Cataract is a self-defence reaction to protect the retina from oxidative damage.

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Cataract extraction is the most common surgical procedure in developed countries. Lutein (L) and zeaxanthin (Z), retinal carotenoids, are the most powerful retinal anti-oxidants and absorb the harmful blue light. The depletion of L+Z induces the development of the lens opacification-cataract. Cataract reduces the retinal oxidative stress (OS), which causes a reduction of the probability to develop AMD. Oxidative Stress at the retinal level is the common pathway in the development of AMD and cataract. AMD and cataract are not two independent processes. Cataract is a self-defense reaction of the retina to reduce OS and retinal damage. Restoring the anti-oxidative capabilities of the retina by increasing intake of L+Z reduces the likelihood of AMD and cataract. Extracting the opaque lens elevates the retinal OS and increases the rate of AMD. Copyright © 2011 Elsevier Ltd. All rights reserved.

Diet, vegetarianism, and cataract risk.

BACKGROUND: Age-related cataract is a major cause of morbidity. Previous studies of diet and cataract risk have focused on specific nutrients or healthy eating indexes but not on identifiable dietary groups such as vegetarians. OBJECTIVE: We investigated the association between diet and cataract risk in a population that has a wide range of diets and includes a high proportion of vegetarians. DESIGN: We used Cox proportional hazards regression to study cataract risk in relation to baseline dietary and lifestyle characteristics of 27,670 self-reported nondiabetic participants aged ≥40 y at recruitment in the Oxford (United Kingdom) arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford) by using data from the Hospital Episode Statistics in England and Scottish Morbidity Records. RESULTS: There was a strong relation between cataract risk and diet group, with a progressive decrease in risk of cataract in high meat eaters to low meat eaters, fish eaters (participants who ate fish but not meat), vegetarians, and vegans. After multivariable adjustment, incidence rate ratios (95% CIs) for moderate meat eaters (50-99 g meat/d), low meat eaters (<50 g meat/d), fish eaters, vegetarians, and vegans compared with high-meat eaters (≥100 g meat/d) were 0.96 (0.84, 1.11), 0.85 (0.72, 0.99), 0.79 (0.65, 0.97), 0.70 (0.58, 0.84), and 0.60 (0.38, 0.96), respectively (P < 0.001 for heterogeneity). Associations between cataract risk and intakes of selected nutrients and foods generally reflected the strong association with diet group. CONCLUSION: Vegetarians were at lower risk of cataract than were meat eaters in this cohort of health-conscious British residents.

The influence of dietary lutein and zeaxanthin on visual performance.

The idea that normal constituents of the diet can influence visual function is not new. As early as 1782, Buzzi identified the yellow of the macula and Schulze (1866) specifically postulated that the yellow pigments led to improvements in human vision. These pigments were later found to be derived from dietary lutein and zeaxanthin that are known to be oxygenated carotenoids (xanthophylls). Walls and Judd (1933) postulated that these yellow intraocular pigments could improve visual performance by absorbing light scattered both within (for example, glare) and outside of the eye (increasing visual range by absorbing blue light scattered in the atmosphere), and by improving spatial vision through enhancing contrast and reducing chromatic blur. In this article, evidence for these ideas is reviewed with particular emphasis towards more recent data on glare effects.

Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial.

Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.

Management of diabetic retinopathy: a systematic review.

CONTEXT: Diabetic retinopathy (DR) is the leading cause of blindness in the working-aged population in the United States. There are many new interventions for DR, but evidence to support their use is uncertain. OBJECTIVE: To review the best evidence for primary and secondary intervention in the management of DR, including diabetic macular edema. EVIDENCE ACQUISITION: Systematic review of all English-language articles, retrieved using a keyword search of MEDLINE (1966 through May 2007), EMBASE, Cochrane Collaboration, the Association for Research in Vision and Ophthalmology database, and the National Institutes of Health Clinical Trials Database, and followed by manual searches of reference lists of selected major review articles. All English-language randomized controlled trials (RCTs) with more than 12 months of follow-up and meta-analyses were included. Delphi consensus criteria were used to identify well-conducted studies. EVIDENCE SYNTHESIS: Forty-four studies (including 3 meta-analyses) met the inclusion criteria. Tight glycemic and blood pressure control reduces the incidence and progression of DR. Pan-retinal laser photocoagulation reduces the risk of moderate and severe visual loss by 50% in patients with severe nonproliferative and proliferative retinopathy. Focal laser photocoagulation reduces the risk of moderate visual loss by 50% to 70% in eyes with macular edema. Early vitrectomy improves visual recovery in patients with proliferative retinopathy and severe vitreous hemorrhage. Intravitreal injections of steroids may be considered in eyes with persistent loss of vision when conventional treatment has failed. There is insufficient evidence for the efficacy or safety of lipid-lowering therapy, medical interventions, or antivascular endothelial growth factors on the incidence or progression of DR. CONCLUSIONS: Tight glycemic and blood pressure control remains the cornerstone in the primary prevention of DR. Pan-retinal and focal retinal laser photocoagulation reduces the risk of visual loss in patients with severe DR and macular edema, respectively. There is currently insufficient evidence to recommend routine use of other treatments.

Sulforaphane can protect lens cells against oxidative stress: implications for cataract prevention.

PURPOSE: Protecting the lens against oxidative stress is of great importance in delaying the onset of cataract. Isothiocyanates, such as sulforaphane (SFN), are proposed to provide cytoprotection against oxidative stress. We therefore tested the ability of SFN to perform this role in lens cells and establish its ability to delay the onset of cataract. METHODS: The human lens epithelial cell line FHL124 and whole porcine lens culture systems were used. The ApoTox-Glo Triplex Assay was used to assess FHL124 cell survival, cytotoxicity, and apoptosis. The MTS assay was used to assess cell populations. To determine levels of DNA strand breaks, the alkaline comet assay was performed and quantified. Lactate dehydrogenase levels in the medium were evaluated to reflect cell damage/death. To assess level of gene expression, an Illumina whole-genome HT-12 v4 beadchip was used. Protein expression was determined by Western blot and immunocytochemistry. RESULTS: Exposures of 30 μM H2O2 to FHL124 cells caused a reduction in cell viability and increased cytotoxicity/apoptosis; these effects were significantly inhibited by 24-hour pretreatment with 1 μM SFN. In addition, 1 μM SFN significantly reduced H2O2-induced DNA strand breaks. When applied to cultured porcine lenses, SFN protected against H2O2-induced opacification. Illumina whole-genome HT-12 v4 beadchip microarray data revealed eight genes upregulated following 24-hour exposure to 1- and 2-μM SFN, which included NQO1 and TXNRD1. This pattern was confirmed at the protein level. Nrf2 translocated to the nucleus in response to 0.5- to 2.0-μM SFN exposure CONCLUSIONS: The dietary component SFN demonstrates an ability to protect human lens cells against oxidative stress and thus could potentially delay the onset of cataract.

The Association of Consumption of Fruits/Vegetables with Decreased Risk of Glaucoma among Older African American Women in the Study of Osteoporotic Fractures

Purpose To explore the association between consumption of fruits and vegetables and the presence of glaucoma in older African American women. Design Cross-sectional study. Methods Disc photographs and suprathreshold visual fields were obtained from the 662 African American participants in the Study of Osteoporotic Fractures. Masked, trained readers graded all discs, and two glaucoma specialists reviewed photos and visual fields. The Block Food Frequency Questionnaire assessed food consumption. Relationships between selected fruit/vegetable/nutrient consumption and glaucoma were evaluated using logistic regression models after adjusting for potential confounders. Results After excluding women missing Food Frequency Questionnaire and disc data, 584 African American women (88.2% of total African American cohort) were included. Glaucoma was diagnosed in at least one eye in 77 subjects (13%). Women who ate 3 or more servings/day of fruits/fruit juices were 79% (odds ratio [OR]=0.21; 95% confidence interval [CI]: 0.08–0.60) less likely to have glaucoma than women who ate less than one serving/day. Women who consumed more than 2 servings/week of fresh oranges (OR=0.18; 95%CI: 0.06–0.51) and peaches (OR=0.30; 95%CI: 0.13–0.67) had a decreased odds of glaucoma compared to those consuming less than one serving/week. For vegetables, >1 serving/week compared to ≤1 serving/month of collard-greens/kale decreased the odds of glaucoma by 57% (OR=0.43; 95%CI: 0.21–0.85). There was a protective trend against glaucoma in those consuming more fruit/fruit juices (p=0.023), fresh oranges (p=0.002), fresh peaches (p=0.002), and collard greens/kale (p=0.014). Higher consumption of carrots (p=0.061) and spinach (p=0.094) also showed some associations. Individual nutrient intake from food sources found protective trends with higher intakes of vitamin A (p=0.011), vitamin C (p=0.018), and α-carotene (p=0.021), and close to statistically significant trends with β-carotene (p=0.052), folate (p=0.056), and lutein/zeaxanthin (p=0.077). Conclusion Higher intake of certain fruits and vegetables high in Vitamins A and C and carotenoids may be associated with a decreased likelihood of glaucoma in older African American women. Randomized controlled trials are needed to determine whether the intake of specific nutrients changes the risk of glaucoma.

Zinc and multi-mineral supplementation should mitigate the pathogenic impact of cadmium exposure.

High-level cadmium (Cd) exposure has long been known to induce nephropathy, severe osteoporosis, and fractures in humans. More recent epidemiology, however, reveals that, in populations not known to have important industrial exposure to this heavy metal, high-normal blood or urine Cd levels correlate with increased risk for vascular disorders, cancers, diabetes, and total mortality, as well as osteoporosis and nephropathy. Since these disorders appear unlikely to expedite Cd absorption, and since Cd has promoted these pathologies in rodent studies, it seems reasonable to conclude that Cd is an important mediating risk factor for these disorders in humans. Avoiding tobacco smoke or frequent ingestion of shellfish or organ meats can lessen humans exposure to Cd, but the chief dietary sources of Cd are plant-derived foods - green leafy vegetables, whole grains, tubers, and root vegetables - typically recommended for their health-supportive properties; indeed, among non-smokers, vegans tend to have the highest Cd body burden. Fortunately, iron sufficiency and ample dietary intakes of calcium, magnesium, and zinc can impede absorption of dietary Cd, both by down-regulating intestinal expression of mineral transporters, and by directly competing with Cd for access to these transporters. Correction of iron deficiency appears to be of particular importance for controlling Cd absorption. Moreover, zinc supplementation can counteract the toxicity of Cd already in the body via induction of metallothionein, which binds Cd avidly via its sulfhydryl groups; so long as it remains sequestered in this form, Cd is innocuous. Zinc supplementation may in any case be recommendable, as optimal zinc status exerts protective anti-inflammatory, antioxidant, and immunosupportive effects. Inasmuch as the toxicity of Cd appears to be mediated in large part by oxidative stress, ingestion of spirulina, lipoic acid, melatonin, and N-acetylcysteine may also have potential for mitigating the risk associated with Cd exposure, as suggested by rodent studies. Hence, although Cd may prove to be a major risk factor for morbidity and mortality in humans, practical strategies for limiting its absorption and pathogenic impact are at hand. Copyright © 2012 Elsevier Ltd. All rights reserved.

Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity.

Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.

Goji berry effects on macular characteristics and plasma antioxidant levels.

PURPOSE: Goji berry (Lycium barbarum L.) is purported to benefit vision because of its high antioxidant (especially zeaxanthin) content, although this effect has not been demonstrated in high-quality human studies. The purpose of this study was to evaluate the effects of daily supplementation with a proprietary milk-based formulation of goji berry, Lacto-Wolfberry (LWB), on macular characteristics and plasma zeaxanthin and antioxidant capacity levels in elderly subjects. METHODS: This was a double-masked, randomized, placebo-controlled trial in healthy elderly subjects (range, 65 to 70 years) receiving 13.7 g/d of LWB (n = 75) or placebo (n = 75) for 90 days. Subjects underwent direct ophthalmic examination to assess pigmentation and soft drusen count in the macula and a blood draw to measure plasma zeaxanthin level and total antioxidant capacity. RESULTS: The placebo group demonstrated hypopigmentation and soft drusen accumulation in the macula, whereas the LWB group remained stable. Both plasma zeaxanthin level and antioxidant capacity increased significantly in the LWB group, by 26% and 57%, respectively, but did not change in the placebo group. No product-related adverse events were reported in either group. CONCLUSIONS: Overall, daily dietary supplementation with goji berry for 90 days increases plasma zeaxanthin and antioxidant levels as well as protects from hypopigmentation and soft drusen accumulation in the macula of elderly subjects. However, the mechanism of action is unclear, given the lack of relationship between change in plasma zeaxanthin and change in macular characteristics.

Microvascular complications. Retinopathy and nephropathy.

Diabetic retinopathy and diabetic nephropathy extract an enormous toll on patients with diabetes and an enormous burden on the health care system. With aggressive control of glycemia and blood pressure, coupled with aggressive use of laser photocoagulation and treatment of microalbuminuria, these problems can largely be eliminated. In the future, specific interventions may emerge that will allow interdiction of the pathophysiologic processes that lead to initiation and progression of these microvascular complications. The challenge for the primary care physician and diabetologist is to attain excellent glycemic control and aggressive control of blood pressure, while assuring that every patient has appropriate dilated fundus examinations at least annually, preferably by an ophthalmologist or retinal specialist, and regular screening for microalbuminuria. With such medical management, appropriate intervention can occur to reduce the risk of blindness and renal failure and to lessen the burden from diabetic retinopathy and nephropathy.

Diabetic retinopathy.

Diabetic retinopathy is a common and specific microvascular complication of diabetes, and remains the leading cause of preventable blindness in working-aged people. It is identified in a third of people with diabetes and associated with increased risk of life-threatening systemic vascular complications, including stroke, coronary heart disease, and heart failure. Optimum control of blood glucose, blood pressure, and possibly blood lipids remains the foundation for reduction of risk of retinopathy development and progression. Timely laser therapy is effective for preservation of sight in proliferative retinopathy and macular oedema, but its ability to reverse visual loss is poor. Vitrectomy surgery might occasionally be needed for advanced retinopathy. New therapies, such as intraocular injection of steroids and antivascular endothelial growth-factor agents, are less destructive to the retina than are older therapies, and could be useful in patients who respond poorly to conventional therapy. The outlook for future treatment modalities, such as inhibition of other angiogenic factors, regenerative therapy, and topical therapy, is promising. Copyright 2010 Elsevier Ltd. All rights reserved.

Vegetarian and vegan diets in type 2 diabetes management.

Vegetarian and vegan diets offer significant benefits for diabetes management. In observational studies, individuals following vegetarian diets are about half as likely to develop diabetes, compared with non-vegetarians. In clinical trials in individuals with type 2 diabetes, low-fat vegan diets improve glycemic control to a greater extent than conventional diabetes diets. Although this effect is primarily attributable to greater weight loss, evidence also suggests that reduced intake of saturated fats and high-glycemic-index foods, increased intake of dietary fiber and vegetable protein, reduced intramyocellular lipid concentrations, and decreased iron stores mediate the influence of plant-based diets on glycemia. Vegetarian and vegan diets also improve plasma lipid concentrations and have been shown to reverse atherosclerosis progression. In clinical studies, the reported acceptability of vegetarian and vegan diets is comparable to other therapeutic regimens. The presently available literature indicates that vegetarian and vegan diets present potential advantages for the management of type 2 diabetes.

Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition.

The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.

Influence of diet on tear function.

The effect of diet on tear function is illustrated clearly by malnutrition-induced xerophthalmia. Dietary habits in well nourished North American society have been implicated as a cause of some tear dysfunction. A review of the ocular literature suggests that sufficient dietary protein, vitamins A, B6 and C, potassium, and zinc may be necessary for normal tear function. Excesses of dietary fats, salt, cholesterol, alcohol, protein, and sucrose have been associated with or suggested as causes of tear dysfunction. No unequivocal link has been established between diet and remission of dry eye states in a well nourished population.

Adherence to WCRF/AICR cancer prevention recommendations and risk of post-menopausal breast cancer

Background In 2007 the World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) released eight recommendations related to body fatness, physical activity and diet aimed at preventing the most common cancers worldwide. However, limited information exists on the association between meeting these recommendations and risks of specific cancers, including breast cancer. Methods We operationalized six recommendations (related to body fatness, physical activity, foods that promote weight gain, plant foods, red and processed meats, and alcohol) and examined their association with invasive breast cancer incidence over 6.7 years of follow-up in the VITamins And Lifestyle (VITAL) study cohort. Participants included 30,797 post-menopausal women ages 50–76 years at baseline in 2000–2002 with no history of breast cancer. Breast cancers (n=899) were tracked through the Western Washington Surveillance, Epidemiology and End Results (SEER) database. Results Breast cancer risk was reduced by 60% in women who met at least five recommendations compared to those who met none (HR: 0.40; 95% CI: 0.25–0.65; Ptrend<0.001). Further analyses that sequentially removed individual recommendations least associated with reduced risk suggested that this reduction is due to meeting recommendations related to body fatness, plant foods and alcohol (HR for meeting vs. not meeting these three recommendations: 0.38; 95% CI: 0.25–0.58; Ptrend <0.001). Conclusions Meeting the WCRF/AICR cancer prevention recommendations, specifically those related to alcohol, body fatness and plant foods, is associated with reduced post-menopausal breast cancer incidence. Impact Increased adherence to the WCRF/AICR cancer prevention recommendations could substantially reduce post-menopausal breast cancer risk in US women.

Secondary prevention of CHD in UK men: the Diet and Reinfarction Trial and its sequel.

The Diet and Reinfarction Trial (DART) involved 2033 men (mean age 56.5 years) recovering from myocardial infarction. They were randomly allocated to receive advice or to receive no advice on each of three dietary factors: an increase in fatty fish intake; a reduction in fat intake with an increase in polyunsaturated fat:saturated fat; an increased intake of cereal fibre. Compliance was satisfactory with the fish and fibre advice, but less so with the fat advice. The men given fish advice had 29% lower 2-year all-cause mortality; the other forms of advice did not have any significant effects. The Diet and Angina Randomized Trial (DART-2) involved 3114 men (mean age 61.1 years) with stable angina, who were followed up for 3-9 years. Advice to eat oily fish or take fish oil did not affect all-cause mortality, but it was associated with a significant increase in sudden cardiac death (P=0.018), and this effect was largely confined to the subgroup given fish oil capsules. Advice to eat more fruit and vegetables had no effect, probably because of poor compliance. The outcome of DART-2 appears to conflict with that of DART and some other studies; various possible explanations are considered. Nutritional interventions are not equally acceptable and should be tailored to the individuals for whom they are intended. Various distinct groups have a raised risk of CHD, and it cannot be assumed that the same nutritional interventions are appropriate to them all. Nutritional supplements do not necessarily have the same effects as the foods from which they are derived.

Gerson regimen.

The Gerson regimen, developed by Max Gerson in the 1930s, is promoted as an alternative cancer treatment. It involves consuming fresh, raw fruit and vegetable juices, eliminating salt from the diet, taking supplements such as potassium, vitamin B12, thyroid hormone, pancreatic enzymes, and detoxifying liver with coffee enemas to stimulate metabolism. Gerson therapy is based on the theory that cancer is caused by alteration of cell metabolism by toxic environmental substances and processed food, which changes its sodium and potassium content. It emphasizes increasing potassium intake and minimizing sodium consumption in an effort to correct the electrolyte imbalance, repair tissue, and detoxify the liver. The coffee enemas are believed to cause dilation of bile ducts and excretion of toxic breakdown products by the liver and through the colon wall. None of these theories has been substantiated by scientific research. Despite proponents' claims of recovery rates as high as 70% to 90%, case reviews by the National Cancer Institute (NCI) and the New York County Medical Society found no evidence of usefulness for the Gerson diet. An NCI-sponsored study of Gonzalez therapy, which is similar to the Gerson diet, showed that patients with inoperable pancreatic adenocarcinoma who underwent standard chemotherapy with gemcitabine (Gemzar) survived three times longer and had better quality of life than those who chose enzyme treatment, which included pancreatic enzymes, nutritional supplements, detoxification, and an organic diet.

A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer.

A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.

Iris color and macular pigment optical density.

The present study was designed to assess the relationship between iris color and macular pigment optical density. Both melanin and carotenoids (responsible for iris color and macular pigment composition, respectively) appear to protect the retina through similar mechanisms and higher concentrations may reduce the incidence of retinal degenerations. To evaluate this relationship, 95 subjects were examined and the following variables were measured: iris color; macular pigment optical density (MP); plasma concentrations of lutein and zeaxanthin and beta-carotene; dietary intake of lutein and zeaxanthin and beta-carotene; and total fat intake. Iris color was determined by self assessment and classified as blue or gray (group I), green or hazel (group II) or brown or black (group III). MP density was measured psychophysically by measuring foveal and parafoveal sensitivities to lights of 460 and 550 nm, using the method of heterochromatic flicker photometry. Plasma carotenoid concentrations were measured using reverse-phase high-performance liquid chromatography. Dietary intake was determined by a detailed food-frequency questionnaire. Despite similarities in diet and in blood concentrations of carotenoids, significant differences in macular pigment density (P < 0.02) were found for different colored irises (group I, n = 38, MP = 0.25; group II, n = 26, MP = 0.32; group III, n = 31, MP = 0.38). The covariation of iris color and MP indicates that past epidemiologic studies have not adequately determined the independent effects of either factor. The relationship of MP and iris color may be the result of one or two factors: the evolution of a shared tendency to accumulate melanin and carotenoids due to similar environmental pressures (e.g. light and oxygen); and/or MP might be depleted due to the tendency for eyes with light irises to transmit more light than eyes with dark irises, thus causing increased oxidative stress.

Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis.

Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.

Dietary modification of human macular pigment density.

PURPOSE: The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether MP density in the retina could be raised by increasing dietary intake of L and Z from foods. METHODS: Macular pigment was measured psychophysically for 13 subjects. Serum concentrations of L, Z, and beta-carotene were measured by high-performance liquid chromatography. Eleven subjects modified their usual daily diets by adding 60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150 g of corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary modification lasted up to 15 weeks. RESULTS: For the subjects fed spinach or spinach and corn, three types of responses to dietary modification were identified: Eight "retinal responders" had increases in serum L (mean, 33%; SD, 22%) and in MP density (mean, 19%; SD, 11%); two "retinal nonresponders" showed substantial increases in serum L (mean, 31%) but not in MP density (mean, -11%); one "serum and retinal nonresponder" showed no changes in serum L, Z, or beta-carotene and no change in MP density. For the two subjects given only corn, serum L changed little (+11%, -6%), but in one subject serum Z increased (70%) and MP density increased (25%). CONCLUSIONS: Increases in MP density were obtained within 4 weeks of dietary modification for most, but not all, subjects. When MP density increased with dietary modification, it remained elevated for at least several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical investigation appears to be feasible for many persons.

Antioxidant intake and primary open-angle glaucoma: a prospective study.

The relation between dietary antioxidant intake and primary open-angle glaucoma risk was examined in participants aged over 40 years in the Nurses' Health Study (n = 76,200) and the Health Professionals Follow-up Study (n = 40,284). They were followed biennially from 1980 and 1986, respectively, to 1996, during periods when they received an eye examination. Dietary intakes were measured repeatedly from 1980 in the Nurses' Health Study and from 1986 in the Health Professionals Follow-up Study using validated food frequency questionnaires. The authors analyzed 474 self-reported glaucoma cases confirmed by medical chart review to have primary open-angle glaucoma with visual field loss. The authors used Cox proportional hazards models for cohort-specific multivariate analyses, and results were pooled using random effects models. The pooled multivariate rate ratios for primary open-angle glaucoma comparing the highest versus lowest quintile of cumulative updated intake were 1.17 (95% confidence interval (CI): 0.87, 1.58) for alpha-carotene, 1.10 (95% CI: 0.82, 1.48) for beta-carotene, 0.95 (95% CI: 0.70, 1.29) for beta-cryptoxanthin, 0.82 (95% CI: 0.60, 1.12) for lycopene, 0.92 (95% CI: 0.69, 1.24) for lutein/zeaxanthin, 1.05 (95% CI: 0.59, 1.89) for vitamin C, 0.97 (95% CI: 0.62, 1.52) for vitamin E, and 1.11 (95% CI: 0.82, 1.51) for vitamin A. In conclusion, the authors did not observe any strong associations between antioxidant consumption and the risk of primary open-angle glaucoma.

Cranberry and blueberry: evidence for protective effects against cancer and vascular diseases.

Growing evidence from tissue culture, animal, and clinical models suggests that the flavonoid-rich fruits of the North American cranberry and blueberry (Vaccinium spp.) have the potential ability to limit the development and severity of certain cancers and vascular diseases including atherosclerosis, ischemic stroke, and neurodegenerative diseases of aging. The fruits contain a variety of phytochemicals that could contribute to these protective effects, including flavonoids such as anthocyanins, flavonols, and proanthocyanidins; substituted cinnamic acids and stilbenes; and triterpenoids such as ursolic acid and its esters. Cranberry and blueberry constituents are likely to act by mechanisms that counteract oxidative stress, decrease inflammation, and modulate macromolecular interactions and expression of genes associated with disease processes. The evidence suggests a potential role for dietary cranberry and blueberry in the prevention of cancer and vascular diseases, justifying further research to determine how the bioavailability and metabolism of berry phytonutrients influence their activity in vivo.

The Association between Glaucoma Prevalence and Supplementation with the Oxidants Calcium and Iron

Purpose. To investigate the relationship between supplementary consumption of the oxidants calcium and iron and the prevalence of glaucoma. Methods. This cross-sectional study included 3833 participants in the National Health and Nutrition Examination Survey (NHANES) for 2007 and 2008, ≥40 years of age, who reported a presence or absence of glaucoma. Participants were interviewed regarding the use of dietary supplements and antacids during the preceding 30-day period. Data pertaining to the supplementary intake of calcium and iron was aggregated and divided into quintiles. Information regarding the presence or absence of glaucoma and demographics, comorbidities, and health-related behavior was obtained via interview. Results. Participants who consumed ≥800 mg/d of supplementary calcium or ≥18 mg/d of supplementary iron had significantly higher odds of having been diagnosed with glaucoma than did those who had not consumed supplementary calcium or iron, after adjustment for potential confounders (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.25–4.76 for calcium; OR 3.80, 95% CI 1.79–8.06 for iron). Concurrent consumption of both calcium and iron above these levels was associated with still greater odds of having been diagnosed with glaucoma (OR 7.24, 95% CI 2.42–21.62). A clear dose–response relationship between quintiles of supplementary calcium or iron intake and glaucoma prevalence was not found. Conclusions. These results suggest that there may be a threshold intake of iron and calcium above which there is an increased risk of development of glaucoma. Prospective longitudinal studies are needed, to assess whether oxidant intake is a risk factor for development and progression of glaucoma.

Diet, nutrition and the prevention of dental diseases.

Oral health is related to diet in many ways, for example, nutritional influences on craniofacial development, oral cancer and oral infectious diseases. Dental diseases impact considerably on self-esteem and quality of life and are expensive to treat. The objective of this paper is to review the evidence for an association between nutrition, diet and dental diseases and to present dietary recommendations for their prevention. Nutrition affects the teeth during development and malnutrition may exacerbate periodontal and oral infectious diseases. However, the most significant effect of nutrition on teeth is the local action of diet in the mouth on the development of dental caries and enamel erosion. Dental erosion is increasing and is associated with dietary acids, a major source of which is soft drinks. Despite improved trends in levels of dental caries in developed countries, dental caries remains prevalent and is increasing in some developing countries undergoing nutrition transition. There is convincing evidence, collectively from human intervention studies, epidemiological studies, animal studies and experimental studies, for an association between the amount and frequency of free sugars intake and dental caries. Although other fermentable carbohydrates may not be totally blameless, epidemiological studies show that consumption of starchy staple foods and fresh fruit are associated with low levels of dental caries. Fluoride reduces caries risk but has not eliminated dental caries and many countries do not have adequate exposure to fluoride. It is important that countries with a low intake of free sugars do not increase intake, as the available evidence shows that when free sugars consumption is <15-20 kg/yr ( approximately 6-10% energy intake), dental caries is low. For countries with high consumption levels it is recommended that national health authorities and decision-makers formulate country-specific and community-specific goals for reducing the amount of free sugars aiming towards the recommended maximum of no more than 10% of energy intake. In addition, the frequency of consumption of foods containing free sugars should be limited to a maximum of 4 times per day. It is the responsibility of national authorities to ensure implementation of feasible fluoride programmes for their country.

Can noncommunicable diseases be prevented? Lessons from studies of populations and individuals.

Noncommunicable diseases (NCDs)--mainly cancers, cardiovascular diseases, diabetes, and chronic respiratory diseases--are responsible for about two-thirds of deaths worldwide, mostly in low- and middle-income countries. There is an urgent need for policies and strategies that prevent NCDs by reducing their major risk factors. Effective approaches for large-scale NCD prevention include comprehensive tobacco and alcohol control through taxes and regulation of sales and advertising; reducing dietary salt, unhealthy fats, and sugars through regulation and well-designed public education; increasing the consumption of fresh fruits and vegetables, healthy fats, and whole grains by lowering prices and improving availability; and implementing a universal, effective, and equitable primary-care system that reduces NCD risk factors, including cardiometabolic risk factors and infections that are precursors to NCDs, through clinical interventions.

Ultraviolet phototoxicity to the retina.

OBJECTIVE: This overview of ultraviolet (UV) phototoxicity considers the interaction of UVA and short-wavelength VIS light with the retina and retinal pigment epithelium. METHODS: The damage mechanisms underlying UV retinal phototoxicity are illustrated with a literature survey and presentation of experimental results. RESULTS: Depending on the wavelength and exposure duration, light interacts with tissue by three general mechanisms: thermal, mechanical, or photochemical. Although the anterior structures of the eye absorb much of the UV component of the optical radiation spectrum, a portion of the UVA band (315-400 nm) penetrates into the retina. Natural sources, such as the sun, emit energetic UV photons in relatively long durations, which typically do not result in energy confinement in the retina, and thus do not produce thermal or mechanical damage but are capable of inducing photochemical damage. Photochemical damage in the retina proceeds through Type 1 (direct reactions involving proton or electron transfers) and Type 2 (reactions involving reactive oxygen species) mechanisms. Commonly used drugs, such as certain antibiotics, nonsteroidal anti-inflammatory drugs, psychotherapeutic agents, and even herbal medicines, may act as photosensitizers that promote retinal UV damage, if they are excited by UVA or visible light and have sufficient retinal penetration. CONCLUSIONS: Although the anterior portion of the eye is the most susceptible to UV damage, the retina is at risk to the longer UV wavelengths that propagate through the ocular media. Some phototoxicity may be counteracted or reduced by dietary intake of antioxidants and protective phytonutrients.

Emerging science in the dietary control and prevention of dental caries.

The key environmental factor involved in caries incidence is fermentable carbohydrates. Because of the high costs of caries treatment, researchers continue to explore dietary control as a promising preventive method. While dietary change has been demonstrated to reduce Streptococcus mutans, a preventive role is expected for "functional foods" and dietary habit alterations. The authors consider how recent advances in the understanding of caries pathology can reveal dietary control as a valuable method in promoting a healthy dentition.

Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART).

A randomised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infarction (MI). 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors: a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat, an increase in fatty fish intake, and an increase in cereal fibre intake. The advice on fat was not associated with any difference in mortality, perhaps because it produced only a small reduction (3-4%) in serum cholesterol. The subjects advised to eat fatty fish had a 29% reduction in 2 year all-cause mortality compared with those not so advised. This effect, which was significant, was not altered by adjusting for ten potential confounding factors. Subjects given fibre advice had a slightly higher mortality than other subjects (not significant). The 2 year incidence of reinfarction plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens. A modest intake of fatty fish (two or three portions per week) may reduce mortality in men who have recovered from MI.

Protein intake, calcium balance and health consequences.

High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.

Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial.

High serum levels of testosterone and estradiol, the bioavailability of which may be increased by Western dietary habits, seem to be important risk factors for postmenopausal breast cancer. We hypothesized that an ad libitum diet low in animal fat and refined carbohydrates and rich in low-glycemic-index foods, monounsaturated and n-3 polyunsaturated fatty acids, and phytoestrogens, might favorably modify the hormonal profile of postmenopausal women. One hundred and four postmenopausal women selected from 312 healthy volunteers on the basis of high serum testosterone levels were randomized to dietary intervention or control. The intervention included intensive dietary counseling and specially prepared group meals twice a week over 4.5 months. Changes in serum levels of testosterone, estradiol, and sex hormone-binding globulin were the main outcome measures. In the intervention group, sex hormone-binding globulin increased significantly (from 36.0 to 45.1 nmol/liter) compared with the control group (25 versus 4%,; P < 0.0001) and serum testosterone decreased (from 0.41 to 0.33 ng/ml; -20 versus -7% in control group; P = 0.0038). Serum estradiol also decreased, but the change was not significant. The dietary intervention group also significantly decreased body weight (4.06 kg versus 0.54 kg in the control group), waist:hip ratio, total cholesterol, fasting glucose level, and area under insulin curve after oral glucose tolerance test. A radical modification in diet designed to reduce insulin resistance and also involving increased phytoestrogen intake decreases the bioavailability of serum sex hormones in hyperandrogenic postmenopausal women. Additional studies are needed to determine whether such effects can reduce the risk of developing breast cancer.

A systematic screening of total antioxidants in dietary plants.

A predominantly plant-based diet reduces the risk for development of several chronic diseases. It is often assumed that antioxidants contribute to this protection, but results from intervention trials with single antioxidants administered as supplements quite consistently do not support any benefit. Because dietary plants contain several hundred different antioxidants, it would be useful to know the total concentration of electron-donating antioxidants (i.e., reductants) in individual items. Such data might be useful in the identification of the most beneficial dietary plants. We have assessed systematically total antioxidants in a variety of dietary plants used worldwide, including various fruits, berries, vegetables, cereals, nuts and pulses. When possible, we analyzed three or more samples of dietary plants from three different geographic regions in the world. Total antioxidants was assessed by the reduction of Fe(3+) to Fe(2+) (i.e., the FRAP assay), which occurred rapidly with all reductants with half-reaction reduction potentials above that of Fe(3+)/Fe(2+). The values, therefore, expressed the corresponding concentration of electron-donating antioxidants. Our results demonstrated that there is more than a 1000-fold difference among total antioxidants in various dietary plants. Plants that contain most antioxidants included members of several families, such as Rosaceae (dog rose, sour cherry, blackberry, strawberry, raspberry), Empetraceae (crowberry), Ericaceae (blueberry), Grossulariaceae (black currant), Juglandaceae (walnut), Asteraceae (sunflower seed), Punicaceae (pomegranate) and Zingiberaceae (ginger). In a Norwegian diet, fruits, berries and cereals contributed 43.6%, 27.1% and 11.7%, respectively, of the total intake of plant antioxidants. Vegetables contributed only 8.9%. The systematic analysis presented here will facilitate research into the nutritional role of the combined effect of antioxidants in dietary plants.

Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an...

Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.

Glaucoma risk and the consumption of fruits and vegetables among older women in the study of osteoporotic fractures.

PURPOSE: To explore the association between the consumption of fruits and vegetables and the presence of glaucoma. DESIGN: Cross-sectional cohort study. METHODS: In a sample of 1,155 women located in multiple centers in the United States, glaucoma specialists diagnosed glaucoma in at least one eye by assessing optic nerve head photographs and 76-point suprathreshold screening visual fields. Consumption of fruits and vegetables was assessed using the Block Food Frequency Questionnaire. The relationship between selected fruit and vegetable consumption and glaucoma was investigated using adjusted logistic regression models. RESULTS: Among 1,155 women, 95 (8.2%) were diagnosed with glaucoma. In adjusted analysis, the odds of glaucoma risk were decreased by 69% (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11 to 0.91) in women who consumed at least one serving per month of green collards and kale compared with those who consumed fewer than one serving per month, by 64% (OR, 0.36; 95% CI, 0.17 to 0.77) in women who consumed more than two servings per week of carrots compared with those who consumed fewer than one serving per week, and by 47% (OR, 0.53; 95% CI, 0.29 to 0.97) in women who consumed at least one serving per week of canned or dried peaches compared with those who consumed fewer than one serving per month. CONCLUSIONS: A higher intake of certain fruits and vegetables may be associated with a decreased risk of glaucoma. More studies are needed to investigate this relationship.

Omega-3 fatty acids and antioxidants in edible wild plants.

Human beings evolved on a diet that was balanced in the omega-6 and omega-3 polyunsaturated fatty acids (PUFA), and was high in antioxidants. Edible wild plants provide alpha-linolenic acid (ALA) and higher amounts of vitamin E and vitamin C than cultivated plants. In addition to the antioxidant vitamins, edible wild plants are rich in phenols and other compounds that increase their antioxidant capacity. It is therefore important to systematically analyze the total antioxidant capacity of wild plants and promote their commercialization in both developed and developing countries. The diets of Western countries have contained increasingly larger amounts of linoleic acid (LA), which has been promoted for its cholesterol-lowering effect. It is now recognized that dietary LA favors oxidative modification of low density lipoprotein (LDL) cholesterol and increases platelet response to aggregation. In contrast, ALA intake is associated with inhibitory effects on the clotting activity of platelets, on their response to thrombin, and on the regulation of arachidonic acid (AA) metabolism. In clinical studies, ALA contributed to lowering of blood pressure, and a prospective epidemiological study showed that ALA is inversely related to the risk of coronary heart disease in men. Dietary amounts of LA as well as the ratio of LA to ALA appear to be important for the metabolism of ALA to longer-chain omega-3 PUFAs. Relatively large reserves of LA in body fat. as are found in vegans or in the diet of omnivores in Western societies, would tend to slow down the formation of long-chain omega-3 fatty acids from ALA. Therefore, the role of ALA in human nutrition becomes important in terms of long-term dietary intake. One advantage of the consumption of ALA over omega-3 fatty acids from fish is that the problem of insufficient vitamin E intake does not exist with high intake of ALA from plant sources.

Optimal management of cytomegalovirus retinitis in patients with AIDS

Cytomegalovirus (CMV) retinitis is the most common cause of vision loss in patients with acquired immunodeficiency syndrome (AIDS). CMV retinitis afflicted 25% to 42% of AIDS patients in the pre-highly active antiretroviral therapy (HAART) era, with most vision loss due to macula-involving retinitis or retinal detachment. The introduction of HAART significantly decreased the incidence and severity of CMV retinitis. Optimal treatment of CMV retinitis requires a thorough evaluation of the patient’s immune status and an accurate classification of the retinal lesions. When retinitis is diagnosed, HAART therapy should be started or improved, and anti-CMV therapy with oral valganciclovir, intravenous ganciclovir, foscarnet, or cidofovir should be administered. Selected patients, especially those with zone 1 retinitis, may receive intravitreal drug injections or surgical implantation of a sustained-release ganciclovir reservoir. Effective anti-CMV therapy coupled with HAART significantly decreases the incidence of vision loss and improves patient survival. Immune recovery uveitis and retinal detachments are important causes of moderate to severe loss of vision. Compared with the early years of the AIDS epidemic, the treatment emphasis in the post- HAART era has changed from short-term control of retinitis to long-term preservation of vision. Developing countries face shortages of health care professionals and inadequate supplies of anti-CMV and anti-HIV medications. Intravitreal ganciclovir injections may be the most cost effective strategy to treat CMV retinitis in these areas.

The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load.

Residents of Okinawa, the southernmost prefecture of Japan, are known for their long average life expectancy, high numbers of centenarians, and accompanying low risk of age-associated diseases. Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products. Many of the characteristics of the diet in Okinawa are shared with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Features such as the low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress. A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables. Deeper analyses of the individual components of the Okinawan diet reveal that many of the traditional foods, herbs, or spices consumed on a regular basis could be labeled "functional foods" and, indeed, are currently being explored for their potential health-enhancing properties.

Diet-induced metabolic acidosis.

The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Overall diet quality and age-related macular degeneration

Objective To examine overall diet quality in relation to advanced age-related macular degeneration (AMD). Methods This case-control study identified 437 advanced AMD patients and 259 unrelated controls using stereoscopic color fundus photographs. Participants were predominantly non-Hispanic white men and women from North Carolina and Tennessee. A 97-item Block food frequency questionnaire was used to gather diet information, and overall diet quality was measured using the Healthy Eating Index (HEI) and Alternate Healthy Eating Index (AHEI). Results Participants in the highest quartile of diet quality had significantly reduced odds of AMD according to the AHEI score (0.54, 95% confidence interval 0.30 – 0.99) and non-significantly reduced odds of AMD according to the HEI (0.75, 0.41 – 1.38). Odds of AMD were also 51% lower in the highest quartile of fish intake compared to the lowest quartile (odds ratio = 0.49, 0.26 – 0.90). Conclusions We found that advanced AMD was significantly related to overall diet quality. The AHEI score may be a useful instrument for assessing AMD risk due to diet, and it could potentially be improved by incorporating more specific information regarding micronutrient intake.

Omega-3 fatty acids for nutrition and medicine: considering microalgae oil as a vegetarian source of EPA and DHA.

Long-chain EPA/DHA omega-3 fatty acid supplementation can be co-preventative and co-therapeutic. Current research suggests increasing accumulated long chain omega-3s for health benefits and as natural medicine in several major diseases. But many believe plant omega-3 sources are nutritionally and therapeutically equivalent to the EPA/DHA omega-3 in fish oil. Although healthy, precursor ALA bio-conversion to EPA is inefficient and production of DHA is nearly absent, limiting the protective value of ALA supplementation from flax-oil, for example. Along with pollutants certain fish acquire high levels of EPA/DHA as predatory species. However, the origin of EPA/DHA in aquatic ecosystems is algae. Certain microalgae produce high levels of EPA or DHA. Now, organically produced DHA-rich microalgae oil is available. Clinical trials with DHA-rich oil indicate comparable efficacies to fish oil for protection from cardiovascular risk factors by lowering plasma triglycerides and oxidative stress. This review discusses 1) omega-3 fatty acids in nutrition and medicine; 2) omega-3s in physiology and gene regulation; 3) possible protective mechanisms of EPA/DHA in major diseases such as coronary heart disease, atherosclerosis, cancer and type 2 diabetes; 4) EPA and DHA requirements considering fish oil safety; and 5) microalgae EPA and DHA-rich oils and recent clinical results.

Effect of the vegetarian diet on non-communicable diseases.

A vegetarian diet generally includes plenty of vegetables and fruits, which are rich in phytochemicals, antioxidants, fiber, magnesium, vitamins C and E, Fe³⁺, folic acid and n-6 polyunsaturated fatty acid (PUFA), and is low in cholesterol, total fat and saturated fatty acid, sodium, Fe²⁺, zinc, vitamin A, B₁₂ and D, and especially n-3 PUFA. Mortality from all-cause, ischemic heart disease, and circulatory and cerebrovascular diseases was significantly lower in vegetarians than in omnivorous populations. Compared with omnivores, the incidence of cancer and type 2 diabetes was also significantly lower in vegetarians. However, vegetarians have a number of increased risk factors for non-communicable diseases such as increased plasma homocysteine, mean platelet volume and platelet aggregability compared with omnivores, which are associated with low intake of vitamin B₁₂ and n-3 PUFA. Based on the present data, it would seem appropriate for vegetarians to carefully design their diet, specifically focusing on increasing their intake of vitamin B₁₂ and n-3 PUFA to further reduce already low mortality and morbidity from non-communicable diseases. © 2013 Society of Chemical Industry.

Iodine Status and Thyroid Function of Boston-Area Vegetarians and Vegans

Context: Adequate dietary iodine is required for normal thyroid function. The iodine status and thyroid function of U.S. vegetarians and vegans have not been previously studied. Environmental perchlorate and thiocyanate (inhibitors of thyroid iodine uptake) exposures may adversely affect thyroid function. Objective: The objective of the study was to assess the iodine status and thyroid function of U.S. vegetarians (consume plant based products, eggs, milk; abstain from meat, poultry, fish, shellfish) and vegans (avoid all animal products) and whether these may be affected by environmental perchlorate and thiocyanate exposures. Design and Setting: This was a cross-sectional assessment of urinary iodine, perchlorate, and thiocyanate concentrations and serum thyroid function in Boston-area vegetarians and vegans. Subjects: One hundred forty-one subjects (78 vegetarians, 63 vegans) were recruited; one vegan was excluded. Results: Median urinary iodine concentration of vegans (78.5 μg/liter; range 6.8–964.7 μg/liter) was lower than vegetarians (147.0 μg/liter; range 9.3–778.6 μg/liter) (P < 0.01). Adjusted for cigarette smoking (confirmed by urinary cotinine levels) and thiocyanate-rich food consumption, median urinary thiocyanate concentration of vegans (630 μg/liter; range 108-3085 μg/liter) was higher than vegetarians (341 μg/liter; range 31–1963 μg/liter) (P < 0.01). There were no between-group differences in urinary perchlorate concentrations (P = 0.75), TSH (P = 0.46), and free T4 (P = 0.77). Urinary iodine, perchlorate, and thiocyanate levels were not associated with TSH (P = 0.59) or free T4 (P = 0.14), even when adjusted for multiple variables. Conclusions: U.S. vegetarians are iodine sufficient. U.S. vegans may be at risk for low iodine intake, and vegan women of child-bearing age should supplement with 150 μg iodine daily. Environmental perchlorate and thiocyanate exposures are not associated with thyroid dysfunction in these groups.

A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson's disease.

This study describes how foods rich in fisetin and hexacosanol added to a strict diet reversed most symptoms of Parkinson's disease (PD) in one patient. This is a case report involving outpatient care. The subject was a dietitian diagnosed with idiopathic PD in 2000 at the age of 53 years old, with a history of exposure to neurotoxins and no family history of PD. A basic diet started in 2000 consisted of predominantly fruits, vegetables, 100% whole grains, extra virgin olive oil, nuts, seeds, nonfat milk products, tea, coffee, spices, small amounts of dark chocolate, and less than 25 g of animal fat daily. The basic diet alone failed to prevent decline due to PD. In 2009, the basic diet was enhanced with a good dietary source of both fisetin and hexacosanol. Six months after the patient started the enhanced diet rich in fisetin and hexacosanol, a clinically significant improvement in symptoms was noted; the patient's attending neurologist reported that the clinical presentation of cogwheel rigidity, micrographia, bradykinesia, dystonia, constricted arm swing with gait, hypomimia, and retropulsion appeared to be resolved. The only worsening of symptoms occurred when the diet was not followed precisely. Little improvement in tremor or seborrhea was observed. The clinical improvement has persisted to date. To the best of our knowledge, this is the first case where adjunctive diet therapy resulted in a significant reduction of symptoms of PD without changing the type or increasing the amount of medications.

Effect of a very-high-fiber vegetable, fruit, and nut diet on serum lipids and colonic function.

We tested the effects of feeding a diet very high in fiber from fruit and vegetables. The levels fed were those, which had originally inspired the dietary fiber hypothesis related to colon cancer and heart disease prevention and also may have been eaten early in human evolution. Ten healthy volunteers each took 3 metabolic diets of 2 weeks duration. The diets were: high-vegetable, fruit, and nut (very-high-fiber, 55 g/1,000 kcal); starch-based containing cereals and legumes (early agricultural diet); or low-fat (contemporary therapeutic diet). All diets were intended to be weight-maintaining (mean intake, 2,577 kcal/d). Compared with the starch-based and low-fat diets, the high-fiber vegetable diet resulted in the largest reduction in low-density lipoprotein (LDL) cholesterol (33% +/- 4%, P <.001) and the greatest fecal bile acid output (1.13 +/- 0.30 g/d, P =.002), fecal bulk (906 +/- 130 g/d, P <.001), and fecal short-chain fatty acid outputs (78 +/- 13 mmol/d, P <.001). Nevertheless, due to the increase in fecal bulk, the actual concentrations of fecal bile acids were lowest on the vegetable diet (1.2 mg/g wet weight, P =.002). Maximum lipid reductions occurred within 1 week. Urinary mevalonic acid excretion increased (P =.036) on the high-vegetable diet reflecting large fecal steroid losses. We conclude that very high-vegetable fiber intakes reduce risk factors for cardiovascular disease and possibly colon cancer. Vegetable and fruit fibers therefore warrant further detailed investigation. Copyright 2001 by W.B. Saunders Company

Lignans and human health.

This review focuses on the possible role in human health of the consumption of lignan-rich foods. Most of the plant lignans in human foods are converted by the intestinal microflora in the upper part of the large bowel to enterolactone and enterodiol, called mammalian or enterolignans. The protective role of these compounds, particularly in chronic Western diseases, is discussed. Evidence suggests that fiber- and lignan-rich whole-grain cereals, beans, berries, nuts, and various seeds are the main protective foods. Many factors, in addition to diet, such as intestinal microflora, smoking, antibiotics, and obesity affect circulating lignan levels in the body. Lignan-rich diets may be beneficial, particularly if consumed for life. Experimental evidence in animals has shown clear anticarcinogenic effects of flaxseed or pure lignans in many types of cancer. Many epidemiological results are controversial, partly because the determinants of plasma enterolactone are very different in different countries. The source of the lignans seems to play a role because other factors in the food obviously participate in the protective effects. The results are promising, but much work is still needed in this area of medicine.

Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study

Background and aims: The causes of relapses of ulcerative colitis (UC) are unknown. Dietary factors have been implicated in the pathogenesis of UC. The aim of this study was to determine which dietary factors are associated with an increased risk of relapse of UC. Methods: A prospective cohort study was performed with UC patients in remission, recruited from two district general hospitals, who were followed for one year to determine the effect of habitual diet on relapse. Relapse was defined using a validated disease activity index. Nutrient intake was assessed using a food frequency questionnaire and categorised into tertiles. Adjusted odds ratios for relapse were determined using multivariate logistic regression, controlling for non-dietary factors. Results: A total of 191 patients were recruited and 96% completed the study. Fifty two per cent of patients relapsed. Consumption of meat (odds ratio (OR) 3.2 (95% confidence intervals (CI) 1.3–7.8)), particularly red and processed meat (OR 5.19 (95% CI 2.1–12.9)), protein (OR 3.00 (95% CI 1.25–7.19)), and alcohol (OR 2.71 (95% CI 1.1–6.67)) in the top tertile of intake increased the likelihood of relapse compared with the bottom tertile of intake. High sulphur (OR 2.76 (95% CI 1.19–6.4)) or sulphate (OR 2.6 (95% CI 1.08–6.3)) intakes were also associated with relapse and may offer an explanation for the observed increased likelihood of relapse. Conclusions: Potentially modifiable dietary factors, such as a high meat or alcoholic beverage intake, have been identified that are associated with an increased likelihood of relapse for UC patients. Further studies are needed to determine if it is the sulphur compounds within these foods that mediates the likelihood of relapse and if reducing their intake would reduce relapse frequency.

Appealing to Vanity: Could Potential Appearance Improvement Motivate Fruit and Vegetable Consumption?

Fruit and vegetable consumption is inadequate among adults in the United States; this contributes to preventable morbidity and mortality. More effective dietary intervention strategies are needed. Recently, interventions that advertise the consequences of behavior for appearance have been successful in modifying sun-exposure habits and tobacco use. Such an approach might also facilitate dietary improvement. Consumption of carotenoid-rich fruit and vegetables positively affects skin color, which influences perceptions of health and attractiveness, and promoting such an effect may motivate target audiences to increase consumption of this important food group. This approach represents a novel direction for the field and is potentially suitable for cost-effective, population-level dissemination through the visual media.

Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented in...

BACKGROUND: While there is a large body of data on the effects of long-chain polyunsaturated fatty acid supplementation of infant formula on visual and cognitive maturation during infancy, longterm visual and cognitive outcome data from randomized trials are scarce. AIM: To evaluate docosahexaenoic acid (DHA) and arachidonic acid (ARA)-supplementation of infant formula on visual and cognitive outcomes at 4 years of age. METHODS: Fifty-two of 79 healthy term infants who were enrolled in a single-center, double-blind, randomized clinical trial of DHA and ARA supplementation of infant formula were available for follow-up at 4 years of age. In addition, 32 breast-fed infants served as a "gold standard". Outcome measures were visual acuity and the Wechsler Preschool and Primary Scale of Intelligence--Revised. RESULTS: At 4 years, the control formula group had poorer visual acuity than the breast-fed group; the DHA- and DHA+ARA-supplemented groups did not differ significantly from the breast-fed group. The control formula and DHA-supplemented groups had Verbal IQ scores poorer than the breast-fed group. CONCLUSION: DHA and ARA-supplementation of infant formula supports visual acuity and IQ maturation similar to that of breast-fed infants.

Insulin secretion as a determinant of pancreatic cancer risk.

New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.

Hypothesis: hyperhomocysteinemia is an indicator of oxidant stress.

Elevated plasma homocysteine levels are associated with an increased risk of atherosclerosis and thrombosis, as well as a variety of other pathologies such as birth defects, Alzheimer's disease and other dementias, osteoporosis, diabetes and renal disease. Homocysteine metabolism is catalyzed by a number of enzymes that require B-vitamins as cofactors, and homocysteine levels are particularly responsive to folate status. The predictive power of plasma homocysteine level as a risk factor for atherothrombotic orders raised the appealing hypothesis that reduction of homocysteine levels by vitamin supplementation might result in a commensurate reduction is the risk of atherothrombotic events. Unfortunately, most clinical trials failed to show a significant benefit of vitamin supplementation on cardiovascular events, in spite of significant lowering of plasma homocysteine levels. Thus, it is not clear whether homocysteine actually plays a causal role in many pathologies with which it is associated, or whether it is instead a marker for some other underlying mechanism. A large body of data links hyperhomocysteinemia and folate status with oxidant stress. In this article I review data that suggests that homocysteine not only promotes cellular and protein injury via oxidant mechanisms, but is also a marker for the presence of pathological oxidant stress. Thus, it is possible that hyperhomocysteinemia is not a common primary cause of atherothrombotic disorders in the general population, but rather a marker of systemic or endothelial oxidant stress that is a major mediator of these disorders. Published by Elsevier Ltd.

The effect of bilberry nutritional supplementation on night visual acuity and contrast sensitivity.

PURPOSE: The purpose of this study was to investigate the effect of bilberry on night visual acuity (VA) and night contrast sensitivity (CS). METHODS: This study utilized a double-blind, placebo-controlled, crossover design. The subjects were young males with good vision; eight received placebo and seven received active capsules for three weeks. Active capsules contained 160 mg of bilberry extract (25-percent anthocyanosides), and the placebo capsules contained only inactive ingredients. Subjects ingested one active or placebo capsule three times daily for 21 days. After the three-week treatment period, a one-month washout period was employed to allow any effect of bilberry on night vision to dissipate. In the second three-week treatment period, the eight subjects who first received placebo were given active capsules, and the seven who first received active capsules were given placebo. Night VA and night CS was tested throughout the three-month experiment. RESULTS: There was no difference in night VA during any of the measurement periods when examining the average night VA or the last night VA measurement during active and placebo treatments. In addition, there was no difference in night CS during any of the measurement periods when examining the average night CS or the last night CS measurement during active and placebo treatments. CONCLUSION: The current study failed to find an effect of bilberry on night VA or night CS for a high dose of bilberry taken for a significant duration. Hence, the current study casts doubt on the proposition that bilberry supplementation, in the forms currently available and in the doses recommended, is an effective treatment for the improvement of night vision in this population.

Total visual blindness is protective against breast cancer.

OBJECTIVE: Observational data, though sparse and based on small studies with limited ability to control for known breast cancer risk factors, support a lower risk of breast cancer in blind women compared to sighted women. Mechanisms influenced by ocular light perception, such as melatonin or circadian synchronization, are thought to account for this lower risk. METHODS: To evaluate whether blind women with no perception of light (NPL) have a lower prevalence of breast cancer compared to blind women with light perception (LP), we surveyed a cohort of 1,392 blind women living in North America (66 breast cancer cases). RESULTS: In multivariate-logistic regression models controlling for breast cancer risk factors, women with NPL had a significantly lower prevalence of breast cancer than women with LP (odds ratio, 0.43; 95% confidence interval, 0.21-0.85). We observed little difference in these associations when restricting to postmenopausal women, non-shift workers or when excluding women diagnosed with breast cancer within 2 or 4 years of onset of blindness. Blind women with NPL appear to have a lower risk of breast cancer, compared to blind women with LP. More research is needed to elucidate the impact of LP on circadian coordination and melatonin production in the blind and how these factors may relate to breast cancer risk.

Paleolithic vs. modern diets--selected pathophysiological implications.

The nutritional patterns of Paleolithic humans influenced genetic evolution during the time segment within which defining characteristics of contemporary humans were selected. Our genome can have changed little since the beginnings of agriculture, so, genetically, humans remain Stone Agers--adapted for a Paleolithic dietary regimen. Such diets were based chiefly on wild game, fish and uncultivated plant foods. They provided abundant protein; a fat profile much different from that of affluent Western nations; high fibre; carbohydrate from fruits and vegetables (and some honey) but not from cereals, refined sugars and dairy products; high levels of micronutrients and probably of phytochemicals as well. Differences between contemporary and ancestral diets have many pathophysiological implications. This review addresses phytochemicals and cancer; calcium, physical exertion, bone mineral density and bone structural geometry; dietary protein, potassium, renal acid secretion and urinary calcium loss; and finally sarcopenia, adiposity, insulin receptors and insulin resistance. While not, yet, a basis for formal recommendations, awareness of Paleolithic nutritional patterns should generate novel, testable hypotheses grounded in evolutionary theory and it should dispel complacency regarding currently accepted nutritional tenets.

Caffeine Consumption and the Risk of Primary Open - Angle Glaucoma: A Prospective Cohort Study

Purpose We investigated whether caffeine, which transiently increases intraocular pressure (IOP) is associated with risk of primary open-angle glaucoma (POAG). Methods We followed 79,120 women from 1980 and 42,052 men from 1986 to 2004 who were 40+ years old, did not have POAG, and reported receiving eye examinations. Information on caffeine consumption, potential confounders and POAG diagnoses were repeatedly updated in validated follow-up questionnaires. We confirmed 1,011 incident POAG cases with medical record review. Cohort-specific and pooled analyses across cohorts were conducted to calculate multivariable rate ratios (RR). Results Compared with daily intake of < 150 mg, the pooled multivariable RRs were 1.05 [95% Confidence Interval (CI), 0.89–1.25] for consuming 150–299 mg, 1.19 [95% CI, 0.99–1.43] for 300 – 449 mg/day, 1.13 [95% CI, 0.89–1.43] for 450–559 mg and 1.17 [95% CI, 0.90, 1.53] for 600+ mg+ [p for trend = 0.11]. However, for consuming 5+ cups of caffeinated coffee daily, RR was 1.61 [95% CI, 1.00, 2.59; p for trend=0.02]; tea or caffeinated cola intake were not associated with risk. Greater caffeine intake was more adversely associated with POAG among those reporting family history of glaucoma, particularly in relation to POAG with elevated IOP (p for trend =0.0009; p-interaction=0.04). Conclusion Overall caffeine intake was not associated with increased risk of POAG. However, in secondary analyses, caffeine appeared to elevate risk of high-tension POAG among those with a family history of glaucoma; this may be due to chance, but warrants further study.

The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors

Background Knowledge of the number of deaths caused by risk factors is needed for health policy and priority setting. Our aim was to estimate the mortality effects of the following 12 modifiable dietary, lifestyle, and metabolic risk factors in the United States (US) using consistent and comparable methods: high blood glucose, low-density lipoprotein (LDL) cholesterol, and blood pressure; overweight–obesity; high dietary trans fatty acids and salt; low dietary polyunsaturated fatty acids, omega-3 fatty acids (seafood), and fruits and vegetables; physical inactivity; alcohol use; and tobacco smoking. Methods and Findings We used data on risk factor exposures in the US population from nationally representative health surveys and disease-specific mortality statistics from the National Center for Health Statistics. We obtained the etiological effects of risk factors on disease-specific mortality, by age, from systematic reviews and meta-analyses of epidemiological studies that had adjusted (i) for major potential confounders, and (ii) where possible for regression dilution bias. We estimated the number of disease-specific deaths attributable to all non-optimal levels of each risk factor exposure, by age and sex. In 2005, tobacco smoking and high blood pressure were responsible for an estimated 467,000 (95% confidence interval [CI] 436,000–500,000) and 395,000 (372,000–414,000) deaths, accounting for about one in five or six deaths in US adults. Overweight–obesity (216,000; 188,000–237,000) and physical inactivity (191,000; 164,000–222,000) were each responsible for nearly 1 in 10 deaths. High dietary salt (102,000; 97,000–107,000), low dietary omega-3 fatty acids (84,000; 72,000–96,000), and high dietary trans fatty acids (82,000; 63,000–97,000) were the dietary risks with the largest mortality effects. Although 26,000 (23,000–40,000) deaths from ischemic heart disease, ischemic stroke, and diabetes were averted by current alcohol use, they were outweighed by 90,000 (88,000–94,000) deaths from other cardiovascular diseases, cancers, liver cirrhosis, pancreatitis, alcohol use disorders, road traffic and other injuries, and violence. Conclusions Smoking and high blood pressure, which both have effective interventions, are responsible for the largest number of deaths in the US. Other dietary, lifestyle, and metabolic risk factors for chronic diseases also cause a substantial number of deaths in the US. Please see later in the article for Editors' Summary Editors' Summary A number of modifiable factors are responsible for many premature or preventable deaths. For example, being overweight or obese shortens life expectancy, while half of all long-term tobacco smokers in Western populations will die prematurely from a disease directly related to smoking. Modifiable risk factors fall into three main groups. First, there are lifestyle risk factors. These include tobacco smoking, physical inactivity, and excessive alcohol use (small amounts of alcohol may actually prevent diabetes and some types of heart disease and stroke). Second, there are dietary risk factors such as a high salt intake and a low intake of fruits and vegetables. Finally, there are “metabolic risk factors,” which shorten life expectancy by increasing a person's chances of developing cardiovascular disease (in particular, heart problems and strokes) and diabetes. Metabolic risk factors include having high blood pressure or blood cholesterol and being overweight or obese. Why Was This Study Done? It should be possible to reduce preventable deaths by changing modifiable risk factors through introducing public health policies, programs and regulations that reduce exposures to these risk factors. However, it is important to know how many deaths are caused by each risk factor before developing policies and programs that aim to improve a nation's health. Although previous studies have provided some information on the numbers of premature deaths caused by modifiable risk factors, there are two problems with these studies. First, they have not used consistent and comparable methods to estimate the number of deaths attributable to different risk factors. Second, they have rarely considered the effects of dietary and metabolic risk factors. In this new study, the researchers estimate the number of deaths due to 12 different modifiable dietary, lifestyle, and metabolic risk factors for the United States population. They use a method called “comparative risk assessment.” This approach estimates the number of deaths that would be prevented if current distributions of risk factor exposures were changed to hypothetical optimal distributions. What Did the Researchers Do and Find? The researchers extracted data on exposures to these 12 selected risk factors from US national health surveys, and they obtained information on deaths from difference diseases for 2005 from the US National Center for Health Statistics. They used previously published studies to estimate how much each risk factor increases the risk of death from each disease. The researchers then used a mathematical formula to estimate the numbers of deaths caused by each risk factor. Of the 2.5 million US deaths in 2005, they estimate that nearly half a million were associated with tobacco smoking and about 400,000 were associated with high blood pressure. These two risk factors therefore each accounted for about 1 in 5 deaths in US adults. Overweight–obesity and physical inactivity were each responsible for nearly 1 in 10 deaths. Among the dietary factors examined, high dietary salt intake had the largest effect, being responsible for 4% of deaths in adults. Finally, while alcohol use prevented 26,000 deaths from ischemic heart disease, ischemic stroke, and diabetes, the researchers estimate that it caused 90,000 deaths from other types of cardiovascular diseases, other medical conditions, and road traffic accidents and violence. What Do These Findings Mean? These findings indicate that smoking and high blood pressure are responsible for the largest number of preventable deaths in the US, but that several other modifiable risk factors also cause many deaths. Although the accuracy of some of the estimates obtained in this study will be affected by the quality of the data used, these findings suggest that targeting a handful of risk factors could greatly reduce premature mortality in the US. The findings might also apply to other countries, although the risk factors responsible for most preventable deaths may vary between countries. Importantly, effective individual-level and population-wide interventions are already available to reduce people's exposure to the two risk factors responsible for most preventable deaths in the US. The researchers also suggest that combinations of regulation, pricing, and education have the potential to reduce the exposure of US residents to other risk factors that are likely to shorten their lives. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000058.

Diet and prevention of oral cancer: strategies for clinical practice.

BACKGROUND: Oral health care professionals can play an important role in preventing oral cancer by performing oral mucosal examinations to detect pre-cancerous changes and by educating patients about oral cancer prevention strategies, including dietary approaches. CONCLUSIONS: Current evidence supports a diet high in fruits, vegetables and plant-based foods for prevention of oral cancer. Dietary supplements-including vitamins and minerals-have not been shown to be effective as substitutes for a diet high in fruits and vegetables. CLINICAL IMPLICATIONS: In addition to discussing tobacco and alcohol use with patients (and, if relevant, betel nut and gutka consumption), as well as the risk of sexual transmission of human papillo-mavirus, clinicians should provide dietary advice for the prevention of oral cancer as part of routine patient education practices.

EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK.

OBJECTIVE: To describe the lifestyle characteristics and nutrient intakes of the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Cohort of men and women recruited through general practices or by post to include a high proportion of non meat-eaters. Dietary, anthropometric and lifestyle data were collected at baseline and four diet groups were defined. SETTING: United Kingdom. PARTICIPANTS: In total, 65 429 men and women aged 20 to 97 years, comprising 33 883 meat-eaters, 10 110 fish-eaters, 18 840 lacto-ovo vegetarians and 2596 vegans. RESULTS: Nutrient intakes and lifestyle factors differed across the diet groups, with striking differences between meat-eaters and vegans, and fish-eaters and vegetarians usually having intermediate values. Mean fat intake in each diet group was below the UK dietary reference value of 33% of total energy intake. The mean intake of saturated fatty acids in vegans was approximately 5% of energy, less than half the mean intake among meat-eaters (10-11%). Vegans had the highest intakes of fibre, vitamin B1, folate, vitamin C, vitamin E, magnesium and iron, and the lowest intakes of retinol, vitamin B12, vitamin D, calcium and zinc. CONCLUSIONS: The EPIC-Oxford cohort includes 31 546 non meat-eaters and is one of the largest studies of vegetarians in the world. The average nutrient intakes in the whole cohort are close to those currently recommended for good health. Comparisons of the diet groups show wide ranges in the intakes of major nutrients such as saturated fat and dietary fibre. Such variation should increase the ability of the study to detect associations of diet with major cancers and causes of death.

The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer

Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.

Reducing exposure to dioxins and related compounds through foods in the next generation.

Dioxins and related compounds are undesirable and unintended contaminants in the food supply, and dietary intake is the major route of exposure. Reducing dietary exposure to dioxins among the most vulnerable segments of the population (i.e., pregnant women, infants, and young girls) is an effective strategy for reducing body burdens in future generations. Exposure to dioxins through foods can be minimized by selecting lower-fat versions of meats, poultry, and dairy products. Consuming all foods, including fatty fish, in recommended amounts is congruent with the goal of reducing dioxin intake exposure and maintaining good health.

What is a high fiber diet?

There is no recognized definition of what constitutes a high fiber diet. Intakes of dietary fiber in different populations internationally vary widely from less than 20 g to more than 80 g per day. The types of foods contributing fiber also vary; in some countries cereals contribute the most fiber, in others leafy or root vegetables predominate. Vegetables have the highest fiber content per Kcal, and in most populations with fiber intakes over 50 g, vegetables contribute over 50% of total fiber intake. In rural Uganda, where the fiber hypothesis was first developed by Burkitt and Trowell, vegetables contribute over 90% of fiber intake. An experimental diet, the "Simian" diet, has been developed to mimic as closely as possible using human foods, the diet consumed by our simian ancestors the great apes. It is also similar to the Ugandan diet in containing large amounts of vegetables and 50 g fiber/1000 Kcal. Though nutritionally adequate, this diet is very bulky and not a suitable model for general recommendations. Dietary guidelines are that fat intake should be < 30% of energy, with a fiber intake of 20-35 g/d. These recommendations are inconsistent with a high fiber diet because, for people consuming more than about 2400 Kcal, low fiber choices for fruits and grains must be selected to keep dietary fiber intake within the range of 20-35 g. In a 30% fat, 1800 Kcal omnivorous diet, selection of wholemeal bread and whole fruit, results in a fiber intake over 35 g/d, and for and 1800 Kcal vegetarian diet, with substitution of modest amounts of peanut butter and beans for meats, dietary fiber intake goes up to 45 g/d. Thus, if it is desirable to promote the use of unrefined foods, the recommended dietary fiber intake should be a minimum of 15-20 g/1000 Kcal.

Dietary factors and oral and pharyngeal cancer risk.

We reviewed data from six cohort studies and approximately 40 case-control studies on the relation between selected aspects of diet and the risk of oral and pharyngeal cancer. Fruit and vegetables were inversely related to the risk: the pooled relative risk (RR) for high vegetable consumption was 0.65 from three cohort studies on upper aerodigestive tract cancers and 0.52 from 18 case-control studies of oral and pharyngeal cancer; corresponding RRs for high fruit consumption were 0.78 and 0.55. beta-carotene, vitamin C and selected flavonoids have been inversely related to the risk, but it is difficult to disentangle their potential effect from that of fruit and vegetables. Whole grain, but not refined grain, intake was also favorably related to oral cancer risk. The results were not consistent with reference to other foods beverages, and nutrients, but it is now possible to exclude a strong relation between these foods and oral and pharyngeal cancer risk. In western countries, selected aspects of diet may account for 20-25% of oral and pharyngeal cancer, and the population attributable risk increases to 85-95% when tobacco and alcohol consumption are also considered.

Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer

Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.

Açai Palm Fruit (Euterpe oleracea Mart.) Pulp Improves Survival of Flies on a High Fat Diet

Reducing oxidative damage is thought to be an effective aging intervention. Açai, a fruit indigenous to the Amazon, is rich in phytochemicals that possesses high anti-oxidant activities, and has anti-inflammatory, anti-cancer and anti-cardiovascular disease properties. However, little is known about its potential anti-aging properties especially at the organismal level. Here we evaluated the effect of açai pulp on modulating lifespan in Drosophila melanogaster. We found that açai supplementation at 2% in the food increased the lifespan of female flies fed a high fat diet compared to the non-supplemented control. We measured transcript changes induced by açai for age-related genes. Although transcript levels of most genes tested were not altered, açai increased the transcript level of l(2)efl, a small heat-shock-related protein, and two detoxification genes, gstD1 and mtnA, while decreasing the transcript level of phosphoenolpyruvate carboxykinase (Pepck), a key gene involved in gluconeogenesis. Furthermore, açai increased the lifespan of oxidative stressed females caused by sod1 RNAi. This suggests that açai improves survival of flies fed a high fat diet through activation of stress response pathways and suppression of Pepck expression. Açai has the potential to antagonize the detrimental effect of fat in the diet and alleviate oxidative stress in aging.

Bronchial reactivity and dietary antioxidants

BACKGROUND: It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants. METHODS: The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity. RESULTS: Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than fivefold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity. CONCLUSIONS: This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.

Postprandial metabolic events and fruit-derived phenolics: a review of the science.

There is increasing evidence that the postprandial state is an important contributing factor to chronic disease. The role of fruit phenolic compounds to protect health and lower disease risk through their actions in mitigating fed-state metabolic and oxidative stressors is of interest and the topic of the present paper. Two main questions are posed: first, what is the role of plant foods, specifically fruits rich in complex and simple phenolic compounds in postprandial metabolic management; and second, does the evidence support consuming these fruits with meals as a practical strategy to preserve health and lower risk for disease? This review provides an overview of the postprandial literature, specifically on the effect of fruits and their inherent phenolic compounds in human subjects on postprandial lipaemia, glycaemia/insulinaemia and associated events, such as oxidative stress and inflammation. Among the identified well-controlled human trials using a postprandial paradigm, >50 % of the trials used wine or wine components and the remaining used various berries. Notwithstanding the need for more research, the collected data suggest that consuming phenolic-rich fruits increases the antioxidant capacity of the blood, and when they are consumed with high fat and carbohydrate 'pro-oxidant and pro-inflammatory' meals, they may counterbalance their negative effects. Given the content and availability of fat and carbohydrate in the Western diet, regular consumption of phenolic-rich foods, particularly in conjunction with meals, appears to be a prudent strategy to maintain oxidative balance and health.

Effects of low animal protein or high-fiber diets on urine composition in calcium nephrolithiasis.

BACKGROUND: The purpose of this article is to evaluate the impact of low protein and high fiber intakes on risk factors of stone recurrence in idiopathic calcium stone formers (ICSFs). METHODS: Ninety-six ICSFs were randomly assigned a low animal protein diet (< 10% of total energy), a high-fiber diet (> 25 g/day), or a usual diet (control group); all patients were recommended to increase their fluid intake. Their daily urine compositions were analyzed at baseline and at four months. Compliance with dietary recommendations was checked by validated food frequency questionnaires. Compliance with total and animal protein intakes was assessed by 24-hour urea and sulfate outputs, respectively. The nutritional intervention (oral instructions, written leaflet, phoning) and food assessment were carried out by a research dietitian. RESULTS: At baseline, diets and the daily urine composition did not differ between the three groups. At four months, while diets differed significantly, the 24-hour output of calcium and oxalate did not differ significantly within and between groups after adjustment for potential confounders (age, sex, and personal and family history of calcium stones) and baseline values. However, as many as 12 out of 31 ICSFs (95% CI, 22 to 58%) assigned to a low animal protein diet achieved a reduction in the urine urea excretion rate of more than 50 mmol/day and also exhibited a significant decrease in urinary calcium excretion that averaged 1.8 mmol/day. A significant correlation between urea and calcium outputs was observed only among patients with hypercalciuria. CONCLUSIONS: These results show that only ICSFs who markedly decrease their animal protein intake, especially those with hypercalciuria, can expect to benefit from dietary recommendations.

Prevalence of Vitamin A Deficiency in South Asia: Causes, Outcomes, and Possible Remedies

Vitamin A deficiency (VAD) has been recognized as a public-health issue in developing countries. Economic constraints, sociocultural limitations, insufficient dietary intake, and poor absorption leading to depleted vitamin A stores in the body have been regarded as potential determinants of the prevalence of VAD in South Asian developing countries. VAD is exacerbated by lack of education, poor sanitation, absence of new legislation and enforcement of existing food laws, and week monitoring and surveillance system. Several recent estimates confirmed higher morbidly and mortality rate among children and pregnant and non-pregnant women of childbearing age. Xerophthalmia is the leading cause of preventable childhood blindness with its earliest manifestations as night blindness and Bitot's spots, followed by blinding keratomalacia, all of which are the ocular manifestations of VAD. Children need additional vitamin A because they do not consume enough in their normal diet. There are three general ways for improving vitamin A status: supplementation, fortification, and dietary diversification. These approaches have not solved the problem in South Asian countries to the desired extent because of poor governmental support and supervision of vitamin A supplementation twice a year. An extensive review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science, and Google Scholar. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. Conclusively, high prevalence of VAD in South Asian developing countries leads to increased morbidity and mortality among infants, children, and pregnant women. Therefore, stern efforts are needed to address this issue of public-health significance at local and international level in lower- and middle-income countries of South Asia.

Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial...

Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.

Reduced or modified dietary fat for preventing cardiovascular disease.

BACKGROUND: Reduction or modification of dietary fat can improve total cholesterol levels, but may also have a variety of effects, both positive and negative, on other cardiovascular risk factors. OBJECTIVES: The aim of this systematic review was to assess the effect of reduction or modification of dietary fats on total and cardiovascular mortality and cardiovascular morbidity over at least 6 months, using all available randomized clinical trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE, CAB s, CVRCT registry and related Cochrane Groups' trial registers were searched through spring 1998, SIGLE to January 1999. Trials known to experts in the field and biographies were included through May 1999. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomized with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) healthy adult humans, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party. DATA COLLECTION AND ANALYSIS: Rate data were extracted by two independent reviewers and meta-analysis performed using random effects methodology. Meta-regression and funnel plots were used. MAIN RESULTS: Twenty seven studies were included (40 intervention arms, 30,901 person-years). There was no significant effect on total mortality (rate ratio 0.98, 95% CI 0.86 to 1.12), a trend towards protection form cardiovascular mortality (rate ratio 0.91, 95% CI 0.77 to 1.07), and significant protection from cardiovascular events (rate ratio 0.84, 95% CI 0.72 to 0.99). The latter became non-significant on sensitivity analysis. Trials where participants were involved for more than 2 years showed significant reductions in the rate of cardiovascular events and a suggestion of protection from total mortality. The degree of protection from cardiovascular events appeared similar in high and low risk groups, but was statistically significant only in the former. REVIEWER'S CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk in trials longer than two years. Lifestyle advice to all those at high risk of cardiovascular disease (especially where statins are unavailable or rationed), and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates.

Potential role of FoxO1 and mTORC1 in the pathogenesis of Western diet-induced acne

Acne in adolescents of developed countries is an epidemic skin disease and has currently been linked to the Western diet (WD). It is the intention of this viewpoint to discuss the possible impact of WD-mediated nutrient signalling in the pathogenesis of acne. High glycaemic load and dairy protein consumption both increase insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) that is superimposed on elevated IGF-1 signalling of puberty. The cell's nutritional status is primarily sensed by the forkhead box transcription factor O1 (FoxO1) and the serine/threonine kinase mammalian target of rapamycin complex 1 (mTORC1). Increased IIS extrudes FoxO1 into the cytoplasm, whereas nuclear FoxO1 suppresses hepatic IGF-1 synthesis and thus impairs somatic growth. FoxO1 attenuates androgen signalling, interacts with regulatory proteins important for sebaceous lipogenesis, regulates the activity of innate and adaptive immunity, antagonizes oxidative stress and most importantly functions as a rheostat of mTORC1, the master regulator of cell growth, proliferation and metabolic homoeostasis. Thus, FoxO1 links nutrient availability to mTORC1-driven processes: increased protein and lipid synthesis, cell proliferation, cell differentiation including hyperproliferation of acroinfundibular keratinocytes, sebaceous gland hyperplasia, increased sebaceous lipogenesis, insulin resistance and increased body mass index. Enhanced androgen, TNF-α and IGF-1 signalling due to genetic polymorphisms promoting the risk of acne all converge in mTORC1 activation, which is further enhanced by nutrient signalling of WD. Deeper insights into the molecular interplay of FoxO1/mTORC1-mediated nutrient signalling are thus of critical importance to understand the impact of WD on the promotion of epidemic acne and more serious mTORC1-driven diseases of civilization.

Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish.

Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.

Effect of dietary patterns on measures of lipid peroxidation: results from a randomized clinical trial.

BACKGROUND: Free radical-mediated oxidative damage to lipids is thought to be an important process in the pathogenesis of atherosclerosis. Although previous studies have demonstrated a beneficial impact of antioxidant vitamin supplements on lipid peroxidation, the effect of dietary patterns on lipid peroxidation is unknown. METHODS AND RESULTS: During the 3-week run-in period of a randomized trial, 123 healthy individuals were fed a control diet, low in fruits, vegetables, and dairy products, with 37% of calories from fat. Participants were then randomized to consume for 8 weeks: (1) the control diet, (2) a diet rich in fruits and vegetables but otherwise similar to the control diet, and (3) a combination diet rich in fruits, vegetables, and low-fat dairy products and reduced in fat. Serum oxygen radical-absorbing capacity, malondialdehyde (an in vitro measure of lipid peroxidation), and breath ethane (an in vivo measure of lipid peroxidation) were measured at the end of run-in and intervention periods. Between run-in and intervention, mean (95% CI) change in oxygen radical-absorbing capacity (U/mL) was -35 (-93, 13) in the control diet, 26 (-15, 67) in the fruits and vegetables diet (P=0.06 compared with control), and 19 (-22, 54) in the combination diet (P=0.10 compared with control). Median (interquartile range) change in ethane was 0.84 (0.10, 1.59) in the control diet, 0.02 (-0.61, 0.83) in the fruits and vegetables diet (P=0.04 compared with control), and -1.00 (-1.97, 0.25) in the combination diet (P=0.005 compared with control). Change in malondialdehyde did not differ between diets. CONCLUSIONS: This study demonstrates that modification of diet can favorably affect serum antioxidant capacity and protect against lipid peroxidation.

Effects of almond consumption on the reduction of LDL-cholesterol: a discussion of potential mechanisms and future research directions.

Diet plays a seminal role in the prevention and treatment of cardiovascular disease. Consumption of tree nuts has been shown to reduce low-density lipoprotein cholesterol (LDL-C), a primary target for coronary disease prevention, by 3-19%. Almonds have been found to have a consistent LDL-C-lowering effect in healthy individuals, and in individuals with high cholesterol and diabetes, in both controlled and free-living settings. Almonds are low in saturated fatty acids, rich in unsaturated fatty acids, and contain fiber, phytosterols, and plant protein. Other cardioprotective nutrients unique to almonds include α-tocopherol, arginine, magnesium, copper, manganese, calcium, and potassium. Mechanisms responsible for the LDL-C reduction observed with almond consumption are likely associated with the nutrients almonds provide. Biologically active by nature, these nutrients target primary mechanistic routes of LDL-C reduction, including decreased (re)absorption of cholesterol and bile acid, increased bile acid and cholesterol excretion, and increased LDL-C receptor activity. The nutrients present in almonds may regulate enzymes involved in de novo cholesterol synthesis and bile acid production. Research is needed to understand all mechanisms by which almonds reduce cardiovascular disease risk. © 2011 International Life Sciences Institute.

Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-defici...

Diet contributes to over one-third of cancer deaths in the Western world, yet the factors in the diet that influence cancer are not elucidated. A reduction in caloric intake dramatically slows cancer progression in rodents, and this may be a major contribution to dietary effects on cancer. Insulin-like growth factor I (IGF-I) is lowered during dietary restriction (DR) in both humans and rats. Because IGF-I modulates cell proliferation, apoptosis, and tumorigenesis, the mechanisms behind the protective effects of DR may depend on the reduction of this multifaceted growth factor. To test this hypothesis, IGF-I was restored during DR to ascertain if lowering of IGF-I was central to slowing bladder cancer progression during DR. Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice using recombinant IGF-I administered via osmotic minipumps. Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression. This is the first mechanistic study demonstrating that IGF-I supplementation abrogates the protective effect of DR on neoplastic progression.

A systematic review and meta-analysis of the effects of pasteurization on milk vitamins, and evidence for raw milk consumption and other health-rel...

Pasteurization of milk ensures safety for human consumption by reducing the number of viable pathogenic bacteria. Although the public health benefits of pasteurization are well established, pro-raw milk advocate organizations continue to promote raw milk as "nature's perfect food." Advocacy groups' claims include statements that pasteurization destroys important vitamins and that raw milk consumption can prevent and treat allergies, cancer, and lactose intolerance. A systematic review and meta-analysis was completed to summarize available evidence for these selected claims. Forty studies assessing the effects of pasteurization on vitamin levels were found. Qualitatively, vitamins B12 and E decreased following pasteurization, and vitamin A increased. Random effects meta-analysis revealed no significant effect of pasteurization on vitamin B6 concentrations (standardized mean difference [SMD], -2.66; 95% confidence interval [CI], -5.40, 0.8; P = 0.06) but a decrease in concentrations of vitamins B1 (SMD, -1.77; 95% CI, -2.57, -0.96; P < 0.001), B2 (SMD, -0.41; 95% CI, -0.81, -0.01; P < 0.05), C (SMD, -2.13; 95% CI, -3.52, -0.74; P < 0.01), and folate (SMD, -11.99; 95% CI, -20.95, -3.03; P < 0.01). The effect of pasteurization on milk's nutritive value was minimal because many of these vitamins are naturally found in relatively low levels. However, milk is an important dietary source of vitamin B2, and the impact of heat treatment should be further considered. Raw milk consumption may have a protective association with allergy development (six studies), although this relationship may be potentially confounded by other farming-related factors. Raw milk consumption was not associated with cancer (two studies) or lactose intolerance (one study). Overall, these findings should be interpreted with caution given the poor quality of reported methodology in many of the included studies.

Effects of vitamins C and E on N-nitroso compound formation, carcinogenesis, and cancer.

The properties of N-nitroso compounds (NNC) and of vitamins C and E are briefly described. The author reviews the ability of vitamins C and E to inhibit NNC formation in chemical systems, in nitrite-preserved meat, in experimental animals and in humans. Dietary vitamins C and E both produced 30% to 60% inhibitions in most carcinogenesis experiments employing preformed carcinogens. Vitamin C reversed transformation in an in vitro system. Carcinogenicity tests of the vitamins are reviewed (vitamin C can promote bladder carcinogenesis). Intake of fresh fruits and vegetables (which contain vitamin C) is negatively correlated with cancer of the stomach, esophagus, larynx, mouth and cervix. For gastric and esophageal cancer, there is evidence that this association is due to an inhibition of in vivo NNC formation. Vitamin C is apparently not a useful treatment for cancer. The author supports the recommendation that fresh fruit and vegetable intake be increased to lower the risk of cancer.

Essentials of Healthy Eating: A Guide

Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.

Does a vegan diet reduce risk for Parkinson's disease?

Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.

Dietary pattern and depressive symptoms in middle age

Background Studies of diet and depression have focused primarily on individual nutrients. Aims To examine the association between dietary patterns and depression using an overall diet approach. Method Analyses were carried on data from 3486 participants (26.2% women, mean age 55.6 years) from the Whitehall II prospective cohort, in which two dietary patterns were identified: ‘whole food’ (heavily loaded by vegetables, fruits and fish) and ‘processed food’ (heavily loaded by sweetened desserts, fried food, processed meat, refined grains and high-fat dairy products). Self-reported depression was assessed 5 years later using the Center for Epidemiologic Studies – Depression (CES–D) scale. Results After adjusting for potential confounders, participants in the highest tertile of the whole food pattern had lower odds of CES–D depression (OR = 0.74, 95% CI 0.56–0.99) than those in the lowest tertile. In contrast, high consumption of processed food was associated with an increased odds of CES–D depression (OR = 1.58, 95% CI 1.11–2.23). Conclusions In middle-aged participants, a processed food dietary pattern is a risk factor for CES–D depression 5 years later, whereas a whole food pattern is protective.

Plant foods and the risk of cerebrovascular diseases: a potential protection of fruit consumption.

Studies on the association between plant foods and cerebrovascular diseases have given contradictory results suggesting the existence of some effect-modifying factors. The present study determines whether the consumption of plant foods (i.e. fruits and berries, vegetables, and cereals) predicts a decreased cerebrovascular disease incidence in a population with low fruit and vegetable and high wholegrain intake. This cohort study on 3932 men and women was based on data from the Finnish Mobile Clinic Health Examination Survey, conducted in 1968-72. The participants were 40-74 years of age and free of cardiovascular diseases at baseline. Data on the plant food consumption were derived from a 1-year dietary history interview. During a 24-year follow-up 625 cases of cerebrovascular diseases occurred, leading to either hospitalisation or death. An inverse association was found between fruit consumption and the incidence of cerebrovascular diseases, ischaemic stroke and intracerebral haemorrhage. The adjusted relative risks (RR) between the highest and lowest quartiles of intake of any cerebrovascular disease, ischaemic stroke and intracerebral haemorrhage were 0.75 (95 % CI 0.59, 0.94), 0.73 (95 % CI 0.54, 1.00) and 0.47 (95 % CI 0.24, 0.92), respectively. These associations were primarily due to the consumption of citrus fruits and occurred only in men. Total consumption of vegetables or cereals was not associated with the cerebrovascular disease incidence. The consumption of cruciferous vegetables, however, predicted a reduced risk of cerebrovascular diseases (RR 0.79; 95 % CI 0.63, 0.99), ischaemic stroke (RR 0.67; 95 % CI 0.49, 0.92) and intracerebral haemorrhage (RR 0.49; 95 % CI 0.25, 0.98). In conclusion, the consumption of fruits, especially citrus, and cruciferous vegetables may protect against cerebrovascular diseases.

Fostering antioxidant defences: up-regulation of antioxidant genes or antioxidant supplementation?

Vitamins have traditionally been considered as food components that are required in the normal diet to prevent deficiencies. However, a newer concept of the function of vitamins in nutrition has taken them beyond simply prevention of deficiency symptoms. This concept considers that many vitamins, when taken in relatively large doses, have important functions beyond preventing deficiencies. Linus Pauling was instrumental in putting forward this concept, particularly for vitamin C. Thus, relatively high intakes of vitamins, and in particular vitamins C and E which are antioxidants, are considered to be healthy for the human population. This may be true in some special situations such as, for instance, the prevention of Alzheimer's disease progression. However, recent epidemiological evidence has not supported the claim that antioxidant vitamins increase well-being and prolong life span. In fact, vitamin supplementation may be even detrimental and reduce life span. A new concept that we would like to put forward is that nutrients up-regulate the endogenous antioxidant defences. This is particularly true in the case of phytoestrogens for example, which bind to oestrogen receptors and eventually up-regulate the expression of antioxidant genes. In this review we discuss the pros and cons of antioxidant vitamin supplementation and also the possibility that the ingestion of some nutrients may be very effective in increasing antioxidant defences by up-regulating the activity of antioxidant enzymes which are normally present in the cell.

Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants.

The need for a dietary supply of docosahexaenoic acid (DHA) and arachidonic aid (AA) in term infants was evaluated in a double-masked randomized clinical trial of the effects of supplementation of term infant formula with DHA (0.35% of total fatty acids) or with DHA (0.36%) and AA (0.72%) on visual acuity development. One hundred and eight healthy term infants were enrolled in the study; 79 were exclusively formula-fed from birth (randomized group) and 29 were exclusively breast-fed (gold standard group). Infants were evaluated at four time points during the first 12 mo of life for blood fatty acid composition, growth, sweep visual evoked potential (VEP) acuity, and forced choice preferential looking acuity. Supplementation of term infant formula with DHA or with DHA and AA during the first 4 mo of life yields clear differences in total red blood cell (RBC) lipid composition. Supplementation of term infant formula with DHA or with DHA and AA also yields better sweep VEP acuity at 6, 17, and 52 wk of age but not at 26 wk of age, when acuity development reaches a plateau. The RBC lipid composition and sweep VEP acuity of supplemented infants was similar to that of human milk-fed infants, whereas the RBC lipid composition and sweep VEP acuity of unsupplemented infants was significantly different from human milk-fed infants. Differences in acuity among diet groups were too subtle to be detected by the forced choice preferential looking protocol. Infants in all diet groups had similar rates of growth and tolerated all diets well. Thus, early dietary intake of preformed DHA and AA appears necessary for optimal development of the brain and eye of the human infant.

Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations.

Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.

Lifestyle recommendations to reduce the risk of kidney stones.

Kidney stones are increasingly common in wealthy industrialized countries. The most frequent form (80%) is idiopathic calcium stone disease. Eating habits and lifestyle have a direct effect on the lithogenic urinary risk factors and the pathogenesis of this condition. A diet characterized by a high intake of fluids, fruits, and vegetables; a low consumption of salt and protein; and a balanced intake of calcium, fats, and carbohydrates constitutes an efficacious approach to the prevention and treatment of this illness. A correct body weight, regular exercise, and a reduction in stressful life events are also useful preventive actions. Copyright © 2011 Elsevier Inc. All rights reserved.

Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area

Pancreatic cancer is highly lethal, and identifying modifiable risk factors could have substantial public health impact. In this population-based case-control study (532 cases, 1701 controls), we used principal component analysis and multivariable unconditional logistic regression models to examine whether a particular dietary pattern was associated with risk of pancreatic cancer, adjusting for other known risk factors. A Prudent dietary pattern, characterized by greater intake of vegetables, fruit, fish, poultry, whole grains, and low-fat dairy, was associated with an approximate 50% reduction in pancreatic cancer risk among men (OR=0.51, 95% CI 0.31-0.84, p-trend=0.001) and women (OR=0.51, 95% CI 0.29-0.90, p-trend=0.04). A Western dietary pattern, characterized by higher intake of red and processed meats, potato chips, sugary beverages, sweets, high fat dairy, eggs, and refined grains, was associated with a 2.4-fold increased risk of pancreatic cancer among men (95% CI 1.3-4.2, p-trend=0.008); but was not associated with risk among women. Among men, those in the upper quintiles of the Western diet and lower quintiles of the Prudent diet had a 3-fold increased risk. Consistent with what has been recommended for several other chronic diseases, consuming a diet rich in plant-based foods, whole grains, and white meat, might reduce risk of pancreatic cancer.

"Towards an even healthier Mediterranean diet".

Dietary guidelines to promote good health are usually based on foods, nutrients, and dietary patterns predictive of chronic disease risk in epidemiologic studies. However, sound nutritional recommendations for cardiovascular prevention should be based on the results of large randomized clinical trials with "hard" end-points as the main outcome. Such evidence has been obtained for the Mediterranean diet from the PREDIMED (Prevención con Dieta Mediterránea) trial and the Lyon Heart Study. The traditional Mediterranean diet was that found in olive growing areas of Crete, Greece, and Southern Italy in the late 1950s. Their major characteristics include: a) a high consumption of cereals, legumes, nuts, vegetables, and fruits; b) a relatively high-fat consumption, mostly provided by olive oil; c) moderate to high fish consumption; d) poultry and dairy products consumed in moderate to small amounts; e) low consumption of red meats, and meat products; and f) moderate alcohol intake, usually in the form of red wine. However, these protective effects of the traditional Mediterranean diet may be even greater if we upgrade the health effects of this dietary pattern changing the common olive oil used for extra-virgin olive oil, increasing the consumption of nuts, fatty fish and whole grain cereals, reducing sodium intake, and maintaining a moderate consumption of wine with meals. © 2013 Elsevier B.V. All rights reserved.

Colon cancer and diet, with special reference to intakes of fat and fiber.

Colon cancer, rare in the past, and in developing populations, currently accounts for 2 to 4% of all deaths in Western populations. Evidence suggests the primary cause to be changes in diet, which affect the bowel milieu intérieur. It is possible that in sophisticated populations, the higher concentrations of fecal bile acids and sterols, and longer transit time, favor the production of potentially carcinogenic metabolites. Of secular changes in diet, evidence suggests that the following may have etiological importance: 1) the fall in intake of fiber-containing foods with its effects on bowel physiology, and 2) the decreased fiber but increased fat intakes, in their respective capacities to raise concentrations of fecal bile acids, sterols, and other noxious substances. For possible prophylaxis against colon cancer, recommendations for a lower fat intake, or a higher intake of fiber-containing foods (apart from fiber ingestion from bran) are extremely unlikely to be adopted. For future research, western populations with considerably lower than average mortality rates, e.g., Seventh Day Adventists, Mormons, the rural Finnish population, as well as developing populations, demand intensive study. Also requiring elucidation are the respective roles of diet and of genetic constitution on concentrations of fecal bile acids, etc., and on transit time, in prone and nonprone populations.

Whole grains and human health.

Epidemiological studies find that whole-grain intake is protective against cancer, CVD, diabetes, and obesity. Despite recommendations to consume three servings of whole grains daily, usual intake in Western countries is only about one serving/d. Whole grains are rich in nutrients and phytochemicals with known health benefits. Whole grains have high concentrations of dietary fibre, resistant starch, and oligosaccharides. Whole grains are rich in antioxidants including trace minerals and phenolic compounds and these compounds have been linked to disease prevention. Other protective compounds in whole grains include phytate, phyto-oestrogens such as lignan, plant stanols and sterols, and vitamins and minerals. Published whole-grain feeding studies report improvements in biomarkers with whole-grain consumption, such as weight loss, blood-lipid improvement, and antioxidant protection. Although it is difficult to separate the protective properties of whole grains from dietary fibre and other components, the disease protection seen from whole grains in prospective epidemiological studies far exceeds the protection from isolated nutrients and phytochemicals in whole grains.

No evidence of insulin resistance in normal weight vegetarians. A case control study.

BACKGROUND: Diets rich in carbohydrates with a low glycemic index and with high fiber content are associated with flat post-prandial rises of blood glucose, minimal post-prandial insulin secretion and maintenance of insulin sensitivity. Protective food commodities in the prevention of cardiovascular disease, insulin resistance syndrome or diabetes are crucial components of the vegetarian diet. AIM OF THE STUDY: Insulin resistance values were assessed in relation to different nutrition. Metabolic abnormality is a predictor of age-related diseases and can be more pronounced in obese subjects. Insulin resistance values in normal weight subjects of two different nutritional habits were correlated with age. METHODS: Fasting concentrations of glucose and insulin as well as calculated values of insulin resistance IR (HOMA) were assessed in two nutritional groups of apparently healthy adult subjects (age range 19 - 64 years) with normal weight (body mass index 18.6 - 25.0 kg/m(2)): a vegetarian group (95 long-term lacto-ovo-vegetarians; duration of vegetarianism 10.2 +/- 0.5 years) and a non-vegetarian control group (107 subjects of general population on traditional western diet). Intake of energy and main nutrients (fats, saccharides, proteins) was similar in both groups. RESULTS: Glucose and insulin concentrations and IR (HOMA) values were significantly lower in vegetarians (glucose 4.47 +/- 0.05 vs. 4.71 +/- 0.07 mmol/l; insulin 4.96 +/- 0.23 vs. 7.32 +/- 0.41 mU/l; IR (HOMA) 0.99 +/- 0.05 vs. 1.59 +/- 0.10). IR (HOMA) dependence on age was only significant in subjects on a western diet. A significant increase of IR was found already in the age range 31-40 years, compared to vegetarians and it continued in later age decades. Age independent and low insulin resistance values in vegetarians are a consequence of an effective diet prevention by long-term frequent consumption of protective food. Vegetarians had a significantly higher consumption of whole grain products, pulses, products from oat and barley. CONCLUSION: The results of age independent and low values of insulin resistance document a beneficial effect of long-term vegetarian nutrition in prevention of metabolic syndrome, diabetes and cardiovascular disease.

High dietary antioxidant intakes are associated with decreased chromosome translocation frequency in airline pilots

Background: Dietary antioxidants may protect against DNA damage induced by endogenous and exogenous sources, including ionizing radiation (IR), but data from IR-exposed human populations are limited. Objective: The objective was to examine the association between the frequency of chromosome translocations, as a biomarker of cumulative DNA damage, and intakes of vitamins C and E and carotenoids in 82 male airline pilots. Design: Dietary intakes were estimated by using a self-administered semiquantitative food-frequency questionnaire. Translocations were scored by using fluorescence in situ hybridization with whole chromosome paints. Negative binomial regression was used to estimate rate ratios and 95% CIs, adjusted for potential confounders. Results: Significant and inverse associations were observed between translocation frequency and intakes of vitamin C, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food (P < 0.05). Translocation frequency was not associated with the intake of vitamin E, α-carotene, or lycopene from food; total vitamin C or E from food and supplements; or vitamin C or E or multivitamin supplements. The adjusted rate ratios (95% CI) for ≥median compared with <median servings per week of high–vitamin C fruit and vegetables, citrus fruit, and green leafy vegetables were 0.61 (0.43, 0.86), 0.64 (0.46, 0.89), and 0.59 (0.43, 0.81), respectively. The strongest inverse association was observed for ≥median compared with <median combined intakes of vitamins C and E, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food: 0.27 (0.14, 0.55). Conclusion: High combined intakes of vitamins C and E, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food, or a diet high in their food sources, may protect against cumulative DNA damage in IR-exposed persons.

Vitamin A, carotenoids, and risk of persistent oncogenic human papillomavirus infection.

Oncogenic human papillomavirus (HPV) infection is the main etiologic factor for cervical neoplasia, although infection alone is insufficient to produce disease. Cofactors such as nutritional factors may be necessary for viral progression to neoplasia. Results from previous studies have suggested that higher dietary consumption and circulating levels of certain micronutrients may be protective against cervical neoplasia. This study evaluated the role of vitamin A and carotenoids on HPV persistence comparing women with intermittent and persistent infections. As determined by the Hybrid Capture II system, oncogenic HPV infections were assessed at baseline and at approximately 3 and 9 months postbaseline. Multivariate logistic regression analysis was used to determine the risk of persistent HPV infection associated with each tertile of dietary and circulating micronutrients. Higher levels of vegetable consumption were associated with a 54% decrease risk of HPV persistence (adjusted odds ratio, 0.46; 95% confidence interval, 0.21-0.97). Also, a 56% reduction in HPV persistence risk was observed in women with the highest plasma cis-lycopene concentrations compared with women with the lowest plasma cis-lycopene concentrations (adjusted odds ratio, 0.44; 95% confidence interval, 0.19-1.01). These data suggest that vegetable consumption and circulating cis-lycopene may be protective against HPV persistence.

Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study.

Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in "low-risk" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in "high-risk" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.

Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal.

Physiological and pharmacological blood concentrations of melatonin inhibit tumorigenesis in a variety of in vivo and in vitro experimental models of neoplasia. Evidence indicates that melatonin's anticancer effects are exerted via inhibition of cell proliferation and a stimulation of differentiation and apoptosis. A new mechanism by which physiological and pharmacological blood levels of melatonin inhibit cancer growth in vivois via a melatonin-induced suppression of tumor linoleic acid (LA) uptake and its metabolism to the important mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin suppresses cAMP formation and inhibits tumor uptake of LA and its metabolism to 13-HODE via a melatonin receptor-mediated mechanism in both tissue-isolated rat hepatoma 7288 CTC and human breast cancer xenografts. It has been postulated that in industrialized societies, light at night, by suppressing melatonin production, poses a new risk for the development of breast cancer and, perhaps, other cancers as well. In support of this hypothesis, light during darkness suppresses nocturnal melatonin production and stimulates the LA metabolism and growth of rat hepatoma and human breast cancer xenografts. Nocturnal dietary supplementation with melatonin, at levels contained in a melatonin-rich diet, inhibits rat hepatoma growth via the mechanisms described above. The nocturnal melatonin signal organizes tumor metabolism and growth within circadian time structure that can be further reinforced by appropriately timed melatonin supplementation. Dietary melatonin supplementation working in concert with the endogenous melatonin signal has the potential to be a new preventive/therapeutic strategy to optimize the host/cancer balance in favor of host survival and quality of life.

Food selection based on high total antioxidant capacity improves endothelial function in a low cardiovascular risk population.

BACKGROUND AND AIMS: Oxidative stress has been advocated as a major cause for cardiovascular disease (CVD), and low plasma antioxidant concentrations are associated with endothelial dysfunction, the first step towards atherosclerosis. However, although the antioxidant content in fruits and vegetables may explain at least in part their protective effect against CVD, supplementation with antioxidant vitamins fails to improve endothelial function and reduce CVD risk. The aim of this study was to investigate the impact of a diet rich in antioxidants on endothelial function measured by flow-mediated dilatation (FMD) in volunteers at low cardiovascular risk. METHODS AND RESULTS: In a crossover trial, 24 subjects (13 women, mean age 61 ± 3 years), received, in a randomised order, a 14-day high (HT) and a 14-day low (LT) antioxidant diets, with a 2-week wash-out (WO) in between. Both diets were comparable in daily portions of fruits and vegetables, and in alcohol, fibre and macronutrient intake, but differed in their total antioxidant capacity. Before and after each diet, anthropometrics, blood pressure, fasting plasma glucose, lipid profile, hepatic enzymes, circulating antioxidant concentrations, high sensitivity C-reactive protein (hs-CRP) and FMD were assessed. FMD increased significantly during the HT diet compared to the LT (p < 0.000). FMD values were 2.3% higher after HT compared with LT (p < 0.001) after adjustment for age, gender and diet order. α-tocopherol increased significantly (p < 0.05) and hs-CRP and of γ-glutamyltranspeptidase decreased significantly (p < 0.05 and p < 0.01, respectively) during the HT diet, compared with the LT diet. CONCLUSIONS: A short-term HT diet improves endothelial function in volunteers at low cardiovascular risk, which may further reduce their risk of CVD. Copyright © 2010 Elsevier B.V. All rights reserved.

Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis.

There is strong evidence indicating that elevated plasma total homocysteine (tHcy) levels are a major independent biomarker and/or a contributor to chronic conditions, such as CVD. A deficiency of vitamin B₁₂ can elevate homocysteine. Vegetarians are a group of the population who are potentially at greater risk of vitamin B₁₂ deficiency than omnivores. This is the first systematic review and meta-analysis to appraise a range of studies that compared the homocysteine and vitamin B₁₂ levels of vegetarians and omnivores. The search methods employed identified 443 entries, from which, by screening using set inclusion and exclusion criteria, six eligible cohort case studies and eleven cross-sectional studies from 1999 to 2010 were revealed, which compared concentrations of plasma tHcy and serum vitamin B₁₂ of omnivores, lactovegetarians or lacto-ovovegetarians and vegans. Of the identified seventeen studies (3230 participants), only two studies reported that vegan concentrations of plasma tHcy and serum vitamin B₁₂ did not differ from omnivores. The present study confirmed that an inverse relationship exists between plasma tHcy and serum vitamin B₁₂, from which it can be concluded that the usual dietary source of vitamin B₁₂ is animal products and those who choose to omit or restrict these products are destined to become vitamin B₁₂ deficient. At present, the available supplement, which is usually used for fortification of food, is the unreliable cyanocobalamin. A well-designed study is needed to investigate a reliable and suitable supplement to normalise the elevated plasma tHcy of a high majority of vegetarians. This would fill the gaps in the present nutritional scientific knowledge.

Diet and risk of kidney stones in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).

The lifetime prevalence of kidney stones is around 10 % and incidence rates are increasing. Diet may be an important determinant of kidney stone development. Our objective was to investigate the association between diet and kidney stone risk in a population with a wide range of diets. This association was examined among 51,336 participants in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition using data from Hospital Episode Statistics in England and Scottish Morbidity Records. In the cohort, 303 participants attended hospital with a new kidney stone episode. Cox proportional hazards regression was performed to calculate hazard ratios (HR) and their 95 % confidence intervals (95 % CI). Compared to those with high intake of meat (>100 g/day), the HR estimates for moderate meat-eaters (50-99 g/day), low meat-eaters (<50 g/day), fish-eaters and vegetarians were 0.80 (95 % CI 0.57-1.11), 0.52 (95 % CI 0.35-0.8), 0.73 (95 % CI 0.48-1.11) and 0.69 (95 % CI 0.48-0.98), respectively. High intakes of fresh fruit, fibre from wholegrain cereals and magnesium were also associated with a lower risk of kidney stone formation. A high intake of zinc was associated with a higher risk. In conclusion, vegetarians have a lower risk of developing kidney stones compared with those who eat a high meat diet. This information may be important to advise the public about prevention of kidney stone formation.

The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia.

Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.

Keratomalacia.

Xerophthalmia and keratomalacia are public health problems of great magnitude which are usually associated with multiple vitamin and protein deficiencies. The authors report the case of a 27-year-old commune member who subjected herself to a bizarre protein and vitamin deficient diet for many months. This ultimately produced nyctalopia, xerophthalmia and keratomalacia with bilateral corneal perforation. Despite therapy, she remained comatose and expired shortly after admission. Ocular pathological changes included bilateral corneal melting with prolapse of intraocular contents, conjunctival epidermidalization, goblet cell atrophy and thinning of the outer nuclear layer of the retina. It is noted that ocular findings in pure avitaminosis A produced experimentalyy include epithelial atrophy followed by keratinization.