A range of natural products for the maternal health market is experiencing booming sales, according to recent industry data. Mark J Tallon, PhD, unveils the scientific state of play behind what may be the next best sustainable functional foods category
During stages of pregnancy and lactation, the nutritional demands placed on a woman?s metabolism are increased to keep pace with the formation of the mammary glands, placenta and related metabolic systems that support perinatal and post-natal development. These systems will influence whole body physiology, as with the placenta, an endocrine organ influencing nutritive supply and hormonal output.1 Over the past two decades, our knowledge regarding the role maternal dietary adequacy plays in foetal development and later life health and well-being has increased vastly, but it is still far from complete. In response to increasing public awareness about paediatric nutrition and dietary needs, producers are bringing fortified foods and maternal-specific nutrients to market, and these have already gained a foothold as an established and formidable product category.
This article will provide an analysis of the many studies related to both supportive and essential maternal nutrition, as well as clarify the emerging science behind such topics as ?foetal programming? and the development of infant formulas.
Pre- and Perinatal Nutrition
Prenatal and perinatal nutrition is a complex area of research that is primarily focused on the nutritional status of the mother both before and during pregnancy. Nutritional manipulation during this period can significantly affect fertility as well as the incidence and severity of several complications during gestation, birth and lactation.2 A brief overview of the current nutrients under scientific scrutiny regarding maternal energy metabolism and the associated clinical consequences of these nutrients is provided below.
Although an effective nutrient, folate?s bioavailability is strongly affected by its delivery vehicle. Studies have generally agreed that the bioavailability of food folates is 20-75 per cent less than that of supplemental, synthetic folic acid.6,7 Dependent upon the food vehicle, folic acid is somewhat less bioavailable in fortified foods than in tablets. The United States used a crude estimate of 85 per cent bioavailability from folic acid-fortified foods to determine dietary folate equivalents.8 Based on this guide, it was estimated that folic acid taken in fortified foods or taken as a supplement with food is 1.7 times more bioavailable than foods that naturally contain folate.7,8
Tissues within the brain, retina and other neural tissues are rich in long chain polyunsaturated fatty acids (LC-PUFAs), some of which are derived from n-6 and n-3 essential fatty acids (EFAs).11 These fatty acids provide the basis for the production of eicosanoids (prostoglandins, prostacyclins, thromboxanes and leukotriens), which are regulators of numerous tissue and cell functions ranging from uterine contractility to blood pressure regulation.
During the period of gestation, research demonstrates a clear correlation between reduced EFA status and reduced neonatal growth.12 Following supplementation with fish oils during pregnancy, increased levels of DHA have been found in mothers and their newborns.13,14 Notably, a recent study supplementing seven lactating women with 20g/day flaxseed oil marketed as a vegetarian source of alpha-linolenic acid (LNA)—and ultimately DHA—increased LNA levels, but this did not correlate to an increase in DHA in the women?s milk.15
However, care must be taken with fish oil supplementation as an excess of specific fatty acids may inhibit certain LC-PUFAs via inhibition of delta-6 and delta-5 desaturases that are essential for foetal growth.16 An excess of linoleic acid has been shown to decrease the formation of arachidonic acid.16 Studies indicate that there may be increased bleeding time with fish oil supplementation, although the clinical significance of this is unknown.17 However, in recent studies there is no evidence of this effect even at relatively high doses.18
As a final note, n-3 fish oil supplementation may be a naturally occurring inhibitor of uterine contractions and as such may delay pre-term deliveries without the associated side effects of current pharmacological interventions.19 Although substantial evidence exists for the positive benefits of selected PUFAs during pregnancy, many not covered within this article, the potential risks should also be carefully weighed and further researched when deciding to implement any fatty acid supplements strategy.
Vitamins and minerals
The assessment of vitamin and mineral status during pregnancy is difficult due to the absence of a clearly defined index for evaluating deficiency states. Although there seems to be a trend for declining vitamin and mineral values as gestation advances, this decline may be an artifact of hemodilution and/or alterations in vitamin and mineral carrier molecules.20 However, there are a few vitamins and minerals that do show significant changes during pregnancy, such as folate, where there is a clearly defined reference intake of above 100 per cent RDA. Therefore it is conceivable other nutrients will be found to also show such changes.
- 300mg transferred to the foetus.
- 50-75mg used for the formation of the placenta.
- 450mg for expansion of red cell mass.
- 200mg lost during delivery.
To prevent iron deficiency and preserve maternal stores, an intake of 9-27mg/day is recommended.22
Mothers with adequate dietary calcium intakes have shown no enhancement of calcium accretion in the neonate.25 Furthering the research dietary calcium may play in foetal health, growth and development, the topic of supplementation has been investigated. In a well-controlled clinical trial, dietary supplementation of 52 pregnant women with 1.5g/day elemental calcium was examined and associated with a lower incidence of pregnancy-induced hypertension.26
On a final note, mothers with multiple pregnancies and low calcium intakes should consider supplementary fortified foods to avoid an increased risk of osteomalacia (softening of bones) in later life.
The importance of postnatal nutrition cannot be over emphasised. The nutritive demands made postpartum (four to six months) are significantly greater than those of pregnancy, as it is a period of rapid growth and development during which infants double the weight accumulated during pregnancy. The significance of early nutrient supply is no more apparent than in the growth, development and composition of the neural system.
The human brain reaches 80 per cent of its total adult weight by the age of 2, whereas whole body weight reaches only 18 per cent, signifying just one aspect of the importance of optimising early postnatal nutrition.
Because of space constraints, this section will cover only three relevant and exciting areas of postnatal nutrition, with a focus on their relevancy to infant formulation.
At present, more than 130 different neutral and acidic OSs have been identified.35 However, there are very few peer-reviewed studies regarding the influence of prebiotics on infant physiology.
A growing catalogue of evidence about human milk OSs such as N-acetly- glucosamine, galactose and fructose oligomers demonstrates the important role of intestinal flora stimulation. Because it?s a new and in some aspects an ethically difficult field of study, there are limited data available regarding the benefits of prebiotics in infant formulations. In the first of only two published studies to date, researchers investigated the influence of a galacto-oligosaccharide (GOS)- and fructo-oligosaccharide (FOS)-containing infant formula on intestinal bacteria.36 Sixty new-born infants received either a 4g or 6g mixture of GOS and FOS/L for one month compared to a placebo. By day 28, a significant dose-dependent increase in bifidobacteria and lactobacilli was observed in faecal measurements than placebo.
A study on pre-term infants given a mixture of short-chain (TOS) and FOS was carried out to meet the molecular size distribution of human milk OSs and to bring about similar prebiotic effects.37 Infants were fed a formula containing 7.2g lactose/dL and supplemented with a mixture of short- (TOS) and long- (FOS) chain prebiotic ingredients (1g/dL). The data demonstrated that prebiotic supplementation resulted in a higher number of beneficial bifidobacteria than infants fed the standard preterm infant formula.
With regard to the safety issues and the wider application of prebiotics for infant formulas in the US, Dr Linda Douglas, manager of scientific affairs at GTC nutrition in Colorado, commented: ?Japanese national surveys of more than 20,000 infants in 1989 and 18,000 infants in 1995 were conducted in order to compare the anthropometric and health data of infants fed these FOS-enhanced formulas with their breastfed counterparts.38,39 These surveys revealed no detrimental effects from formulas enhanced with short-chain FOS. The data constitutes the largest body of evidence in existence on the safety of short-chain FOS for infant formulas.
?In the US, short-chain FOS are approved for use in foods for infants older than 4 months old. Based on the current regulations, the strength of the Japanese surveys and the history of safe use in that country for infant feeding, the eventual inclusion of short-chain FOS into infant formulas seems likely.?
Several studies have shown the effect that different sources of postnatal protein can have on growth and development. When the option of breastfeeding or its continuation for six months is not possible, the use of infant formulas becomes even more important in the delivery of a wide spectrum of amino acids and associated peptides. This issue is further complicated by cows milk protein allergies in the infant and finding a suitable alternative that is as biologically effective as human milk. As mentioned previously, the use of LC-PUFAs and prebiotics play a central role in an effective formula, as does the use of protein in meeting postnatal nutritional needs. Recent studies have shed light on the use of a selection of proteins including rice hydrolysates and whey- and soy-based mixes.
The issues that are still raising concern in finding a successful alternative to human milk is that of the concentration and ratio of constituent amino acids and peptides. These differ markedly from those in soy, rice and whey-based proteins.41
In bovine milk, for example, the ratio of whey to casein is approximately 20:80 but 60:40 in human milk.41 Other dominant protein profiles follow suit; for example, beta-lactoglobulin, the dominant protein found in human milk, is relatively low in formulas. Soy-based mixtures have typically been high in phytic acid, which has led to a decrease in the absorption of vital vitamins and minerals such as iron.42
Because of technical advances in protein isolation and extraction methods, the availability of fortified bovine sources of whey and casein are overcoming previous difficulties associated with low concentrations of beta-lactoglobulin, alpha-lactalbumin and tryptophan.41 Similar processing advances in soy-based formulas are leading to a fall in phytic acid concentrations from 300mg/kg to less than 6mg/kg of soy isolate.42 Recent data on dephytinised soy protein isolate and the absorption of mineral and trace elements42 demonstrated zinc was absorbed to a significantly greater extent using the dephytinised formula. However, as phytic acid still remains within the formula, the authors recommend the use of additional iron and ascorbate fortification to compensate for any possible shortfalls in absorption.
Although these studies point to favourable outcomes, others show little if any effect of zinc supplementation.49 The difficulty in drawing any comprehensive outcome arises in part because of study design wherein many confounding variables such as bioavailability, timing, compliance and duration of the supplementation period will no doubt influence study outcome. The greatest application and positive data can be recognised in the use of zinc supplementation in low birth weight or small-for-gestational-age infants.
Overall, there seems to be a general trend for improved growth rates suggesting perinatal deficiencies in zinc intake, which can be corrected with postnatal zinc supplementation. The application of supplemental zinc may be best placed as an addition fortification to soy-based formulas that have not been dephytinised.
Infant foods grow up
As one of the fastest-growing functional food sectors, maternal and infant nutrition still has some way to go, scientifically speaking, before we can provide efficacious and safe formulations with known and applicable clinical outcomes. There have been a variety of other potentially applicable nutrients that have been omitted from this article such as botanicals, postnatal lipids, prenatal fish oils, and a selection of vitamins and minerals that have a definite place in infant and maternal health, growth and development. The central argument in this field is whether we need to find supplementation and/or fortification to address dietary deficient states, or if supraphysiological doses of individual or mixed nutrients can provide beneficial and safe clinical outcomes above and beyond currently recommended DRIs.
The future development of functional foods and nutraceuticals may indeed follow the route of nutritional programming as outlined by Dr Das (See ?Science Viewpoint,? below), but due to many invasive procedures needed to assess the efficacy of intervention-based research such as isotope-labelled nutrients, widescale studies may be impossible.
The recent developments in the use of biomarkers are becoming more specific in their ability to link specific interventions to more informative outcomes. This integration of biomarkers into nutrition science offers a real opportunity for the appropriate design of infant formulas and a reduction in study length of long-term epidemiological trials.50
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