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,**2
*
TNO Nutrition and Food Research, 3700 AJ Zeist, The Netherlands;
Division of Human Nutrition and Epidemiology, Wageningen UR, 6700 EV Wageningen, The Netherlands; and
**
TNO-WU Centre for Micronutrient Research, Wageningen, The Netherlands
2To whom correspondence and reprint requests should be addressed.
 |
ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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-carotene, 121% (94–149); ß-carotene, 45% (28–62); and vitamin
C, 64% (51–77) (P < 0.05). The high group had an
11% (-18 to -4) lower final plasma homocysteine and a 15% (0.8–30)
higher plasma folate concentration compared with the low group
(P < 0.05). This is the first trial to show that a
mix of fruits and vegetables, with a moderate folate content, decreases
plasma homocysteine concentrations in humans.
KEY WORDS: • fruits • vegetables • carotenoids • vitamins • homocysteine • humans
|
INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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,
Miller 1990
, Negri et al. 1991
,
Steinmetz and Potter 1991
, Weisburger 1991
). A high consumption of fruits and vegetables may also be
beneficial with respect to cardiovascular disease risk (Gey et al. 1993
, Gramenzi et al. 1990
, Hertog et al. 1993
, Palgi 1981
). The potential health
benefits of fruits and vegetables have been attributed to the effects
of specific components therein, i.e., vitamins, minerals, dietary fiber
and a wide range of secondary metabolites (phytochemicals) responsible
for characteristics such as color, flavor and taste. Several of these
components have been hypothesized to exert an important influence on
human physiologic status (Tomás-Barberán and Robins 1997
). One possible defense mechanism of fruits and vegetables
is the antioxidant capacity of several components, for example,
carotenoids and vitamin C and E. Plasma carotenoids have been
associated with a decreased risk of cancer (Astorg 1997
)
and cardiovascular disease (Palace et al. 1999
). Two
specific carotenoids, lutein and zeaxanthin, may be important for
protecting the macula lutea in the eye (Eye Disease Case-Control Study Group 1992
and 1993
). Another protective
mechanism of fruits and vegetables could be the potential influence of
folate on homocysteine metabolism. Observational epidemiologic research
has shown that a high plasma concentration of homocysteine may be a
risk factor for cardiovascular disease. Several intervention studies
have shown that supplementation with folic acid is effective in
reducing plasma homocysteine concentration (Brouwer et al. 1999a
, De Bree et al. 1997
, Ubbink et al. 1994
). Previous studies on increased fruit and vegetable
consumption have been published, but these focused on specific
nutrients or products. Zino et al. (1997)
and
Yeum et al. (1996)
showed that plasma carotenoid and
vitamin concentrations increased as a result of an increased intake of
vegetables and fruits. However, fat intake, an important determinant of
bioavailability of carotenoids, especially of lutein esters
(unpublished observations), was not controlled in the study of
Zino et al. (1997)
. Yeum et al. (1996)
controlled the diet for fat, but selected specifically
carotenoid-rich vegetables and fruits. In contrast, De Pee et al. (1995)
suggested that ß-carotene from vegetables may
be poorly bioavailable in tropical diets. Brouwer et al. (1999b)
concluded that consumption of foods rich in folate
(vegetables and citrus fruits) could improve folate and homocysteine
status. The current recommendation of health authorities
(Steinmetz and Potter 1996
) is to increase fruit and
vegetable consumption in general (e.g., "five a day"). This is the
first study to investigate the effects of this recommendation in a
mixed population. The present study investigated whether an increased
intake of a mix of fruits and vegetables with a controlled Western diet
had effects in human volunteers on plasma carotenoids, vitamin C,
-tocopherol, plasma homocysteine, vitamin B-12 and folate. |
MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Subjects aged 40–60 y were recruited from the pool of volunteers of the Institute and through an advertisement in a local newspaper. They were preselected on the basis of a low habitual fruit and vegetable consumption (<250 g/d) and a regular Dutch food intake pattern according to a questionnaire. The protocol was explained to the volunteers before they gave their informed consent. The major inclusion criteria were a body mass index [BMI; body weight (kg)/height2 (m2)] <35 kg/m2, alcohol consumption <40 g/d ethanol (men) and 30 g/d ethanol (women), no use of vitamins or other food supplements, no metabolic or endocrine disease, no allergies to fruits and vegetables, not pregnant and/or lactating, no prescribed medication (except paracetamol and oral contraceptives) and a serum cholesterol concentration <8 mmol/L. A total of 48 (24 men and 24 women) eligible volunteers entered the study; 12 were smokers, 6 of each gender.
Study protocol.
The study was performed according to the guidelines for Good Clinical Practice of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, and was approved by an external Medical Ethical Committee. We performed a 4-wk randomized, single-blind, parallel, diet-controlled intervention study. By design, participants were stratified for gender and smoking habits. Further, several random group (high/low) allocations were generated by a computer program. The random solution on the group level that yielded the most homogeneous age and BMI distribution was then selected. Volunteers (n = 24) received a diet low in fruits and vegetables (100 g/d; "low" group); another 24 volunteers received a diet high in fruits and vegetables (500 g/d; "high" group) and also drank fruit juices (200 mL/d).
Food intakes were monitored every day by consumption of the evening meal under supervision at the Institute between 1700 and 1900 h. Remaining parts of the dinner were weighed and recorded. The rest of the daily diet (breakfast and lunch) was handed out to the volunteers in a box after the contents were checked. When the subjects returned the next evening, the consumption of breakfast and lunch was controlled and recorded by checking the box. The volunteers had to complete a form with the questions "Did you consume the total supplied amount of food today?" and "Did you consume foodstuffs and drinks other then the provided food and drinks?" The study was executed at the Department of Nutritional Physiology of TNO Nutrition and Food Research, Zeist from September 1997 to October 1997.
Diets.
All volunteers received the same basic diet with different energy
levels according to need (7.7, 8.7, 9.7, 10.7, 11.7 and 12.7 MJ/d). The
energy intake of breakfast, lunch and snacks differentiated the energy
levels of the diets. The diets were controlled for energy, fat, protein
and carbohydrates. During the study period, body weights were measured
twice weekly before the evening meal. If the measured body weight
deviated 
1.5 kg compared with the reference body weight at d 0, the
subjects were shifted to a diet one energy level higher or lower.
Following the Dutch National Food Consumption Survey-2, fruits and
vegetables normally consumed in the age group 40–60 y were selected.
Table 1
shows the 7-d menu cycle of fruits and vegetables of the two diets.
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On d 1 and 29, blood samples were collected from fasting subjects. For
the analysis of carotenoids, vitamin C and -tocopherol, blood was
collected in tubes containing lithium heparin (Vacutainer systems,
Becton Dickinson, Leiden, The Netherlands) and further prepared in
yellow light. Within 30 min, the tubes were centrifuged (2000 x g, 10 min, 4°C). Metaphosphoric acid solution (50 g/L;
J.T. Baker, Deventer, The Netherlands) was added to the plasma for the
analysis of vitamin C. Samples were stored at -80°C until analysis.
Blood was collected in tubes containing K3EDTA (Vacutainer
systems, Becton Dickinson) for the analysis of vitamin B-12, folate and
homocysteine. Within 15 min, blood was centrifuged (2000 x g, 10 min, 4°C). Plasma samples were immediately
frozen in liquid nitrogen and stored at -80°C until analysis.
Analyses were carried out after all samples were collected.
Biochemical analyses.
Carotenoid profiles and -tocopherol in plasma were quantified by
HPLC using a modified version of a method described previously
(Van Vliet et al. 1991
). After precipitation of proteins
by ethanol (J.T. Baker), carotenoids and tocopherols were extracted
from plasma by n-hexane (Merck, Darmstadt, Germany) and
separated by HPLC (Hyperchrome column; Bisschof, Leonberg, Germany).
Two absorbency detectors (ABI Analytical Kratos Division, South
Yorkshire, UK) were used in series for the colorimetric determination
of carotenoid profiles (450 nm) and -tocopherol (286 nm). The CV
were as follows: lutein, 
16.6%; zeaxanthin, 36.8%;
ß-cryptoxanthin, 7.5%; lycopene, 9.7%; -carotene, 23.4%;
ß-carotene, 6.3%; and -tocopherol, 3.2%.
Vitamin C in plasma containing metaphosphoric acid was quantified by
HPLC using a modified version of a method previously described
(Speek et al. 1984
). All ascorbic acid was oxidized to
dehydro-L-ascorbic acid using ascorbate oxidase
(Boehringer). Quinoxaline derivate was separated by reversed phase HPLC
(Hyperchrome column, Bisschof) after condensation with
1,2-diaminobenzene (Merck). A fluorescence detector (Jasco, Tokyo,
Japan) was used for the detection of vitamin C (CV 11.6%).
Vitamin B-12 and folate were quantified by competitive
protein-binding assay (Simultrac Radioassay Kit Vitamin B-12
[57Co] Folate [125I], ICN Pharmaceuticals,
ICN Biomedicals, Zoetermeer, the Netherlands), according to Dunn and Foster (1973)
, Lau et al. (1965)
and
Kolhouse et al. (1978)
. In summary, vitamin B-12 and
folate in plasma were extracted by heat denaturation of the endogenous
binding proteins. In the presence of potassium cyanide (ICN
Biomedicals) cobalamins were converted to cyanocobalamin. To prevent
oxidation of 5-methyltetrahydrofolic acid, dithiotreitol (ICN
Biomedicals) was added. After incubation with 57CoB-12,
125I folic acid, Intrinsic Factor (ICN Biomedicals) and
-lactoglobuline (ICN Biomedicals), the radioactivity was counted.
The CV were 11.6% and 13.0% for vitamin B-12 and folate,
respectively.
Total plasma homocysteine was determined by HPLC with fluorescence
detection using a method previously described (Ubbink et al. 1991
). Before reversed-phase HPLC analysis, the plasma
thiols were derivatized with ammonium
7-fluorobenzo-2-oxa-1,3-diazole-4-sulfonate (SBD-F), a thiolspecific
fluorogenic probe that is commercially available. Retention of
SBD-homocysteine was sensitive to pH, and a mobile phase pH of 2.1
ensured baseline separation of plasma thiols within 6 min. The CV was
4.5%.
Chemical analyses of diet.
Total weekly high and low diets were mixed and homogenates were made. Because the meals differed in energy level according to the need of the volunteers, a high and a low diet with a calculated energy level of 10.7 MJ was used for analysis. The homogenates were used for the analysis of vitamin C, carotenoids, vitamin E, vitamin B-6, folate and total energy. Another part of the homogenate was freeze-dried and ground, using a strainer. This freeze-dried homogenate was used for the analysis of protein, fatty acids, carbohydrates, sugars, fiber and glucosinolates. Flavonoid analyses were carried out only in fruits and vegetables with a measurable amount of flavonoids. All of these analyses were performed using standard methods. References are available upon request.
Statistical analysis.
Data analyses were performed using the statistical software package SAS/STAT (Version 6, SAS Institute, Cary, NC, General Linear Models procedure). First, for description of our data, baseline values were compared between groups (t test), and baseline and final values within groups were examined by a paired t test. Second, to quantify the unbiased overall effect of the intervention, we used ANOVA to calculate the differences in final values of each variable between the low and high group after adjustment for gender, smoking habits and baseline plasma concentrations of each variable. Analysis of covariance was used for statistical testing. Data are reported as mean ± SD unless stated otherwise and P < 0.05 indicated significant difference.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). At baseline, plasma zeaxanthin concentrations were significantly
different between the groups (P < 0.05). One
participant in the low fruit and vegetable consumption group, a
nonsmoking female, did not complete the study and was not replaced.
Data for this subject were not used in the statistical analysis. The
daily energy intakes of the low and high groups during the trial were
10.2 ± 1.6 and 10.1 ± 1.2 MJ, respectively. The total
energy content of both diets was similar. In both diets, the energy
percentages (en%) from fat, protein and carbohydrate were near those
recommended for protein (12–13 en%), carbohydrate (40–55 en%) and
fat (30–35 en%). The amounts of vitamin C, total carotenoids, folate,
glucosinolates and flavonoids were 1.7-, 3.6-, 0.7-, 5.3- and 4.0-fold
higher, respectively, in the high diet than in the low diet. The amount
of -tocopherol and vitamin B-6 were comparable in the two diets
(Table 3).
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In the low group, the concentrations of the carotenoids decreased
significantly by 31–67%, depending on the carotenoid (Table 4). Vitamin C concentrations decreased significantly by 13%
(P < 0.05) and -tocopherol concentrations decreased
by 8% (P < 0.05) in this group. In the high group,
there were significant increases in plasma concentrations of
-carotene (67%), vitamin C (50%) and ß-cryptoxanthin (28%),
(P < 0.05). Plasma lutein and ß-carotene
concentrations did not change but plasma lycopene decreased by 56%
(P < 0.05). Plasma -tocopherol concentrations
decreased by 11% (P < 0.05), similar to the change in
the low group.
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-carotene, +121%
(+94 to +149); ß-carotene, +45% (+28 to +62); and vitamin C, +64%
(+51 to +77).
No significant changes were found in either group for folate and
vitamin B-12 after 4 wk of dietary intervention. Plasma homocysteine
concentrations decreased significantly by 10% (P < 0.05) in the high group (Table 5
). Differences in final plasma levels between the high group and the low
group (high-low) were as follows: folate, +15% (+0.8 to +30;
P < 0.05) and homocysteine, -11% (-18 to -4;
P < 0.05). Plasma vitamin B-12 concentrations did not
differ between the two groups.
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|
DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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-carotene (121%),
ß-carotene (45%) and vitamin C (64%). Other important findings are
an 11% lower plasma homocysteine concentration in the high group than
in the low group. Furthermore, we found a small but significant plasma
effect on folate (15%). Plasma concentrations of zeaxanthin,
-tocopherol and vitamin B-12 were not affected by the intervention,
as could be expected. In this single blind trial, volunteers were carefully prestratified and were administered a habitual Dutch diet, which was completely controlled for energy, fat, protein and carbohydrate content. Reported compliance was very good because the major part of the diet containing fruits and vegetables was consumed under supervision. After the consumption for 4 wk of 100 g fruits and vegetables, plasma concentrations of carotenoids and vitamins decreased. The selected volunteers had an initial consumption of ~150 g/d fruits and vegetables. The observed decrease of plasma concentrations is not surprising. Also, our brief questionnaire may have underestimated fruit and vegetable consumption somewhat.
Plasma lycopene concentrations of subjects that consumed 500 g of
fruits and vegetables were 22% greater after 4 wk compared with
subjects that consumed 100 g fruits and vegetables. However,
lycopene concentrations decreased in both groups. In a study of
Yeum et al. (1996)
, lycopene concentrations increased
significantly after consumption of a diet with a high carotenoid
content (of the 16 mg/d, 3.3 mg/d was lycopene). Possible explanations
for the decrease of plasma lycopene during our study include a lower
lycopene intake during the study in comparison with the prestudy period
and a limited bioavailability of lycopene from the nonprocessed
products (Van het Hof et al. 1998
). The preselection of
volunteers was based on fruit and vegetable intake as a whole. The
lycopene intake cannot be estimated from this questionnaire. In the
prospective cohort study on diet and cancer in the Netherlands, the
mean daily intake of lycopene was 1.05 ± 1.56 and 1.33 ± 1.88 mg/d for men and women, respectively (Goldbohm et al. 1998
). These daily intakes are ~0.4–0.7 mg/d higher that of
the high diet. In a study of Van het Hof et al. (1999)
,
plasma concentrations of lycopene decreased by ~38% after
consumption of 490 g/d vegetables with a lycopene content even higher
(1.1 mg/d) than that of our high diet.
Concentrations of ß-carotene showed a difference of +45% in
the high group in comparison with the low group. However, the
concentrations remained more or less stable in the high group and
decreased significantly in the low group. Zino et al. (1997)
performed a trial in which the intervention group was
asked to increase their fruit and vegetable consumption to eight
servings (~1000 g) per day. The plasma concentration of ß-carotene
was higher after 4 wk compared with the present trial, but the
ß-carotene content of the intervention diet in the trial of
Zino et al. (1997)
was ~1.5 mg/d higher than in our
trial. Also, subjects in the Zino study continued to consume their
freely chosen habitual diet, including processed foods.
No difference between the changes in plasma zeaxanthin and
-tocopherol concentrations were observed between the low and high
group. The CV for zeaxanthin measurements could be the reason for the
lack of a significant difference. The daily dietary intake of
-tocopherol was comparable between the groups because fruits and
vegetables do not contain a high amount of vitamin E. Therefore, no
major differences between the diet treatments would be expected.
The strength of this study in comparison with previously described trials is the completely controlled intervention period for energy, fat, protein and carbohydrate intake and the good compliance. Therefore, effects on plasma (fat-soluble) vitamins and carotenoids can be attributed to the differences in fruit and vegetable consumption alone. We examined the effects of increased fruit and vegetable consumption as a whole and not an increase of a specific micronutrient and/or specific fruit or vegetable as is to be expected in a population.
In this study, the daily low diet contained 1.6 mg vitamin B-6 and 131
µg folate, whereas the daily high diet contained 2.0 mg
vitamin B-6 and 228 µg folate. These differences in intake
could theoretically not be expected to have a major influence on plasma
homocysteine. Minimal doses of supplemented folic acid of 250
µg/d with a high bioavailability have been reported to
lower homocysteine concentrations (Brouwer et al. 1999a
). Food contains folate polyglutamate derivatives, which
are hydrolyzed to monoglutamate forms in the gut before absorption.
Therefore the bioavailability of food folate is lower than the
bioavailability of folic acid supplements. In the intervention trial of
Brouwer et al. (1999b)
, folate status was improved by 7
nmol/L and homocysteine concentrations were decreased by 2
µmol/L after consumption of vegetables and citrus fruits
high in folate (560 µg/d). In comparison, the high diet in
our trial contained 228 µg/d. During the study, the
volunteers consumed a normal Dutch diet, not a diet with vegetables and
fruits high in folate concentration. Although we can only speculate
here, our results suggest that other components in fruits and
vegetables may influence plasma homocysteine.
The biological relevance of an 11% lower plasma homocysteine concentration, ~1.4 µmol/L, is not clear, but observational epidemiologic studies have found an inverse relationship between plasma homocysteine and cardiovascular disease. Thus, it is advisable to increase fruit and vegetable consumption, which could lower homocysteine concentrations.
In conclusion, our study suggests that a 4-wk period of 500 g/d fruit
and vegetable consumption in comparison with 100 g/d of fruits and
vegetables with a diet controlled for energy, fat, protein and
carbohydrates significantly increases plasma carotenoids, vitamin C,
folate and decreases homocysteine concentrations, but has no effect on
zeaxanthin, vitamin B-12 and -tocopherol plasma concentrations.
Extra consumption of fruits and vegetables (400 g) and 200 mL/d fruit
juices with an equal fat consumption could increase plasma carotenoid
and vitamin concentrations by 22–128% and influence plasma folate and
homocysteine. Plasma homocysteine (in addition to carotenoids) can be
an important indicator of fruit and vegetable intake and is responsive
to changes in the intakes of these foods.
Whether changes in plasma concentrations of vitamins and carotenoids
have an effect on disease risk remains to be established. High plasma
homocysteine concentrations are considered to be a risk factor for
cardiovascular disease (Hankey and Eikelboom 1999
). This
is the first trial that shows that a mix of fruits and vegetables, with
a moderate folate content, will decrease plasma homocysteine levels.
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FOOTNOTES |
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Manuscript received December 19, 2000. Initial review completed January 6, 2000. Revision accepted February 22, 2000.
|
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 J. P. Pierce, L. Natarajan, S. Sun, W. Al-Delaimy, S. W. Flatt, S. Kealey, C. L. Rock, C. A. Thomson, V. A. Newman, C. Ritenbaugh, et al. Increases in Plasma Carotenoid Concentrations in Response to a Major Dietary Change in the Women's Healthy Eating and Living Study. Cancer Epidemiol. Biomarkers Prev., October 1, 2006; 15(10): 1886 - 1892. [Abstract] [Full Text] [PDF]
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P. L Lutsey, L. M Steffen, H. A Feldman, D. H Hoelscher, L. S Webber, R. V Luepker, L. A Lytle, M. Zive, and S. K Osganian Serum homocysteine is related to food intake in adolescents: the Child and Adolescent Trial for Cardiovascular Health Am. J. Clinical Nutrition, June 1, 2006; 83(6): 1380 - 1386. [Abstract] [Full Text] [PDF]
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 C. L. Rock, S. W. Flatt, L. Natarajan, C. A. Thomson, W. A. Bardwell, V. A. Newman, K. A. Hollenbach, L. Jones, B. J. Caan, and J. P. Pierce Plasma Carotenoids and Recurrence-Free Survival in Women With a History of Breast Cancer J. Clin. Oncol., September 20, 2005; 23(27): 6631 - 6638. [Abstract] [Full Text] [PDF]
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A. Brevik, S. E. Vollset, G. S Tell, H. Refsum, P. M. Ueland, E. B. Loeken, C. A Drevon, and L. F. Andersen Plasma concentration of folate as a biomarker for the intake of fruit and vegetables: the Hordaland Homocysteine Study Am. J. Clinical Nutrition, February 1, 2005; 81(2): 434 - 439. [Abstract] [Full Text] [PDF]
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C. Sanchez-Moreno, M. P. Cano, B. de Ancos, L. Plaza, B. Olmedilla, F. Granado, and A. Martin Consumption of High-Pressurized Vegetable Soup Increases Plasma Vitamin C and Decreases Oxidative Stress and Inflammatory Biomarkers in Healthy Humans J. Nutr., November 1, 2004; 134(11): 3021 - 3025. [Abstract] [Full Text] [PDF]
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D. Heber Phytochemicals beyond Antioxidation J. Nutr., November 1, 2004; 134(11): 3175S - 3176S. [Full Text] [PDF]
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 R. P. Bogers, P. van Assema, A. D. M. Kester, K. R. Westerterp, and P. C. Dagnelie Reproducibility, Validity, and Responsiveness to Change of a Short Questionnaire for Measuring Fruit and Vegetable Intake Am. J. Epidemiol., May 1, 2004; 159(9): 900 - 909. [Abstract] [Full Text] [PDF]
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X. Gao, O. I. Bermudez, and K. L. Tucker Plasma C-Reactive Protein and Homocysteine Concentrations Are Related to Frequent Fruit and Vegetable Intake in Hispanic and Non-Hispanic White Elders J. Nutr., April 1, 2004; 134(4): 913 - 918. [Abstract] [Full Text] [PDF]
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X. Gao, M. Yao, M. A. McCrory, G. Ma, Y. Li, S. B. Roberts, and K. L. Tucker Dietary Pattern Is Associated with Homocysteine and B Vitamin Status in an Urban Chinese Population J. Nutr., November 1, 2003; 133(11): 3636 - 3642. [Abstract] [Full Text] [PDF]
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C. Sanchez-Moreno, M P. Cano, B. de Ancos, L. Plaza, B. Olmedilla, F. Granado, and A. Martin Effect of orange juice intake on vitamin C concentrations and biomarkers of antioxidant status in humans Am. J. Clinical Nutrition, September 1, 2003; 78(3): 454 - 460. [Abstract] [Full Text] [PDF]
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C. Sanchez-Moreno, M. P. Cano, B. de Ancos, L. Plaza, B. Olmedilla, F. Granado, and A. Martin High-Pressurized Orange Juice Consumption Affects Plasma Vitamin C, Antioxidative Status and Inflammatory Markers in Healthy Humans J. Nutr., July 1, 2003; 133(7): 2204 - 2209. [Abstract] [Full Text] [PDF]
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 M. K. Kim, S. Sasazuki, S. Sasaki, S. Okubo, M. Hayashi, and S. Tsugane Effect of Five-Year Supplementation of Vitamin C on Serum Vitamin C Concentration and Consumption of Vegetables and Fruits in Middle-Aged Japanese: A Randomized Controlled Trial J. Am. Coll. Nutr., June 1, 2003; 22(3): 208 - 216. [Abstract] [Full Text]
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R. P. Bogers, P. C. Dagnelie, K. R. Westerterp, A. D. M. Kester, J. D. van Klaveren, A. Bast, and P. A. van den Brandt Using a Correction Factor to Correct for Overreporting in a Food-Frequency Questionnaire Does Not Improve Biomarker-Assessed Validity of Estimates for Fruit and Vegetable Consumption J. Nutr., April 1, 2003; 133(4): 1213 - 1219. [Abstract] [Full Text] [PDF]
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J. H Ledikwe, H. Smiciklas-Wright, D. C Mitchell, G. L Jensen, J. M Friedmann, and C. D Still Nutritional risk assessment and obesity in rural older adults: a sex difference Am. J. Clinical Nutrition, March 1, 2003; 77(3): 551 - 558. [Abstract] [Full Text] [PDF]
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R. Freese, G. Alfthan, M. Jauhiainen, S. Basu, I. Erlund, I. Salminen, A. Aro, and M. Mutanen High intakes of vegetables, berries, and apples combined with a high intake of linoleic or oleic acid only slightly affect markers of lipid peroxidation and lipoprotein metabolism in healthy subjects Am. J. Clinical Nutrition, November 1, 2002; 76(5): 950 - 960. [Abstract] [Full Text] [PDF]
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 D. Heber and Q.-Y. Lu Overview of Mechanisms of Action of Lycopene Experimental Biology and Medicine, November 1, 2002; 227(10): 920 - 923. [Abstract] [Full Text] [PDF]
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B. J Venn, J. I Mann, S. M Williams, L. J Riddell, A. Chisholm, M. J Harper, and W. Aitken Dietary counseling to increase natural folate intake: a randomized, placebo-controlled trial in free-living subjects to assess effects on serum folate and plasma total homocysteine Am. J. Clinical Nutrition, October 1, 2002; 76(4): 758 - 765. [Abstract] [Full Text] [PDF]
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E. S Ford, C. Gillespie, C. Ballew, A. Sowell, and D. M Mannino Serum carotenoid concentrations in US children and adolescents Am. J. Clinical Nutrition, October 1, 2002; 76(4): 818 - 827. [Abstract] [Full Text] [PDF]
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M.-L. Silaste, M. Rantala, M. Sampi, G. Alfthan, A. Aro, and Y. A. Kesaniemi Polymorphisms of Key Enzymes in Homocysteine Metabolism Affect Diet Responsiveness of Plasma Homocysteine in Healthy Women J. Nutr., October 1, 2001; 131(10): 2643 - 2647. [Abstract] [Full Text] [PDF]
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T. E. Rohan Invited Commentary: Serum Carotenoids and Breast Cancer Am. J. Epidemiol., June 15, 2001; 153(12): 1148 - 1150. [Full Text] [PDF]
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R. van den Berg, T. van Vliet, W. M. R. Broekmans, N. H. P. Cnubben, W. H. J. Vaes, L. Roza, G. R.M.M. Haenen, A. Bast, and H. van den Berg A Vegetable/Fruit Concentrate with High Antioxidant Capacity Has No Effect on Biomarkers of Antioxidant Status in Male Smokers J. Nutr., June 1, 2001; 131(6): 1714 - 1722. [Abstract] [Full Text]
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D. Heber Colorful cancer prevention: {alpha}-carotene, lycopene, and lung cancer Am. J. Clinical Nutrition, October 1, 2000; 72(4): 901 - 902. [Full Text] [PDF]
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