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Am J Clin Nutr Supplement to December 2004

EDITORIAL: Whole grains and coronary heart disease: the whole kernel of truth James W Anderson Am. J. Clinical Nutrition,  Dec 2004;  801459 - 1460.

“the consumption of whole grain is linked to protection against ischemic stroke (7), diabetes (8), insulin resistance (9), obesity (10), and premature death (7)… As are soybeans, whole grains are sources of phytoestrogens, which may affect serum lipoprotein concentrations, vascular reactivity, bone metabolism, and many other cellular metabolic processes (11, 19). Whole grains are rich sources of lignans”


Butter and walnuts, but not olive oil, elicit postprandial activation of nuclear transcription factor B in peripheral blood mononuclear cells from healthy men Cecilia Bellido, et al Am. J. Clinical Nutrition,  Dec 2004;  801487 - 1491.

Conclusions:Consumption of an olive oil–enriched meal does not activate NF-B in monocytes as do butter and walnut-enriched meals. This effect could enhance the cardioprotective effect of olive oil–enriched diets.”  A Mediterranean diet with olive oil as the principal source of fat reduces the risk of heart disease.  Olive oil and red wine polyphenols inhibit endothelial adhesion molecule expression.  Oxidant stress and oxidized LDL activate NF-kB which is very harmful.

Whole grain content of different foods Page 1494 Table 1

  Amount,g whole grain,g
Bran Muffin
Popcorn 1 cup
Brown rice 1 cup
Oatmeal 1 cup
Corn flakes
Shredded wheat


Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts Paul Knekt et al  Am. J. Clinical Nutrition,  Dec 2004;  801508 - 1520.

Design:A cohort study pooling 9 prospective studies that included information on intakes of vitamin E, carotenoids, and vitamin C and that met specific criteria was carried out. During a 10-y follow-up, 4647 major incident CHD events occurred in 293 172 subjects who were free of CHD at baseline.

Results:… Compared with subjects who did not take supplemental vitamin C, those who took >700 mg supplemental vitamin C/d had a relative risk of CHD incidence of 0.75…Supplemental vitamin E intake was not significantly related to reduced CHD risk.

Conclusions:The results suggest a reduced incidence of major CHD events at high supplemental vitamin C intakes. ..

trans Fatty acids and systemic inflammation in heart failure Dariush Mozaffarian et al Am. J. Clinical Nutrition,  Dec 2004;  801521 - 1525.

Background:trans Fatty acid (TFA) intake increases systemic inflammation in healthy persons. However, the effect in patients with established heart disease is unknown.

Conclusion: TFAs are strongly associated with systemic inflammation in patients with heart disease, which suggests that attention to TFA intake may be important for secondary prevention efforts.

Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement Susanne M Henning et al Am. J. Clinical Nutrition,  Dec 2004;  801558 - 1564.

Conclusions: Our observations suggest that green tea extract supplements retain the beneficial effects of green and black tea and may be used in future chemoprevention studies to provide a large dose of tea polyphenols without the side effects of caffeine associated with green and black tea beverages.

Association between depressive symptoms and serum concentrations of homocysteine in men: a population study Tommi Tolmunen et al Am. J. Clinical Nutrition,  Dec 2004;  801574 - 1578.

Results: Those in the upper tertile for serum homocysteine had a more than twofold higher risk of being depressed than did those in the lowest tertile... Conclusion: High serum concentrations of tHcy may be associated with depression in middle-aged men.

Cognitive aging, childhood intelligence, and the use of food supplements: possible involvement of n–3 fatty acids Lawrence J Whalley et al Am. J. Clinical Nutrition,  Dec 2004;  801650 - 1657.

Results: …At the age of 64 y, cognitive function was higher in food supplement users than in nonusers before adjustment for childhood IQ. After adjustment for childhood IQ, digit symbol (mental speed) test scores were higher in food supplement users. Fish-oil supplement users consumed more vitamin C and vegetable and cereal fiber than did non-supplement-users. In a nested case-control study, erythrocyte membrane n–3 content was higher in fish-oil supplement users than in nonusers, but cognitive function did not differ significantly between groups. Total erythrocyte n–3 fatty acids and the ratio of docosahexaenoic acid to arachidonic acid was associated with better cognitive function in late life before and after adjustment for childhood IQ.

Conclusions: Food supplement use and erythrocyte n–3 content are associated with better cognitive aging. If associations with n–3 content are causal, optimization of n–3 and n–6 fatty acid intakes could improve retention of cognitive function in old age.

Science Nov, 04
What's on the Label?
Science 306:1101 (12 Nov 04)
" When you are buying, are you one of the 30% of shoppers...who always reads the labels, or one of the 20% who rarely...give them a glance? [One difference is that Europe labels genetically modified foods.] The US Food and Drug Administration has a three-tiered system for [specific] health claims [for foods]...Over the next decade, increases in our understanding of the relationship between an individual's genetic makeup and his or her nutritional needs will open up a whole new area for debate about what goes on the label. The world of choice is not going to get any easier." -John Krebs

J Nutrition Dec. 2004

Adherence to the Traditional Mediterranean Diet Is Inversely Associated with Body Mass Index and Obesity in a Spanish Population1

Helmut Schr?der2, Jaume Marrugat, Juan Vila, Maria I. Covas and Roberto Elosua

The Mediterranean diet is a healthy eating pattern with protective effects on chronic diseases. The purpose of this study was to assess the relation between BMI and obesity and the level of adherence to the traditional Mediterranean diet. The subjects were Spanish men (n = 1547) and women (n = 1615) aged 25–74 y...These data suggest that the traditional Mediterranean dietary pattern is inversely associated with BMI and obesity.

Xanthophylls and -Tocopherol Decrease UVB-Induced Lipid Peroxidation and Stress Signaling in Human Lens Epithelial Cells  Chureeporn Chitchumroonchokchai*, Joshua A. Bomser*,, Jayme E. Glamm and Mark L. Failla*

Explains why vitamin E, lutein, and zeaxanthin prevent cataracts. 


Molecular Mechanisms of the Chemopreventive Effects of Resveratrol and Its Analogs in Colorectal Cancer: Key Role of Polyamines?

Freya Wolter, Sandra Ulrich and JY?Nrgen Stein

Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to exhibit a wide range of biological and pharmacological properties. It has been speculated that dietary resveratrol may act as an antioxidant, promote nitric oxide production, inhibit platelet aggregation, and increase high-density lipoprotein cholesterol and thereby serve as a cardioprotective agent (the so-called "French paradox"). Recently, it was demonstrated that resveratrol can function as a cancer chemopreventive agent, [Mechanism involves polyamines, blocking cancer too.]


J. Nutrition Supplement Internatioanl Conference on Food, Nutrition, and Cancer Dec. 2004

Review of the International Research Conference on Food, Nutrition, and Cancer, 20041

Helen A. Norman2, Vay Liang W. Go* and Ritva R. Butrum

"More than 400 attendees from 24 different countries... Human health studies have linked higher calorie intakes to increased risk of developing prostate, breast, gastrointestinal tract, and brain cancer...[FISH OIL STORY STILL UNCLEAR?] The (n-3) fatty acids eicosapentaenoic acid and docosahexaenoic acid have been shown to inhibit the proliferation of breast and prostate cell lines in vitro and to reduce the risk and progression of these tumors in animal models. However, as discussed by the first speaker in this session, the data from epidemiological studies does not consistently support these findings. Most studies have not shown an association between fish consumption or marine fatty acid intake and risk of hormone-related cancers...  The fourth presentation discussed the potential efficacy of (n-3) fatty acids used in combination with standard therapies to improve cancer treatment outcomes and to suppress cachexia and improve quality of life in cancer patients.. [LYCOPENE, CRUCIFEROUS VEGETABLES] The second presentation further emphasized this recommendation in a comparison of the reduction of prostate tumor incidence in rats fed either isolated lycopene or tomato powder. The latter was more effective than lycopene alone. Furthermore, in a rat Dunning tumor model, broccoli powder plus tomato powder had the greatest effect in reducing tumor growth, supporting the AICR recommendation of a diet rich in different kinds of vegetables for cancer prevention. The third speaker presented his research on indole-3-carbinol and prostate cancer. This compound, found in cruciferous vegetables, inactivates nuclear factor-B and Akt signaling pathways, and induces prostate cancer cell apoptosis...



In their landmark publication in 1997, AICR and WCRF issued 14 recommendations regarding diet and lifestyle factors designed to reduce cancer incidence and mortality on a global basis...

 Study participants were assessed for subsequent cancer incidence and mortality after following up to 9 of these recommendations. The overall data support that adherence to the AICR/WCRF recommendations, independently and in conjunction with not smoking, is likely to have a substantial public health impact on reducing cancer incidence and, to a lesser degree, cancer mortality at the population level.


J. Nutrition Nov. 2004


Soy and Mammographic Breast Density: Plausible Hypothesis but Limited Evidence in Humans     -      Marian L. Neuhouser

"The hypothesis that consumption of soy-containing foods may lower breast cancer risk comes from the observation that breast cancer incidence rates are substantially lower in Asian countries where soy consumption is high, compared with Western countries where soy consumption is low (1,2)... It is in these contexts that soy foods and isoflavones are of particular interest in relation to the prevention of hormone-dependent cancers, such as breast cancer. .. In general, breast density was greater among women with at least some soy consumption at all phases of life compared with women with no or minimal soy intake, but the results were significant only among Caucasian women."



Dietary Linolenic Acid Reduces Inflammatory and Lipid Cardiovascular Risk Factors in Hypercholesterolemic Men and Women   Guixiang Zhao*, Terry D. Etherton*,, Keith R. Martin*, Sheila G. West**, Peter J. Gillies and Penny M. Kris-Etherton*,2

Linolenic acid (ALA) reduces cardiovascular disease (CVD) risk, possibly by favorably changing vascular inflammation and endothelial dysfunction. Inflammatory markers and lipids and lipoproteins were assessed in hypercholesterolemic subjects (n = 23) fed 2 diets low in saturated fat and cholesterol, and high in PUFA varying in ALA (ALA Diet) and linoleic acid (LA Diet) compared with an average American diet (AAD).,, The 2 high-PUFA diets decreased serum total cholesterol, LDL cholesterol and triglycerides similarly (P < 0.05); the ALA Diet decreased HDL cholesterol and apolipoprotein AI compared with the AAD (P < 0.05). ALA appears to decrease CVD risk by inhibiting vascular inflammation and endothelial activation beyond its lipid-lowering effects.



Calcium and Dairy Products Inhibit Weight and Fat Regain during Ad Libitum Consumption Following Energy Restriction in Ap2-Agouti Transgenic Mice1,2

Xiaocun Sun and Michael B. Zemel3


We demonstrated previously that dietary calcium suppression of calcitriol reduces adipocyte Ca2+, suppresses lipogenesis, and increases lipid utilization during energy restriction. Notably, dairy calcium sources exert markedly greater effects...Thus, high-Ca diets elicit a shift in energy partitioning and reduction of weight gain during refeeding, with dairy Ca sources exerting markedly greater effects.


VERY USEFUL UPDATE: Supplement: Free Radicals: The Pros and Cons of Antioxidants:

Full Text

Executive Summary Report

Seifried et al. J. Nutr..2004; 134: 3143-3163.

BENEFITS OF ACETYL CARNITINE: Experimental studies indicate that there is a decrease in the level of cardiolipin, a key lipid in the mitochondrial membrane, responsible for the membraneOs electrical potential, causing reduced utilization of oxygen and increased production of oxygen radicals. Studies in rats show that young rats have 24,000 oxidative lesions in DNA per cell, increasing to 67,000 oxidative lesions per cell in older rats.


Animal studies from Italy report that old rats fed acetyl carnitine (ALC), the transporter that carries the fatty acid "fuel" into the mitochondria, have less mitochondrial damage and less DNA damage than old rats not fed ALC.



"The high doses selected in the trials using ?˜-carotene supplements probably play a role in lung cancer development because they produce high serum concentrations of the vitamin that are not physiologic. These higher levels may be in the range to act oxidatively. "



" If available, iron can greatly amplify the damage caused by free radical generation. There is an ongoing discussion within the scientific community concerning whether there is a healthy level of iron stores in the body. ..One potential negative effect of increased iron stores is their ability to react with superoxide to form iron-loaded ferritin, which is reduced from ferric to ferrous valence and then released to participate in redox reactions. Ferritin only binds ferric iron, but it binds it so strongly that the iron is redox inactive. When the iron is released, it becomes redox reactive and can react with hydrogen peroxide to generate another secondary radical, the hydroxyl radical, which is the second most potent oxidizing species. .. In addition, 14% of Americans carry a mutant HFE gene, which causes hemochromatosis. Humans accumulate iron as they age, which may contribute to and amplify disease processes. "



"One of the most troubling aspects of antioxidant research is that clinicians do not have the information they need to make recommendations to patients regarding antioxidant supplementation. There are very strong market forces that tell the public about supplements, but there is very little reliable advice about them. In addition, the amount of contradictory advice is confusing to consumers. Also, physician training is inadequate on this issue; only one-quarter of the nationOs medical schools have required courses in nutrition, so most physicians have no training in this area. "

pg. 3162S "Dr. Clinton commented that there is a lot of information already known, although clinicians do not have the guidance necessary to make the decisions they must make. "



"There may be as many as 25,000 phytochemicals in the human diet, with many having physiological antioxidative effects, but these effects are not directly related to their many other effects on cellular signaling pathways, gap junctions, and metabolic enzyme induction,"



"Lycopene is a phytochemical antioxidant with no pro–vitamin A activity that is found in tomatoes, which have only been widespread in the human diet for 500 y. Having the highest antioxidative activity among all carotenoids, lycopene exists in tomatoes and derived products as one of numerous phytochemicals, many with similar structures and properties. Epidemiological data suggest that lycopene may reduce the risk of prostate cancer."



"Research shows that epigallocatechin-3-gallate (EGCG), an antioxidative polyphenol in tea, can inhibit the activity of the ?˜-catenin/Tcf signaling pathway in vitro. More than 80% of human colon cancers have a mutation in the APC gene, and those that do not have mutations in ?˜-catenin. "



Antioxidants Suppress Apoptosis

"many of the drugs and treatments used to kill cancer cells (chemotherapy and radiation) work by generating ROS to activate apoptotic pathways and kill cells. ..Studies have investigated the effects of antioxidant supplementation on cancer therapy. Studies on cisplatin indicate that it kills breast cancer cells by apoptosis and necrosis, and that the addition of vitamin E blocks much of the apoptotic process. High-dose vitamin E reduces the efficacy of cisplatin, although the normal cells involved would be protected by vitamin E...Oversupplementation may actually produce an environment that is beneficial to the tumor and allow it to survive. "



"Green tea and green tea polyphenols inhibit tumorigenesis at different organ sites, including the skin, lung, oral cavity, esophagus, stomach, liver, pancreas, and prostate. Studies on skin and lung demonstrate that tea is an effective inhibitor when given to animals at the initiation, promotion and progression stages of carcinogenesis. "


Rationale for Using High-Dose Multiple Antioxidants as an Adjunct to Radiation Therapy and Chemotherapy [I RECOMMEND YOU READ THIS ARTICLE PG. 3151S WITH YOUR DOCTOR IF YOU HAVE CANCER]

Kedar Prasad, University of Colorado Health Sciences Center

"Given these facts, it seems that antioxidants might enhance the effects of radiation and chemotherapy on tumor cells but not on normal cells, but supporting data are scant. .. It is not recommended that low doses of antioxidants be given in any therapeutic situation. [THIS MEANS NO MULTIVITAMIN?]


Pg. 3152S  How to design antioxidant studies properly



" in 2002, 79% of consumers were aware of the association between calcium and osteoporosis; 54% for antioxidants and cancer; and 35% for soy protein and heart disease...many consumers do not seem convinced that antioxidants are as great a health benefit as reported in the media. ..Factors for health message effectiveness include the seriousness of the disease expressed in the claim (e.g., cancer is more serious than osteoporosis), the knowledge of the component (e.g., fruits and vegetables have many benefits), the association with supplements (e.g., consumers do not know what foods contain vitamin E), and the availability of the component (e.g., calcium is perceived to be in many foods; therefore, supplements are not as necessary).

Antioxidant Supplement Use in Cancer Survivors and the General Population  Cheryl Rock, University of California—San Diego  Approximately one-half of the general population takes dietary supplements, and use is higher among individuals with health concerns, especially those diagnosed with cancer. Researchers have suggested that there may be both beneficial and adverse effects of supplement use among individuals diagnosed with cancer.

pg 3158S Kenneth A. Conklin, M.D., Ph.D., Clinical Professor, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California—Los Angeles, discussed the controversy surrounding the use of antioxidants during chemotherapy (18). Approximately 300 to 400 preclinical studies have been published on this topic[chemotherapy and antioxidants], and most show that antioxidants do not interfere with the mechanism of action of therapeutic agents.


Balz Frei: "Identified biomarkers of oxidative stress in vivo include F2-isoprostanes, 8-oxo-2'-deoxyguanosine, and protein carbonyls. For example, F2-isoprostanes are validated biomarkers of lipid oxidative damage. F2-isoprostanes are oxidation products of arachidonic acid and are elevated in humans with many conditions, including AlzheimerOs disease, hepatic cirrhosis, and atherosclerosis, and with coronary risk factors such as cigarette smoking, diabetes, obesity, hypercholesterolemia, and hyperhomocysteinemia. A gap in knowledge exists because of the lack of prospective studies and clinical trials to clearly establish a link between oxidative stress (assessed by validated oxidative biomarkers) and increased disease risk. ..The European Prospective Investigation of Cancer (EPIC) Trial, a multinational survey on diet, lifestyle, and physical activity involving >500,000 volunteers, found a strong inverse association between plasma vitamin C levels and total, cardiovascular, and cancer mortality. However, whether this is a beneficial effect of vitamin C itself or fruit and vegetable consumption in general (for which plasma vitamin C serves as a marker) remains unclear."



Pg 3158S "Ascorbic acid is oxidized to dehydroascorbate (DHA) outside cells and then transported intracellularly by the facilitative glucose transporters. Inside the cell, DHA is quickly reduced back to ascorbate, where it serves as an antioxidant to protect the cell from oxidation. Another mechanism for the cell to accumulate vitamin C is through the sodium-ascorbate cotransporter system, which allows vitamin C to be directly transported into the cell. Studies in mice show that vitamin C crosses the blood-brain barrier in the form of DHA through the glucose transporters. The therapeutic importance of this finding is that DHA injections provide significant neuroprotection in a stroke model in mice. ..[PROTECTS THE BRAIN] P 3159S  In the brain, vitamin E plays an important role in protecting neurons and acetylcholine receptors from free radical damage and prevents apoptosis in neural cells. In glioblastoma, vitamin E may help increase apoptosis and activates capsase-3 enzyme activity.



TABLE 1 Micronutrient deficiencies in U.S. individuals1

Nutrient  Population group  Current RDA % Consuming < RDA % Consuming <0.5 RDA
Iron Women 20–30 y 18 mg 75 25
  Women 50+ y  8 mg 25 5
Zinc Women 50+y 8 mg 50 10
  Men 50+ y 11 mg 50 10
Folate 2 Women 20+ y 400 ƒÊg    75 50
  Men 20+ y 400 ƒÊg    75 25
B-6 Women 20+ y 1.5 mg 50 10
  Men 20+ y

1.7 mg

50 10
B-12 Women 20+ y 2.4 ƒÊg 25 10
  Men 20+ y 2.4 ƒÊg 100 5
C Women 20+ y 75 mg 50 25
  Men 20+ y 90 mg 500 25

1 Data adapted from Wakimoto & Block (6); dietary intakes include food fortification but not supplement use.

2 Folate intake before U.S. fortification in 1998.

AJCN November 2004


Conclusions: Our data indicate that high intakes of lactose and dairy products, particularly milk, are associated with an increased risk of serous ovarian cancer but not of other subtypes of ovarian cancer. Future studies should consider ovarian cancer subtypes separately. ROC'S NOTE: This is the sort of study often reported by the media. It is "statistically significant", but the worry it causes may be more harmful.

servings of dairy cases of epithelial tumors
<2 61
2-3 71
>4 69

So women who consumed more dairy had more epithelial cancers. However, people who consume more milk are also much thinner. And obesity is one of the greatest causes of disease.


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