PLASTICIDAD DE UN SUELO

The assessment of the relationship of specific dietary components and health outcomes and the use of experimental dietary interventions in human subjects is extremely challenging. The optimisation of specific foods and their bioactive compounds represents a sensible, non-invasive and cost-effective method of reducing the global burden of cancer and other chronic diseases 73. However the identification of dietary compounds which are critical to human health is compounded by the thousands of compounds which are introduced into the human body by diet 39. There also exists a lack of dietary exposure quantitation for many compounds commonly consumed in the

8 human diet, which makes extrapolation of actual contribution to health outcomes difficult to assess. For example humans consume over 5000 different flavanoids, of these only a few individual compounds have been assessed for their beneficial health properties 73. Many plant phytochemicals remain entirely uninvestigated and the individual treatment of phytochemical components of food in isolation can lead to confusion of the role of diet and health. A holistic approach to the investigation of diet and beneficial/detrimental human health outcome is essential, particularly as it is thought that synergistic interactions among food components are crucial to their beneficial effects and many isolated components do not always result in the similar outcomes as in the intact plant material 71, 74.

In many cases in vitro empirical evidence is directly extrapolated from the laboratory bench to a supposed effect in vivo in humans. The observed effects should be used as an indication of potential in vivo effect and as a guide to further complete study within human subjects. Proposed mechanisms of action within cell culture is not necessarily true within the complex endogenous and microbiotic metabolism of a human ―superorganism‖ 75

. Pleiotrophic factors influence the absorption, bioavailabilty, exposure and action within human subjects.

For example, the majority of evidence concerning the anticarcinogenicity of cruciferous vegetables and their glucosinolate hydrolysis products comes from in vivo animal studies and in vitro cell cultures in which the ITC or indole has been used in isolation 76. In animal models and cell systems, combinations of ITCs have been shown to confer protection against genotoxic agents better than individual ITCs 77. The focus on the individual components ignores the potential for chemical interactions and chemoprotective contributions from other compounds found in the normal matrix of cruciferous vegetables. Inter-species differences and the use of doses of the hydrolysed glucosinolate and carcinogenic compounds far in excess of the estimated levels in a normal human diet hinder extrapolation of the results of animal studies in relation to humans. Quantities of ITC‘s utilised in in vitro studies are usually far in excess of human exposure levels and cause acute cellular stress which may promote apoptosis and cell cycle arrest and may not be a relevant effect in human subjects 78.

9 However, in vivo human studies have strongly supported the beneficial effects of CV at high but realistic consumption levels 16, 79-82. This is in accordance with the epidemiological evidence of the negative correlation between high cruciferous vegetable consumption and the incidence of diet-related cancers 71.

The design of scientific experiments assessing the effects of dietary interventions in humans and experimental animals is crucial to establish correct nutritional advocation, addressing the relationship of diet and disease and acquiring a holistic picture of the interactions of plant phytochemical and other dietary components 83. The limiting factor remains the design of well defined nutritional interventions that assess the long-term effects of bioactive food components and foods, particularly the speed of discovery and cost of set-up.

Further problems arise in nutritional intervention studies in humans where dietary restrictions and incomplete or falsified food diaries/food questionnaires can confound data interpretation and produce false positive or negative results. Estimation of dietary intake is prone to error as many people‘s diets are extremely complex and consist of many different foods which are consumed intermittently. The two most commonly used form of dietary assessment are food frequency questionnaires (FFQ) and 24hr dietary recalls. The FFQ is a convenient and inexpensive way to measure an individual‘s dietary intake over a long period of time, however they are prone to incorrect dietary ―self-reporting‖ 84

with an under-reporting of energy and protein intake by 20-50% 85. This is even more detrimental when considering dietary components consumed at concentrations several orders of magnitude lower, such as plant phytochemicals and micronutrients. Twenty-four hour dietary recalls provide more in depth information but yet again when a dietary intervention is based on restriction or a reduction of consumption of certain foodstuffs, these can be falsified and intake on a single day is a poor predictor of long-term intakes. These methods of assessment are also costly both in time and financially 86.

The compositional analysis of food also presents analytical problems where a great variation in macro- and micronutrient contents exists. The specific cultivar and growing conditions of plants can determine a great variation in the content of many phytochemicals and micronutrients. For example the concentration of glucoraphanin in

10 broccoli is known to vary by as much as 25 fold depending on the cultivar 87. Also the selenium content of many plants is affected by the selenium content of the soil 88.

The method of food processing is also very important in the absorption of dietary food components, as has been observed in increased lycopene availability in tomatoes following cooking and processing 89 and the decreased enzymatic activity reducing the cancer-protectant properties in heated garlic 90.

The quantification of dietary components is essential to a scientifically sound dietary intervention study, however the methods of processing and cooking should also be considered. These factors can all affect the absorption, metabolism, distribution and excretion of dietary food components and therefore exposure of the compound to the target organs and tissues of interest. It is of great interest to combine the assessment of dietary intake, the interplay of genetic factors, the influence of the gut microbiota, the pharmacokinetics, pattern of intakes and effects of other environmental factors in nutritional intervention studies. This represents one of the major challenges of modelling ―mammalian biocomplexity‖ and the effects of dietary components in both health and disease 75.