What Should We Eat Pdf

Invited review for book ‘New Research on Food Habits’. Ed. F. Columbus. Nova Science Publishers, New York. Accepted March 2008.

What should we eat: contradictory researches and the confused consumer! Poonam C. Mittal, Biochemistry Department, University of Allahabad, Allahabad – 211002, India. e-mail: [email protected].

Abstract: Food habits are constantly being impacted by the perpetually increasing amount of information available to every person. Print and electronic media is full of advise regarding what should be eaten and why. Recommendations are often conflicting. Many foods are declared detrimental to health on one day and beneficial the next. The average consumer ends up being confused or even disillusioned by the scientific method. A major reason for the confusion is that any food item is a heterogeneous mixture of hundreds of compounds, and the effect of one isolated compound may be the opposite of another compound in the same food. Taking the case of chocolate, if studied for the effect of sugar, it is declared harmful, but when studied for its flavonoids, it is declared desirable because it contributes to reduction in oxidative stress. Confusion also arises due to the fact that findings regarding effect of various food components on health are based on a variety of experimental and empirical models. These include epidemiological and experimental studies on humans, animal models, and in vitro studies of several types, involving tissue culture, cell isolates, and organelle isolates. But what may work in a simple in vitro model may not be validated by a more complex living system with more elaborate feedback controls. Another reason may be that experimental studies generally employ much higher concentrations of an isolated compound than is found in the natural food. Adding to the confusion are questions regarding the absorbability of the active compound and the role and feedback responses of the recipient system, which is ultimately the human body as a whole. Further, differences may exist between short term and long-term feedback responses from the recipient system, thus affecting the practical application of a laboratory finding. The present review will seek to identify controversies regarding the impact of some common foods on health, study conflicting reports from existing research, and seek reasons to explain them in the light of the foregoing. It may finally help us to conclude that dogmas with regard to food habits are harmful, but may get reinforced if the average, educated consumer gets a feeling that research is always conflicting and therefore not to be relied upon.

What should we eat: contradictory researches and the confused consumer! Poonam C. Mittal, Biochemistry Department, University of Allahabad, Allahabad – 211002, India. e-mail: [email protected].

Introduction In the early stages of evolution, eating was a biological act, without any capacity for thinking about what should be eaten and what should be avoided. Selection pressures must have favored those who got to be programmed with better ability to eat desirable foods and avoid undesirable ones. At some stage, the capacity must have developed for observing the effects of eating different things, memorizing, and passing the information so gained to others, particularly to offspring. Natural selection would now have favored those who developed this capacity better. It is no wonder that eating habits form an important component of all cultures. Probably in all cultures, food habits, though different, center around the consumption of cereals and legumes together, making full use of the complementary nature of their amino acid composition. The ancient seers must have deduced the importance of various foods and their combinations by keen observation. Records of some of these have been found, the Vedas being among the earliest records which originated in the last years of the second millennium and the early years of the first millennium BC. They contain much food related information as part of the indigenous Indian system called ayurveda. Nonetheless, both the biological and the cultural determinants of food habits are inadequate in today’s world. There are several reasons for this. Biologically, we are tuned to living in a food scarce world. By and large, cultural habits have also evolved for such a world. However, for large numbers of people in today’s world, any amount of food is available just for the asking, without any struggle, without any realistic fear of having to go hungry the next day. Biological adjustment cannot be expected to evolve in a short time. Cultural habits have also barely changed to accommodate this new reality. As a result, there are more people suffering from an excess of food and consequent obesity than from the problem of scarcity and hunger. Another recent phenomenon is that the modern world has a huge food processing industry which introduces artificial foods and molecules at a very rapid rate, compared to the slow assimilation of food habits as an evolutionary process. Then there is the pronounced intermingling of cultures due to movement of people and food products. More and more people are enjoying foods of other cultures. It is not clear what effects food from other cultures has, when taken by a body that has evolved in a different niche.

Clearly, in the modern world, neither biology (my taste buds must have evolved to know what is best for me) nor conventional wisdom about eating practices (our society has learnt the right eating practices over centuries best suited to our environment) can provide adequate guidance. Today science is an important component of human culture. The scientific method is expected to provide objective, bias free and reliable guidance to modify our food habits in order to live a healthier life. Lavoisier who lived in the 18 th century is credited with having laid the foundations of modern nutrition. Through the late 19th century till the early part of the 20th century, major developments took place in the area of nutrition, linking observations of deficiency symptoms to possible causes, leading to discovery of many vitamins. This was followed by more quantitative concepts to answer questions related to how much of each nutrient is required, and nutrition became a more organized science. This involved dependence on other sciences such as physics and technology for hitherto unknown methodologies, and interaction with newly developing subjects such as biochemistry for understanding the mechanisms by which food functioned in the body. A large part of the 20th century had seen war, famine and strife. Naturally, nutritional studies focused on food shortage and nutrient deficiencies. It was only towards the seventh decade that the links between affluence, obesity and consequent harmful effects on health became important issues requiring attention. The advent of the internet and its easy availability for the common man in the last two decades, has led to unprecedented access to information. Advice regarding what should be eaten and why, occupies substantial space in print and electronic media. Food habits are constantly being influenced by the perpetually increasing amount of information. Despite this, or because of it, there are more dogmas and misconceptions related to food and diet related issues than to most other areas of scientific study. Recommendations are often conflicting, so that many foods are declared detrimental to health on one day and beneficial the next. To inculcate rationality with regard to food habits, and to ensure that the average consumer is not disillusioned by the scientific method, it is desirable to examine some of the reasons for this trend. Scientific analysis of food related questions can be divided into two approaches. The first approach deals with analysis of different food items as chemical compounds and understanding the mechanisms and processes that take place when these compounds enter the body. The second approach is empirical. It tries to study the effects of a particular food on a large experimental group, as compared to a control group using statistical analysis. Of course, the two approaches interact with each other, knowledge gained from one aiding the design and interpretation of the other. Every food is a mixture of ‘healthy’ and ‘unhealthy’ compounds: Conventional wisdom was mostly based on observation, propagated by folklore and handed down generations. Much of folklore may not withstand the test of modern

scientific methods, for example, the classification of foods into hot and cold categories. This concept is found in many cultures such as Indian, Chinese and Latin American, but agreement with regard to details is lacking. For example, rice is considered cold in the Indian ayurvedic system but neutral in the Chinese system [1]. On the other hand, the utility of some traditional preparations like Chyawanprash, has been vindicated by present methods of science. Chyawanprash, an ayurvedic preparation, said to have been assembled by ancient sages two millenia ago, has the Indian gooseberry as its main ingredient, now known to be one of the richest sources of ascorbic acid, and also contains scores of herbs which contribute to the micronutrients required by the body. It has been found to prevent steroid-induced cataracts [2], induce a greater beneficial effect on glucose tolerance and lipoprotein profile as compared to vitamin C alone [3], and show genoprotective efficacy on smokers [4]. Developments in chromatographic, colorimetric, spectroscopic, microbiological many other techniques have led to an understanding of biological phenomenon biochemical mechanisms. These have found widespread applications to study foods their effects on the body. They have also led to better methods of analysis characterization of large numbers of compounds in a food.

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One of the major reasons for confusion with regard to benefits or harmful effects of any food is that almost every food item is a heterogeneous mixture of hundreds of compounds, and the effect of one isolated compound may be the opposite of another compound in the same food. Therefore, the reported desirability of a particular food would depend on which of its components has been investigated. Another investigation based on a different component could lead to a contrary recommendation. Also, if a food is a mixture of several compounds, and the experiment is designed to ensure that intake of just one of these compounds is different, the effect attributed to that compound may actually be because the compound under study interacts with some ingredient in the food to produce the effect but may not function if taken alone as a supplement. Such fluctuating reports can leave the general public confused. Chocolate is just one example that can help explain this statement. Chocolates were long condemned as junk foods, bad for the teeth, major causative for dental caries, an unhealthy source of empty calories, full of sugar and saturated fat. Then it came to be known that chocolates are a rich source of polyphenols such as (-)-epicatechin and (+)catechin, and their oligomers called procyanidins, all of which belong to the class of plant compounds known as flavanols. So they started being investigated for their possible healthy properties. This was because the health promoting properties of vegetables and fruit were attributed to the various flavonoids in them [5]. Flavonoids belong to a class of compounds known as polyphenolics. There are thousands of polyphenolics in the plant kingdom, of which flavonoids are the most abundant [6]. Soon there was a surge of studies to investigate the relationship between flavonoids in chocolate and health. The early years of this decade reported their role in protection against cardiovascular diseases [6], hypertension [7] and diabetes [8].

Chocolates have also been recognized as ‘feel good’ food because of their phenylethylamine content, which however, has also been implicated in the migraine triggering effect of chocolate. According to a 1998 report [9] analysts have detected more than 300 chemicals in chocolate. It is not clear whether this includes the polyphenols. Chocolates also contain alkaloids caffeine and the chemically similar theobromine [10]. Caffeine has been implicated as the reason of popularity of several drinks such as tea, coffee and colas because it raises heart rate, blood pressure, and stimulates the brain by raising dopamine. Theobromine has been implicated in the cough controlling function of chocolate as well as in its anti-hypertensive function [11, 12]. Chocolate also contains saturated fat and cholesterol, long considered harmful. However, it is now reported that cocoa butter which is the saturated fat in chocolate, does not raise bad cholesterol and is actually beneficial because it prevents the chocolate from sticking to teeth and causing dental caries. Moreover, it has a melting point just below body temperature at 350 C, which gives the melt-in-the-mouth quality to the final product. Apart from the constituents of the cocoa bean, chocolate also contains milk solids and sugar, so any attributes of chocolates have to be examined in the total product. Chocolates, as marketed, are also said to promote pimples and acne because of the milk fat that they contain, but since cocoa contains an abundance of antioxidant properties, the overall effect on the skin remains an open question [13]. The high sugar content of chocolates has also been a cause for concern due to a large number of detrimental effects attributed to sugar [14, 15, 16]. However, the conclusions of a workshopError: Reference source not found [17] in 2003 on ‘Sugars and Health’ failed to establish health concerns for which a direct association with sugar could be established. The only confirmatory evidence available at reasonable intakes of sugar was its link to an increased risk and incidence of dental caries. At high levels of intake of more than 125 g (the equivalent of 25 teaspoons) on a 2000 kcal diet, sugar was found to result in lowering of micronutrient intake (especially calcium). The final verdict was that “negative energy balance (for example, sedentary lifestyles) are more important in weight management, insulin sensitivity, and blood lipid concentrations than is the inclusion or exclusion of any particular dietary component, including sugars.” In this context, chocolate is also a calorie-rich food with a high fat content, so daily intake of chocolate requires reducing caloric intake of other foods. It is pertinent to note that the beneficial effects of chocolate on insulin sensitivity and blood pressure, described by Grassi and associates [8], were on intakes of 100g of dark chocolate, providing 480 kcal. The controversies continue, even as a recent study has reported that older women who consumed chocolate daily had lower bone density and strength [18]. These are just a few of the studies, based on some of the compounds in one food product which demonstrate how research findings can confuse a consumer. The Indian food table [19] lists about six hundred raw foods items, which can be combined in thousands of ways. Each food, be it wheat, rice or one of hundreds of vegetables, contains thousands of compounds, which can be studied for their individual properties,

and if the findings of each of these studies makes media headlines, the ensuing confusion can well be imagined. In this context, it is noteworthy that there is an explosion of research studies that are easily accessible to scientists as well as others, due to the internet. More than 15 million citations are available in MEDLINE, and 10 to 20 thousand are added every week [ 20]. These studies have varying methodology, are conducted on different populations, use differing test conditions and interventions [21]. Even highly accepted studies are refuted by subsequent work by the same and/or other investigators [22], so that experts are also confused by different answers to the same question. Other reasons for complications with regard to research findings that have been extensively discussed elsewhere include the biases introduced due to financial and/or career interests of the researchers, the funding agencies and the food industry [23, 24, 25, 26]. Varied models of research make similar eye-catching headlines: Confusion also arises because findings regarding effect of various food components on health are based on a variety of diverse experimental models and empirical studies. Experimental models may involve in vitro techniques, where the experiment is performed in a controlled environment, for example in cell isolates or organelle isolates, or where the cell is made to grow outside the living organism in tissue culture. Since test conditions may not correspond to those inside a living organism, results may not always replicate in vivo conditions. Studies may also be conducted in situ, which is intermediate between in vivo and in vitro conditions, for example in a cell within the intact organ, but after the animal is sacrificed, or ex vivo, where experimentation is done in or on living tissue in an artificial environment outside the organism. Experiments are also conducted on non-human animals such as rats, mice, dogs or guinea pigs, and results applied to humans, because there is large physiological similarity between them. Such studies enable researchers to perform experiments that are not ethical or feasible in humans. However, in all these models, there is the element of extrapolation. Studies involving humans are typically empirical, where research is based on evidence and not just theory. These include limited experimental studies involving intervention and clinical assessment, but are largely based on epidemiological models such as cohort, case-control and observational studies. The variables in such studies are enormous, so findings attributed to a particular event or phenomenon may actually be caused by another reason. Varied applications of statistics to such studies can also often yield diverse results for the same data. We will seek to illustrate this conjecture, based on recent researches on flavonoids, because in recent years, flavonoids are unparalleled in the media attention that they have attracted as wonder molecules, and have been at the centre stage of investigation for their role as anti-oxidants. The advice available to a consumer with regard to this group of compounds has perhaps occupied more newsprint than any other, with people being

advised to consume large amounts of tea, chocolates, beer, wine, soybean, various berries. The list of flavonoid-rich healthy foods can go on. Over 5000 naturally occurring flavonoids, responsible for color and flavor, have been characterized from various plants, and the USDA database [27] lists the content of several selected flavonoids in 225 commonly consumed foods. As mentioned earlier, the beneficial effects of fruits, vegetables and beverages such as tea, coffee, beer, wine and fruit drinks have been attributed more to flavonoids than to traditional antioxidant vitamins. This is partly because foods contain quantitatively more flavonoids than the antioxidant vitamins, ascorbic acid, the tocopherols, the carotenoids [28, 29, 30] . Consequently, the dietary intakes of ascorbic acid, the tocopherols, the carotenoids have been found to be one order of magnitude less (70, 7-10 and 2-3 mg respectively) than that of total flavonoids. Early studies reported flavonoid intakes to be 1 and 1.1 g/day [31]. Later studies, using better analytic methodologies, corroborate that the recommended nine daily servings of fruits and vegetables and moderate amounts of tea, coffee, wine, beer, or chocolate can provide well over 1000 mg of total phenols per day [32]. A large number of studies have demonstrated that ingestion of flavonoid-rich foods raises the antioxidant levels of blood and tissues, which in turn is responsible for their antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor functions, and also for prevention of cancer and cardiovascular diseases [33, 34]. These conclusions have been derived from studies on animals [35, 36, 37], cell isolates [37, 38, 39], in vitro models of human or animal tissues[40, 41]. Thus the strong antioxidant capacity and free-radical scavenging activities of flavonoids in vitro seems indubitable and interest in the possible health benefits of flavonoids has increased. Studies on humans have mostly indicated a protective effect of flavonoids [42, 43, 44] even though there are a few reports to the contrary [45]. Yet, epidemiologic studies exploring the role of flavonoids in human health have been inconclusive. Some studies support a protective effect of flavonoid consumption in cardiovascular disease and cancer, other studies demonstrate no effect, and a few studies suggest potential harm. Because there are many biological activities attributed to the flavonoids, some of which could be beneficial or detrimental depending on specific circumstances, it has been suggested that further studies in both the laboratory and with populations are required [46]. Questions have also been raised with regard to their absorption, and the emerging view is that their absorption is much lower and their half-life much shorter than that of other dietary antioxidants such as ascorbic acid and tocopherols, suggestive of the viewpoint that their capability to act as antioxidants in vivo is limited [47]. However, in vivo studies have consistently shown an increase in total antioxidant capacity of plasma on ingestion of flavonoids rich foods, leading to more questions regarding these conflicting findings. It has now been postulated that the increase in total plasma antioxidant capacity on ingestion of a wide variety of flavonoid rich fruits and vegetables is a secondary phenomenon resulting from their extensive metabolism to urate in vivo,

and that the macro- and micronutrients present in fruits and vegetables may directly or indirectly affect the total antioxidant capacity of plasma [32]. So the question regarding the in vivo efficacy of flavonoid-rich foods for their health promoting functions remains wide open, even as, in addition to the natural sources, the market is replete with nutritional supplements of specific flavonoids, such as quercetin, isoflavones, catechins and various other bioflavonoids. In this context, the question arises whether an isolated flavonoid will provide the same health benefit as it would, if it were present in the whole food, and even whether the isolated compound may actually be harmful [48]. Notwithstanding whether flavonoids have the beneficial effects attributed to them in recent times or not, it is likely that if each of the studies on flavonoids made newspaper headlines, as they have been found to do, dietary advise to the public to drink ‘n’ number of cups of tea / coffee / wine / juice of any of several berries, and include ‘x’ bars of chocolate and ‘y’ servings of tofu, yoghurt, salads, honey, fish, green chillies, olive oil etc. etc. per day would add up to several kilograms of food. It is more likely than not that this would translate into an excessive intake of energy, consequent obesity, and damage to health! Quantity matters! Physiological vs. pharmacological levels of intake: Experimental studies generally employ much higher concentrations of an isolated compound than is found in the natural food. When findings of such researches reach the common man, he looks for ways to achieve them, and is led to non-dietary sources of the nutrient. Thus nutritional supplements, called nutraceuticals, have become very popular. The amounts of various nutrients, especially vitamins and minerals, recommended by national and international agencies such as the Food and Nutrition Board (US) [49, 50] the FAO [51] and the ICMR [52 ] are generally much lower than those supplied as supplements. They are also not in the proportions as recommended, or as found in natural foods. The question arises whether our metabolic machinery is designed to handle amounts that are larger than can be obtained from diet. It is well known that fat-soluble vitamins are absorbed readily, stored for prolonged periods in the liver but cannot be readily excreted in urine. What is not clear is whether the large stores impact the metabolism in the body. A recent meta-analysis of studies dealing with vitamin E supplementation spanning from 1966 to 2004 revealed that high dosage >400 IU/d of vitamin E supplements may increase all-cause mortality and should be avoided, even as lower doses (< 150 IU/d )may have beneficial effects [53]. The amounts typically available from dietary sources are approximately 14 IU/d) [54]. Similarly, high doses of β -carotene supplementation have been reported to increase mortality rates [55]. Supplements of minerals are also common, but it is well accepted that minerals can have negative interactions with other minerals, which can impact their intestinal absorption, transport, utilization and storage.

Calcium and iron are two minerals, the absorption of which are known to depend on need of the body, because they are heavy metals, not easily excreted in the urine due to low solubility of their salts. Iron deficiency is the most common nutritional deficiency in the world, and has been implicated in a wide range of problems, such as developmental delays, behavioral disturbances and cognitive deficits in children and increased risk for a preterm delivery and low-birth weight babies in women. Supplementation of iron has been prescribed, almost universally, for pregnant women, adolescent girls, and newborns. However, concerns have been raised with regard to its possible harmful effects [56], and maternal complications consequent to oxidative stress have been reported when iron is given as a prophylactic to pregnant women who do not have iron-deficiency anemia [57]. The necessity of routine iron supplementation during pregnancy has been debated in industrialized countries, but is still advocated in developing countries, because traditional diets provide inadequate iron and where malaria and other infections causing increased losses are endemic [58]. Ascorbic acid is routinely administered with inorganic iron supplements to keep the ferrous salt in the reduced state. However, this has been reported to have adverse effects, such as oxidative DNA damage and consequently cancer in well nourished adults [59] and increased oxidative stress in the gastrointestinal tract [60]. High tissue iron concentrations have been associated with the development and progression of several pathological conditions, including certain cancers, liver and heart disease, diabetes, hormonal abnormalities, and immune system dysfunctions, due to free radical-mediated tissue damage, even as ingestion of antioxidant rich foods may prevent or delay primary and secondary effects associated with iron overload-related diseases. [61]. Absorption of zinc is known to get reduced by non-heme iron supplementation, although postabsorptive interactions between these nutrients are less clear [62]. Excessive intake of zinc can reduce copper absorption, and excessive copper intake can result in reduced absorption of manganese, zinc, and iron [63]. Among the macrominerals, calcium has attracted maximum attention as a desirable supplement, especially for elderly women who are at risk for osteoporosis. Dietary calcium deficiency has not been established as the major etiological factor for osteoporosis, yet supplements are being taken by most postmenopausal women and even elderly males as a prophylactic measure against osteoporosis. Apart from its benefits on bone health, calcium supplementation has been linked to increase in high density lipoprotein cholesterol and decrease in low density lipoprotein cholesterol [64]. However, calcium supplementation has been reported to adversely affect vascular health [65] by accelerating vascular calcification [66, 67, 68, 69]. More recently, calcium supplementation in healthy postmenopausal women has been found to be associated with upward trends in cardiovascular event rates [70]. It has also been implicated in development of brain lesions [71]. Such examples, of positive and negative consequences of supplements providing doses of known nutrients, which are nutritionally unattainable, abound in literature.

Distinction is required between physiological and pharmacological doses. It is therefore important that pharmacological doses should not be taken without sufficient reason, that the consumer should be informed of possible harmful effects, that they should be administered under supervision, and that their potentially detrimental effect should be balanced against the likely benefits. Amounts obtained from a balanced diet cannot be excessive, and therefore are unlikely to cause harm, so they should be encouraged. Pharmacological doses of nutritional supplements should also be regulated like other medicines, to be taken only under medical advice. Short-term responses are different from long-term responses: It is generally assumed that more is better, and this stands true for nutrients, growth rates and parameters such as blood hemoglobin, even as it has been argued that functional criteria are preferable [72]. However, calorie restriction is beneficial in the long run, and promotes longevity [73, 74, 75 ], even though in the short run, growth is compromised. It is possible that short-term responses to any deficiency are different from the long term responses. So in case of energy deficits, for example, the immediate response is slowing down of growth, but in the long run, as an adaptive measure, the organism is known to reduce metabolic rates and achieve catch up. Life has evolved through shortages, and the physiology of all organisms is designed to hold on to nutrients. Our digestive system is designed to absorb several times the amounts of dietary fuels, carbohydrate, protein and fat, normally present in the diet. However, it is unable to adapt to the relatively recent phenomenon of availability of excessive food by reducing digestion and absorption. Our adipose tissue is designed to hold on to the absorbed excess. Anyone who has lost weight knows how difficult it is to keep it off. There is intricate metabolic regulation to conserve body fat, and regain it even if availability of energy remains low, as in continued dieting. It has been suggested that the human body is likely to have a genetically determined setpoint weight that is controlled by metabolic hormones and fat cell enzymes [76]. On the other hand, in countries such as India, poor children continue to grow on dietary energy intakes barely above those required for basal metabolism, and the gestation and lactation performance of poor women compares favorably in many respects with that of upper class women [77]. In animal studies it has been shown that the nutritional inadequacy of the diet is, to a large extent, compensated for, by better utilization of dietary energy, protein and improved efficiency of nitrogen utilization [78, 79, 80 81 , ]. Also, rats switched from a low protein diet in early life to a moderate protein diet, and back to a low protein diet were found to display a more efficient and rapid adaptation to the switches, as judged by growth as well as rate of serum protein turnover, than those switched from a high protein to a low protein diet after an intervening period on a moderate protein diet [82]. This suggests that adaptive mechanisms that come into play during periods of protein deprivation appear to persist later when the stress is reduced, and may in fact be beneficial to the organism. Similarly, it is interesting to find that rats fed carotene as the only source of vitamin A in early life were more efficient in converting it to vitamin A later in life, than those fed preformed vitamin A throughout [ 83] emphasizing the long term responses of the organism to nutrient utilization.

The difference between short term and long-term feedback responses from the recipient system are also likely to affect the practical application of laboratory findings, because of elaborate feedback controls found in the complex living system. The role of feedback responses of the recipient system: the complex human body. The recipient system of any nutrient can consist of a fairly homogenous system such as found in a cell isolate or tissue culture, or it can be as heterogeneous and complex as the human body. The human body is a conglomerate of about a hundred trillion cells (which incidentally is four orders of magnitude more than all the Homo sapiens on earth!) and they work in marvelous unison to maintain homeostasis, (or is it homeodynamics?). To do this, there are intricate feedback mechanisms, so the effect of a particular compound on the homogenous system may not get extrapolated to the complex system. In biochemistry, it is generally found that if one set of chemicals drives the system in a given direction, another set of chemicals will drive it in an opposing direction. If one or both of these opposing influences are non-linear, an equilibrium point(s) results to which the system gravitates. Any perturbation, generally in the form of a chemical stimulus resulting from the influx of a nutrient, nutrient supplement, drug, or even thought, can trigger a negative feedback system to reestablish the equilibrium. Since ultimately the system moves to a predetermined equilibrium, there may be results of an immediate response to an intervention, which are often not sustained in the long run, as feedback systems come into play. As a consequence of negative feedback mechanisms, many qualitatively different stimuli oppose each other, and finally arrive at a point close to the equilibrium point. By positive feedback, the system responds in the same direction as the perturbation, so the signal is amplified. In biological systems, the controls are typically based on negative feedback, through varied mechanisms. Many multienzyme pathways in metabolism are regulated; the final product inhibits an early reaction in the pathway, after it is formed in sufficient quantities, thus preventing excessive amounts of its own formation. Hormonal regulation of blood sugar, blood pressure, body temperature and erythropoiesis are but a few examples of well documented negative feedback controls. Disruption of negative feedback can lead to undesirable results. Once the principle that equilibrium is to be maintained in the long run is acknowledged, it is logical to accept that all perturbations will eventually get attenuated, explaining why many drugs, supplements and nutrients produce the expected result in short term studies, but in the long run, the efficacy is lost. Most traditional methodologies used in biological sciences have adopted the reductionist approach to knowledge. However, as discussed in relation to feedback approaches, the system is likely to behave differently when impacted by diverse stimuli, than when it is in a controlled environment. One of the great current debates in biology concerns whether the observed behavior of a system can be accounted for in terms of the

behaviors of its subcomponents, and it has been suggested that holistic approaches may be more predictive and make for better understanding of the functioning of the body. Systems biology develops these concepts and attempts to understand the integrated function of complex, multicomponent biological systems ranging from interacting proteins that carry out specific tasks to whole organisms [84] Scientists dealing with varied aspects of food, nutrition and nutritional biochemistry have more recently been involved in developing new approaches to accommodate the complexities of the organism, leading to the development of new disciplines such as nutrigenomics, which has the potential to prescribe tailored dietary regimens specific to the individuals’ requirements. Nutrigenomics links genomics, transcriptomics, proteomics and metabolomics to human nutrition. Genomics allows the study of the genetic abilities of an individual to metabolize nutrients based on its entire genome. It includes the study of genome-nutrient interactions, including the role of nutrients and dietary components in regulation of genome structure, expression and stability and the role of genetic variation on individual nutrient requirements. Transcriptomics allows the global study of gene expression at the RNA level, which will ultimately determine the extent of transcription of a gene. Knowing the proteomics will help in determining whether the enzymes and other required proteins have the desired conformation to perform optimal catalytic function as required. Finally, it includes metabolomics, the development of which began in 1970, to investigate the ideas of Linus Pauling with a view to studying relationships between biological variability and wide ranges of nutritional requirements. Metabolomics [85], specifically nutritional metabolomics, is concerned with metabolic pathways and networks and includes regulation of metabolic pathways and networks by nutrients and other food components. It summates all the metabolites in body fluids, which are impacted by endogenous factors such as age, sex, body composition, genetics, underlying pathologies, circadian rhythms and resting metabolic rate and exogenous factors such as diet, including all known and hitherto unknown nutrients as well as non-nutrients such as dietary fiber, additives, pollutants, drugs etc., and the large number of signals from the intestinal microflora. A very large number of compounds make the metabolome, which can be likened to a metabolic fingerprint which reflects the balance of an individual’s metabolism. These compounds need to be identified, quantified and their relative proportions analyzed and interpreted. This has led to the development of metabonomics which is concerned with the quantitative measurement of the metabolome. [85]. Metabolomics requires the establishment of analytical methods that can profile human serum and urinary metabolites to assess nutritional imbalances and disease risk. Such analysis will require the application of sensitive techniques such as nuclear magnetic resonance, functional magnetic resonance imaging and high performance liquid chromatography, and handling of a large amount of mathematical data.

It should be clear from the foregoing, that the utilization of compounds from food in the body is an extremely complex issue, with large individual variations due to interactions between genetics and overall food habits. It is generally not true that every laboratory finding is applicable to every one in the population. Therefore, categorical statements about the benefits, or otherwise, of a food do not apply universally. Such statements are inherently misleading and should be avoided. Limitations of the methodology of science: The role and responsibility of the media: Statistics forms the basis for evaluating the results of modern scientific studies, whether based on observation or on varied experimental designs. But even the basic assumptions, on which statistical tests are based, are not devoid of controversy. Usually, inferences are drawn, in a mechanical manner, using statistical techniques, without appreciation of the assumptions on which these techniques are based. Very often the techniques are based on assumptions of normal distribution, even for such data as are not drawn from normal distribution. If different samples are taken from a normal population, they will usually yield different sample means. One of the most frequently used statistical techniques, the null hypothesis testing, provides the probability that two samples have been drawn from the same normal distribution. If this probability is less than an arbitrarily chosen number p (usually 0.05, 0.01, or 0.001), the two samples (experimental group and the control group) are regarded as drawn from different populations. It is usual to interpret this by the statement that the treatment given to the experimental group has been effective at the significance level p. The null hypothesis testing is used in a very wide variety of experimental designs because it allows a crisp decision – to accept or reject a hypothesis. It is used to compare an experimental group with a control group, to determine whether they belong to the same normal population, with regard to the parameter under investigation. It is assumed that the populations under study are matched with regard to all other variables except the one being investigated. Results are presented as dichotomous –the null hypothesis is accepted or not, thereby concluding that the effect is / is not observed. In the above procedure, the conventional choice of p = 0.05, 0.01 or 0.001 seems to be arbitrary. The choice of p should depend on the nature of the question asked and an assessment of the benefits and risks involved. The practice of using the p value for testing the null hypothesis has been criticized for arbitrarily dividing results into significant and not significant [86, 87]. Extremely small differences can become statistically significant if the sample size is sufficiently large, and find their way into scientific writings of repute. Null hypothesis significance testing has been called a ‘research quality assurance test’ and is a requirement for experimental research to be published. However, it is not always appreciated that this widely used

statistical methodology is not without its problems when extended to practical advice; small statistically significant differences may not be of practical significance. It is important that reports of scientific research are conveyed to the consumers in a reasonably accurate manner. As discussed earlier, there is an extremely large, and often conflicting, amount of scientific data being generated, and the consumer ends up being confused. It is important that the consumer is guided to be able to make informed choices with regard to healthy food and desirable food habits. Media should desist from giving the misleading impression that everyone who eats a particular food, or follows a particular practice, will benefit from it. It is therefore suggested that media should report scientific findings to the consumer only when reasonable consensus has been reached on a particular issue. In the absence of such a consensus, the reports should include full details of the study design and findings in a language that is comprehensible to the typical educated consumer yet does not give misleading impressions. For example, they should give the sample size and the extent of the effect observed, how many among the experimental group/s exhibited a response in a direction opposite to the group average and how many among the control group showed the response even without the intervention. The consumer should also be made aware of the limitations of the scientific methodology. The tendency to reduce a study to a simple statement expressing that ‘x’ food / habit causes ‘y’ effect needs to be restricted, both by scientists and media. The common man should be encouraged to take his own decisions regarding whether to try out a particular food for a particular condition. The media should facilitate such decision making, by improving its information content, and seek to educate the consumer to take informed decisions, rather than make categorical headlines about foods as if they apply to all individuals in a society. For example instead of saying ‘Eat chocolates for lowering blood pressure’, media should be encouraged to say that of ‘n’ persons who ate ‘m’ grams of chocolate everyday, ‘x’ persons showed a ‘y-z’ percent reduction in blood pressure. Headlines based on laboratory findings based on in vitro or animal studies can be even more damaging. For example if a purified compound from a plant shows a health benefit on rats, but makes media headlines that everyone who consumes a food containing that compound will benefit from it, the result can sometimes even be harmful. We need to have guidelines for media to refrain from making potentially irresponsible headlines. Conclusion In the final analysis, we can conclude that there is a never-before quantum of information available at the click of a button, but uncertainties and methodological limitations are inherent in the scientific method. This is certainly not to denigrate research per se, which, despite conflicting observations, or because of them, certainly promotes

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