slight, albeit nonsignificant, positive association with foods high in refined sugars. There was no association observed with fruit or soy-legume intake in this study. Among nondietary variables, a family history of colorectal carcinoma conferred a significant increase in risk (OR, 6.7; 95% CI 2.4-18.7). CONCLUSIONS: Meat intake and vegetable intake were associated significantly with risk of colorectal carcinoma in this Asian population, and further studies on the effects of changes in these specific types of food may shed light on how best to reduce the rapid increase in rates in similar populations. | CC | N F/S/L | ||||
| Cancer: colo rectal |
Forman MR | Components of variation in serum carotenoid concentrations: the Polyp Prevention Trial. Forman MR, Borkowf CB, Cantwell MM, Steck S, Schatzkin A, Albert PS, Lanza E. Eur J Clin Nutr. 2009 Jun;63(6):763-70. Epub 2008 Apr 16. | 2009 | OBJECTIVES: The intra- and interindividual variations and season and center effects were estimated from a series of serum carotenoid concentrations in the Polyp Prevention Trial (PPT) participants. SUBJECTS/METHODS: Fasting blood was collected annually for 4 years in all 1905 participants, and a subcohort of 901 participants were selected within each (of eight) center(s), by gender and dietary arm of the study, for measurement of five major carotenoid peaks. Using variance of component methods, the variation in serum carotenoid concentrations about the underlying mean was partitioned into explanatory components attributed to various sources. RESULTS: The contributions of the inter- and intraindividual variances to the overall variation in carotenoid concentrations were in the range of 61-70 and 20-35%, respectively, whereas center and center-by-season effects provided 2.6-9.5 and 0.2-1.4%, respectively. The highest percent (35%) of intraindividual variation was exhibited by lycopene, and the highest percent (70% apiece) of interindividual variation was exhibited by lutein/zeaxanthin and beta-carotene. Serum lycopene had the highest ratio of intra- to interindividual variation of 0.57, whereas lutein had the lowest ratio of 0.29. We estimate that the ratio of intra- to interindividual variance around the mean carotenoid concentration can be reduced greatly by collecting 3-4 compared to 1 blood measurement in large-scale trials like the PPT. CONCLUSION: In the largest study of components of variation in individuals at high risk for colorectal cancer, the largest contributors to variation in serum carotenoid concentrations were intra- and interindividual effects followed by center and center-by-season effects. | PC | Variation testing serum [lyco] ↑intra(-) & inter subject variation |
