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March 2008 Highlights of This Issue
Cruciferous Vegetables May Decrease Risk of Breast Cancer in Some Women
Background Studies suggest that what we eat can affect our risk of cancer, but this relation is complex. Among the foods that may be
protective are cruciferous vegetables, which comprise any member of the Cruciferae family of plants, including kale, collard greens, broccoli,
cauliflower, cabbage, Brussels sprouts, and turnips. This group of vegetables contains compounds called isothiocyanates, which may be cancer protective. Not
all people, however, seem to benefit from cruciferous vegetables, and some studies suggest this may be due to differences in genetic makeup. One such
variation (or polymorphism) may be in a gene that encodes for glutathione S-transferases (GSTs), enzymes involved in detoxification. In the March 2008 issue
of The American Journal of Clinical Nutrition, researchers from Vanderbilt University and the Shanghai Cancer Institute report the results from a
human study designed to test whether having a relatively common polymorphism of the gene encoding for GST might influence the relation between cruciferous
vegetable intake and risk of breast cancer.
Study Design This trial was designed as a population-based, case-control study and was conducted in Shanghai, China. Women diagnosed as
having breast cancer (cases, n = 3452) were identified from the Shanghai Cancer Registry, whereas those without breast cancer (controls, n =
3474) were selected randomly from the general population. Blood and cheek cell samples were collected, and their DNA was analyzed. Specifically, 3
polymorphisms of GSTP1, which is the gene that encodes for a GST enzyme, were identified: Ile/Ile, Ile/Val, and Val/Val.
Cruciferous vegetable intake was estimated by using a food-frequency questionnaire, and intake of isothiocyanates was also estimated.
Results There was no overall association between risk of breast cancer and cruciferous vegetable intake. However, women consuming the
most turnips had a 19–35% lower risk than did those consuming the least, and women consuming the most isothiocyanates had an 18% lower risk of breast
cancer than did women consuming the least. When all women were considered together, having the Val/Val polymorphism of the GSTP1 gene was
associated with a 50% greater risk of breast cancer than was having the more common Ile/Ile genotype. This negative relation was strongest in women
who consumed the lowest amounts of cruciferous vegetables, especially in premenopausal women with the Val/Val genotype, who were more than twice as
likely to have breast cancer than were women with the Ile/Ile or Ile/Val genotypes who consumed the greatest amounts of these foods.
Conclusions These data lend strong support to the long-held belief that dietary intake can interact with genetics to influence health.
In this case, higher consumption of cruciferous vegetables may ameliorate the potentially negative effect of having the Val/Val polymorphism for risk
of breast cancer. Studies such as this bring scientists and clinicians one step closer to being able to provide specific dietary advice to individuals based
on their genetic makeup.
Reference Lee S-A, Fowke JH,
Lu W, et al. Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer. American Journal of Clinical
Nutrition 2008;87:753–60.
For More Information For the complete article, please go to the following URL:
http://www.ajcn.org/cgi/reprint/87/3/753
To contact the corresponding author, Jay Fowke, please send an e-mail to jay.fowke{at}vanderbilt.edu.
Background Cancer is the second leading cause of mortality in the United States, and breast cancer results in over 34,000 deaths among
American women annually. Although there are many risk factors for cancer, diet plays an important role. For example, many studies suggest that the correct
balance of folate, vitamin B-6, and vitamin B-12 is important. Results have been somewhat inconclusive, however, partly because circulating concentrations
of these vitamins have not been reported, and many studies have used small sample sizes. Understanding the relation between these vitamins and breast
cancer, however, has garnered significant scientific and public health interest since the mandatory folic acid fortification of enriched cereal grain
products almost 10 years ago. In the March 2008 issue of The American Journal of Clinical Nutrition, Lin and coworkers report the results of a
prospective human study with a relatively large sample size in which the relations offolate, vitamin B-6, and vitamin B-12 to risk of breast cancer were
investigated. In an accompanying commentary, Smith and colleagues discuss the question "Is folic acid good for everyone?"
Study Design This prospective, case-control, epidemiologic study was conducted as part of the Women's Health Study, a trial initiated
in 1993 when 39,876 cancer-free, US female health professionals (mean age: ~54 years) were enrolled. Women provided a blood sample and completed a
food-frequency questionnaire at the beginning of the study. Blood was analyzed for folate, vitamin B-6, and vitamin B-12. By 2004, there were 889 confirmed
incident cases of invasive breast cancer. Each case was matched to another woman (control) without breast cancer, which resulted in 848 breast cancer cases
and 848 matched controls.
Results Simple analyses adjusted for age and original treatment assignment indicated that dietary intakes and plasma concentrations of
folate, vitamin B-6, and vitamin B-12 were not different between cancer patients and control subjects. Additionally, no interactions were observed between
these 3 plasma nutrients in terms of breast cancer risk. However, analyses with additional adjustment for potential confounding factors such as family
history of breast cancer and smoking suggested that women consuming the highest total amounts of folate or vitamin B-12 had a moderately higher risk of
breast cancer than did those consuming the lowest amounts. Circulating B vitamin concentrations also interacted with menopausal status such that high
concentrations of vitamin B-6 were related to reduced risk of breast cancer in postmenopausal (but not premenopausal) women, but higher folate
concentrations increased risk in premenopausal (but not postmenopausal) women.
Conclusions Data from this study suggest that if there are associations between circulating B vitamins and overall breast cancer risk,
they are likely complex. Smith and colleagues pose the timely question of whether fortification of the food system with folic acid might have unintended,
negative consequences in some segments of the population. For example, they build a convincing case for the plausibility that folate has a dual effect on
cancer whereby it inhibits initiation but facilitates progression. Combined, these papers highlight the need for careful scrutiny of the available data and
additional focused research related to increased folate intake and overall health during the entire human lifespan.
Reference Lin J, Lee I-M,
Cook NR, et al. Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women. American Journal of Clinical Nutrition
2008;87:734–43.
Smith AD, Kim Y-I, Refsum H. Is folic acid good for everyone? American Journal of Clinical Nutrition 2008;87:517–33.
For More Information For the complete article, please go to the following URL:
http://www.ajcn.org/cgi/reprint/87/3/734
To contact the authors, please send an e-mail to Jennifer Lin at jhlin{at}rics.bwh.harvard.edu.
For the complete editorial, please go to the following URL:
http://www.ajcn.org/cgi/reprint/87/1/517
To contact the corresponding author, David Smith, please send an e-mail to
david.smith{at}pharm.ox.ac.uk.
Can Intestinal Bacteria in Infants Protect Them from Later Obesity?
Background With 66% of adults and 18% of children currently overweight or obese, obesity may represent today's most pressing health
concern. The etiology of obesity is complex, making it difficult to both prevent and treat. Recent evidence from animal studies suggests that the presence
of certain intestinal bacteria (microbiota) in early life may decrease long-term risk of obesity. Whether intestinal colonization of specific bacteria
during infancy might predict risk of obesity during later life has not been explored in humans. In the March 2008 issue of The American Journal of
Clinical Nutrition, Kalliomäki and coworkers from the University of Turku in Finland evaluated intestinal microbiota in infants in relation to
their body weight 7 y later.
Study Design Subjects were selected from a prospective, longitudinal, epidemiologic trial originally designed to investigate the
relation between probiotic intake and allergic disease. A subset (n = 25) of this larger population was chosen to participate in this study if they
were classified as being overweight or obese at 7 y of age. Healthy-weight children (n = 24; controls) were chosen from the same cohort and matched
for gestational age at delivery, body mass index (BMI; in kg/m2) at birth, mode of delivery, probiotic intervention, duration of breastfeeding,
use of antibiotics during infancy, and indicators of allergy. Subjects' weights and heights were measured at birth, 6 and 12 mo, and 7 y. Intestinal
microbiota types and counts were analyzed in fecal samples collected at 6 and 12 mo of age by using 1) fluorescent in situ hybridization (FISH) with flow
cytometry, 2) FISH with microscopic detection, and 3) quantitative real-time polymerase chain reaction (qRT-PCT) methodologies.
Results By design, the average BMI of the control children was lower than that of the overweight children (15.5 and 19.7, respectively;
P < 0.0001). No other clinical differences were noted, however, between groups. When analyzed by FISH and flow cytometry, average bacterial counts
of bifidobacteria in fecal samples at 6 and 12 mo were twice as high in children maintaining healthy weight than in those who became overweight (P
= 0.02). Similar tendencies were found with FISH and microscopic detection and qRT-PCR, although these results were not statistically significant.
Conversely, children who maintained healthy body weights had lower fecal Staphylococcus aureus in infancy than did those who became overweight or
obese.
Conclusions Although the number of infants studied was very small, the data from this study are consistent with a recent report in
adults that gut flora are altered in obese individuals. This study expands on the adult data by suggesting, for the first time, that differences in
intestinal microbiota in early life may precede later development of obesity in humans. In particular, high numbers of bifidobacteria and low numbers of
Staphylococcus aureus may be protective. Because bifidobacteria dominate the gut microbiota of breastfed infants, and breastfeeding is associated
with a lower risk of obesity, the authors suggest that bifidobacteria may constitute an internal link between breastfeeding and weight development.
Reference Kalliomäki M,
Collado MC, Salminen S, Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. American Journal of Clinical
Nutrition 2008; 87:534–8.
For More Information For the complete article, please go to the following URL:
http://www.ajcn.org/cgi/reprint/87/3/534
To contact the corresponding author, Marko Kalliomäki, please send an e-mail to marko.kalliomaki{at}utu.fi.
Are All trans Fatty Acids Created Equal?
Background The term "trans fatty acid (TFA)" refers to any unsaturated fatty acid in which the hydrogen atoms flanking the
double bond are positioned on opposite sides of the molecule. This is in contrast to cis fatty acids, in which the hydrogen atoms are on the same
side. Most naturally occurring unsaturated fatty acids in the diet are in the cis conformation, whereas most dietary TFAs are produced industrially
during the partial hydrogenation of vegetable oils. Nonetheless, there are naturally occurring TFAs, most of which are found in dairy and beef (ie,
ruminant) products. Many studies have shown that consumption of industrially produced TFAs increases the risk of cardiovascular disease (CVD) via
alterations in circulating lipoprotein concentrations. However, whether this effect is true for the naturally occurring TFAs is not as well established.
The March 2008 issue of The American Journal of Clinical Nutrition highlights the first 2 human intervention trials designed to specifically compare
the effect of TFA source on CVD risk factors in healthy, young adults. An accompanying editorial by Willett and Mozaffarian from Harvard University places
the results from these studies within the context of modern dietary recommendations and public policy.
Study Design To examine the potentially differential effects of industrial versus ruminant TFAs on risk of CVD, Motard-Bélanger
and colleagues conducted a double-blind, randomized, crossover, controlled study in 38 healthy men. For 4 wk each, subjects were provided 3 meals/d of each
of 4 experimental diets: high ruminant TFA, moderate ruminant TFA, high industrial TFA, and low total TFA (control). All diets contributed the same number
of calories per day and were adjusted for each person depending on their caloric needs. In the second study, Chardigny, Destaillats, and colleagues
similarly conducted a randomized, double-blind, controlled, crossover study in healthy subjects; both men and women were enrolled (n = 19 and 21,
respectively). These subjects each experienced two 3-wk dietary regimens: high ruminant TFA and high industrial TFA. In both studies, the high ruminant TFA
interventions utilized "designer" dairy products containing elevated amounts of TFAs, whereas the industrial TFA interventions used partially hydrogenated
fats and oils. At the beginning of each study and at the completion of each dietary intervention period, plasma HDL cholesterol, LDL cholesterol, and total
cholesterol concentrations were assessed.
Results Results from Motard-Bélanger and colleagues indicate that, when compared with the control or moderate-ruminant-TFA
diets, consumption of the high-ruminant-TFA treatment increased LDL and decreased HDL cholesterol concentrations. Consumption of the industrial TFA diet
elevated LDL cholesterol compared with the moderate-ruminant-TFA treatment. Compared with the control diet, consumption of the moderate-ruminant-TFA diet
did not alter any of the measured CVD risk factors. Interestingly, data from Chardigny, Destaillats, and colleagues showed a somewhat complex interaction
between sex and TFA source on CVD risk, such that women (but not men) consistently responded differentially to the 2 types of TFA. Specifically, when women
consumed the diet high in natural TFAs, they had increased HDL and LDL cholesterol concentrations compared with when they consumed the diet enriched with
industrial TFAs.
Conclusions The results of these studies provide no evidence that consumption of naturally occurring TFAs at intakes well above the
upper limit of current human consumption affects CVD risk. This is in opposition to a body of data from previous studies showing that consumption of
industrial TFAs can have negative effects. Furthermore, the finding that men and women may respond differentially to these various types of TFAs is
intriguing and warrants additional study. In their accompanying editorial, Willett and Mozaffarian point out that the critical public health question
remains how to identify ways to reduce the intake of industrial TFAs in a healthful and safe manner. As such, they urge continued efforts to eliminate
consumption of partially hydrogenated vegetable oils worldwide.
Reference Motard-
Bélanger A, Charest A, Grenier G, et al. Study of the effect of trans fatty acids from ruminants on blood lipids and other risk factors for
cardiovascular disease. American Journal of Clinical Nutrition 2008;87:593–9.
Chardigny J-M, Destaillats F, Malpuech-Brugère C, et al. Do trans fatty acids from industrially produced sources and from natural sources
have the same effect on cardiovascular disease risk factors in healthy subjects? Results of the trans Fatty Acids Collaboration (TRANSFACT) study.
American Journal of Clinical Nutrition 2008;87:558–66.
Willett W, Mozaffarian D. Ruminant or industrial sources of trans fatty acids: public health issue or food label skirmish? American Journal of
Clinical Nutrition 2008;87:515–6.
For More Information For the complete articles, please go to the following URLs:
http://www.ajcn.org/cgi/reprint/87/3/593
http://www.ajcn.org/cgi/reprint/87/3/558
To contact the corresponding authors, please send e-mails to benoit.lamarche{at}inaf.ulaval.ca and
frederic.destaillats{at}rdls.nestle.com, respectively.
For the complete editorial, please go to the following URL: http://www.ajcn.org/cgi/reprint/87/3/515
To contact the corresponding author, Walter Willett, please send an e-mail to
walter.willett{at}channing.harvard.edu.
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