TOP NUTRITION NEWSLETTER

VOLUME 2, NO 2:FEBRUARY 1999

Editorial

This is the second issue of TOP NUTRITION NEWSLETTER in 1999. In this issue, nutritional markers, anemia and mental retardation, essential but overlooked nutrient, and antioxidant therapy are updated for your interest.

Is there any ideal single endpoint for nutritional intervention? Can you recognize potential pitfalls and errors in several endpoints? Developing strategies for the interpretation of the data is critical at the outset of any interventional management strategy.Selection of nutritional and metabolic endpoints must be in part dependent on the disease process involved, the potential magnitude of the interventional effect and must be utilized in the context of a carefully designed experimental protocol with a well focused question. Nutritional and metabolic endpoints will help you select the optimal endpoints for your malnourished patients.

Previous several studies did correlate early childhood anemia and mental retardation. This study stimulates us to prevent infant anemia so that any degree of mental retardation could be terminated. Early childhood anemia and mild to moderate mental retardation emphasizes us to provide adequate nutrition during early childhood.

A portion of population in United States may suffer from chronic mild dehydration....a shocking news ? How about the people from hot climate countries who may be complaining of impaired physiological and performance responses. You won't be suprised if you hear that " water consumption in particular can have an effect on the risk of urinary stone disease; cancers of the breast, colon, and urinary tract; childhood and adolescent obesity; mitral valve prolapse; salivary gland function; and overall health in the elderly". We should check the research paper of " Water: essential but overlooked nutrient" in detail. At the same time, how professional athletics can increase performance by hyperhydrating agent is also related to essential water consumption.

Antioxidants have been implicated in the prevention of coronary heart disease. According to Ministry of Public Health of Thailand (1994) , CVD mortality was 110 per 100,000 population (compared to 55 per 100,000 population in USA). It is a serious question whether antioxidant supplementation is effective as primary or secondary prevention of CHD. Although there is no solid evidence that antioxidants will prolong life or not, vitamin E may prevent heart disease in patients with heart disease. " What is the scientific evidence for antioxidant therapy " may inform you whether you should take or not.

Happy Reading.

Dr Shwe Win

Editor

Nutritional and Metabolic Endpoints


Reference:J Nutrition 1999;129(1):273S-278S.

None of the metabolic indicators which have been used to date provides a single or necessarily ideal endpoint for interventional management in wasting disorders. Some of these indicators may provide better endpoints for the acute rather than the chronic wasting conditions. In addition, it is imperative that more than one endpoint be selected to be assured that there is concordance in the findings. However, prior to the selection of any endpoint measure, the investigators involved must be fully cognizant of the potential pitfalls and errors that can occur in every one of the selected methodologies. In anticipating these potential problems, developing strategies for the interpretation of the data is critical at the outset of any interventional management strategy. The manufacturers, the regulators and the investigators involved in the interventional management of chronic and acute wasting disorders must agree on the endpoints to be used and these endpoints must provide the most appropriate and valid information. Selection of nutritional and metabolic endpoints must be in part dependent on the disease process involved, the potential magnitude of the interventional effect and must be utilized in the context of a carefully designed experimental protocol with a well focused question(s).

Immunocompetence is a frequent co-morbidity factor in individuals with wasting and/ or catabolic conditions. In situations in which protein and energy malnutrition have occurred, the absolute lymphocyte concentration is found to be decreased. This decrease is distributed to all categories of lymphocytes not just T-cells.

Of particular note is the well-established decrease in delayed hypersensitivity known to occur in situations of protein energy malnutrition . This is most easily assessed using intradermal injections of antigens to challenge an individual's immune recall. Intradermal injections of antigens of Candida albicans or streptococcal bacteria or sensitization to chemical compounds known to induce delayed hypersensitivity (e.g., dinitrofluorobenzene) have traditionally been used as methodologies for determining delayed hypersensitivity. The presence of anergy in a patient with wasting and malnutrition is a grave prognostic indicator. Such immunocompromise in the face of underlying protein and energy malnutrition places the host at significant risk for infections and septicemia. Such infections will result in even further significant protein wasting. Under these circumstances, the individual is unable to mount an adequate immune defense and is at high risk of dying. Anergy in the face of protein wasting generally reflects the severity of the illness and not necessarily the nutritional status of the patient.

A large number of studies have pursued the relative importance of circulating proteins in monitoring the nutritional status of patients. A number of circulating plasma protein concentrations are dramatically altered with injury, trauma, infection and protein wasting conditions. The plasma concentrations of some proteins are decreased in response to such insults, while those of other proteins are increased. Negative protein indicators include prealbumin, insulin-like growth factor I (IGF-I), transferrin and albumin. The plasma protein (excluding IGF-I), whose concentration is most dramatically decreased is prealbumin (transthyretin) which has the shortest half life, followed by transferrin and then albumin. Of these negative indicating proteins, albumin and transferrin are stated to have the best accuracy and precision in predicting protein calorie malnutrition under conditions of both acute and chronic conditions followed by prealbumin and IGF-I. However, it must be pointed out that in terms of sensitivity and specificity for protein-energy malnutrition, these four circulating proteins are only "good to fair". Thus, a decrease in the concentration of these circulating proteins is most appropriately utilized as adjunctive correlations to other metabolic endpoints and clinical findings.

Early childhood anemia and mild or moderate mental retardation

Reference: Am J Clin Nutr 1999;69:115-9.

Background: Previous studies questioned the link between early childhood anemia and detrimental child development.

Objective: A population-based study was conducted to examine the association between early childhood anemia and mild or moderate metal retardation at 10 y of age.

Design: The present study linked early childhood nutrition data collected by the Special Supplemental Program for Women, Infants, and Children (WIC) and school records. Hemoglobin values were used to determine the relation between anemia in early life and children's placementin special education classes for mild or moderate mental retardation. Subjects were all participants in the WIC program. A computer program was used to link data from birth, WIC, and school records.

Results: Logistic regression showed an increased likelihood of mild or moderate mental retardation associated with anemia, independent of birth weight, maternal education, sex, race-ethnicity, the mother's age, or the child's age at entry into the WIC program.

Conclusion: These findings support the proposition that efforts to prevent mild and moderate mental retardation should include providing children with adequate nutrition during early childhood.

Water: An essential but overlooked nutrient

Reference:J Am Diet Assoc. 1999;99:200-206

Water is an essential nutrient required for life. To be well hydrated, the average sedentary adult man must consume at least 2,900 mL (12 c) fluid per day, and the average sedentary adult woman at least 2,200 mL (9 c) fluid per day, in the form of noncaffeinated, nonalcoholic beverages, soups, and foods. Solid foods contribute
approximately 1,000 mL (4 c) water, with an additional 250 mL (1 c) coming from the water of oxidation. The Nationwide Food Consumption Surveys indicate that a portion of the population may be chronically mildly dehydrated. Several factors may increase the likelihood of chronic, mild dehydration, including a poor thirst
mechanism, dissatisfaction with the taste of water, common consumption of the natural diuretics caffeine and alcohol, participation in exercise, and environmental conditions. Dehydration of as little as 2% loss of body weight results in impaired physiological and performance responses. New research indicates that fluid
consumption in general and water consumption in particular can have an effect on the risk of urinary stone disease; cancers of the breast, colon, and urinary tract; childhood and adolescent obesity; mitral valve prolapse; salivary gland function; and overall health in the elderly. Dietitians should be encouraged to promote and
monitor fluid and water intake among all of their clients and patients through education and to help them design a fluid intake plan. The influence of chronic mild dehydration on health and disease merits further research.

Small decreases in hydration status can result in a dramatic decrement in athletic performance and greatly increase the risk of thermal injury. Because of its osmotic properties, which enable greater fluid retention than the ingestion of water alone, glycerol has been proposed as a hyperhydrating agent. In fact, glycerol is now
commercially available and marketed as a sport supplement to be ingested with water or sport drinks; thus, dietitians need to be cognizant of this new addition to the sports nutrition table. The results of glycerol-induced hyperhydration research have been equivocal, most likely because of methodologic differences between
studies, such as variations in the intensity of exercise, environmental conditions, and concentration or dose of glycerol administered. Although the suggested dosage of glycerol depends on body size and varies between manufacturers, 1 g/kg body weight with an additional 1.5 L fluid taken 60 to 120 minutes before competition is standard. Some test subjects reported feeling bloated or nauseated after ingesting glycerol. This review examines glycerol-induced hyperhydration research and the safety of ingesting glycerol, discusses commercial availability of glycerol, and makes recommendations for glycerol-induced hyperhydration research

What is the Scientific Evidence for Antioxidant Therapy?

Reference: American Heart Association-71st Scientific Sessions, November 8-11, 1998; Dallas, Texas
Speaker: John F. Keaney, Jr., MD, Boston University School of Medicine

Cardiovascular disease remains a major clinical problem in developed countries. Statistics from 1990 estimate that 55 out every 100,000 Americans will die of  coronary artery disease each year. The economic costs of cardiovascular disease exceed $250 billion annually in this country (including lost productivity). Treatments that can reduce the incidence of coronary artery disease have great potential to reduce healthcare costs, especially because the prevention of cardiovascular disease is generally much more economical than its treatment.

    Background -- Is There a Link Between Atherosclerosis and Antioxidant Intake?

Although the link between elevated total cholesterol and atherosclerosis is well-established, we still do not know precisely how cholesterol leads to heart attacks and stroke. We do, however, know that LDL cholesterol particles cannot cause atherosclerosis unless they are oxidized. This knowledge has stimulated interest in the role of antioxidants in preventing heart disease. There is currently a wealth of epidemiological data examining the interaction between antioxidant intake or antioxidant status and the development of vascular disease. The data consist of a collection of descriptive studies, case-controlled studies, prospective cohort studies, and a limited number of randomized data. The distinction between study types is important because only randomized, controlled studies should be used to make public health recommendations.

    Evidence From Descriptive Studies

Descriptive studies examine the characteristics of a population and its associated disease rates, and compare the data sets from one time period or country to the next. In general, descriptive studies suffer from the inability to control for potential confounding factors. These studies may be valuable, however, because they generate hypotheses which may be tested by more rigorous formats for data comparison.

A total of five descriptive studies published since 1975 has shown an inverse association between fresh fruit and vegetable consumption and cardiovascular disease rates or, in some cases, between certain vitamins (ie, vitamin C, vitamin A) and cardiovascular disease mortality rates. The strongest theme from these studies is an observed trend across populations, and within populations over time, that fresh fruit and vegetable consumption protects against cardiovascular disease. Whether this is due to the intake of dietary antioxidants or the replacement by fresh fruits and vegetables of potentially harmful dietary components (ie, animal fats) cannot be determined.

    Evidence From Case-control Studies

Case-control studies consist of data gathered retrospectively on dietary or lifestyle exposures of interest, as well as data on a variety of potential confounding variables. Individual cases are compared with appropriate controls in an attempt to isolate the effect of the variable of interest from potentially confounding variables.

Three such studies -- one study each to support an association between lower vitamin E, vitamin C, and tissue beta-carotene levels in cases with cardiovascular disease compared with controls -- suggest that natural antioxidants reduce the risk of cardiovascular disease. The strength of conclusions that may be drawn from these studies is still limited -- for example, the selection of cases and controls may introduce bias, and the chosen controls may also not adequately represent the intended population. In addition, uncharacterized or unknown variables may have a significant impact on results that go unexamined.

Evidence From Prospective Cohort Studies

Prospective studies offer the advantage of measuring exposure prior to the development of disease, which minimizes the impact of selection and recall bias. This study design also minimizes the effects that the disease may have on exposure related variables, such as dietary habits.In general, the strongest evidence supports an association between vitamin E and reduced risk, with little or no evidence for beta-carotene or vitamin C. In studies that show a positive effect, supplemental intake of these antioxidant vitamins seems to be necessary to obtain the observed positive effects, because levels achieved from dietary intake were insufficient to account for the inverse associations. However, in order to definitively determine a cause-and-effect relationship, one needs data from randomized, double-blind, placebo-controlled trials.

Evidence From Randomized Trials

To date, only two randomized, placebo-controlled studies look specifically at cardiovascular disease and antioxidant intake. These are the Physicians' Health Study and the Cambridge Heart Antioxidant Study (CHAOS). In the Physicians' Health Study, 22,071 US male physicians were treated with beta-carotene for 10 years. There was no effect on any parameter of vascular disease. The CHAOS trial examined 2002 men and women with known coronary artery disease. In this trial, treatment with vitamin E reduced the incidence of heart attacks by 77% with no significant effect on overall mortality.

Some studies principally conducted to look at cancer shed light on cardiovascular disease as well. In one study, 29,000 Finnish smokers were treated with beta-carotene and/or vitamin E daily. Neither antioxidant affected cardiovascular disease rates. A similar study of the effect of beta-carotene on cancer incidence again found no effect on cardiovascular disease.

The Annals of Internal Medicine recently published a meta-analysis exploring the relationship between antioxidant vitamin intake and cardiovascular disease. In this article, the authors make a compelling argument that available epidemiological data suggest antioxidant vitamins reduce cardiovascular disease,vitamin E being the most effective.

Perhaps the most disappointing has been the evidence for a favorable effect of vitamin C. Despite the fact that vitamin C is the most effective antioxidant in vivo by a wide margin, the evidence supporting a beneficial effect of vitamin C is largely lacking.

Conclusions

Two ongoing trials may provide a definitive answer to the debate about whether antioxidant supplementation is effective as primary or secondary prevention of CHD. The first is the women's health study of primary and secondary prevention of CHD, including over 40,000 healthy US female nurses. In the other large-scale trial, the Supplementation en Vitamines et Minéraux Antioxidants (SU. VI. M. AX) trial, 15,000 healthy men and women received a mixture of antioxidant vitamins and minerals consisting of beta-carotene, alpha tocopherol, vitamin C, selenium, and zinc. Until these studies are completed, there is no solid evidence that antioxidants will or will not prolong life. Vitamin E supplementation may prevent heart attacks, but this indication is based on only one study of patients with existing heart disease