0699nl

TOP NUTRITION NEWSLETTER VOLUME 2, NO 6: JUNE 1999

Editorial

This is the sixth issue of TOP NUTRITION NEWSLETTER in 1999. In this issue the following topics are updated for your interest.

1. Evolution of infant nutrition
2. Immune response during disease and recovery in the elderly
3. Docosahexaenoic Acid and Smoking-Related Chronic Obstructive Pulmonary Disease
4. Intradialytic parenteral nutrition in malnourished hemodialysis patients:a prospective long-term study.

Any comments or suggestions to include the interesting topics are welcomed for future issues.

Dr Shwe Win
Editor

Evolution of infant nutrition Reference: Br J Nutr 1999;81(5):359.
The relative safety in the use of breast-milk substitutes in the developed areas of the world depends on greatly improved standards of hygiene and living conditions in the home as well as on the availability of infant foods made to exacting standards of manufacture, nutritional quality and packaging. Because such a large proportion, often the majority, of mothers in the developed world are unwilling to breast-feed, the possible effects of these artificial foods is of considerable concern and has been discussed by numerous international and national committees and conferences. The recommendations of these bodies are rapidly implemented by the infant-food industry and modified as new findings are established. These expert groups generally agree that an infant formula should resemble breast milk as, for instance, noted by a working party which stated: ‘Although human milk, because of its variability, cannot be used as an exact chemical model for the composition of an infant feed, the Working Party is of the opinion that human milk does provide the most useful reference “standard„. The further the composition of any artificial feed departs from that of average mature human milk, the greater is the possibility of untoward effects in the infant to whom it is fed. It is important to ensure that infants are safeguarded from unsuitable foods.’ The general recommendation is that the artificial milk should: ‘approximate to the composition of breast milk as nearly as is practicable’ or ‘should resemble human milk as far as is possible’

The importance of LA as an essential fatty acid in human nutrition had been known for many years but the need for a dietary source of another essential fatty acid, i.e. a-linolenic acid (18 : n-3; LNA), the parent of the n-3 fatty acid series, was not widely recognized until the late 1980s. The n-6 and n-3 essential fatty acids are LA (18 : 2n-6) and LNA (18 : 3n-3) respectively. The essential nature of LNA as the parent of the n-3 series had not been widely recognized at the time the advisory bodies made their recommendations. As a consequence the new formulations were prepared by the manufacturers to meet the required levels of LA, the n-6 essential fatty acid, but with much lower relative proportions of the essential n-3 fatty acid LNA than in breast milk or even in the previously employed infant foods based on butterfat.

The essential fatty acids LA and LNA are not interconvertible but are respectively the parents of the n-6 and n-3 series of fatty acids from which all of the n-6 and n-3 fatty acids can be derived, e.g. the long-chain polyunsaturated fatty acids (LCPUFA) including arachidonic acid (20 : 4n-6; AA), eicosapentaenoic acid (20 : 5n-3) and docosahexaenoic acid (22 : n-3; DHA). LA and LNA play important roles not only in providing LCPUFA which act as components of cellular membranes but also as precursors of other essential metabolites such as the prostacyclins and prostaglandins controlling a variety of body functions.

Normal neurological development is now thought to depend on the availability of DHA derived from LNA. Both LNA and DHA are present in breast milk and in butterfat and hence, albeit in low concentrations, in the old-fashioned infant foods based on full-cream cows' milk. The novel infant foods, made to meet the recommended compositions, contained vegetable fats to provide sufficient LA to meet increased recommendations. Some vegetable oils are excellent sources of LNA, e.g. linseed, soyabean and rapeseed, but are prone to rancidity and so avoided in infant formulas.

DHA is a major component of brain and retinal rod lipid membranes and has been shown, by animal studies, to be required for normal retinal and brain function. The depletion of tissue DHA requires diets with both low levels of n-3 fatty acids and high levels of the n-6 fatty acids. The degree of deficiency induced is largely determined by the LA : LNA ratio because high levels of the n-6 series fatty acids depress conversion of LNA to DHA by competitive inhibition of the D6 desaturase enzyme . The LNA content is low in the vegetable oils commonly used to meet the LA requirement in infant foods. The LA : LNA ratio in these oils was also very high, about 150 : 1 for safflower, sunflower and arachis oils and 50 : 1 in maize oil, i.e. ratios that largely suppress the conversion of LNA to the other necessary LCPUFA of the n-3 series.

The need for LNA in infant formula was not officially recognized until the 1990s, thus many infant formulas, from the mid-1970s to the early 1990s, may have provided much less of the n-3 essential fatty acids than would now be advised. Observations in very carefully controlled, multicentre trials by have shown that preterm infants given a formula feed had significantly lower intelligence quotients at 1·5 and 7·5–8 years of age than those receiving breast milk as the total or partial source of nourishment and that this difference was still evident after accounting for possible confounding factors such as, inter alia, parental smoking and/or drinking or socio-economic status.

The formula feed used in these studies met the then accepted recommendations, i.e. high levels of n-6 with low levels of n-3 essential fatty acids. The authors noted that the differences in neural development reported might have resulted from a deficiency in long-chain lipids essential for development of the nervous system but not present in the preterm formula, or alternatively, it might be that human milk contains hormones and trophic factors influencing brain growth as well as pre-formed AA and DHA.

If this neurological problem resulted from a deficiency in LNA the difficulty could be overcome by increasing the LNA content of the formula. However addition of pre-formed DHA to the formula would be expected to relieve the condition whether resulting from LNA deficiency or from an absence, in the immature, preterm infant, of the functional enzyme system essential for formation of LCPUFA from their precursors.

Many trials have been carried out to determine if the observations resulted from a deficiency of the DHA and AA required to supply the needs of the brain and visual systems in the rapidly growing preterm infant. In a recent review, there is good evidence that use of conventional formulas leads to depression of LCPUFA status, especially in the preterm baby, and that this fall can be reduced by addition of DHA to the formula. However, the inconsistencies of the published findings on neurological function are such that it is not possible yet to say whether addition of DHA to a formula will be of benefit, This uncertainty suggests, may well be caused by inadequate sample size, confounding factors or variations in the LNA content of the formula used.It also discusses the experimental design and numbers of propositi needed to ensure differences of means with 80 % power at 5 % significance.Three large studies are now in progress to determine the effects of formulas containing added AA and DHA in comparison with breast milk on neurological development in preterm and full-term infants. These trials involve over 1300 infants and include subjects randomly assigned to infant formulas with and without LCPUFA together with breast-milk-fed reference groups. Two of these studies, one on term infants and another on preterm infants, have passed an 18-month developmental assessment follow-up period.) These are calculated to be of sufficient size to determine what effects (whether beneficial or adverse) may be anticipated to follow LCPUFA additions to formulas, but so far as the work has progressed, there is no evidence of benefit to full-term infants from the addition of LCPUFA to a formula of the type now advised.

Current UK recommendations on the composition of infant foods define the LA : LNA contents and ratios permissible in infant formulas and also permit, within limits, the presence of LCPUFA, notably AA, DHA and eicosapentaenoic acid in infant formulas. The volume and composition of breast milk can vary greatly reported that: ‘a plentiful milk supply with a baby losing weight seems to be a not uncommon clinical syndrome’ and that this failing may be caused by a low fat content. It is also very likely that some mothers, because of certain features of their milk, may be better able to provide for the future health of their offspring by, for instance, providing known nutrients in better proportions, or metabolites, enzymes, hormones or other unidentified agents to facilitate optimal maturation and development of the infant's faculties to permit full health in the adult.

An unanswered problem is to find out if differences in the composition of breast milk (or infant formula) affect the health and well-being of the infant and perhaps even the quality of life of the adult. Investigation of these possibilities could involve epidemiological studies of relations between breast-feeding and subsequent child and adult health. There would be technical difficulties in determining nutrient intakes as well as in the subsequent lifelong studies from infancy to ultimate demise. There would also be a need to retain samples for investigation for substances as yet unrecognized, by methods not now available. Application of the methods of multivariate analyses now commonly employed to determine the combined interactive effects of numerous variables (e.g. of diet in farm stock, or sensory appreciation in human subjects) might reveal associations between nutrition of the juvenile and health of the adult.

Could a milk be devised better able to meet these varied needs than present artificial formula or even of breast milk itself? Long-term feeding trials might also be employed, but for ethical reasons it would not now be possible to carry out comparisons between the progress of infants on deficient v. supplemented formulas as in the classical investigations report on essential fatty acid requirements.

Immune response during disease and recovery in the elderly

Reference: Reviews of Nutrition Society 1999;58(1):85.

The present article reviews immune ageing and its relationship with nutritional ageing, with a particular insight into the influences of disease on both ageing processes. Immune ageing can be described primarily as the progressive appearance of immune dysregulations, mainly acquired immunity (mature: immature, naive: memory T lymphocyte subset decreases) leading to gradual increases in T-helper 2: T-helper 1 cells. This change is due initially to decreased thymic function, and later to accumulative antigen pressure over the lifespan. In contrast, innate immunity (macrophage functions) is preserved during the ageing process and in the elderly this leads to macrophage-lymphocyte dysequilibrium, which is particularly critical during on-going disease. Indeed, any disease induces long-lasting acute-phase reactions in aged patients and leads to body nutritional reserve (mainly protein) losses. Episodes of disease in the aged patient progressively deplete body nutritional reserves and lead to protein-energy malnutrition, undernutrition-associated immunodeficiency, and finally cachexia. Undernutrition is a common symptom in the elderly ; protein-energy malnutrition is found in more than 50 % of hospitalized elderly patients and in most elderly diseased subjects. In addition, micronutrient deficit or low levels are common in home-living self-sufficient apparently-healthy elderly subjects. All these nutritional deficits induce decreased immune responses, and micronutrient deficits are now thought to be partly responsible for the decreased immune responses (immune ageing?) observed in the apparently-healthy elderly. Indeed, several studies have shown that micronutrient supplements induce increased immune responses in the healthy elderly. The progression of infectious diseases depends on immune responses and on nutritional status before the onset of illness in aged subjects. In addition, recovery depends on the intensity of acute-phase responses in the undernourished elderly. In fact, chronic acute-phase responses, commonly associated with diseases in aged patients, lead to progressive lowering of metabolic responses in the undernourished elderly. This can be quantified by increased production of free radicals during treatment and these increases may explain the difficulty in successfully treating aged patients. Nutritive therapy in order to improve metabolic processes and also to maintain body reserves should be considered as a necessary adjuvant therapy in the treatment of elderly patients.

Ageing of the immune system is characterized by the appearance of progressive dysregulation between different functions of the immune system. With ageing there are gradual increases in immature : mature, memory : naive, T lymphocyte TH1 : TH2 and B lymphocyte CD5+ : CD5-. These changes are induced by two main factors, i.e. decreased thymic function, and antigenic pressures over the lifespan. These changes are important during early life (up to 30-40 years of age in human subjects), a period which is important in acquiring adapted immune responses against foreign antigens. Nevertheless, similar changes in immune responses continue with age, but at a lower rate. Ageing is also characterized (mainly in the second half of life) by a progressive dysregulation between monocyte function (which is unchanged) and lymphocyte function (which decreases). It appears that acquired immunity weakens with age, probably because its adaptive capacity is limited by its own regulation, while innate immunity, a more primitive system, is unchanged.

Ageing is well-known to be associated with lower adaptive capacities. This is true for acquired immunity, not only in facing antigenic challenges but also in relation to metabolic changes such as those resulting from underfeeding and/or nutritional responses to disease (hypercata syndrome). Aged subjects are particularly sensitive to nutritional influences, and any nutritional deficit (i.e. energy, protein or even micronutrient) may lower the immune responses of the elderly. As nutritional deficits are frequent in diseased subjects, many, if not all, elderly diseased subjects exhibit decreased immune response and a lower capacity to fight disease. Furthermore, micronutrient deficits are also frequent in the elderly, and some of the age-related change in immune response may be due to lower nutritional status. The declines in nutritional status and in immune response with age are interrelated. The lower capacity of the elderly to fight disease partly results from the dysregulation of the immune system, i.e. from the dysequilibrium between macrophage function (innate immunity) and lymphocyte function (acquired immunity). This dysequilibrium forces macrophages to play a more intense role in defence mechanisms of the elderly, i.e. to secrete more cytokines. Consequently, acute-ase responses are more intense and/or of longer duration in the elderly, leading to greater use of body nutritional reserves. Furthermore, the age-related decrease in metabolism is responsible for incomplete rebuilding of nutritional reserves during recovery. In the absence of nutritional treatment (which is necessary to help the elderly respond to the nutritional consequences of diseases) after recovery, the elderly have lower body reserves and lower immune responses. As a result of successive bouts of disease, the elderly progressively become frail. Nutritional therapy must be given to all elderly patients for both the duration of the disease and throughout the recovery period (which is of longer duration in aged patients). In addition, it may be necessary to consider higher micronutrient intakes in apparently-healthy elderly subjects, either to boost immune responses or to prevent a decline in immune response.

Docosahexaenoic Acid and Smoking-Related Chronic Obstructive Pulmonary Disease Reference:Am.J.Respir.Crit. Care Med., 1999;159(6):1780.

If the inflammatory response to inhalation of cigarette smoke causes chronic obstructive pulmonary disease (COPD), suppression of that natural response might be beneficial. We hypothesized that a smoker's risk of developing COPD is inversely related to physiologic levels of two fatty acids that have antiinflammatory properties: eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6). The proportion of each fatty acid in plasma lipids was measured in 2,349 current or former smokers. COPD was identified and defined by clinical symptoms and/or spirometry. After adjustment for smoking exposure and other possible confounders, the prevalence odds of COPD were inversely related to the DHA (but not to the EPA) content of plasma lipid components in most of the models. For example, as compared with the first quartile of the DHA distribution, the prevalence odds ratios (ORs) for chronic bronchitis were 0.98, 0.88, and 0.69 for the second, third, and fourth quartiles, respectively (p for linear trend = 0.09). The corresponding ORs for COPD as defined spirometrically, were 0.65, 0.51, and 0.48 (p < 0.001). Among 543 current heavy smokers, adjusted mean values of FEV1 (lowest to highest DHA quartile) were 2,706, 2,785, 2,801, and 2,854 ml. DHA may have a role in preventing or treating COPD and other chronic inflammatory conditions of the lung. Pilot testing of that hypothesis in experimental models seems warranted.

Intradialytic parenteral nutrition in malnourished hemodialysis patients: a prospective long-term study. Reference: JPEN 1999;23(2):90-5.

BACKGROUND: Malnutrition is a frequent problem of patients on intermittent hemodialysis and substantially contributes to their morbidity and mortality. METHODS: In 26 hemodialysis patients who, despite dietary advice and oral nutritional supplements, still had malnutrition, the feasibility and effects of a specific intradialytic parenteral nutritional (IPN) regimen were evaluated during a 9-month study period. An IPN solution consisting of 250 mL glucose 50%, 250 mL lipids 20%, and 250 mL amino acids 7% was infused i.v. three times a week during the dialysis session. At the end of each dialysis session an additional volume of 250 mL amino acids was infused as a rinsing fluid. Insulin was administered i.v. before dialysis.

RESULTS:Of the 26 enrolled patients, 16 completed the study. The remaining 10 patients withdrew mainly because of muscle cramps and nausea during the initiation phase of the treatment, when sodium was not present in the IPN fluid but was supplemented intermittently. In the 16 treated patients, body weight, which had decreased in the pretreatment period from 58.2+/-1.3 kg (-6 months) to 54.8+/-10.1 kg at the start of the study, increased again up to 57.1+/-10.7 kg after 9 months IPN (p < .05). Serum transferrin and prealbumin rose from 1.7+/-0.4 to 2.0+/-0.4 g/L and from 0.23+/-0.05 to 0.27+/-0.10 g/L, respectively. Bone densitometry showed an increase of tissue mass, mostly related to a rise in fat tissue. Triceps skinfold (p < .05) and arm muscle compartment of the midarm (p = .07) increased as well. No such changes were observed in the patients who withdrew from treatment.

CONCLUSIONS: An i.v. hyperalimentation regimen applied to malnourished hemodialysis patients results in a rise of body weight and in a limited, but significant, change of some parameters of nutritional status. The rise in body weight is at least in part attributable to an increase of body fat, without changes in plasma lipid levels.