Nutrition and Disease Prevention

This page brings you the latest developments in nutritional sciences on the role of food antioxidants and other nutrients in tuning-up the metabolism so that health is improved and aging slowed down. It is becoming clear that good healthy nutrition will be the preventive medicine of the future.

Through healthy nutrition we gain better health and improve the quality of life.
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So, another page on nutrition as if there were not too many already out there. However, this page won't bring you "news" such as good health is achieved through proper nutrition i.e. plenty of fresh fruit and vegetables and less meat, more exercise and outdoor activities, less stress and alike. This is common sense but good advice is seldom followed as we all know. If the above were headed there would not be so much obesity, degenerative diseases and all kind of other ailments that plague the western hemisphere today. Preventive medicine of which nutrition is an important part is still a concept not fully grasped by many people in the developed world.

The aim of this page is to focus on research in the nutrition sciences devoted to the role of food antioxidant factors in maintaining the redox balance of the cell, which is essential for the normal functioning of metabolism. To that end we will bring to your attention the latest in research articles on the relationship between dietary antioxidants and the health status of the individual as well as the mechanisms by which these antioxidants exert their action at cellular level. At times we will turn our attention to other micronutrients that were shown to help keep the metabolism tuned-up, which is crucial for maintaining good health.

In the following we shall look at research articles that report on the role of food antioxidants as free radical scavangers and as modulators of redox homeostasis of cells and signal tranductions pathways and possibly other cellular processes. As more and more people turn away from the expediency of fast foods to healthier diets nutrition experts are debating whether there really is a need for nutritional supplements to be added to our daily diet. Last May, as if in response to the continuing hype from the nutraceuticals industry, with an annual business of $12 billion a review paper was published in the Annals of Internal Medicine in which it was stated that: "....our conclusion is that the strength of evidence is insufficient to support the presence or the absence of a benefit from routine use of multivitamin and mineral supplements by adults in the United States for primary prevention of cancer, cardiovascular disease, hypertension, cataracts, or age-related macular degeneration,...." (1). On the other hand, numerous studies in the nutrition sciences journals and reports published by government health agencies indicate that a significant segment of North American population is deficient in folic acid and B12 vitamins and minerals such as zinc, selenium, magnesium. The fruit and vegetables in many North American supermarkets no longer contain the full spectrum of vitamins and minerals they once had. Organically-grown vegetables are rather expensive so supplementation appears a good choice for many people especially for those on a low income.

A topic that is getting more and more attention nowadays from biomedical researchers and consumers as well is the obesity epidemic and its related health problems. Numerous studies provided evidence that by reducing energy intake marked improvements in several biochemical / physiological markers of age-related illnesses could be documented. Thus, besides weight loss there was a clear increase in insulin / leptin sensitivity, a noticeable drop in blood pressure, which are hallmarks of better carbohydrate metabolism and liver function. We shall pay close attention to current research efforts in this field.

On this page you can also read about relevant scientific meetings devoted to the relationship between food/nutrition and disease prevention. Links to the original papers will allow you to explore in depth these exciting topics. Occasionally, articles written by well known experts in nutrition sciences and news from the nutraceuticals industry will be presented.

Science meetings

1. International Research Conference on Food, Nutrition and Cancer, July 13-14, 2006, Washington DC, USA.
Out of a variety of topics presented at the conference such as Nutritional and lifestyle factors in cancer prognosis, Lifestyle factors and survival in women with breast cancer, DNA metabolism an associated proteins (histones) and carcinogenesis, Molecular mechanisms in carcinogenesis, we shall focus on the communications devoted to the role of antioxidants in cancer prevention. In one presentation the role of ginseng preparations as potential cancer prevention/treatment agents and anti-inflammatory factors is discussed. Thus, ginseng appears to possess a potent effect on key players in the inflammatory cascade (2). In addition, ginseng can also inhibit other mediators of the inflammatory-to-cancer sequence. There is hope that better understanding of the mechanism of action of these natural antioxidants may provide an effective weapon in cancer prevention/therapy.

Cranberry fruit is rich in flavonoids (antocyanins and proanthocyanidins), catechins, hydroxycinamic acid and other phenols and triterpenoids. Besides their known antioxidant properties, these compounds were shown to possess anti- inflammatory activity, induce apoptosis in certain tumor cells and modulate the activity of two enzymes (ornithine decarboxylase and spermidine/spermine N-acetyltransferase) that control the cellular level of spermidine and spermine. These polyamines are involved in cell growth and proliferation and overexpression of the afore mentioned enzymes has been observed in cancer cell lines. The relevance of these findings in relation to cancer prevention strategies is discussed in another communication (3).

Certain dietary polyphenols from green tea and genistein from soybean were shown to inhibit DNA methylation in vitro. Activation of some methylation-silenced genes has been observed in several cancer cell lines and it has been speculated that the inhibition of methylation-induced inactivation of key tumor suppression genes may provide important clues for developing a strategy for cancer prevention. On the other hand, excessive intakes of polyphenols-containing dietary supplements may affect DNA methylation status and thus the turning on/off of genes that are associated with carcinogenesis (4). Caution should be exercised when taking dietary supplements since many naturally occurring antioxidants such as polyphenols and bioflavonoids exert their biological action at different cellular levels and too much of these compounds may have the reverse effect than the one being sought. Moreover, many such compounds undergo chemical modification in the body and the observed biological effects are often due to their chemical offsprings and not to the original compound present in food or dietary supplement.


Research articles and reviews

Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials. MacPherson, H. et al. (2013) Am.J.Clin.Nutr. 97, 437-444.
Taking multivitamin-multimineral (multivit/min) supplements is very fashionable nowadays in the developed world. But is it of any use? There is still disagreement among nutritionists, life biomedical sciences researchers and medical practitioners over the use of multivit/min supplements especially in the case of healthy people. It has been suggested that supplementation may be beneficial in the prevention of certain degenerative conditions. However, there is still controversy as to its value for curing diseases. Moreover, recent epidemiologic findings have suggested that multivit/min use may actually increase mortality risk. To have any real benefit supplementation must be considered in the wider context of healthy diet and lifestyle choices.
The aim of the present study was to determine whether multivit/min treatment used for primary or secondary prevention, increases the risk of mortality in free-living adults. The trials included in the meta-analysis looked at the daily multivit/min supplementation for a period longer than 1 year (the average duration of supplementation was 45 months). The results showed no effect of multivit/min treatment on all-cause mortality. There was a trend for a reduced risk of all-cause mortality across primary prevention trials. The supplementation had no effect on mortality due to vascular events or cancer. The conclusion of this analysis was that multivit/min supplementation has no effect on mortality risk.

High dietary intake of saturated fat is associated with reduced semen quality among 701 young Danish men from the general population. Jensen, T.K. et al. (2013) 97(2) 411-418.
The study found a low sperm concentration and total sperm count in men with a high intake of saturated fat. No association between semen quality and intake of other types of fat was observed. The findings reported here are important in the view of the changes in the diet over the past five decades that led to detrimental effects not only on general health but on the reproductive health as well.

Plasma uric acid is associated with increased risk of T2DM independent of diet and metabolic risk factors. Sluijs, I. et al. (2013) J.Nutr. 143, 80-85.
The authors used a case-cohort nested in the European Prospective Investigation into Cancer and Nutrition - Netherlands study. The study included over 2300 subcohort members and 845 incident diabetes cases with a mean follow-up of 10 years. The conclusion of the study was that high uric acid concentrations are associated with increased diabetes risk. However, a large part of the association can be explained by the degree of adiposity. It was also found that a uric acid-related dietary pattern did not confound the association.

In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. Bode, L.M. et al. (2013) Am.J.Clin.Nutr. 97, 205-309.
Human gut microbiota metabolize trans-resveratrol to dihydroresveratrol, 3,4'-dihydro-trans-stilbene and 3,4'-dihydroxybibenzyl (lunularin). The findings of this investigation indicated that the formation of these compounds varied among the healthy subjects enrolled in the intervention study reported here. It is important to remember that most of ingested trans-resveratrol's biological effects are due to its metabolites produced by the gut microbiota. That goes true also for all bioflavonoids present in the diet or nutritional supplements.

Plasma pyridoxal-5-phosphate is inversely associated with systemic markers of inflammation in a population of U.S. adults. Jakakeeny, L. et al. (2012) J.Nutr. 142, 1280-1285.
Low vitamin B-6 status (based on plasma concentrations of pyridoxal-5-phosphate) is associated with inflammatory disorders such as CVD, RA, IBS and diabetes. The study found a significant inverse relationship between plasma PLP and functionally related markers, including acute phase reactants, e.g. C-reactive protein, cytokines and adhesion molecules. Oxidative stress markers were also increased in individuals with low vitamin B-6 status.

Marginal vitamin B-6 deficiency decreases plasma (n-3) and (n-6) PUFA concentrations in healthy men and women. Zhao, M. et al. (2012) J.Nutr. 142, 1791-1797.
Short-term (28 days) vitamin B-6 restriction decreases plasma w-3 and w-6 PUFA concentrations and increases plasma w-6 to w-3 ratio. Plasma HDL and LDL cholesterol concentrations, FFA concentration and erythrocyte and peripheral blood mononuclear cells membrane fatty acid composition did not significantly changed after a short-term vitamin B-6 dietary restriction.

Grape polyphenols reduce blood pressure and increase flow-mediated vasodilation in men with metabolic syndrome. Barona, J. et al. (2012) J.Nutr. 142, 1626-1632.
The results of this study show that supplementation with a freeze-dried grape polyphenol powder for 30 days led to a reduction in systolic blood pressure and plasma soluble intercellular adhesion molecule 1 in men with metabolic syndrome. The findings of this study further lend support to the notion that grape polyphenols help improve vascular function in subjects with higher blood pressure.

Consumption of breakfast and the type of breakfast consumed are positively associated with nutrient intakes and adequacy of Canadian adults. Barr, S.I. et al. (2013) J.Nutr. 143 (1) , 86-92.
The study examined associations among breakfast, nutrient intakes and nutrient adequacy in Canadian adults. Breakfast eaters who included cereals in the menu had significantly lower prevalences below the EARs for vitamin A, magnesium, calcium, thiamin. vitamin D and iron than breakfast nonconsumers or those who did not add cereals to the menu. A cereal-containing breakfast is associated with improved nutrient adequacy.

Greater whole-grain intake is associated with lower risk of type 2 diabetes, coronary heart disease and weight gain. Ye, E.Q. et al. (2012) J.Nutr. 142, 1304-1313.
The aim of this study was to examine longitudinal studies looking at whole-grain and fiber intake in relation to risk of T2DM, CVD, wight gain and metabolic syndrome risk factors. The meta-analysis of 45 prospective cohort studies and 21 randomized-controlled trials carried out during the last 40 years indicated that an intake of up to 80 grams whole-grains per day significantly reduced the risk of developing T2DM, CVD and consistently resulted in less weight gain.

Caloric restriction in humans: Impact on physiological, psychological and behavioral outcomes. (Review article) L.M. Redman and E. Ravussin (2011) Antioxid. Redox Signal. 14(2) 275-287.
Faced with an ever increasing world obesity epidemic and the challenges it poses to managing a variety of disorders among which the metabolic syndrome plays center stage biomed researchers are looking into ways to address the issue other than through administration of drugs. This is not only because escalating medical costs for treating obesity-related conditions but also because we as a species want to live longer and happy lives free of age-related chronic degenerative diseases.
From the data accumulated so far caloric restriction (CR) appears to be a very promising way to solve the obesity problem and the ever growing number of articles devoted to this bear witness to that effect. The authors of this excellent recent review article looked at some completed clinical studies that investigated the effects of controlled, high quality and CR diets on biomarkers of longevity as well as on the development of age-related disorders. Observational (Okinawa centenarians, Biospere 2 project) as well as controlled epidemiological studies indicated that an average of 20% reduction in energy intake (mostly as carbohydrates) has many health benefits. The results showed that in overweight and obese subjects there was an improvement in insulin sensitivity, glucose and fatty acids homeostasis. Lower blood insulin and glucose concentrations have been linked to reduced protein glycation and mitogenic activity, which were known to contributeto premature aging. One important study sponsored by the National Institute on Aging and called CALERIE (comprehensive assessment of the long-term of reducing intake of energy) is the first randomized trial of CR in nonobese humans. CR is the only known intervention that can slow primary aging and protect against secondary aging. Although the final results are expected in a few years, preliminary data show favorable changes in body composition (reduction of fat mass) and in biomarkers of longevity (dehydroepiandrosterone sulfate and insulin) as well as in physiological and behavioral outcomes. CR was associated with a significant decrease in energy metabolism including a lowering of resting metabolic rate and a decrease in the energy cost of physical activity. It is still unclear whether total energy expenditure is reduced beyond the expected level, e.g. metabolic adaptation for the reduction in the metabolizing mass.
A matter of considerable concern is the behavioral aspect of engaging in a long term CR practice and this is particularly important for non-obese people. Thus, a reduction of up to 50% of energy intake was found, by one study to be associated with the development of eating disorders such as binge eating, among healthy men.
One of the main points advanced by this article is that based on the results of randomized trials of CR (generally short in duration) one can safely state that there is a reduction in the risk of age-related diseases and some positive outcomes of biomarkers of longevity. The question is, how many people can abide by a CR regimen in our obesogenic environment that is so conducive to over-eating and for how long? If the research into "CR mimetics" yields positive results it may be possible that a "wonder pill" might spare most of us of the pain of CR diets.

Green tea consumption enhances exercise-induced abdominal fat loss in overweight and obese adults. Maki, K.C. et al. (2009) J.Nutr. 139(2) 264-270.
Never underestimate the power of exercise especially when the aim is losing weight. And if natural "chemical" help is available so much the better. That chemical helper made use of in this study are a group of flavonoids called catechins, which are present in green tea. The findings reported in this paper indicate that overweight and obese people who consumed a beverage containing 625 mg of catechins and exercised moderately three hours per week experienced a reduction in abdominal and subcutaneous fat area as well as fasting serum triglycerides. However, percentage changes in fat mass did not differ between the catechins- consuming and control group. Besides their known antioxidant properties the different classes of flavonoids exert various other effects the mechanism of which is now begining to unravel. It is possible that the flavonoids as such or their metabolites activate some pathways in fatty acids degradation under hormonal control coupled with neuronal changes triggered by exercise. It is not clear from this study however, what effects if any would catechins have on abdominal fat reduction in the absence of exercise.

Grapes and human health: a perspective. (Review article). Pezzuto, J.M. (2008) J.Agric. Food Chem. 56(16) 6777-6784.
The role of nutrients in modulating disease. (Review article). Chan, D.L. (2008) J. Small Anim.Pract. 49(6) 266-271.

There is growing interest in how certain nutrients can be used to modify the metabolism of diseased tissues in order to bring them back to a healthy status. For instance, studies on a phytochemical that occurs in grapes, called resveratrol have suggested that this nutrient may have cardiovascular benefits.
The research reported in these two papers represents a growing trend in mainstream biochemical research. What was quite obvious to many nutritionists some 30 years ago, i.e. a diet rich in fresh fruit and vegetables helps ward off disease has begun to gain acceptance by the medical establishment and has become the norm of a healthy lifestyle. It is also important to note that most clinical trials on the effect of nutritional supplements on disease prevention dealt with nutritional factors in pure form and not as found in whole foods. As well, the doses administreated to the clinical trial participants were much higher than normally found in whole foods. Since all nutrients occur in whole foods in well defined proportions relative to each other and act synergystically in the body "as nature intended" it is advisable, in our opinion to use nutritional factors in conjunction with preparations from whole foods so all nutrients are there albeit one or two may be in higher amount depending on the design and duration of the clinical trial. Nutrients that were tested in clinical trials for their possible effect in modulating disease included antioxidant vitamins and minerals such as vitamins C, E and selenium, copper and zinc, respectively, omega-3 fatty acids as well as certain amino acids and their derivatives. These nutrients showed most promise in managing conditions such as cardiovascular disease, rheumatoid arthritis and possibly cancer. The earlier the stage of the disease the better the prospect of reversing that condition. Nutritional therapies are particularly promising when a combination of approaches are used in the program and the rationale of such approaches are discussed in the second review article (The role of nutrients in modulating disease).

Nutrition impacts the prevalence of peripheral arterial disease in the United States. Lane, J.S. et al. (2008) J.Vasc.Surg. 48(4) 897-904.
This is another paper that clearly demonstrates the power of nutritional supplementation in strengthening the case for the use of specific nutrients for the prevention of certain conditions. Higher consumption of antioxidant factors (vitamins A, C, E), vitamin B6, folate, a-linolenic acid and fiber significantly reduces the risk of peripheral arterial disease. The protective effect of these nutrients was found to be irrespective of traditional cardiovascular risk factors such as smoking, hypertension and diabetes.

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Combined R-a-lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson's disease. Zhang, H. et al.(2008) J.Cell.Mol.Med. Published in E-form in the June issue. (not yet in print form).
This paper provides direct evidence that combining biologically active nutrients such as a-lipoic acid and acetyl-L-carnitine rather than feeding them separately has a beneficial effect on brain cells in culture. Thus, it was found that when a lipoic acid + carnitine pre-treated human neuroblastoma cell line was challenged with rotenone (known to induce Parkinson's disease like features the cells were protected against mitochondrial dysfunction and oxidative stress. Furthermore, when the cells are treated with both nutrients at the same time the doses for these nutrients were 100 to 1000 times lower than for those of the nutrients administered alone. What is not mentioned in the paper, although very important to know is how close the low doses in the 0.1-1.0 micromolar range are from those found in whole foods.

Almond consumption reduces oxidative DNA damage and lipid peroxidation in male smokers. Li, N. et al. (2007) J.Nutr. 137, 2717-2722.
This is a neat paper that clearly demonstrated the antioxidant and protective effect of almond supplementation in male smokers (5- 20 cigarettes per day). Following almond consumption the antioxidant defenses represented by a-tocopherol, superoxide dismutase and glutathione peroxidase were significantly increased whereas the markers of oxidative stress such as urinary 8-hydroxy-deoxyguanosine, malone dialdehyde and DNA strand breaks were significantly decreased. Almonds contain phenolic acids and flavonoids, a-tocopherol, which can explain the observed effects.

Using nutrition for intervention and prevention against environmental chemical toxicity and associated diseases. Hennig, B. et al. (2007) Environ. Health Perspect. 115(4) 493-495.
There is growing evidence that long term exposure to persistent, fat-soluble organic pollutants such as polychlorinated biphenyls (PCBs) may play a role in the development of inflammatory diseases such as cardiovascular disease and rheumatoid arthritis. There is also a strong connection between exposure to environmental pollutants, diet, genetic makeup and susceptibility to disease.
The aim of this article was to draw the attention to the fact basic research and epidemiologic studies in the last 20 years or so suggest that nutrition and lifestyle changes may improve conditions associated with environmental insults. For example, it was shown that green tea catechins can modulate the level of the lipid-soluble PCBs in the body by decreasing their absorption and increasing their excretion. Supplementation with calcium was shown to significantly lower the plasma lead level in women who had a long time exposure to lead. Antioxidant therapy led to a marked improvement in nonalcoholic steatohepatitis induced by exposure to industrial pollutants. All these examples lend strong support to the notion that nutritional intervention could be a valuable instrument in the overall strategy of reducing the risk of disease in our over polluted environment. It could also mean that we need to take a fresh look at our dietary and lifestyle habits and change them accordingly. This can lead to drastic reductions in health care costs, improved quality of life and a longer life expectancy.

Mortality in randomized trials of antioxidant supplements for primary and secondary prevention. Systematic review and meta-analysis. Bjelakovic, G. et al. (2007) J.Am.Med.Assoc. 297(8) 842-857.
The objective of this study was to assess the effect of antioxidant supplementation on all-cause mortality in randomized primary and secondary prevention trials. By analyzing 68 published randomized trials with some 232,606 participants and by using complex statistical analysis the authors concluded that b-carotene, vitamin A and vitamin E may increase mortality whereas vitamin C and selenium had no effect on mortality. An earlier study on vitamin E supplementation indicated that high daily doses of vitamin E (higher than 400 IU) may increase all-cause mortality (Annals of Internal Medicine, January 2005). Thus, it would appear that of all antioxidant vitamins vitamin C seems to be, if not beneficial at least "neutral" in the eyes of many investigators of the potential health benefit of antioxidant supplementation. The best advice one can give at the moment is that a diet containing 5 servings of fresh fruit and vegetables per day should provide all necessary antioxidant factors that ensure good health. This is in addition to a healthy lifestyle and proper rest.


References
1. Huang, H-Y et al. (2006) Ann.Intern.Med. 145(5) 372-385. The efficacy and safety of multivitamin and     mineral supplement use to prevent cance and chronic disease in adults: A systematic review for a       NIH state-of-the-science conference.
2. Hofseth, L.J. & Wargovich, M.J. (2007) J.Nutr. 137, 183S-185S. Inflammation, cancer and targets of     ginseng.
3. Neto, C.C. (2007) J.Nutr. 137, 186S-193S. Cranberry and its phytochemicals: A review of in vitro           anticancer studies.
4. Fang, M. et al. (2007) J.Nutr. 137, 223S-228S. Dietary polyphenols may affect DNA methylation.




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